US20050129668A1 - Methods, instruments and materials for chondrocyte cell transplantation - Google Patents
Methods, instruments and materials for chondrocyte cell transplantation Download PDFInfo
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- US20050129668A1 US20050129668A1 US11/050,523 US5052305A US2005129668A1 US 20050129668 A1 US20050129668 A1 US 20050129668A1 US 5052305 A US5052305 A US 5052305A US 2005129668 A1 US2005129668 A1 US 2005129668A1
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- support matrix
- cartilage
- collagen
- site
- defect
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- A61L2430/00—Materials or treatment for tissue regeneration
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Definitions
- the present invention relates to the field of chondrocyte cell transplantation, bone and cartilage grafting, healing, joint repair and the prevention of arthritic pathologies.
- the present invention is directed to new methods and instruments for chondrocyte cell transplantation and cartilage regeneration, as previously described in U.S. provisional patent application No. 60/096,597, filed Aug. 14, 1998, and a U.S. provisional patent application No. 60/146,683, filed Aug. 2, 1999, both of which are hereby incorporated by reference.
- a method for regeneration-treatment of cartilage would be most useful and could be performed at an earlier stage of joint damage, thus reducing the number of patients needing artificial joint replacement surgery. With such preventive methods of treatment, the number of patients developing osteoarthritis would also decrease.
- Wakitani et al. (Tissue Engineering 4 (4), 429 (1989) described the use of collagen Type I gels in animal experiments to repair cartilage defects. In all instances, the major problem was the lack of biomechanical properties required for functional tissue repair.
- the articular chondrocytes are specialized mesenchymal derived cells found exclusively in cartilage.
- Cartilage is an avascular tissue whose physical properties depend on the extracellular matrix produced by the chondrocytes.
- chondrocytes undergo a maturation leading to cellular hypertrophy, characterized by the onset of expression of type X collagen (Upholt, W. B. and Olsen, R. R., In: Cartilage Molecular Aspects (Hall, B. & Newman, S., Eds.) CRC Boca Raton 1991, 43; Reichenberger, E. et al., Dev. Biol. 1991, 148, 562; Kirsch, T. et al., Differentiation, 1992, 52, 89; Stephens, M. et al., J. Cell Sci. 1993, 103, 1111).
- the present invention provides an implantable article including a support matrix which can support the growth and attachment of cells thereto, and a method of implanting such an article to regenerate cells at an implantation location.
- the present invention provides a method for the effective treatment of articulating joint surface cartilage in an animal by the transplantation of an implantable article including chondrocyte cells retained on an absorbable support matrix.
- the support matrix is made from collagen such as Type I or Type II collagen, and the chondrocyte cells are autologous or homologous.
- the implantable article preferably is secured to the transplantation site by an adhesive or mechanical retention means.
- the present invention also is directed to an instrument for placing and manipulating the implantable article at the site of implantation, and a retention device for securing the implantable article to the site of implantation.
- the present invention is also directed to an implantable article for cartilage repair in an animal, the implantable article including chondrocyte cells retained to an absorbable support matrix, and a method of making same.
- FIG. 1A shows a typical articulating end of a bone in a knee joint, having an articulating surface with a cartilaginous cap.
- FIG. 1B shows a cartilage defect or injury to a cartilaginous cap of an articulating end of a bone.
- FIG. 2 shows one embodiment of an implantable article according to the present invention.
- FIG. 3 shows how the implantable article of FIG. 2 may be disposed for implantation in an arthroscopic introducer such as that shown in FIG. 4 .
- FIG. 4 shows an arthroscopic introducer for implanting the implantable article at the site of implantation, according to the present invention.
- FIG. 5 is a drawing schematically illustrating the placement of the implantable article of FIG. 3 at the site of defect or injury in the cartilaginous cap using two access channels which can accommodate arthroscopic instruments.
- FIG. 6 is a schematic cross section of cartilage with a defect or injury which does not extend into the subchondral layer, and an implantable article according to the present invention secured by adhesive to the site of defect or injury.
- FIG. 7 is a schematic cross section of cartilage with a defect or injury which does not extend into the subchondral layer, and an implantable article secured to the site of defect or injury by a mechanical retainer.
- FIG. 8 illustrates one embodiment of the mechanical retainer used to secure the implantable article to the site of defect or injury.
- FIG. 9 is a schematic cross section of cartilage with a defect or injury which extends into the subchondral layer, and an implantable article according to the present invention secured by adhesive to the site of defect or injury.
- FIG. 10 is a schematic cross section of cartilage with a defect or injury which extends into the subehondral layer, and an implantable article secured to the site of defect or injury by a mechanical retainer.
- FIG. 11A is a black and white copy of a color microphotograph of histological specimen of a solid support matrix at the beginning of chondrocyte cell growth thereon.
- FIG. 11A A is the color microphotograph of FIG. 11A .
- FIG. 11B is a black and white copy of a color microphotograph showing the support matrix of FIG. 11A loaded with chondrocyte cells after three weeks of chondrocyte cell growth thereon.
- FIG. 11B B is the color microphotograph of FIG. 11B .
- FIG. 11C is a photograph showing a support matrix formed of collagen having chondrocyte cells grown thereon, shown by immunohistochemical staining.
- FIG. 11D is a photograph showing a support matrix formed of collagen, and having chondrocyte cells grown thereon in a bioreactor system, shown by immunohistochemical staining.
- FIG. 1A shows a typical articulating end of a bone in a human knee joint 10 .
- Knee joint 10 is formed by the juncture of femur 12 and tibia 14 , and healthy cartilage 16 covering the articulating end of femur 12 .
- FIG. 1B shows a circular area of defect or injury 18 (hereinafter sometimes defect 18 ) in cartilage 16 .
- the present invention includes a cartilage repair implant and implantation method and apparatus for such an implant.
- the implant comprises a support matrix and autologous or homologous chondrocyte cells retained thereon.
- the support matrix is a material which will support chondrocyte cell growth and which, over time will be absorbed in a body of a patient receiving the implant.
- the transplantation procedure may be by arthroscopic, minimally invasive or open surgery technique.
- the method of the invention also contemplates the use of suitable allogenic and xenogenic chondrocyte cells for the repair of a cartilage defect.
- FIG. 2 shows such an implant. More specifically, an implantable article 20 includes a support matrix 22 having chondrocyte cells 24 retained thereon.
- a suitable support matrix 22 will be a solid or gel-Like, scaffold characterized by being able to hold a stable form for a period of time to enable the growth of chondrocytes cells thereon, both before transplant and after transplant, and to provide a system similar to the natural environment of the chondrocyte cells to optimize chondrocyte cell growth differentiation.
- Support matrix 22 will be stable for a period of time sufficient to allow full cartilage repair and then be absorbed by the body over time, for example, within two to three months without leaving any significant traces and without forming toxic degradation products.
- the term “absorbed” is meant to include processes by which the support matrix is broken down by natural biological processes, and the broken down support matrix and degradation products thereof are disposed of, for example, through the lymphatics or blood vessels.
- support matrix 22 preferably is a physiologically absorbable, non-antigenic membrane-like material.
- support matrix 22 preferably is in a sheet like form having one relatively smooth side 21 and one relatively rough side 23 .
- Rough side 23 for example, is fibrous and typically faces cartilage defect 18 and promotes chondrocyte cell ingrowth, while the smooth side 21 typically faces away from cartilage defect 18 and impedes tissue ingrowth.
- support matrix 22 is formed of polypeptides or proteins.
- the polypeptides or proteins are obtained from natural sources, e.g., from mammals. Artificial materials, however, having physical and chemical properties comparable to polypeptides or proteins from natural sources, may also be used to form support matrix 22 . It is also preferred that support matrix 22 is reversibly deformable as it is handled by the user so implantable article 20 can be manipulated and then returns to its original shape as described below, during one aspect of the present invention.
- a preferred material from which support matrix 22 can be formed is collagen such as obtained from equine, porcine, bovine, ovine, and chicken. Suitable materials from which support matrix 22 can be formed include Chondro-Cell® (a commercially available type II collagen matrix pad, Ed. Geistlich Söhne, Switzerland), and Chondro-Gide® (a commercially available type I collagen matrix pad, Ed. Geistlich Söhne, Switzerland).
- a support matrix 22 formed of collagen Type I is somewhat stiffer than a support matrix formed from collagen Type II, although Type II collagen matrixes may also be used.
- An implantable article as described above may be made, for example, by culturing chondrocyte cells on this support matrix as described in more detail below.
- a cartilage biopsy first is harvested by arthroscopic technique from a non-weight bearing area in a joint of the patient and transported to the laboratory in a growth media containing 20% fetal calf serum.
- the cartilage biopsy is then treated with an enzyme such as trypsin ethylenediaminetetraacetic acid (EDTA), a proteolytic enzyme and binding agent, to isolate and extract cartilage chondrocyte cells.
- EDTA trypsin ethylenediaminetetraacetic acid
- the extracted chondrocyte cells are then cultured in the growth media from an initial cell count of about 50,000 cells to a final count of about 20 million chondrocyte cells or more.
- the growth media is exchanged for a transplant media which contains 10% autologous serum (that is, serum extracted from the patient's blood as described below). Then, the cultured chondrocyte cells in the transplant media are soaked into and penetrate support matrix 22 , and continue multiplying to form implantable article 22 . Implantable article 22 is then implanted at a site of cartilage defect 18 in the patient.
- a transplant media which contains 10% autologous serum (that is, serum extracted from the patient's blood as described below).
- defect or injury 18 can be treated directly, enlarged slightly, or sculpted by surgical procedure prior to implant, to accommodate implantable article 20 .
- the culturing procedure as well as the growth and transplant medias are described by way of example, in detail below, starting first with a description of a laboratory procedure used to process the harvested cartilage biopsy and to culture the chondrocyte cells according to the present invention.
- the growth media used to treat the cartilage biopsy during the culturing process and to grow the cartilage chondrocyte cells is prepared by mixing together 2.5 ml gentomycin suflate (concentration 70 micromole/liter), 4.0 ml amphotericin (concentration 2.2 micromole/liter; tradename Fungizone®, an antifungal available from Squibb), 15 ml 1-ascorbic acid (300 micromole/liter), 100 ml fetal calf serum (final concentration 20%), and the remainder DMEM/F12 media to produce about 400 ml of growth media. (The same growth media is also used to transport the cartilage biopsy from the hospital to the laboratory in which the chondrocyte cells are extracted and multiplied.)
- Blood obtained from the patient is centrifuged at approximately 3,000 rpm to separate the blood serum from other blood constituents.
- the separated blood serum is saved and used at a later stage of the culturing process and transplant procedure.
- Cartilage biopsy previously harvested from a patient for autologous transplantation is shipped in the growth media described above to the laboratory where it will be cultured.
- the growth media is decanted to separate out the cartilage biopsy, and discarded upon arrival at the laboratory.
- the cartilage biopsy is then washed in plain DMEM/F12 at least three times to remove the film of fetal calf serum on the cartilage biopsy.
- the cartilage biopsy is then washed in a composition which includes the growth media described above, to which 28 ml trypsin EDTA (concentration 0.055) has been added. In this composition it is incubated for five to ten minutes at 37° C., and 5% CO 2 . After incubation, the cartilage biopsy is washed two to three times in the growth media, to cleanse the biopsy of any of the trypsin enzyme. The cartilage is then weighed. Typically, the minimum amount of cartilage required to grow cartilage chondrocyte cells is about 80-100 mg. A somewhat larger amount, such as 200 to 300 mg, is preferred.
- the cartilage After weighing, the cartilage is placed in a mixture of 2 ml collagenase (conentration 5,000 enzymatic units; a digestive enzyme) in approximately 50 ml plain DMEM/F12 media, and minced to allow the enzyme to partially digest the cartilage. After mincing, the minced cartilage is transferred into a bottle using a funnel, and approximately 50 ml of the collagenase and plain DMEM/F12 mixture is added to the bottle. The minced cartilage is then incubated for 17 to 21 hours at 37° C., and 5% CO 2 .
- collagenase conentration 5,000 enzymatic units; a digestive enzyme
- approximately 50 ml of the collagenase and plain DMEM/F12 mixture is added to the bottle.
- the minced cartilage is then incubated for 17 to 21 hours at 37° C., and 5% CO 2 .
- the incubated minced cartilage is then strained using 40 ⁇ m mesh, centrifuged (at 1054 rpm, or 200 times gravity) for 10 minutes, and washed twice with growth media.
- the chondrocyte cells are then counted to determine their viability, following which the chondrocyte cells are incubated in the growth media for at least two weeks at 37° C., and 5% CO 2 , during which time the growth media was changed three to four times.
- the chondrocyte cells are removed by trypsinization and centrifugation from the growth media, and transferred to a transplant media containing 1.25 ml gentomycin sulfate (concentration 70 micromole/liter), 2.0 ml amphotericin (concentration 2.2 micromole/liter; tradename Fungizone®, an antifungal available from Squibb), 7.5 ml 1-ascorbic acid (300 micromole/liter), 25 ml autologous blood serum (final concentration 10%), and the remainder DMEM/F12 media to produce about 300 ml of transplant media.
- gentomycin sulfate concentration 70 micromole/liter
- 2.0 ml amphotericin concentration 2.2 micromole/liter
- tradename Fungizone® an antifungal available from Squibb
- 7.5 ml 1-ascorbic acid 300 micromole/liter
- 25 ml autologous blood serum final concentration 10%
- the remainder DMEM/F12 media to produce
- Support matrix 22 is then cut to a suitable size fitting into the bottom of a well in a NUNCLONTM cell culture tray, and then placed under aseptic conditions on the bottom of the well with 1-2 ml transplant media.
- a sufficient number of cultivated cartilage chondrocyte cells e.g. 3-10 million chondrocyte cells
- support matrix 22 is then soaked into support matrix 22 , and incubated approximately 72 hours at 37° C., and 5% CO 2 to allow the chondrocyte cells to continue to grow. During this incubation, the chondrocyte cells arrange in clusters and adhere to support matrix 22 .
- support matrix 22 supports the growth and retention of chondrocyte cells thereon in a sufficient number to form implantable article 20 , without significant loss of the biomechanical properties of support matrix 22 .
- Support matrix 22 also provides an environment to support continued growth of chondrocyte cells after implantation of the implantable article at the site of cartilage defect.
- the chondrocyte cells are transferred to the transplant media and then grown directly on support matrix 22 for a period of at least two weeks.
- implantable article 20 temporarily can be deformed without mechanical destruction or loss of the chondrocyte cells adhered to support matrix 22 . This deformation is completely reversible once implantable article 20 is introduced into the joint or is placed on the surface to be treated, as described below.
- support matrix 22 onto which chondrocyte cells are grown or loaded in a sufficient number temporarily can be deformed in a way that allows its introduction into the working device of an arthroscope without mechanical destruction or loss of its chondrocyte cell load.
- this matrix can be secured by adhesive or mechanical retention means, to the cartilage defect area without impairing the further in situ differentiation of the chondrocytes and the regeneration of the natural cartilage matrix material.
- Other aspects of the present invention include instruments to place implantable article 20 at the implantation site, and a mechanical retention device to hold implantable article 20 at the implantation site.
- the implantation procedure is performed by an arthroscopic technique.
- FIG. 3 shows how implantable article 20 can be rolled across the diameter thereof to form a spirally would transplant cylindrical so that implantable article 20 can be delivered to an implantation site through a working channel 26 of an arthroscopic introducer 28 .
- a suitable arthroscopic introducer is depicted in FIG. 4 .
- an arthroscopic introducer 30 includes a working channel 32 having a diameter and length suitable to enter the joint of interest and to deliver the desired dimension of implantable article 20 .
- the diameter of working channel 32 is approximately 8-20 mm, and the length is approximately 30-60 cm.
- an injection channel 34 accommodating a retractable and removable needle 36 .
- Injection channel 32 is attached to a handle 38 which is telescopically depressible at least partially into working channel 32 .
- Needle 36 extends the length of injection channel 34 and allows fluids to pass therethrough to the site of implantation.
- Injection channel 34 is moved within working channel 32 by telescopically moving handle 38 toward or away from the implantation site.
- Introducer 30 also includes a cap 40 made of rubber or other suitable material, slideably engaged on introducer 30 .
- cap 40 surrounds the site of cartilage defect and excludes fluids, such as blood and other natural fluids, from flowing into the site of cartilage defect.
- Introducer 30 also has two or more outwardly biased gripping elements 42 attached to handle 38 , for grasping, introducing and placing implantable article 20 at the implantation site.
- gripping elements 42 engage the inside of working channel 32 and are moved toward each other in a gripping manner (as handle 38 is moved toward the user), and away from each other to release the grip (as handle 38 is moved away from the user).
- Such telescopic movement may be controlled by a biasing element (not shown) disposed within handle 38 which allows injection channel 34 and gripping elements 42 to be slideably advanced and retracted within working channel 42 .
- FIGS. 5-7 show a typical arthroscopic procedure for implanting implantable article 22 at a site of implantation such as knee joint 10 .
- Defective cartilage 18 is removed from the site of defect, preferably to a depth above subchondral layer 44 leaving a well 46 (See FIGS. 6-7 ).
- the defect site is prepared to receive implantable article 22 . If the subchondral layer has been disturbed to the point that bleeding occurs at the implantation site, the site may first be covered with any absorbable material which acts as a hemostatic barrier.
- site preparation may include injection of a biocompatible glue through needle 36 into well 46 .
- a biocompatible glue seen as adhesive 48 in FIG. 6
- Implantable article 20 previously cut to the desired dimension, and rolled into a spiral cylindrical shape as shown in FIG. 5 is then gripped by gripping elements 42 and held within the end of arthroscopic introducer 30 .
- Arthroscopic introducer 30 holding implantable article 20 within its end is then advanced to the site of implantation through an access channel 33 , released from gripping elements 42 , and unrolled using gripping elements 42 or allowed to unroll as it exits working channel 32 .
- Access channel 33 includes one or more channels that allow instruments such as introducer 30 and visualization instruments, to access the transplantation site.
- gripping elements 42 implantable article 20 is manipulated such that rough side 23 of implantable article 20 faces well 46 and is gently held in place in well 46 to allow adhesive 48 to harden and bind implantable article 20 in well 46 .
- FIG. 7 mechanical retention means such as absorbable pins, anchors, screws or sutures are used to secure implantable article 20 in well 46 .
- Suitable pins 50 include Ortho-PinTM (a commercially available lactide co-polymer pin, Ed. Geistlich Söhne, Switzerland).
- FIG. 8 shows one embodiment of absorbable pin 50 .
- pin 50 includes head 52 , intramedullar channel 54 within shaft 56 , and one or more retention rings 58 .
- pin 50 will vary with the particular use, but, typically, pin 50 is about 10-15 mm in length, head 52 is about 4 mm in diameter, intramedullar channel 54 is approximately 1.2 mm in diameter, shaft 56 is approximately 2 mm in diameter, and retention rings 58 are about 2.5 mm in diameter. Retention rings 58 serve to anchor pin 50 into healthy cartilage surrounding the cartilage defect.
- Pin 50 is formed from any material that will not harm the body and can be absorbed or otherwise broken down by the body after a period of time.
- pin 50 may be made from polylactide.
- a second access channel having one or more channels may be used to allow access of instruments to the site of implantation to assist in placement of the implantable article, adhesive and/or mechanical retention means, or to allow for access or visualization instruments to the site of implantation.
- Such a separate access channel may also be used to perform one or more of the functions described in relation to arthroscopic introducer 30 or other arthroscopic instruments.
- the above procedure is modified to include placement of a hemostatic barrier 62 in well 46 prior to placement of implantable article 20 .
- Hemostatic barrier 62 inhibits the growth or invasion of vascular tissue, osteocytes, fibroplasts, etc. into developing cartilage. This is believed to allow hyaline cartilage to grow at the transplantation site. Suitable hemostatic barriers will inhibit vascularization and cellular invasion into the developing cartilage to optimize formation of cartilage and to achieve growth of the full thickness of cartilage at the defect site.
- the hemostatic barrier is stable for an extended period of time to allow full cartilage repair, and then will be absorbed or otherwise broken down by the body over time.
- a suitable hemostatic barrier is Surgicel® W1912 (Ethicon, Ltd., United Kingdom), an absorbable hemostat formed of oxidized regenerated sterile cellulose.
- the above described surgical instruments are manufactured from any material, such as metal and/or plastic or silicone, suitable for making disposable or multi-use reusable surgical instruments.
- Certain aspects of the invention have been exemplified by using an in vitro system to study the behavior of chondrocyte cells when in contact with different support matrices. This in vitro testing predicts the ability of certain materials to mechanically withstand the arthroscopic procedure and also provides information as to chondrocyte cell growing behavior.
- Chondrocyte cells were grown for three weeks in the growth media described above in a CO 2 incubator at 37° C. and handled in a Class 100 laboratory at Verigen Transplantation Service ApS, Copenhagen, D K or at University of Lübeck, Lübeck, Germany. [Note that other compositions of growth media may also be used for culturing the chondrocyte cells.] The cells were trypsinised using trypsin EDTA for 5 to 10 minutes and counted using Trypan Blue viability staining in a Bürker-Türk chamber. The cell count was adjusted to 7.5 ⁇ 10 5 chondrocyte cells per milliliter. One NUNCLONTM plate was uncovered in the Class 100 laboratory.
- a support matrix material specifically a Chondro-Gide® collagen membrane, was cut to a suitable size to fit into the bottom of a well in a NUNCLONTM cell culture tray. In this case a circle of a size of approximately 4 cm was placed under aseptic conditions on the bottom of the well.
- chondrocyte cells were transferred from the growth media to the transplant media described above, and approximately 5 ⁇ 10 6 chondrocyte cells in 5 ml transplant media were placed directly on top of the support matrix and dispersed over the surface thereof.
- the plate was incubated in a CO 2 incubator at 37° C. for 3 days. After this period the chondrocyte cells had arranged in clusters and started to grow on the support matrix, and could not be removed from the support matrix by rinsing it with medium or even by mechanically exerting mild pressure on the matrix.
- the transplant media was decanted and the support matrix holding chondrocyte cells grown thereon was cold refrigerated in 2.5% glutaraldehyde containing 0.1 M sodium salt of dimethylarsinic acid, added as fixative.
- the support matrix was stained with Safranin O for histological evaluation.
- a black and white copy of a color microphotograph thereof is shown in FIG. 11A .
- a color version of the microphotograph is also submitted as FIG. 11A A to better illustrate the features of the microphotograph.
- Chondrocytes were grown for three weeks in the growth media described above in a CO 2 incubator at 37° C. and handled in a Class 100 laboratory at Verigen Transplantation Service ApS, Copenhagen, D K or at University of Lübeck, Germany. The cells were trypsinised using trypsin EDTA for 5 to 10 minutes and counted using Trypan Blue viability staining in a Bürker-Türk chamber. The chondrocyte cell count was adjusted to 5 ⁇ 10 5 chondrocyte cells per milliliter. One NUNCLONTM plate was uncovered in the Class 100 laboratory.
- the Chondro-Gide® support matrix as in Example 1, was cut to a suitable size fitting into the bottom of a well in the NUNCLONTM cell culture tray. In this case a circle of approximately 4 cm in diameter was placed under aseptic conditions on the bottom of the well.
- the chondrocyte cells were transferred from the growth media to the transplant media described above, and approximately 5 ⁇ 10 5 cells in 5 ml transplant media were placed directly on top of the support matrix and dispersed over the surface of the support matrix.
- the plate was incubated in a CO 2 incubator at 37° C. for 3 weeks.
- the transplant media was decanted, and the support matrix holding the chondrocyte cells thereon was cold refrigerated in 2.5% glutaraldehyde containing 0.1 M sodium salt of dimethylarsinic acid, added as fixative.
- the support matrix was stained with Safranin O for histological evaluation.
- collagene membranes were fixed in methanol-acetone and stained for aggrecane and Type II collagen using rabbit anti-human type II collagen and mouse anti-humane aggrecane.
- Primary antibodies were visualized using fluorescent secondary antibodies.
- a black and white copy of a color microphotograph thereof is shown in FIG. 11B showing chondrocyte cells 24 .
- the color version is also submitted as FIG. 1B B to better illustrate the features of the microphotograph.
- the chondrocyte cells were observed to have grown and multiplied on the support matrix building clusters in the center of the carrier and lining up along the surface.
- Chondrocytes were grown for three weeks in the growth media described above in a CO 2 incubator at 37° C. and handled in a Class 100 laboratory at Verigen Transplantation Service ApS, Copenhagen, D K or at University of Lübeck, Germany.
- the chondrocyte cells were trypsinised using trypsin EDTA for 5 to 10 minutes and counted using Trypan Blue viability staining in a Bürker-Türk chamber.
- the chondrocyte cell count was adjusted to 5 ⁇ 10 5 chondrocyte cells per milliliter.
- One NUNCLONTM plate was uncovered in the Class 100 laboratory.
- the Chondro-Gide® support matrix as in Example 1, was cut to a suitable size fitting into the bottom of a well in the NUNCLONTM cell culture tray. In this case a circle of approximately 4 cm in diameter was placed under aseptic conditions on the bottom of the well.
- the chondrocyte cells were transferred from the growth media to the transplant media described above, and approximately 5 ⁇ 10 6 cells in 5 ml transplant media were placed directly on top of the support matrix and dispersed over the surface of the support matrix.
- the plate was incubated in a CO 2 incubator at 37° C. for 3 weeks.
- the support matrix holding the grown chondrocyte cells was then incubated with collagenase for 16 hours.
- the support matrix holding the chondrocyte cells was then centrifuged.
- Cells were seeded on a NUNCLONTM plate and an aliquot counted using Trypan Blue viability staining in a Bürker-Türk chamber. A microphotograph thereof is shown in FIG. 11C .
- the total calculated cell number was found to be 6 ⁇ 10 6 and the viability was >95%.
- the chondrocyte cells produced from this cartilage were grown on a support matrix according to Example 3 for a period of six weeks.
- chondrocyte cells loaded on a Chondro-Gide® support matrix were then implanted via an arthroscopic surgery technique. Fixation occurred in one sheep by gluing the matrix to the treated area with fibrin glue, and in the other sheep the matrix was fixed using polylactide pins as described above according to the present invention.
- the sheep were kept isolated and the knee was kept in a fixed dressing for one week.
- the present invention also includes a method of growing chondrocyte cells on a support matrix in a bioreactor such as bioreactor Model No. 1302 available from MinuCells GMBH Ltd., D-93077 Bad Abbach, Germany.
- a bioreactor such as bioreactor Model No. 1302 available from MinuCells GMBH Ltd., D-93077 Bad Abbach, Germany.
- a bioreactor constant flow of growth or transplant media is passed by the support matrix, and chondrocyte cells can be grown on the support matrix at a faster rate without having to replace the growth or transplant media, for example, every 24 to 96 hours as required when using the NUNCLONTM plate.
- Culturing of the chondrocyte cells can take place in the growth media for the entire cell culturing process or in the transplant media for the entire cell culturing process. That is, no transfer of the chondrocyte cells from the growth media to the transplant media is required.
- the chondrocyte cells can be transferred from the growth media to the transplant media, and vice versa, at any point in the culturing process, depending on the particular condition of the chondrocyte cells, the stage of growth of the chondrocyte cells, and/or the condition of the patient.
- the chondrocyte cells, whether in the growth media or in transplant media need to be soaked into the support matrix for a period of only about 2-3 hours before transplantation to allow attachment of a sufficient number of chondrocyte cells to the support matrix.
- the growth media or transplant media whichever is being used at the particular stage of the culturing process, must be replaced, for example, about every 24 to 96 hours depending, for example, on the number and viability of the cells.
- this invention encompasses essentially any article (and use thereof) comprising a support matrix, preferably flexible and preferably absorbable in a living body, which support matrix acts as a support for living cells, which are typically grown thereon for some minimum period of time and attached thereto. Such attachment may be by virtue of cell growth penetrating the surface of the matrix.
- the support matrix provides sufficient physical integrity to the implantable article to facilitate its manipulation, such as the manipulation necessary to implant it into a living body.
Abstract
The present invention provides a method for the effective treatment of articulating joint surface cartilage in an animal by the transplantation of an implantable article including chondrocyte cells retained to an absorbable support matrix. The present invention is also directed to an instrument for placing and manipulating the implantable article at the site of implantation, and a retention device for securing the implantable article to the site of implantation. The present invention is also directed to an implantable article for cartilage repair in an animal, the implantable article including chondrocyte cells retained on an absorbable support matrix, and a method of making same. This invention also encompasses, in general, an article comprising an absorbable flexible support matrix for living cells grown and adhered thereto.
Description
- The present invention relates to the field of chondrocyte cell transplantation, bone and cartilage grafting, healing, joint repair and the prevention of arthritic pathologies. In particular, the present invention is directed to new methods and instruments for chondrocyte cell transplantation and cartilage regeneration, as previously described in U.S. provisional patent application No. 60/096,597, filed Aug. 14, 1998, and a U.S. provisional patent application No. 60/146,683, filed Aug. 2, 1999, both of which are hereby incorporated by reference.
- More than 500,000 arthroplastic procedures and total joint replacements are performed each year in the United States. Approximately the same number of similar procedures are performed in Europe. Included in this number in Europe are about 90,000 total knee replacements and around 50,000 procedures to repair defects in the knee. These numbers are essentially the same in the U.S. (Praemer A., Furner S., Rice, D. P., Musculoskeletal conditions in the United States, American Academy of Orthopaedic Surgeons, Park Ridge, Ill., 1992, 125).
- A method for regeneration-treatment of cartilage would be most useful and could be performed at an earlier stage of joint damage, thus reducing the number of patients needing artificial joint replacement surgery. With such preventive methods of treatment, the number of patients developing osteoarthritis would also decrease.
- Techniques used for resurfacing the cartilage structure in joints have mainly attempted to induce the repair of cartilage using subchondral drilling, abrasion and other methods whereby there is excision of diseased cartilage and subchondral bone, leaving vascularized cancerous bone exposed (Insall, J., Clin, Orthop. 1974, 101, 61; Ficat R. P. et al., Clin. Orthop. 1979, 144, 74; Johnson L. L., in Operative Arthroscopy, McGinty J. B., Ed., Raven Press, New York, 1991, 341).
- Coon and Cahn (Science 1966, 153, 1116 ) described a technique for the cultivation of cartilage synthesizing cells from chick embryo somites. Later, Cahn and Lasher (PNAS USA 1967, 58, 1131) used the system for analysis of the involvement of DNA synthesis as a prerequisite for cartilage differentiation. Chondrocyte cells respond to both EFG and FGF by growth (Gospodarowicz and Mescher, J. Cell Physiology) 1977, 93, 117), but ultimately lose their differentiated function (Benya et al., Cell 1978, 15, 1313). Methods for growing chondrocyte cells were described and are principally being used with minor adjustments by Brittberg, M. et al. (new Engl. J. Med. 1994, 331, 889). Cells grown using these methods were used as autologous transplants into knee joints of patients. Additionally, Kolettas et al. (J. Cell Science 1995, 108, 1991) examined the expression of cartilage-specific molecules such as collagens and proteoglycans under prolonged cell culturing. They found that despite morphological changes during culturing in monolayer cultures (Aulthouse, A. et al., In vitro Cell Dev. Biol., 1989, 25, 659; Archer, C. et al., J. Cell Sci. 1990, 97, 361; Hänselmann, H. et al., J. Cell Sci. 1994, 107, 17; Bonaventure, J. et al., Exp. Cell Res. 1994, 212, 97), when compared to suspension cultures grown over agarose gels, alginate beads or as spinner cultures (retaining a round cell morphology) tested by various scientists did not change the chondrocyte—expressed markers such as types II and IX collagens and the large aggregating proteoglycans, aggrecan, versican and link protein did not change (Kolettas, E. et al., J. Cell Science 1995, 108, 1991 ).
- Wakitani et al. (Tissue Engineering 4 (4), 429 (1989) described the use of collagen Type I gels in animal experiments to repair cartilage defects. In all instances, the major problem was the lack of biomechanical properties required for functional tissue repair.
- The articular chondrocytes are specialized mesenchymal derived cells found exclusively in cartilage. Cartilage is an avascular tissue whose physical properties depend on the extracellular matrix produced by the chondrocytes. During endochondral ossification, chondrocytes undergo a maturation leading to cellular hypertrophy, characterized by the onset of expression of type X collagen (Upholt, W. B. and Olsen, R. R., In: Cartilage Molecular Aspects (Hall, B. & Newman, S., Eds.) CRC Boca Raton 1991, 43; Reichenberger, E. et al., Dev. Biol. 1991, 148, 562; Kirsch, T. et al., Differentiation, 1992, 52, 89; Stephens, M. et al., J. Cell Sci. 1993, 103, 1111).
- Excessive degradation of type II collagen in the outer layers of articular surfaces of joints is also caused by osteoarthritis. The collagen network is accordingly weakened and subsequently develops fibrillation whereby matrix substances such as proteoglycans are lost and eventually displaced entirely. Such fibrillation of weakened osteoarthritis cartilage can reach down to the calcified cartilage and into the subchondral bone (Kempson, G. E. et al., Biochem. Biophys. Acta 1976, 428, 741; Rot, V. and Mow, V. C., J. Bone Joint Surgery, 1980, 62A, 1102; Woo, S. L.-Y. et al., in Handbook of Bioengineering (R. Skalak and S. Chien Eds), McGraw-Hill, New York, 1987, pp. 4.14.44).
- Descriptions of the basic development, histological and microscopic anatomy of bone, cartilage and other such connective tissues can be found for example in Wheater, Burkitt and Daniels, Functional Histology, 2nd Edition (Churchill Livingstone, London 1987, Chp. 4). Descriptions of the basic histological anatomy of defects in bone, cartilage and other connective tissue also can be found for example in Wheater, Burkitt, Stevens and Lowe, Basic Histopathology, (Churchill Livingstone, London, 1985, Chp. 21).
- Although the need for chondrocyte cell transplantation has been described at length at least in the above mentioned references, there remains a need for a satisfactory and effective procedure for cartilage repair either by transplantation or otherwise.
- The present invention provides an implantable article including a support matrix which can support the growth and attachment of cells thereto, and a method of implanting such an article to regenerate cells at an implantation location. In one embodiment, the present invention provides a method for the effective treatment of articulating joint surface cartilage in an animal by the transplantation of an implantable article including chondrocyte cells retained on an absorbable support matrix. In one embodiment, the support matrix is made from collagen such as Type I or Type II collagen, and the chondrocyte cells are autologous or homologous. The implantable article preferably is secured to the transplantation site by an adhesive or mechanical retention means. The present invention also is directed to an instrument for placing and manipulating the implantable article at the site of implantation, and a retention device for securing the implantable article to the site of implantation.
- The present invention is also directed to an implantable article for cartilage repair in an animal, the implantable article including chondrocyte cells retained to an absorbable support matrix, and a method of making same.
- The present invention may be better understood by reference to the description which follows taken together with the accompanying figures which illustrate the present invention wherein:
-
FIG. 1A shows a typical articulating end of a bone in a knee joint, having an articulating surface with a cartilaginous cap. -
FIG. 1B shows a cartilage defect or injury to a cartilaginous cap of an articulating end of a bone. -
FIG. 2 shows one embodiment of an implantable article according to the present invention. -
FIG. 3 shows how the implantable article ofFIG. 2 may be disposed for implantation in an arthroscopic introducer such as that shown inFIG. 4 . -
FIG. 4 shows an arthroscopic introducer for implanting the implantable article at the site of implantation, according to the present invention. -
FIG. 5 is a drawing schematically illustrating the placement of the implantable article ofFIG. 3 at the site of defect or injury in the cartilaginous cap using two access channels which can accommodate arthroscopic instruments. -
FIG. 6 is a schematic cross section of cartilage with a defect or injury which does not extend into the subchondral layer, and an implantable article according to the present invention secured by adhesive to the site of defect or injury. -
FIG. 7 is a schematic cross section of cartilage with a defect or injury which does not extend into the subchondral layer, and an implantable article secured to the site of defect or injury by a mechanical retainer. -
FIG. 8 illustrates one embodiment of the mechanical retainer used to secure the implantable article to the site of defect or injury. -
FIG. 9 is a schematic cross section of cartilage with a defect or injury which extends into the subchondral layer, and an implantable article according to the present invention secured by adhesive to the site of defect or injury. -
FIG. 10 is a schematic cross section of cartilage with a defect or injury which extends into the subehondral layer, and an implantable article secured to the site of defect or injury by a mechanical retainer. -
FIG. 11A is a black and white copy of a color microphotograph of histological specimen of a solid support matrix at the beginning of chondrocyte cell growth thereon. -
FIG. 11A A is the color microphotograph ofFIG. 11A . -
FIG. 11B is a black and white copy of a color microphotograph showing the support matrix ofFIG. 11A loaded with chondrocyte cells after three weeks of chondrocyte cell growth thereon. -
FIG. 11B B is the color microphotograph ofFIG. 11B . -
FIG. 11C is a photograph showing a support matrix formed of collagen having chondrocyte cells grown thereon, shown by immunohistochemical staining. -
FIG. 11D is a photograph showing a support matrix formed of collagen, and having chondrocyte cells grown thereon in a bioreactor system, shown by immunohistochemical staining. - As discussed above, one joint of the human body where cartilage damage and defects often occur is the knee.
FIG. 1A shows a typical articulating end of a bone in a human knee joint 10. Knee joint 10 is formed by the juncture offemur 12 andtibia 14, andhealthy cartilage 16 covering the articulating end offemur 12.FIG. 1B shows a circular area of defect or injury 18 (hereinafter sometimes defect 18) incartilage 16. - The present invention includes a cartilage repair implant and implantation method and apparatus for such an implant. The implant comprises a support matrix and autologous or homologous chondrocyte cells retained thereon. Generally, the support matrix is a material which will support chondrocyte cell growth and which, over time will be absorbed in a body of a patient receiving the implant. The transplantation procedure may be by arthroscopic, minimally invasive or open surgery technique. The method of the invention also contemplates the use of suitable allogenic and xenogenic chondrocyte cells for the repair of a cartilage defect.
-
FIG. 2 shows such an implant. More specifically, animplantable article 20 includes asupport matrix 22 havingchondrocyte cells 24 retained thereon. Asuitable support matrix 22 will be a solid or gel-Like, scaffold characterized by being able to hold a stable form for a period of time to enable the growth of chondrocytes cells thereon, both before transplant and after transplant, and to provide a system similar to the natural environment of the chondrocyte cells to optimize chondrocyte cell growth differentiation. -
Support matrix 22 will be stable for a period of time sufficient to allow full cartilage repair and then be absorbed by the body over time, for example, within two to three months without leaving any significant traces and without forming toxic degradation products. The term “absorbed” is meant to include processes by which the support matrix is broken down by natural biological processes, and the broken down support matrix and degradation products thereof are disposed of, for example, through the lymphatics or blood vessels. Accordingly,support matrix 22 preferably is a physiologically absorbable, non-antigenic membrane-like material. Further,support matrix 22 preferably is in a sheet like form having one relativelysmooth side 21 and one relativelyrough side 23.Rough side 23, for example, is fibrous and typically facescartilage defect 18 and promotes chondrocyte cell ingrowth, while thesmooth side 21 typically faces away fromcartilage defect 18 and impedes tissue ingrowth. - In one embodiment,
support matrix 22 is formed of polypeptides or proteins. Preferably, the polypeptides or proteins are obtained from natural sources, e.g., from mammals. Artificial materials, however, having physical and chemical properties comparable to polypeptides or proteins from natural sources, may also be used to formsupport matrix 22. It is also preferred thatsupport matrix 22 is reversibly deformable as it is handled by the user soimplantable article 20 can be manipulated and then returns to its original shape as described below, during one aspect of the present invention. - A preferred material from which support
matrix 22 can be formed is collagen such as obtained from equine, porcine, bovine, ovine, and chicken. Suitable materials from which supportmatrix 22 can be formed include Chondro-Cell® (a commercially available type II collagen matrix pad, Ed. Geistlich Söhne, Switzerland), and Chondro-Gide® (a commercially available type I collagen matrix pad, Ed. Geistlich Söhne, Switzerland). Asupport matrix 22 formed of collagen Type I is somewhat stiffer than a support matrix formed from collagen Type II, although Type II collagen matrixes may also be used. - An implantable article as described above may be made, for example, by culturing chondrocyte cells on this support matrix as described in more detail below.
- For an autologous implant, a cartilage biopsy first is harvested by arthroscopic technique from a non-weight bearing area in a joint of the patient and transported to the laboratory in a growth media containing 20% fetal calf serum. The cartilage biopsy is then treated with an enzyme such as trypsin ethylenediaminetetraacetic acid (EDTA), a proteolytic enzyme and binding agent, to isolate and extract cartilage chondrocyte cells. The extracted chondrocyte cells are then cultured in the growth media from an initial cell count of about 50,000 cells to a final count of about 20 million chondrocyte cells or more.
- Three (3) days before reimplantation, the growth media is exchanged for a transplant media which contains 10% autologous serum (that is, serum extracted from the patient's blood as described below). Then, the cultured chondrocyte cells in the transplant media are soaked into and penetrate
support matrix 22, and continue multiplying to formimplantable article 22.Implantable article 22 is then implanted at a site ofcartilage defect 18 in the patient. - It is understood that defect or
injury 18 can be treated directly, enlarged slightly, or sculpted by surgical procedure prior to implant, to accommodateimplantable article 20. The culturing procedure as well as the growth and transplant medias are described by way of example, in detail below, starting first with a description of a laboratory procedure used to process the harvested cartilage biopsy and to culture the chondrocyte cells according to the present invention. - Growth media (hereinafter, “the growth media”) used to treat the cartilage biopsy during the culturing process and to grow the cartilage chondrocyte cells is prepared by mixing together 2.5 ml gentomycin suflate (concentration 70 micromole/liter), 4.0 ml amphotericin (concentration 2.2 micromole/liter; tradename Fungizone®, an antifungal available from Squibb), 15 ml 1-ascorbic acid (300 micromole/liter), 100 ml fetal calf serum (
final concentration 20%), and the remainder DMEM/F12 media to produce about 400 ml of growth media. (The same growth media is also used to transport the cartilage biopsy from the hospital to the laboratory in which the chondrocyte cells are extracted and multiplied.) - Blood obtained from the patient is centrifuged at approximately 3,000 rpm to separate the blood serum from other blood constituents. The separated blood serum is saved and used at a later stage of the culturing process and transplant procedure.
- Cartilage biopsy previously harvested from a patient for autologous transplantation is shipped in the growth media described above to the laboratory where it will be cultured. The growth media is decanted to separate out the cartilage biopsy, and discarded upon arrival at the laboratory. The cartilage biopsy is then washed in plain DMEM/F12 at least three times to remove the film of fetal calf serum on the cartilage biopsy.
- The cartilage biopsy is then washed in a composition which includes the growth media described above, to which 28 ml trypsin EDTA (concentration 0.055) has been added. In this composition it is incubated for five to ten minutes at 37° C., and 5% CO2. After incubation, the cartilage biopsy is washed two to three times in the growth media, to cleanse the biopsy of any of the trypsin enzyme. The cartilage is then weighed. Typically, the minimum amount of cartilage required to grow cartilage chondrocyte cells is about 80-100 mg. A somewhat larger amount, such as 200 to 300 mg, is preferred. After weighing, the cartilage is placed in a mixture of 2 ml collagenase (conentration 5,000 enzymatic units; a digestive enzyme) in approximately 50 ml plain DMEM/F12 media, and minced to allow the enzyme to partially digest the cartilage. After mincing, the minced cartilage is transferred into a bottle using a funnel, and approximately 50 ml of the collagenase and plain DMEM/F12 mixture is added to the bottle. The minced cartilage is then incubated for 17 to 21 hours at 37° C., and 5% CO2.
- In one embodiment, the incubated minced cartilage is then strained using 40 μm mesh, centrifuged (at 1054 rpm, or 200 times gravity) for 10 minutes, and washed twice with growth media. The chondrocyte cells are then counted to determine their viability, following which the chondrocyte cells are incubated in the growth media for at least two weeks at 37° C., and 5% CO2, during which time the growth media was changed three to four times.
- At least three days before re-implantation in the patient, the chondrocyte cells are removed by trypsinization and centrifugation from the growth media, and transferred to a transplant media containing 1.25 ml gentomycin sulfate (concentration 70 micromole/liter), 2.0 ml amphotericin (concentration 2.2 micromole/liter; tradename Fungizone®, an antifungal available from Squibb), 7.5 ml 1-ascorbic acid (300 micromole/liter), 25 ml autologous blood serum (
final concentration 10%), and the remainder DMEM/F12 media to produce about 300 ml of transplant media. -
Support matrix 22 is then cut to a suitable size fitting into the bottom of a well in a NUNCLON™ cell culture tray, and then placed under aseptic conditions on the bottom of the well with 1-2 ml transplant media. A sufficient number of cultivated cartilage chondrocyte cells (e.g. 3-10 million chondrocyte cells) in approximately 5-10 ml of the transplant media, are then soaked intosupport matrix 22, and incubated approximately 72 hours at 37° C., and 5% CO2 to allow the chondrocyte cells to continue to grow. During this incubation, the chondrocyte cells arrange in clusters and adhere to supportmatrix 22. Using this method, it has been found thatsupport matrix 22 supports the growth and retention of chondrocyte cells thereon in a sufficient number to formimplantable article 20, without significant loss of the biomechanical properties ofsupport matrix 22.Support matrix 22 also provides an environment to support continued growth of chondrocyte cells after implantation of the implantable article at the site of cartilage defect. - In another embodiment, following the 17-21 hour incubation period and after determining cell count and viability as discussed above, the chondrocyte cells are transferred to the transplant media and then grown directly on
support matrix 22 for a period of at least two weeks. - It has been found that
implantable article 20 temporarily can be deformed without mechanical destruction or loss of the chondrocyte cells adhered to supportmatrix 22. This deformation is completely reversible onceimplantable article 20 is introduced into the joint or is placed on the surface to be treated, as described below. - Accordingly, and in accordance with another aspect of the present invention,
support matrix 22 onto which chondrocyte cells are grown or loaded in a sufficient number, temporarily can be deformed in a way that allows its introduction into the working device of an arthroscope without mechanical destruction or loss of its chondrocyte cell load. - At the same time it has been found that this matrix can be secured by adhesive or mechanical retention means, to the cartilage defect area without impairing the further in situ differentiation of the chondrocytes and the regeneration of the natural cartilage matrix material.
- Other aspects of the present invention include instruments to place
implantable article 20 at the implantation site, and a mechanical retention device to holdimplantable article 20 at the implantation site. - In one embodiment of the present invention, the implantation procedure is performed by an arthroscopic technique.
FIG. 3 shows howimplantable article 20 can be rolled across the diameter thereof to form a spirally would transplant cylindrical so thatimplantable article 20 can be delivered to an implantation site through a workingchannel 26 of anarthroscopic introducer 28. A suitable arthroscopic introducer is depicted inFIG. 4 . - In
FIG. 4 , anarthroscopic introducer 30 includes a workingchannel 32 having a diameter and length suitable to enter the joint of interest and to deliver the desired dimension ofimplantable article 20. For example, for most procedures, the diameter of workingchannel 32 is approximately 8-20 mm, and the length is approximately 30-60 cm. Within and longitudinally movable with respect to workingchannel 32 is aninjection channel 34 accommodating a retractable andremovable needle 36.Injection channel 32 is attached to ahandle 38 which is telescopically depressible at least partially into workingchannel 32.Needle 36 extends the length ofinjection channel 34 and allows fluids to pass therethrough to the site of implantation.Injection channel 34 is moved within workingchannel 32 by telescopically movinghandle 38 toward or away from the implantation site. -
Introducer 30 also includes acap 40 made of rubber or other suitable material, slideably engaged onintroducer 30. In use, cap 40 surrounds the site of cartilage defect and excludes fluids, such as blood and other natural fluids, from flowing into the site of cartilage defect.Introducer 30 also has two or more outwardly biasedgripping elements 42 attached to handle 38, for grasping, introducing and placingimplantable article 20 at the implantation site. In use, ashandle 38 is telescopically moved toward and away from the user,gripping elements 42 engage the inside of workingchannel 32 and are moved toward each other in a gripping manner (ashandle 38 is moved toward the user), and away from each other to release the grip (ashandle 38 is moved away from the user). Such telescopic movement may be controlled by a biasing element (not shown) disposed withinhandle 38 which allowsinjection channel 34 andgripping elements 42 to be slideably advanced and retracted within workingchannel 42. -
FIGS. 5-7 show a typical arthroscopic procedure for implantingimplantable article 22 at a site of implantation such as knee joint 10.Defective cartilage 18 is removed from the site of defect, preferably to a depth abovesubchondral layer 44 leaving a well 46 (SeeFIGS. 6-7 ). Aftercartilage defect 18 is removed, the defect site is prepared to receiveimplantable article 22. If the subchondral layer has been disturbed to the point that bleeding occurs at the implantation site, the site may first be covered with any absorbable material which acts as a hemostatic barrier. - Otherwise, site preparation may include injection of a biocompatible glue through
needle 36 intowell 46. Such a biocompatible glue, seen as adhesive 48 inFIG. 6 , may comprise an organic fibrin glue (e.g., Tisseel®, fibrin based adhesive, Baxter, Austria or a fibrin glue prepared in the surgical theater using autologous blood samples). -
Implantable article 20 previously cut to the desired dimension, and rolled into a spiral cylindrical shape as shown inFIG. 5 is then gripped by grippingelements 42 and held within the end ofarthroscopic introducer 30.Arthroscopic introducer 30 holdingimplantable article 20 within its end, is then advanced to the site of implantation through anaccess channel 33, released fromgripping elements 42, and unrolled usinggripping elements 42 or allowed to unroll as it exits workingchannel 32.Access channel 33 includes one or more channels that allow instruments such asintroducer 30 and visualization instruments, to access the transplantation site. Usinggripping elements 42,implantable article 20 is manipulated such thatrough side 23 ofimplantable article 20 faces well 46 and is gently held in place in well 46 to allow adhesive 48 to harden and bindimplantable article 20 inwell 46. - In another embodiment (
FIG. 7 ), mechanical retention means such as absorbable pins, anchors, screws or sutures are used to secureimplantable article 20 inwell 46.Suitable pins 50 include Ortho-Pin™ (a commercially available lactide co-polymer pin, Ed. Geistlich Söhne, Switzerland).FIG. 8 shows one embodiment ofabsorbable pin 50. In this embodiment,pin 50 includeshead 52,intramedullar channel 54 withinshaft 56, and one or more retention rings 58. The dimensions ofpin 50 will vary with the particular use, but, typically,pin 50 is about 10-15 mm in length,head 52 is about 4 mm in diameter,intramedullar channel 54 is approximately 1.2 mm in diameter,shaft 56 is approximately 2 mm in diameter, and retention rings 58 are about 2.5 mm in diameter. Retention rings 58 serve to anchorpin 50 into healthy cartilage surrounding the cartilage defect.Pin 50 is formed from any material that will not harm the body and can be absorbed or otherwise broken down by the body after a period of time. For example, pin 50 may be made from polylactide. - It is also contemplated to be within the scope of the present invention to use a combination of adhesive 48 and mechanical retention means such as
pins 50 to secureimplantable article 20 inwell 46. - As shown in
FIG. 6 , a second access channel having one or more channels may be used to allow access of instruments to the site of implantation to assist in placement of the implantable article, adhesive and/or mechanical retention means, or to allow for access or visualization instruments to the site of implantation. Such a separate access channel may also be used to perform one or more of the functions described in relation toarthroscopic introducer 30 or other arthroscopic instruments. - As indicated above, where
cartilage defect 18 extends into or belowsubchondral layer 44, or requires removal of cartilage into or belowsubchondral layer 44 as shown inFIGS. 9 and 10 , the above procedure is modified to include placement of ahemostatic barrier 62 in well 46 prior to placement ofimplantable article 20.Hemostatic barrier 62 inhibits the growth or invasion of vascular tissue, osteocytes, fibroplasts, etc. into developing cartilage. This is believed to allow hyaline cartilage to grow at the transplantation site. Suitable hemostatic barriers will inhibit vascularization and cellular invasion into the developing cartilage to optimize formation of cartilage and to achieve growth of the full thickness of cartilage at the defect site. Preferably, the hemostatic barrier is stable for an extended period of time to allow full cartilage repair, and then will be absorbed or otherwise broken down by the body over time. A suitable hemostatic barrier is Surgicel® W1912 (Ethicon, Ltd., United Kingdom), an absorbable hemostat formed of oxidized regenerated sterile cellulose. - The above described surgical instruments are manufactured from any material, such as metal and/or plastic or silicone, suitable for making disposable or multi-use reusable surgical instruments.
- Certain aspects of the invention have been exemplified by using an in vitro system to study the behavior of chondrocyte cells when in contact with different support matrices. This in vitro testing predicts the ability of certain materials to mechanically withstand the arthroscopic procedure and also provides information as to chondrocyte cell growing behavior.
- These and other aspects of the instant invention may be better understood from the following examples, which are meant to illustrate but not to limit the present invention.
- Chondrocyte cells were grown for three weeks in the growth media described above in a CO2 incubator at 37° C. and handled in a Class 100 laboratory at Verigen Transplantation Service ApS, Copenhagen, D K or at University of Lübeck, Lübeck, Germany. [Note that other compositions of growth media may also be used for culturing the chondrocyte cells.] The cells were trypsinised using trypsin EDTA for 5 to 10 minutes and counted using Trypan Blue viability staining in a Bürker-Türk chamber. The cell count was adjusted to 7.5×105 chondrocyte cells per milliliter. One NUNCLON™ plate was uncovered in the Class 100 laboratory.
- A support matrix material, specifically a Chondro-Gide® collagen membrane, was cut to a suitable size to fit into the bottom of a well in a NUNCLON™ cell culture tray. In this case a circle of a size of approximately 4 cm was placed under aseptic conditions on the bottom of the well.
- After three weeks, chondrocyte cells were transferred from the growth media to the transplant media described above, and approximately 5×106 chondrocyte cells in 5 ml transplant media were placed directly on top of the support matrix and dispersed over the surface thereof. The plate was incubated in a CO2 incubator at 37° C. for 3 days. After this period the chondrocyte cells had arranged in clusters and started to grow on the support matrix, and could not be removed from the support matrix by rinsing it with medium or even by mechanically exerting mild pressure on the matrix.
- At the end of the incubation period, the transplant media was decanted and the support matrix holding chondrocyte cells grown thereon was cold refrigerated in 2.5% glutaraldehyde containing 0.1 M sodium salt of dimethylarsinic acid, added as fixative. The support matrix was stained with Safranin O for histological evaluation. A black and white copy of a color microphotograph thereof is shown in
FIG. 11A . A color version of the microphotograph is also submitted asFIG. 11A A to better illustrate the features of the microphotograph. - Chondrocytes were grown for three weeks in the growth media described above in a CO2 incubator at 37° C. and handled in a Class 100 laboratory at Verigen Transplantation Service ApS, Copenhagen, D K or at University of Lübeck, Germany. The cells were trypsinised using trypsin EDTA for 5 to 10 minutes and counted using Trypan Blue viability staining in a Bürker-Türk chamber. The chondrocyte cell count was adjusted to 5×105 chondrocyte cells per milliliter. One NUNCLON™ plate was uncovered in the Class 100 laboratory.
- The Chondro-Gide® support matrix, as in Example 1, was cut to a suitable size fitting into the bottom of a well in the NUNCLON™ cell culture tray. In this case a circle of approximately 4 cm in diameter was placed under aseptic conditions on the bottom of the well.
- After three weeks, the chondrocyte cells were transferred from the growth media to the transplant media described above, and approximately 5×105 cells in 5 ml transplant media were placed directly on top of the support matrix and dispersed over the surface of the support matrix. The plate was incubated in a CO2 incubator at 37° C. for 3 weeks.
- At the end of the incubation period, the transplant media was decanted, and the support matrix holding the chondrocyte cells thereon was cold refrigerated in 2.5% glutaraldehyde containing 0.1 M sodium salt of dimethylarsinic acid, added as fixative. The support matrix was stained with Safranin O for histological evaluation. For immunohistochemistry, collagene membranes were fixed in methanol-acetone and stained for aggrecane and Type II collagen using rabbit anti-human type II collagen and mouse anti-humane aggrecane. Primary antibodies were visualized using fluorescent secondary antibodies. A black and white copy of a color microphotograph thereof is shown in
FIG. 11B showingchondrocyte cells 24. The color version is also submitted asFIG. 1B B to better illustrate the features of the microphotograph. - During the three week incubation period on the Chondro-Gide® support matrix, the chondrocyte cells were observed to have grown and multiplied on the support matrix building clusters in the center of the carrier and lining up along the surface.
- Chondrocytes were grown for three weeks in the growth media described above in a CO2 incubator at 37° C. and handled in a Class 100 laboratory at Verigen Transplantation Service ApS, Copenhagen, D K or at University of Lübeck, Germany. The chondrocyte cells were trypsinised using trypsin EDTA for 5 to 10 minutes and counted using Trypan Blue viability staining in a Bürker-Türk chamber. The chondrocyte cell count was adjusted to 5×105 chondrocyte cells per milliliter. One NUNCLON™ plate was uncovered in the Class 100 laboratory.
- The Chondro-Gide® support matrix, as in Example 1, was cut to a suitable size fitting into the bottom of a well in the NUNCLON™ cell culture tray. In this case a circle of approximately 4 cm in diameter was placed under aseptic conditions on the bottom of the well.
- After three weeks, the chondrocyte cells were transferred from the growth media to the transplant media described above, and approximately 5×106 cells in 5 ml transplant media were placed directly on top of the support matrix and dispersed over the surface of the support matrix. The plate was incubated in a CO2 incubator at 37° C. for 3 weeks.
- The support matrix holding the grown chondrocyte cells was then incubated with collagenase for 16 hours. The support matrix holding the chondrocyte cells was then centrifuged. Cells were seeded on a NUNCLON™ plate and an aliquot counted using Trypan Blue viability staining in a Bürker-Türk chamber. A microphotograph thereof is shown in
FIG. 11C . The total calculated cell number was found to be 6×106 and the viability was >95%. - Animal studies were performed in the facilities of the University of Lübeck, Germany.
- Four 7 mm diameter round cartilage defects were induced in the cartilage of the knees of two sheep. All interventions were performed in i.v. Ketanest/Rompun total anesthesia. The defects were induced by drilling two holes in the cartilage of the weight bearing areas of the medial femur condyle, and two holes in the area of the femuropatellar- and tibiofemural articulations. In the two areas of damage, one of each of the two holes extended through the tidemark of the cartilage and subchondral layer over the bone, while the remaining hole at each area did not extend through the tidemark of the cartilage and subchondral layer.
- At the same time a piece of cartilage had been harvested from a non-weight bearing area of the sheep knees.
- The chondrocyte cells produced from this cartilage were grown on a support matrix according to Example 3 for a period of six weeks.
- The chondrocyte cells loaded on a Chondro-Gide® support matrix were then implanted via an arthroscopic surgery technique. Fixation occurred in one sheep by gluing the matrix to the treated area with fibrin glue, and in the other sheep the matrix was fixed using polylactide pins as described above according to the present invention.
- The sheep were kept isolated and the knee was kept in a fixed dressing for one week.
- Afterwards the sheep were free to move around. Evaluation of the joint showed a healing of the defect, the attachment of the cell-support matrix implant to the site of cartilage defect, and regeneration of the cartilage at the site of cartilage defect.
- Although the above discussion pertains in part to a process for growing chondrocyte cells on a support matrix in glassware such as a NUNCLON™ plate and changing the growth or transplant media as required for proper cell culturing, the present invention also includes a method of growing chondrocyte cells on a support matrix in a bioreactor such as bioreactor Model No. 1302 available from MinuCells GMBH Ltd., D-93077 Bad Abbach, Germany. Using a bioreactor, constant flow of growth or transplant media is passed by the support matrix, and chondrocyte cells can be grown on the support matrix at a faster rate without having to replace the growth or transplant media, for example, every 24 to 96 hours as required when using the NUNCLON™ plate. It is understood that using such a bioreactor causes angled growth of the chondrocyte cells due to flow of the growth or transplant media through the bioreactor. A microphotograph of chondrocyte cells grown on the support matrix in the bioreactor is shown in
FIG. 11D . - Culturing of the chondrocyte cells, whether cultured in glassware or on a support matrix, can take place in the growth media for the entire cell culturing process or in the transplant media for the entire cell culturing process. That is, no transfer of the chondrocyte cells from the growth media to the transplant media is required. The chondrocyte cells can be transferred from the growth media to the transplant media, and vice versa, at any point in the culturing process, depending on the particular condition of the chondrocyte cells, the stage of growth of the chondrocyte cells, and/or the condition of the patient. The chondrocyte cells, whether in the growth media or in transplant media, need to be soaked into the support matrix for a period of only about 2-3 hours before transplantation to allow attachment of a sufficient number of chondrocyte cells to the support matrix.
- Where a bioreactor is not used, it is also understood that the growth media or transplant media, whichever is being used at the particular stage of the culturing process, must be replaced, for example, about every 24 to 96 hours depending, for example, on the number and viability of the cells.
- While this invention has been described with respect to specific embodiments thereof, it is not limited thereto. In its most general sense, this invention encompasses essentially any article (and use thereof) comprising a support matrix, preferably flexible and preferably absorbable in a living body, which support matrix acts as a support for living cells, which are typically grown thereon for some minimum period of time and attached thereto. Such attachment may be by virtue of cell growth penetrating the surface of the matrix. Preferably, also the support matrix provides sufficient physical integrity to the implantable article to facilitate its manipulation, such as the manipulation necessary to implant it into a living body.
- The subjoined claims therefore are intended to be construed to cover not only those embodiments of this invention disclosed above but also to cover all such embodiments, variants and equivalents of the invention as may be made by those skilled in the art to which the invention pertains, which embodiments, variant and equivalents are within the true spirit and scope of this invention.
Claims (20)
1-49. (canceled)
50. A method for treatment of a cartilage defect in an animal, said method comprising
(a) arthroscopically implanting an article comprising chondrocyte cells retained on a support matrix, the support matrix being absorbable by the animal; and
(b) securing the article at the site of the cartilage defect.
51. The method of claim 50 , further comprising removing defective cartilage from the cartilage defect.
52. The method of claim 50 , further comprising placing a hemostatic barrier adjacent the defect.
53. The method of claim 50 , wherein the support matrix comprises polypeptides.
54. The method of claim 50 , wherein the support matrix comprises proteins.
55. The method of claim 50 , wherein the support matrix is collagen.
56. The method according to claim 55 , wherein the collagen is selected from the group consisting of Type I, Type II, Type III, equine, porcine, bovine, ovine, and chicken collagen, and combinations thereof.
57. The method according to claim 55 , wherein the collagen is porcine collagen.
58. The method according to claim 55 , wherein the collagen is collagen Type I.
59. The method according to claim 55 , wherein the collagen is collagen Type II.
60. The method according to claim 50 , wherein the support matrix is solid.
61. The method according to claim 50 , wherein the support matrix is gel-like.
62. The method according to claim 50 , wherein in said step (b) the article is secured to the site of defect with an adhesive.
63. The method according to claim 62 , wherein the adhesive is a fibrin glue.
64. The method according to claim 50 , wherein in said step (b) the article is secured to the site of defect with absorbable mechanical retention means.
65. The method according to claim 64 , wherein said mechanical retention means is a pin.
66. The method according to claim 50 , wherein the animal is human.
67. The method according to claim 50 , further comprising configuring the article to fit within an arthroscope.
68. The method according to claim 50 , wherein the chondrocyte cells are added to said support matrix in a concentration of from about 7.5×105 cells per milliliter to about 2×106 cells per milliliter.
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Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090214614A1 (en) * | 2005-09-02 | 2009-08-27 | Interface Biotech A/S | Method for Cell Implantation |
US7815926B2 (en) | 2005-07-11 | 2010-10-19 | Musculoskeletal Transplant Foundation | Implant for articular cartilage repair |
US7837740B2 (en) | 2007-01-24 | 2010-11-23 | Musculoskeletal Transplant Foundation | Two piece cancellous construct for cartilage repair |
US7901457B2 (en) | 2003-05-16 | 2011-03-08 | Musculoskeletal Transplant Foundation | Cartilage allograft plug |
USRE42208E1 (en) | 2003-04-29 | 2011-03-08 | Musculoskeletal Transplant Foundation | Glue for cartilage repair |
US8109935B2 (en) | 2009-05-15 | 2012-02-07 | Musculoskeletal Transplant Foundation | Implant inserter device |
US8292968B2 (en) | 2004-10-12 | 2012-10-23 | Musculoskeletal Transplant Foundation | Cancellous constructs, cartilage particles and combinations of cancellous constructs and cartilage particles |
US8435551B2 (en) | 2007-03-06 | 2013-05-07 | Musculoskeletal Transplant Foundation | Cancellous construct with support ring for repair of osteochondral defects |
US9701940B2 (en) | 2005-09-19 | 2017-07-11 | Histogenics Corporation | Cell-support matrix having narrowly defined uniformly vertically and non-randomly organized porosity and pore density and a method for preparation thereof |
US10077420B2 (en) | 2014-12-02 | 2018-09-18 | Histogenics Corporation | Cell and tissue culture container |
Families Citing this family (438)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6569172B2 (en) * | 1996-08-30 | 2003-05-27 | Verigen Transplantation Service International (Vtsi) | Method, instruments, and kit for autologous transplantation |
US7468075B2 (en) | 2001-05-25 | 2008-12-23 | Conformis, Inc. | Methods and compositions for articular repair |
US8083745B2 (en) * | 2001-05-25 | 2011-12-27 | Conformis, Inc. | Surgical tools for arthroplasty |
US8771365B2 (en) | 2009-02-25 | 2014-07-08 | Conformis, Inc. | Patient-adapted and improved orthopedic implants, designs, and related tools |
US8735773B2 (en) | 2007-02-14 | 2014-05-27 | Conformis, Inc. | Implant device and method for manufacture |
US8545569B2 (en) | 2001-05-25 | 2013-10-01 | Conformis, Inc. | Patient selectable knee arthroplasty devices |
US20040133276A1 (en) | 2002-10-07 | 2004-07-08 | Imaging Therapeutics, Inc. | Minimally invasive joint implant with 3-Dimensional geometry matching the articular surfaces |
US7618451B2 (en) * | 2001-05-25 | 2009-11-17 | Conformis, Inc. | Patient selectable joint arthroplasty devices and surgical tools facilitating increased accuracy, speed and simplicity in performing total and partial joint arthroplasty |
US8480754B2 (en) | 2001-05-25 | 2013-07-09 | Conformis, Inc. | Patient-adapted and improved articular implants, designs and related guide tools |
US9603711B2 (en) | 2001-05-25 | 2017-03-28 | Conformis, Inc. | Patient-adapted and improved articular implants, designs and related guide tools |
US8882847B2 (en) | 2001-05-25 | 2014-11-11 | Conformis, Inc. | Patient selectable knee joint arthroplasty devices |
US8556983B2 (en) | 2001-05-25 | 2013-10-15 | Conformis, Inc. | Patient-adapted and improved orthopedic implants, designs and related tools |
US7534263B2 (en) | 2001-05-25 | 2009-05-19 | Conformis, Inc. | Surgical tools facilitating increased accuracy, speed and simplicity in performing joint arthroplasty |
US7239908B1 (en) * | 1998-09-14 | 2007-07-03 | The Board Of Trustees Of The Leland Stanford Junior University | Assessing the condition of a joint and devising treatment |
JP2002532126A (en) | 1998-09-14 | 2002-10-02 | スタンフォード ユニバーシティ | Joint condition evaluation and damage prevention device |
US9289153B2 (en) * | 1998-09-14 | 2016-03-22 | The Board Of Trustees Of The Leland Stanford Junior University | Joint and cartilage diagnosis, assessment and modeling |
WO2001008610A1 (en) * | 1999-08-02 | 2001-02-08 | Verigen Transplantation Service International Ag | Kit for chondrocyte cell transplantation |
WO2002022014A1 (en) * | 2000-09-14 | 2002-03-21 | The Board Of Trustees Of The Leland Stanford Junior University | Assessing the condition of a joint and devising treatment |
CA2425089A1 (en) | 2000-09-14 | 2002-03-21 | Philipp Lang | Assessing condition of a joint and cartilage loss |
JP2002233567A (en) * | 2000-12-06 | 2002-08-20 | Mitsuo Ochi | Tissue equivalent for transplantation and its method of manufacture |
BR0116641A (en) * | 2000-12-28 | 2004-02-17 | Fidia Advanced Biopolymers S P | Use of a biological material containing three-dimensional frames of hyaluronic acid derivatives for arthroscopic implant preparation and an instrument kit for insertion of said biological material by arthroscopy |
US8951260B2 (en) | 2001-05-25 | 2015-02-10 | Conformis, Inc. | Surgical cutting guide |
US8439926B2 (en) * | 2001-05-25 | 2013-05-14 | Conformis, Inc. | Patient selectable joint arthroplasty devices and surgical tools |
WO2002096268A2 (en) | 2001-05-25 | 2002-12-05 | Imaging Therapeutics, Inc. | Methods and compositions for articular resurfacing |
MXPA04005940A (en) * | 2002-01-22 | 2004-09-13 | Pfizer | 3-(imidazolyl)-2-aminopropanoic acids for use as tafi-a inhibitors for the treatment of thrombotic diseases. |
US20040136968A1 (en) * | 2002-09-27 | 2004-07-15 | Verigen Ag | Autologous cells on a support matrix for tissue repair |
EP3075356B1 (en) | 2002-11-07 | 2023-07-05 | ConforMIS, Inc. | Method of selecting a meniscal implant |
AU2003900620A0 (en) * | 2003-02-12 | 2003-02-27 | Australian Surgical Design And Manufacture Pty Limited | Arthroscopic chondrocyte implantation method and device |
US20050222687A1 (en) * | 2004-04-02 | 2005-10-06 | Gordana Vunjak-Novakovic | Cartilage implant assembly and method for implantation |
US7416546B2 (en) * | 2003-05-05 | 2008-08-26 | Boston Scientific Scimed, Inc. | Tissue patches and related delivery systems and methods |
US8034048B2 (en) * | 2003-05-05 | 2011-10-11 | Boston Scientific Scimed, Inc. | Tissue patches and related delivery systems and methods |
US7488348B2 (en) * | 2003-05-16 | 2009-02-10 | Musculoskeletal Transplant Foundation | Cartilage allograft plug |
US9060770B2 (en) | 2003-05-20 | 2015-06-23 | Ethicon Endo-Surgery, Inc. | Robotically-driven surgical instrument with E-beam driver |
US20070084897A1 (en) | 2003-05-20 | 2007-04-19 | Shelton Frederick E Iv | Articulating surgical stapling instrument incorporating a two-piece e-beam firing mechanism |
ES2396689T3 (en) | 2003-12-11 | 2013-02-25 | Isto Technologies Inc. | Particle Cartilage System |
US7311674B2 (en) * | 2004-06-28 | 2007-12-25 | Scimed Life Systems, Inc. | End effector assembly cap and tissue removal device and related methods |
GB0415080D0 (en) | 2004-07-05 | 2004-08-04 | Ucl Biomedica Plc | Methods for preparing tissue equivalent implants and products thereof |
US8215531B2 (en) | 2004-07-28 | 2012-07-10 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument having a medical substance dispenser |
US11896225B2 (en) | 2004-07-28 | 2024-02-13 | Cilag Gmbh International | Staple cartridge comprising a pan |
US8697139B2 (en) | 2004-09-21 | 2014-04-15 | Frank M. Phillips | Method of intervertebral disc treatment using articular chondrocyte cells |
US8043315B2 (en) * | 2004-09-23 | 2011-10-25 | Arthrex, Inc. | Osteochondral repair using plug fashioned from partial distal allograft femur or condyle |
DE102005010988A1 (en) | 2005-03-03 | 2006-09-14 | Karl Storz Gmbh & Co. Kg | Medical instrument for autologous chondrocyte transplantation |
JP2006314759A (en) * | 2005-04-11 | 2006-11-24 | Hiroko Yanaga | Cartilage composition for transplantation |
US20060251631A1 (en) * | 2005-05-05 | 2006-11-09 | Isto Technologies, Inc. | Treatment of joint disease, methods and apparatuses therefor |
KR100774089B1 (en) * | 2005-07-20 | 2007-11-06 | 세원셀론텍(주) | Simple Method of Autologous Chondrocyte Transplantation ? Injectable Chondrocyte Transplantation |
US8480757B2 (en) * | 2005-08-26 | 2013-07-09 | Zimmer, Inc. | Implants and methods for repair, replacement and treatment of disease |
US9237891B2 (en) | 2005-08-31 | 2016-01-19 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical stapling devices that produce formed staples having different lengths |
US10159482B2 (en) | 2005-08-31 | 2018-12-25 | Ethicon Llc | Fastener cartridge assembly comprising a fixed anvil and different staple heights |
US11246590B2 (en) | 2005-08-31 | 2022-02-15 | Cilag Gmbh International | Staple cartridge including staple drivers having different unfired heights |
US7934630B2 (en) | 2005-08-31 | 2011-05-03 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
US7669746B2 (en) | 2005-08-31 | 2010-03-02 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
US11484312B2 (en) | 2005-08-31 | 2022-11-01 | Cilag Gmbh International | Staple cartridge comprising a staple driver arrangement |
CA2621153C (en) | 2005-09-02 | 2016-10-18 | Ed. Geistlich Soehne Ag Fuer Chemische Industrie | Method of repairing meniscal tears using a collagen membrane material |
WO2007035843A2 (en) * | 2005-09-21 | 2007-03-29 | Dask Technologies, Llc | Methods and compositions for organ and tissue functionality |
US20070106317A1 (en) | 2005-11-09 | 2007-05-10 | Shelton Frederick E Iv | Hydraulically and electrically actuated articulation joints for surgical instruments |
CN100475276C (en) * | 2005-12-19 | 2009-04-08 | 北京市创伤骨科研究所 | Composite structured tissue engineering cartilage graft and preparation method thereof |
US8708213B2 (en) | 2006-01-31 | 2014-04-29 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a feedback system |
US11793518B2 (en) | 2006-01-31 | 2023-10-24 | Cilag Gmbh International | Powered surgical instruments with firing system lockout arrangements |
US8820603B2 (en) | 2006-01-31 | 2014-09-02 | Ethicon Endo-Surgery, Inc. | Accessing data stored in a memory of a surgical instrument |
US8186555B2 (en) | 2006-01-31 | 2012-05-29 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting and fastening instrument with mechanical closure system |
US7753904B2 (en) | 2006-01-31 | 2010-07-13 | Ethicon Endo-Surgery, Inc. | Endoscopic surgical instrument with a handle that can articulate with respect to the shaft |
US20110295295A1 (en) | 2006-01-31 | 2011-12-01 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical instrument having recording capabilities |
US11278279B2 (en) | 2006-01-31 | 2022-03-22 | Cilag Gmbh International | Surgical instrument assembly |
US7845537B2 (en) | 2006-01-31 | 2010-12-07 | Ethicon Endo-Surgery, Inc. | Surgical instrument having recording capabilities |
US11224427B2 (en) | 2006-01-31 | 2022-01-18 | Cilag Gmbh International | Surgical stapling system including a console and retraction assembly |
US20120292367A1 (en) | 2006-01-31 | 2012-11-22 | Ethicon Endo-Surgery, Inc. | Robotically-controlled end effector |
US20110024477A1 (en) | 2009-02-06 | 2011-02-03 | Hall Steven G | Driven Surgical Stapler Improvements |
CA2641241A1 (en) | 2006-02-06 | 2007-08-16 | Conformis, Inc. | Patient selectable joint arthroplasty devices and surgical tools |
US8623026B2 (en) | 2006-02-06 | 2014-01-07 | Conformis, Inc. | Patient selectable joint arthroplasty devices and surgical tools incorporating anatomical relief |
US8992422B2 (en) | 2006-03-23 | 2015-03-31 | Ethicon Endo-Surgery, Inc. | Robotically-controlled endoscopic accessory channel |
US8322455B2 (en) | 2006-06-27 | 2012-12-04 | Ethicon Endo-Surgery, Inc. | Manually driven surgical cutting and fastening instrument |
CN101332314B (en) * | 2008-07-22 | 2012-11-14 | 广东冠昊生物科技股份有限公司 | Biotype articular cartilage repair piece |
US10568652B2 (en) | 2006-09-29 | 2020-02-25 | Ethicon Llc | Surgical staples having attached drivers of different heights and stapling instruments for deploying the same |
US20080154233A1 (en) * | 2006-12-20 | 2008-06-26 | Zimmer Orthobiologics, Inc. | Apparatus for delivering a biocompatible material to a surgical site and method of using same |
PT2097116E (en) * | 2006-12-22 | 2012-12-06 | Medidom Lab | In situ system for intra-articular chondral and osseous tissue repair |
US8684253B2 (en) | 2007-01-10 | 2014-04-01 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between a control unit of a robotic system and remote sensor |
US8652120B2 (en) | 2007-01-10 | 2014-02-18 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between control unit and sensor transponders |
US11291441B2 (en) | 2007-01-10 | 2022-04-05 | Cilag Gmbh International | Surgical instrument with wireless communication between control unit and remote sensor |
US8827133B2 (en) | 2007-01-11 | 2014-09-09 | Ethicon Endo-Surgery, Inc. | Surgical stapling device having supports for a flexible drive mechanism |
US11039836B2 (en) | 2007-01-11 | 2021-06-22 | Cilag Gmbh International | Staple cartridge for use with a surgical stapling instrument |
EP2591756A1 (en) | 2007-02-14 | 2013-05-15 | Conformis, Inc. | Implant device and method for manufacture |
US7669747B2 (en) | 2007-03-15 | 2010-03-02 | Ethicon Endo-Surgery, Inc. | Washer for use with a surgical stapling instrument |
AU2008240191B2 (en) | 2007-04-12 | 2013-09-19 | Zimmer, Inc. | Compositions and methods for tissue repair |
US8931682B2 (en) | 2007-06-04 | 2015-01-13 | Ethicon Endo-Surgery, Inc. | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US11857181B2 (en) | 2007-06-04 | 2024-01-02 | Cilag Gmbh International | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US7753245B2 (en) | 2007-06-22 | 2010-07-13 | Ethicon Endo-Surgery, Inc. | Surgical stapling instruments |
US11849941B2 (en) | 2007-06-29 | 2023-12-26 | Cilag Gmbh International | Staple cartridge having staple cavities extending at a transverse angle relative to a longitudinal cartridge axis |
US7552602B2 (en) * | 2007-10-12 | 2009-06-30 | Seamless Technologies, Llc | Forming a tubular knit fabric for a paint roller cover |
US8246570B2 (en) * | 2007-12-21 | 2012-08-21 | Japan Medical Materials Corporation | Device for cell transplantation |
BRPI0901282A2 (en) | 2008-02-14 | 2009-11-17 | Ethicon Endo Surgery Inc | surgical cutting and fixation instrument with rf electrodes |
US7819298B2 (en) | 2008-02-14 | 2010-10-26 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus with control features operable with one hand |
US8636736B2 (en) | 2008-02-14 | 2014-01-28 | Ethicon Endo-Surgery, Inc. | Motorized surgical cutting and fastening instrument |
US8573465B2 (en) | 2008-02-14 | 2013-11-05 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical end effector system with rotary actuated closure systems |
US7866527B2 (en) | 2008-02-14 | 2011-01-11 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus with interlockable firing system |
US9179912B2 (en) | 2008-02-14 | 2015-11-10 | Ethicon Endo-Surgery, Inc. | Robotically-controlled motorized surgical cutting and fastening instrument |
US8758391B2 (en) | 2008-02-14 | 2014-06-24 | Ethicon Endo-Surgery, Inc. | Interchangeable tools for surgical instruments |
US9770245B2 (en) | 2008-02-15 | 2017-09-26 | Ethicon Llc | Layer arrangements for surgical staple cartridges |
WO2009111626A2 (en) | 2008-03-05 | 2009-09-11 | Conformis, Inc. | Implants for altering wear patterns of articular surfaces |
JP2011519713A (en) | 2008-05-12 | 2011-07-14 | コンフォーミス・インコーポレイテッド | Devices and methods for treatment of facet joints and other joints |
US9005230B2 (en) | 2008-09-23 | 2015-04-14 | Ethicon Endo-Surgery, Inc. | Motorized surgical instrument |
US9386983B2 (en) | 2008-09-23 | 2016-07-12 | Ethicon Endo-Surgery, Llc | Robotically-controlled motorized surgical instrument |
US8210411B2 (en) | 2008-09-23 | 2012-07-03 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting instrument |
US11648005B2 (en) | 2008-09-23 | 2023-05-16 | Cilag Gmbh International | Robotically-controlled motorized surgical instrument with an end effector |
US8608045B2 (en) | 2008-10-10 | 2013-12-17 | Ethicon Endo-Sugery, Inc. | Powered surgical cutting and stapling apparatus with manually retractable firing system |
US8517239B2 (en) | 2009-02-05 | 2013-08-27 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument comprising a magnetic element driver |
CA2751664A1 (en) | 2009-02-06 | 2010-08-12 | Ethicon Endo-Surgery, Inc. | Driven surgical stapler improvements |
US8808303B2 (en) | 2009-02-24 | 2014-08-19 | Microport Orthopedics Holdings Inc. | Orthopedic surgical guide |
US9017334B2 (en) | 2009-02-24 | 2015-04-28 | Microport Orthopedics Holdings Inc. | Patient specific surgical guide locator and mount |
WO2010099231A2 (en) | 2009-02-24 | 2010-09-02 | Conformis, Inc. | Automated systems for manufacturing patient-specific orthopedic implants and instrumentation |
US8808297B2 (en) | 2009-02-24 | 2014-08-19 | Microport Orthopedics Holdings Inc. | Orthopedic surgical guide |
SG10201401326SA (en) * | 2009-04-16 | 2014-10-30 | Conformis Inc | Patient-specific joint arthroplasty devices for ligament repair |
US9744123B2 (en) | 2009-06-30 | 2017-08-29 | Kensey Nash Corporation | Biphasic implant device providing gradient |
CA2766913A1 (en) * | 2009-06-30 | 2011-01-06 | Kensey Nash Corporation | Multi-phasic implant device for the repair or replacement of cartilage tissue |
US10016278B2 (en) | 2009-06-30 | 2018-07-10 | Dsm Ip Assets B.V. | Biphasic implant device providing joint fluid therapy |
AU2010327987B2 (en) | 2009-12-11 | 2015-04-02 | Conformis, Inc. | Patient-specific and patient-engineered orthopedic implants |
US8220688B2 (en) | 2009-12-24 | 2012-07-17 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting instrument with electric actuator directional control assembly |
US8851354B2 (en) | 2009-12-24 | 2014-10-07 | Ethicon Endo-Surgery, Inc. | Surgical cutting instrument that analyzes tissue thickness |
US8783543B2 (en) | 2010-07-30 | 2014-07-22 | Ethicon Endo-Surgery, Inc. | Tissue acquisition arrangements and methods for surgical stapling devices |
US11298125B2 (en) | 2010-09-30 | 2022-04-12 | Cilag Gmbh International | Tissue stapler having a thickness compensator |
US9629814B2 (en) | 2010-09-30 | 2017-04-25 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator configured to redistribute compressive forces |
US9351730B2 (en) | 2011-04-29 | 2016-05-31 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprising channels |
US10945731B2 (en) | 2010-09-30 | 2021-03-16 | Ethicon Llc | Tissue thickness compensator comprising controlled release and expansion |
US8978954B2 (en) | 2010-09-30 | 2015-03-17 | Ethicon Endo-Surgery, Inc. | Staple cartridge comprising an adjustable distal portion |
US11812965B2 (en) | 2010-09-30 | 2023-11-14 | Cilag Gmbh International | Layer of material for a surgical end effector |
US9320523B2 (en) | 2012-03-28 | 2016-04-26 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprising tissue ingrowth features |
US11849952B2 (en) | 2010-09-30 | 2023-12-26 | Cilag Gmbh International | Staple cartridge comprising staples positioned within a compressible portion thereof |
US9592050B2 (en) | 2010-09-30 | 2017-03-14 | Ethicon Endo-Surgery, Llc | End effector comprising a distal tissue abutment member |
US8695866B2 (en) | 2010-10-01 | 2014-04-15 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a power control circuit |
CN103476363B (en) | 2011-02-15 | 2017-06-30 | 康复米斯公司 | Operation and the instrument of change and/or asymmetry are dissected in improved suitable patient's type joint implant and treatment, assessment, correction, modification and/or adaptation |
CA2834649C (en) | 2011-04-29 | 2021-02-16 | Ethicon Endo-Surgery, Inc. | Staple cartridge comprising staples positioned within a compressible portion thereof |
US11207064B2 (en) | 2011-05-27 | 2021-12-28 | Cilag Gmbh International | Automated end effector component reloading system for use with a robotic system |
US9072535B2 (en) | 2011-05-27 | 2015-07-07 | Ethicon Endo-Surgery, Inc. | Surgical stapling instruments with rotatable staple deployment arrangements |
US9044230B2 (en) | 2012-02-13 | 2015-06-02 | Ethicon Endo-Surgery, Inc. | Surgical cutting and fastening instrument with apparatus for determining cartridge and firing motion status |
CN104334098B (en) | 2012-03-28 | 2017-03-22 | 伊西康内外科公司 | Tissue thickness compensator comprising capsules defining a low pressure environment |
RU2648884C2 (en) * | 2012-03-28 | 2018-03-28 | Этикон Эндо-Серджери, Инк. | Expandable tissue thickness compensator |
JP6305979B2 (en) | 2012-03-28 | 2018-04-04 | エシコン・エンド−サージェリィ・インコーポレイテッドEthicon Endo−Surgery,Inc. | Tissue thickness compensator with multiple layers |
JP6224070B2 (en) | 2012-03-28 | 2017-11-01 | エシコン・エンド−サージェリィ・インコーポレイテッドEthicon Endo−Surgery,Inc. | Retainer assembly including tissue thickness compensator |
US9486226B2 (en) | 2012-04-18 | 2016-11-08 | Conformis, Inc. | Tibial guides, tools, and techniques for resecting the tibial plateau |
US9675471B2 (en) | 2012-06-11 | 2017-06-13 | Conformis, Inc. | Devices, techniques and methods for assessing joint spacing, balancing soft tissues and obtaining desired kinematics for joint implant components |
US9101358B2 (en) | 2012-06-15 | 2015-08-11 | Ethicon Endo-Surgery, Inc. | Articulatable surgical instrument comprising a firing drive |
BR112014032776B1 (en) | 2012-06-28 | 2021-09-08 | Ethicon Endo-Surgery, Inc | SURGICAL INSTRUMENT SYSTEM AND SURGICAL KIT FOR USE WITH A SURGICAL INSTRUMENT SYSTEM |
US11278284B2 (en) | 2012-06-28 | 2022-03-22 | Cilag Gmbh International | Rotary drive arrangements for surgical instruments |
US9649111B2 (en) | 2012-06-28 | 2017-05-16 | Ethicon Endo-Surgery, Llc | Replaceable clip cartridge for a clip applier |
US20140001234A1 (en) | 2012-06-28 | 2014-01-02 | Ethicon Endo-Surgery, Inc. | Coupling arrangements for attaching surgical end effectors to drive systems therefor |
US20140001231A1 (en) | 2012-06-28 | 2014-01-02 | Ethicon Endo-Surgery, Inc. | Firing system lockout arrangements for surgical instruments |
US9289256B2 (en) | 2012-06-28 | 2016-03-22 | Ethicon Endo-Surgery, Llc | Surgical end effectors having angled tissue-contacting surfaces |
CN104487005B (en) | 2012-06-28 | 2017-09-08 | 伊西康内外科公司 | Empty squeeze latching member |
US10016527B2 (en) | 2012-10-23 | 2018-07-10 | Orthovita, Inc. | Materials and methods for repair of cartilage defects |
US20140178343A1 (en) | 2012-12-21 | 2014-06-26 | Jian Q. Yao | Supports and methods for promoting integration of cartilage tissue explants |
MX368026B (en) | 2013-03-01 | 2019-09-12 | Ethicon Endo Surgery Inc | Articulatable surgical instruments with conductive pathways for signal communication. |
MX364729B (en) | 2013-03-01 | 2019-05-06 | Ethicon Endo Surgery Inc | Surgical instrument with a soft stop. |
US9629629B2 (en) | 2013-03-14 | 2017-04-25 | Ethicon Endo-Surgey, LLC | Control systems for surgical instruments |
US9629623B2 (en) | 2013-03-14 | 2017-04-25 | Ethicon Endo-Surgery, Llc | Drive system lockout arrangements for modular surgical instruments |
US10405857B2 (en) | 2013-04-16 | 2019-09-10 | Ethicon Llc | Powered linear surgical stapler |
BR112015026109B1 (en) | 2013-04-16 | 2022-02-22 | Ethicon Endo-Surgery, Inc | surgical instrument |
CN106028966B (en) | 2013-08-23 | 2018-06-22 | 伊西康内外科有限责任公司 | For the firing member restoring device of powered surgical instrument |
US9808249B2 (en) | 2013-08-23 | 2017-11-07 | Ethicon Llc | Attachment portions for surgical instrument assemblies |
US9480516B2 (en) * | 2013-09-09 | 2016-11-01 | Globus Medical, Inc. | Percutaneous bone screw device and method |
US9962161B2 (en) | 2014-02-12 | 2018-05-08 | Ethicon Llc | Deliverable surgical instrument |
US9820738B2 (en) | 2014-03-26 | 2017-11-21 | Ethicon Llc | Surgical instrument comprising interactive systems |
US9733663B2 (en) | 2014-03-26 | 2017-08-15 | Ethicon Llc | Power management through segmented circuit and variable voltage protection |
BR112016021943B1 (en) | 2014-03-26 | 2022-06-14 | Ethicon Endo-Surgery, Llc | SURGICAL INSTRUMENT FOR USE BY AN OPERATOR IN A SURGICAL PROCEDURE |
BR112016023825B1 (en) | 2014-04-16 | 2022-08-02 | Ethicon Endo-Surgery, Llc | STAPLE CARTRIDGE FOR USE WITH A SURGICAL STAPLER AND STAPLE CARTRIDGE FOR USE WITH A SURGICAL INSTRUMENT |
CN106456176B (en) | 2014-04-16 | 2019-06-28 | 伊西康内外科有限责任公司 | Fastener cartridge including the extension with various configuration |
BR112016023807B1 (en) | 2014-04-16 | 2022-07-12 | Ethicon Endo-Surgery, Llc | CARTRIDGE SET OF FASTENERS FOR USE WITH A SURGICAL INSTRUMENT |
US10299792B2 (en) | 2014-04-16 | 2019-05-28 | Ethicon Llc | Fastener cartridge comprising non-uniform fasteners |
US20150297225A1 (en) | 2014-04-16 | 2015-10-22 | Ethicon Endo-Surgery, Inc. | Fastener cartridges including extensions having different configurations |
US11311294B2 (en) | 2014-09-05 | 2022-04-26 | Cilag Gmbh International | Powered medical device including measurement of closure state of jaws |
US10135242B2 (en) | 2014-09-05 | 2018-11-20 | Ethicon Llc | Smart cartridge wake up operation and data retention |
BR112017004361B1 (en) | 2014-09-05 | 2023-04-11 | Ethicon Llc | ELECTRONIC SYSTEM FOR A SURGICAL INSTRUMENT |
US10105142B2 (en) | 2014-09-18 | 2018-10-23 | Ethicon Llc | Surgical stapler with plurality of cutting elements |
CN107427300B (en) | 2014-09-26 | 2020-12-04 | 伊西康有限责任公司 | Surgical suture buttress and buttress material |
US11523821B2 (en) | 2014-09-26 | 2022-12-13 | Cilag Gmbh International | Method for creating a flexible staple line |
US10076325B2 (en) | 2014-10-13 | 2018-09-18 | Ethicon Llc | Surgical stapling apparatus comprising a tissue stop |
US9924944B2 (en) | 2014-10-16 | 2018-03-27 | Ethicon Llc | Staple cartridge comprising an adjunct material |
US11141153B2 (en) | 2014-10-29 | 2021-10-12 | Cilag Gmbh International | Staple cartridges comprising driver arrangements |
US10517594B2 (en) | 2014-10-29 | 2019-12-31 | Ethicon Llc | Cartridge assemblies for surgical staplers |
US9844376B2 (en) | 2014-11-06 | 2017-12-19 | Ethicon Llc | Staple cartridge comprising a releasable adjunct material |
US10736636B2 (en) | 2014-12-10 | 2020-08-11 | Ethicon Llc | Articulatable surgical instrument system |
US9844375B2 (en) | 2014-12-18 | 2017-12-19 | Ethicon Llc | Drive arrangements for articulatable surgical instruments |
BR112017012996B1 (en) | 2014-12-18 | 2022-11-08 | Ethicon Llc | SURGICAL INSTRUMENT WITH AN ANvil WHICH IS SELECTIVELY MOVABLE ABOUT AN IMMOVABLE GEOMETRIC AXIS DIFFERENT FROM A STAPLE CARTRIDGE |
US9968355B2 (en) | 2014-12-18 | 2018-05-15 | Ethicon Llc | Surgical instruments with articulatable end effectors and improved firing beam support arrangements |
US9844374B2 (en) | 2014-12-18 | 2017-12-19 | Ethicon Llc | Surgical instrument systems comprising an articulatable end effector and means for adjusting the firing stroke of a firing member |
US10085748B2 (en) | 2014-12-18 | 2018-10-02 | Ethicon Llc | Locking arrangements for detachable shaft assemblies with articulatable surgical end effectors |
US9987000B2 (en) | 2014-12-18 | 2018-06-05 | Ethicon Llc | Surgical instrument assembly comprising a flexible articulation system |
US11154301B2 (en) | 2015-02-27 | 2021-10-26 | Cilag Gmbh International | Modular stapling assembly |
US9901342B2 (en) | 2015-03-06 | 2018-02-27 | Ethicon Endo-Surgery, Llc | Signal and power communication system positioned on a rotatable shaft |
US10441279B2 (en) | 2015-03-06 | 2019-10-15 | Ethicon Llc | Multiple level thresholds to modify operation of powered surgical instruments |
US10548504B2 (en) | 2015-03-06 | 2020-02-04 | Ethicon Llc | Overlaid multi sensor radio frequency (RF) electrode system to measure tissue compression |
US10687806B2 (en) | 2015-03-06 | 2020-06-23 | Ethicon Llc | Adaptive tissue compression techniques to adjust closure rates for multiple tissue types |
US9993248B2 (en) | 2015-03-06 | 2018-06-12 | Ethicon Endo-Surgery, Llc | Smart sensors with local signal processing |
US10245033B2 (en) | 2015-03-06 | 2019-04-02 | Ethicon Llc | Surgical instrument comprising a lockable battery housing |
JP2020121162A (en) | 2015-03-06 | 2020-08-13 | エシコン エルエルシーEthicon LLC | Time dependent evaluation of sensor data to determine stability element, creep element and viscoelastic element of measurement |
US10617412B2 (en) | 2015-03-06 | 2020-04-14 | Ethicon Llc | System for detecting the mis-insertion of a staple cartridge into a surgical stapler |
US10390825B2 (en) | 2015-03-31 | 2019-08-27 | Ethicon Llc | Surgical instrument with progressive rotary drive systems |
CN104906633A (en) * | 2015-05-14 | 2015-09-16 | 杭州市第一人民医院 | Injectable bone repair material and preparation method therefor |
CN104826167A (en) * | 2015-05-14 | 2015-08-12 | 杭州市第一人民医院 | Injectable autologous bone repair material and preparation method thereof |
US10617418B2 (en) | 2015-08-17 | 2020-04-14 | Ethicon Llc | Implantable layers for a surgical instrument |
US10238386B2 (en) | 2015-09-23 | 2019-03-26 | Ethicon Llc | Surgical stapler having motor control based on an electrical parameter related to a motor current |
US10105139B2 (en) | 2015-09-23 | 2018-10-23 | Ethicon Llc | Surgical stapler having downstream current-based motor control |
US10299878B2 (en) | 2015-09-25 | 2019-05-28 | Ethicon Llc | Implantable adjunct systems for determining adjunct skew |
US10980539B2 (en) | 2015-09-30 | 2021-04-20 | Ethicon Llc | Implantable adjunct comprising bonded layers |
US10271849B2 (en) | 2015-09-30 | 2019-04-30 | Ethicon Llc | Woven constructs with interlocked standing fibers |
US10524788B2 (en) | 2015-09-30 | 2020-01-07 | Ethicon Llc | Compressible adjunct with attachment regions |
US11890015B2 (en) | 2015-09-30 | 2024-02-06 | Cilag Gmbh International | Compressible adjunct with crossing spacer fibers |
US10292704B2 (en) | 2015-12-30 | 2019-05-21 | Ethicon Llc | Mechanisms for compensating for battery pack failure in powered surgical instruments |
US10368865B2 (en) | 2015-12-30 | 2019-08-06 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US9943414B2 (en) * | 2015-12-30 | 2018-04-17 | Wasas, Llc. | System and method for non-binding allograft subtalar joint implant |
US10265068B2 (en) | 2015-12-30 | 2019-04-23 | Ethicon Llc | Surgical instruments with separable motors and motor control circuits |
US11213293B2 (en) | 2016-02-09 | 2022-01-04 | Cilag Gmbh International | Articulatable surgical instruments with single articulation link arrangements |
CN108882932B (en) | 2016-02-09 | 2021-07-23 | 伊西康有限责任公司 | Surgical instrument with asymmetric articulation configuration |
US10448948B2 (en) | 2016-02-12 | 2019-10-22 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US11224426B2 (en) | 2016-02-12 | 2022-01-18 | Cilag Gmbh International | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10617413B2 (en) | 2016-04-01 | 2020-04-14 | Ethicon Llc | Closure system arrangements for surgical cutting and stapling devices with separate and distinct firing shafts |
US10426467B2 (en) | 2016-04-15 | 2019-10-01 | Ethicon Llc | Surgical instrument with detection sensors |
US10828028B2 (en) | 2016-04-15 | 2020-11-10 | Ethicon Llc | Surgical instrument with multiple program responses during a firing motion |
US11607239B2 (en) | 2016-04-15 | 2023-03-21 | Cilag Gmbh International | Systems and methods for controlling a surgical stapling and cutting instrument |
US10335145B2 (en) | 2016-04-15 | 2019-07-02 | Ethicon Llc | Modular surgical instrument with configurable operating mode |
US10357247B2 (en) | 2016-04-15 | 2019-07-23 | Ethicon Llc | Surgical instrument with multiple program responses during a firing motion |
US10456137B2 (en) | 2016-04-15 | 2019-10-29 | Ethicon Llc | Staple formation detection mechanisms |
US11179150B2 (en) | 2016-04-15 | 2021-11-23 | Cilag Gmbh International | Systems and methods for controlling a surgical stapling and cutting instrument |
US10492783B2 (en) | 2016-04-15 | 2019-12-03 | Ethicon, Llc | Surgical instrument with improved stop/start control during a firing motion |
US20170296173A1 (en) | 2016-04-18 | 2017-10-19 | Ethicon Endo-Surgery, Llc | Method for operating a surgical instrument |
US11317917B2 (en) | 2016-04-18 | 2022-05-03 | Cilag Gmbh International | Surgical stapling system comprising a lockable firing assembly |
US10363037B2 (en) | 2016-04-18 | 2019-07-30 | Ethicon Llc | Surgical instrument system comprising a magnetic lockout |
US10537325B2 (en) | 2016-12-21 | 2020-01-21 | Ethicon Llc | Staple forming pocket arrangement to accommodate different types of staples |
US10492785B2 (en) | 2016-12-21 | 2019-12-03 | Ethicon Llc | Shaft assembly comprising a lockout |
US10736629B2 (en) | 2016-12-21 | 2020-08-11 | Ethicon Llc | Surgical tool assemblies with clutching arrangements for shifting between closure systems with closure stroke reduction features and articulation and firing systems |
US20180168609A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Firing assembly comprising a fuse |
JP6983893B2 (en) | 2016-12-21 | 2021-12-17 | エシコン エルエルシーEthicon LLC | Lockout configuration for surgical end effectors and replaceable tool assemblies |
US20180168615A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Method of deforming staples from two different types of staple cartridges with the same surgical stapling instrument |
US10485543B2 (en) | 2016-12-21 | 2019-11-26 | Ethicon Llc | Anvil having a knife slot width |
US20180168598A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Staple forming pocket arrangements comprising zoned forming surface grooves |
US11134942B2 (en) | 2016-12-21 | 2021-10-05 | Cilag Gmbh International | Surgical stapling instruments and staple-forming anvils |
US20180168575A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Surgical stapling systems |
US10881401B2 (en) | 2016-12-21 | 2021-01-05 | Ethicon Llc | Staple firing member comprising a missing cartridge and/or spent cartridge lockout |
US20180168625A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Surgical stapling instruments with smart staple cartridges |
US10568625B2 (en) | 2016-12-21 | 2020-02-25 | Ethicon Llc | Staple cartridges and arrangements of staples and staple cavities therein |
US10980536B2 (en) | 2016-12-21 | 2021-04-20 | Ethicon Llc | No-cartridge and spent cartridge lockout arrangements for surgical staplers |
US10973516B2 (en) | 2016-12-21 | 2021-04-13 | Ethicon Llc | Surgical end effectors and adaptable firing members therefor |
US11419606B2 (en) | 2016-12-21 | 2022-08-23 | Cilag Gmbh International | Shaft assembly comprising a clutch configured to adapt the output of a rotary firing member to two different systems |
JP7010956B2 (en) | 2016-12-21 | 2022-01-26 | エシコン エルエルシー | How to staple tissue |
MX2019007311A (en) | 2016-12-21 | 2019-11-18 | Ethicon Llc | Surgical stapling systems. |
US10980537B2 (en) | 2017-06-20 | 2021-04-20 | Ethicon Llc | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified number of shaft rotations |
USD879809S1 (en) | 2017-06-20 | 2020-03-31 | Ethicon Llc | Display panel with changeable graphical user interface |
US10813639B2 (en) | 2017-06-20 | 2020-10-27 | Ethicon Llc | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on system conditions |
US10881396B2 (en) | 2017-06-20 | 2021-01-05 | Ethicon Llc | Surgical instrument with variable duration trigger arrangement |
US10888321B2 (en) | 2017-06-20 | 2021-01-12 | Ethicon Llc | Systems and methods for controlling velocity of a displacement member of a surgical stapling and cutting instrument |
USD890784S1 (en) | 2017-06-20 | 2020-07-21 | Ethicon Llc | Display panel with changeable graphical user interface |
US10624633B2 (en) | 2017-06-20 | 2020-04-21 | Ethicon Llc | Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument |
US11517325B2 (en) | 2017-06-20 | 2022-12-06 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured displacement distance traveled over a specified time interval |
US11090046B2 (en) | 2017-06-20 | 2021-08-17 | Cilag Gmbh International | Systems and methods for controlling displacement member motion of a surgical stapling and cutting instrument |
US10307170B2 (en) | 2017-06-20 | 2019-06-04 | Ethicon Llc | Method for closed loop control of motor velocity of a surgical stapling and cutting instrument |
US10881399B2 (en) | 2017-06-20 | 2021-01-05 | Ethicon Llc | Techniques for adaptive control of motor velocity of a surgical stapling and cutting instrument |
USD879808S1 (en) | 2017-06-20 | 2020-03-31 | Ethicon Llc | Display panel with graphical user interface |
US10779820B2 (en) | 2017-06-20 | 2020-09-22 | Ethicon Llc | Systems and methods for controlling motor speed according to user input for a surgical instrument |
US10646220B2 (en) | 2017-06-20 | 2020-05-12 | Ethicon Llc | Systems and methods for controlling displacement member velocity for a surgical instrument |
US11071554B2 (en) | 2017-06-20 | 2021-07-27 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on magnitude of velocity error measurements |
US11382638B2 (en) | 2017-06-20 | 2022-07-12 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified displacement distance |
US11653914B2 (en) | 2017-06-20 | 2023-05-23 | Cilag Gmbh International | Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument according to articulation angle of end effector |
US10993716B2 (en) | 2017-06-27 | 2021-05-04 | Ethicon Llc | Surgical anvil arrangements |
US10631859B2 (en) | 2017-06-27 | 2020-04-28 | Ethicon Llc | Articulation systems for surgical instruments |
US11266405B2 (en) | 2017-06-27 | 2022-03-08 | Cilag Gmbh International | Surgical anvil manufacturing methods |
US10772629B2 (en) | 2017-06-27 | 2020-09-15 | Ethicon Llc | Surgical anvil arrangements |
US11324503B2 (en) | 2017-06-27 | 2022-05-10 | Cilag Gmbh International | Surgical firing member arrangements |
US10856869B2 (en) | 2017-06-27 | 2020-12-08 | Ethicon Llc | Surgical anvil arrangements |
US11564686B2 (en) | 2017-06-28 | 2023-01-31 | Cilag Gmbh International | Surgical shaft assemblies with flexible interfaces |
US11259805B2 (en) | 2017-06-28 | 2022-03-01 | Cilag Gmbh International | Surgical instrument comprising firing member supports |
US10765427B2 (en) | 2017-06-28 | 2020-09-08 | Ethicon Llc | Method for articulating a surgical instrument |
US11246592B2 (en) | 2017-06-28 | 2022-02-15 | Cilag Gmbh International | Surgical instrument comprising an articulation system lockable to a frame |
USD906355S1 (en) | 2017-06-28 | 2020-12-29 | Ethicon Llc | Display screen or portion thereof with a graphical user interface for a surgical instrument |
US10716614B2 (en) | 2017-06-28 | 2020-07-21 | Ethicon Llc | Surgical shaft assemblies with slip ring assemblies with increased contact pressure |
EP3420947B1 (en) | 2017-06-28 | 2022-05-25 | Cilag GmbH International | Surgical instrument comprising selectively actuatable rotatable couplers |
US10588633B2 (en) | 2017-06-28 | 2020-03-17 | Ethicon Llc | Surgical instruments with open and closable jaws and axially movable firing member that is initially parked in close proximity to the jaws prior to firing |
US10903685B2 (en) | 2017-06-28 | 2021-01-26 | Ethicon Llc | Surgical shaft assemblies with slip ring assemblies forming capacitive channels |
US11389161B2 (en) | 2017-06-28 | 2022-07-19 | Cilag Gmbh International | Surgical instrument comprising selectively actuatable rotatable couplers |
US10898183B2 (en) | 2017-06-29 | 2021-01-26 | Ethicon Llc | Robotic surgical instrument with closed loop feedback techniques for advancement of closure member during firing |
US10932772B2 (en) | 2017-06-29 | 2021-03-02 | Ethicon Llc | Methods for closed loop velocity control for robotic surgical instrument |
US11007022B2 (en) | 2017-06-29 | 2021-05-18 | Ethicon Llc | Closed loop velocity control techniques based on sensed tissue parameters for robotic surgical instrument |
US11944300B2 (en) | 2017-08-03 | 2024-04-02 | Cilag Gmbh International | Method for operating a surgical system bailout |
US11304695B2 (en) | 2017-08-03 | 2022-04-19 | Cilag Gmbh International | Surgical system shaft interconnection |
US11471155B2 (en) | 2017-08-03 | 2022-10-18 | Cilag Gmbh International | Surgical system bailout |
USD917500S1 (en) | 2017-09-29 | 2021-04-27 | Ethicon Llc | Display screen or portion thereof with graphical user interface |
US11399829B2 (en) | 2017-09-29 | 2022-08-02 | Cilag Gmbh International | Systems and methods of initiating a power shutdown mode for a surgical instrument |
US10765429B2 (en) | 2017-09-29 | 2020-09-08 | Ethicon Llc | Systems and methods for providing alerts according to the operational state of a surgical instrument |
USD907648S1 (en) | 2017-09-29 | 2021-01-12 | Ethicon Llc | Display screen or portion thereof with animated graphical user interface |
USD907647S1 (en) | 2017-09-29 | 2021-01-12 | Ethicon Llc | Display screen or portion thereof with animated graphical user interface |
US10743872B2 (en) | 2017-09-29 | 2020-08-18 | Ethicon Llc | System and methods for controlling a display of a surgical instrument |
US11090075B2 (en) | 2017-10-30 | 2021-08-17 | Cilag Gmbh International | Articulation features for surgical end effector |
US11134944B2 (en) | 2017-10-30 | 2021-10-05 | Cilag Gmbh International | Surgical stapler knife motion controls |
US10779903B2 (en) | 2017-10-31 | 2020-09-22 | Ethicon Llc | Positive shaft rotation lock activated by jaw closure |
US10842490B2 (en) | 2017-10-31 | 2020-11-24 | Ethicon Llc | Cartridge body design with force reduction based on firing completion |
US11033267B2 (en) | 2017-12-15 | 2021-06-15 | Ethicon Llc | Systems and methods of controlling a clamping member firing rate of a surgical instrument |
US11071543B2 (en) | 2017-12-15 | 2021-07-27 | Cilag Gmbh International | Surgical end effectors with clamping assemblies configured to increase jaw aperture ranges |
US11006955B2 (en) | 2017-12-15 | 2021-05-18 | Ethicon Llc | End effectors with positive jaw opening features for use with adapters for electromechanical surgical instruments |
US10687813B2 (en) | 2017-12-15 | 2020-06-23 | Ethicon Llc | Adapters with firing stroke sensing arrangements for use in connection with electromechanical surgical instruments |
US10779825B2 (en) | 2017-12-15 | 2020-09-22 | Ethicon Llc | Adapters with end effector position sensing and control arrangements for use in connection with electromechanical surgical instruments |
US10743875B2 (en) | 2017-12-15 | 2020-08-18 | Ethicon Llc | Surgical end effectors with jaw stiffener arrangements configured to permit monitoring of firing member |
US10779826B2 (en) | 2017-12-15 | 2020-09-22 | Ethicon Llc | Methods of operating surgical end effectors |
US10743874B2 (en) | 2017-12-15 | 2020-08-18 | Ethicon Llc | Sealed adapters for use with electromechanical surgical instruments |
US10828033B2 (en) | 2017-12-15 | 2020-11-10 | Ethicon Llc | Handheld electromechanical surgical instruments with improved motor control arrangements for positioning components of an adapter coupled thereto |
US10869666B2 (en) | 2017-12-15 | 2020-12-22 | Ethicon Llc | Adapters with control systems for controlling multiple motors of an electromechanical surgical instrument |
US11197670B2 (en) | 2017-12-15 | 2021-12-14 | Cilag Gmbh International | Surgical end effectors with pivotal jaws configured to touch at their respective distal ends when fully closed |
US10966718B2 (en) | 2017-12-15 | 2021-04-06 | Ethicon Llc | Dynamic clamping assemblies with improved wear characteristics for use in connection with electromechanical surgical instruments |
US10716565B2 (en) | 2017-12-19 | 2020-07-21 | Ethicon Llc | Surgical instruments with dual articulation drivers |
US10835330B2 (en) | 2017-12-19 | 2020-11-17 | Ethicon Llc | Method for determining the position of a rotatable jaw of a surgical instrument attachment assembly |
US11045270B2 (en) | 2017-12-19 | 2021-06-29 | Cilag Gmbh International | Robotic attachment comprising exterior drive actuator |
US11020112B2 (en) | 2017-12-19 | 2021-06-01 | Ethicon Llc | Surgical tools configured for interchangeable use with different controller interfaces |
USD910847S1 (en) | 2017-12-19 | 2021-02-16 | Ethicon Llc | Surgical instrument assembly |
US10729509B2 (en) | 2017-12-19 | 2020-08-04 | Ethicon Llc | Surgical instrument comprising closure and firing locking mechanism |
US11076853B2 (en) | 2017-12-21 | 2021-08-03 | Cilag Gmbh International | Systems and methods of displaying a knife position during transection for a surgical instrument |
US11751867B2 (en) | 2017-12-21 | 2023-09-12 | Cilag Gmbh International | Surgical instrument comprising sequenced systems |
US11311290B2 (en) | 2017-12-21 | 2022-04-26 | Cilag Gmbh International | Surgical instrument comprising an end effector dampener |
US11129680B2 (en) | 2017-12-21 | 2021-09-28 | Cilag Gmbh International | Surgical instrument comprising a projector |
KR101976346B1 (en) | 2018-06-07 | 2019-05-08 | 김찬우 | Cartilage Minced Machine |
US11083458B2 (en) | 2018-08-20 | 2021-08-10 | Cilag Gmbh International | Powered surgical instruments with clutching arrangements to convert linear drive motions to rotary drive motions |
US11045192B2 (en) | 2018-08-20 | 2021-06-29 | Cilag Gmbh International | Fabricating techniques for surgical stapler anvils |
US11324501B2 (en) | 2018-08-20 | 2022-05-10 | Cilag Gmbh International | Surgical stapling devices with improved closure members |
US11039834B2 (en) | 2018-08-20 | 2021-06-22 | Cilag Gmbh International | Surgical stapler anvils with staple directing protrusions and tissue stability features |
US11207065B2 (en) | 2018-08-20 | 2021-12-28 | Cilag Gmbh International | Method for fabricating surgical stapler anvils |
US10842492B2 (en) | 2018-08-20 | 2020-11-24 | Ethicon Llc | Powered articulatable surgical instruments with clutching and locking arrangements for linking an articulation drive system to a firing drive system |
US11253256B2 (en) | 2018-08-20 | 2022-02-22 | Cilag Gmbh International | Articulatable motor powered surgical instruments with dedicated articulation motor arrangements |
US10779821B2 (en) | 2018-08-20 | 2020-09-22 | Ethicon Llc | Surgical stapler anvils with tissue stop features configured to avoid tissue pinch |
US10856870B2 (en) | 2018-08-20 | 2020-12-08 | Ethicon Llc | Switching arrangements for motor powered articulatable surgical instruments |
USD914878S1 (en) | 2018-08-20 | 2021-03-30 | Ethicon Llc | Surgical instrument anvil |
US10912559B2 (en) | 2018-08-20 | 2021-02-09 | Ethicon Llc | Reinforced deformable anvil tip for surgical stapler anvil |
US11291440B2 (en) | 2018-08-20 | 2022-04-05 | Cilag Gmbh International | Method for operating a powered articulatable surgical instrument |
CN108852477A (en) * | 2018-09-12 | 2018-11-23 | 上海交通大学医学院附属第九人民医院 | Filling prosthetic device for stem-cell therapy human articular cartilage defect |
US11172929B2 (en) | 2019-03-25 | 2021-11-16 | Cilag Gmbh International | Articulation drive arrangements for surgical systems |
US11696761B2 (en) | 2019-03-25 | 2023-07-11 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11147551B2 (en) | 2019-03-25 | 2021-10-19 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11147553B2 (en) | 2019-03-25 | 2021-10-19 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11253254B2 (en) | 2019-04-30 | 2022-02-22 | Cilag Gmbh International | Shaft rotation actuator on a surgical instrument |
US11452528B2 (en) | 2019-04-30 | 2022-09-27 | Cilag Gmbh International | Articulation actuators for a surgical instrument |
US11648009B2 (en) | 2019-04-30 | 2023-05-16 | Cilag Gmbh International | Rotatable jaw tip for a surgical instrument |
US11432816B2 (en) | 2019-04-30 | 2022-09-06 | Cilag Gmbh International | Articulation pin for a surgical instrument |
US11903581B2 (en) | 2019-04-30 | 2024-02-20 | Cilag Gmbh International | Methods for stapling tissue using a surgical instrument |
US11426251B2 (en) | 2019-04-30 | 2022-08-30 | Cilag Gmbh International | Articulation directional lights on a surgical instrument |
US11471157B2 (en) | 2019-04-30 | 2022-10-18 | Cilag Gmbh International | Articulation control mapping for a surgical instrument |
US11298127B2 (en) | 2019-06-28 | 2022-04-12 | Cilag GmbH Interational | Surgical stapling system having a lockout mechanism for an incompatible cartridge |
US11464601B2 (en) | 2019-06-28 | 2022-10-11 | Cilag Gmbh International | Surgical instrument comprising an RFID system for tracking a movable component |
US11259803B2 (en) | 2019-06-28 | 2022-03-01 | Cilag Gmbh International | Surgical stapling system having an information encryption protocol |
US11684434B2 (en) | 2019-06-28 | 2023-06-27 | Cilag Gmbh International | Surgical RFID assemblies for instrument operational setting control |
US11497492B2 (en) | 2019-06-28 | 2022-11-15 | Cilag Gmbh International | Surgical instrument including an articulation lock |
US11426167B2 (en) | 2019-06-28 | 2022-08-30 | Cilag Gmbh International | Mechanisms for proper anvil attachment surgical stapling head assembly |
US11376098B2 (en) | 2019-06-28 | 2022-07-05 | Cilag Gmbh International | Surgical instrument system comprising an RFID system |
US11224497B2 (en) | 2019-06-28 | 2022-01-18 | Cilag Gmbh International | Surgical systems with multiple RFID tags |
US11246678B2 (en) | 2019-06-28 | 2022-02-15 | Cilag Gmbh International | Surgical stapling system having a frangible RFID tag |
US11523822B2 (en) | 2019-06-28 | 2022-12-13 | Cilag Gmbh International | Battery pack including a circuit interrupter |
US11399837B2 (en) | 2019-06-28 | 2022-08-02 | Cilag Gmbh International | Mechanisms for motor control adjustments of a motorized surgical instrument |
US11553971B2 (en) | 2019-06-28 | 2023-01-17 | Cilag Gmbh International | Surgical RFID assemblies for display and communication |
US11660163B2 (en) | 2019-06-28 | 2023-05-30 | Cilag Gmbh International | Surgical system with RFID tags for updating motor assembly parameters |
US11771419B2 (en) | 2019-06-28 | 2023-10-03 | Cilag Gmbh International | Packaging for a replaceable component of a surgical stapling system |
US11291451B2 (en) | 2019-06-28 | 2022-04-05 | Cilag Gmbh International | Surgical instrument with battery compatibility verification functionality |
US11627959B2 (en) | 2019-06-28 | 2023-04-18 | Cilag Gmbh International | Surgical instruments including manual and powered system lockouts |
US11241235B2 (en) | 2019-06-28 | 2022-02-08 | Cilag Gmbh International | Method of using multiple RFID chips with a surgical assembly |
US11051807B2 (en) | 2019-06-28 | 2021-07-06 | Cilag Gmbh International | Packaging assembly including a particulate trap |
US11298132B2 (en) | 2019-06-28 | 2022-04-12 | Cilag GmbH Inlernational | Staple cartridge including a honeycomb extension |
US11478241B2 (en) | 2019-06-28 | 2022-10-25 | Cilag Gmbh International | Staple cartridge including projections |
US11219455B2 (en) | 2019-06-28 | 2022-01-11 | Cilag Gmbh International | Surgical instrument including a lockout key |
US11638587B2 (en) | 2019-06-28 | 2023-05-02 | Cilag Gmbh International | RFID identification systems for surgical instruments |
US11529139B2 (en) | 2019-12-19 | 2022-12-20 | Cilag Gmbh International | Motor driven surgical instrument |
US11576672B2 (en) | 2019-12-19 | 2023-02-14 | Cilag Gmbh International | Surgical instrument comprising a closure system including a closure member and an opening member driven by a drive screw |
US11911032B2 (en) | 2019-12-19 | 2024-02-27 | Cilag Gmbh International | Staple cartridge comprising a seating cam |
US11304696B2 (en) | 2019-12-19 | 2022-04-19 | Cilag Gmbh International | Surgical instrument comprising a powered articulation system |
US11607219B2 (en) | 2019-12-19 | 2023-03-21 | Cilag Gmbh International | Staple cartridge comprising a detachable tissue cutting knife |
US11504122B2 (en) | 2019-12-19 | 2022-11-22 | Cilag Gmbh International | Surgical instrument comprising a nested firing member |
US11446029B2 (en) | 2019-12-19 | 2022-09-20 | Cilag Gmbh International | Staple cartridge comprising projections extending from a curved deck surface |
US11701111B2 (en) | 2019-12-19 | 2023-07-18 | Cilag Gmbh International | Method for operating a surgical stapling instrument |
US11529137B2 (en) | 2019-12-19 | 2022-12-20 | Cilag Gmbh International | Staple cartridge comprising driver retention members |
US11844520B2 (en) | 2019-12-19 | 2023-12-19 | Cilag Gmbh International | Staple cartridge comprising driver retention members |
US11234698B2 (en) | 2019-12-19 | 2022-02-01 | Cilag Gmbh International | Stapling system comprising a clamp lockout and a firing lockout |
US11931033B2 (en) | 2019-12-19 | 2024-03-19 | Cilag Gmbh International | Staple cartridge comprising a latch lockout |
US11291447B2 (en) | 2019-12-19 | 2022-04-05 | Cilag Gmbh International | Stapling instrument comprising independent jaw closing and staple firing systems |
US11464512B2 (en) | 2019-12-19 | 2022-10-11 | Cilag Gmbh International | Staple cartridge comprising a curved deck surface |
US11559304B2 (en) | 2019-12-19 | 2023-01-24 | Cilag Gmbh International | Surgical instrument comprising a rapid closure mechanism |
US11223960B2 (en) | 2020-05-13 | 2022-01-11 | T-Mobile Usa, Inc. | Network planning tool for forecasting in telecommunications networks |
US10880754B1 (en) | 2020-05-13 | 2020-12-29 | T-Mobile Usa, Inc. | Network planning tool for retention analysis in telecommunications networks |
USD975278S1 (en) | 2020-06-02 | 2023-01-10 | Cilag Gmbh International | Staple cartridge |
USD976401S1 (en) | 2020-06-02 | 2023-01-24 | Cilag Gmbh International | Staple cartridge |
USD975851S1 (en) | 2020-06-02 | 2023-01-17 | Cilag Gmbh International | Staple cartridge |
USD967421S1 (en) | 2020-06-02 | 2022-10-18 | Cilag Gmbh International | Staple cartridge |
USD974560S1 (en) | 2020-06-02 | 2023-01-03 | Cilag Gmbh International | Staple cartridge |
USD975850S1 (en) | 2020-06-02 | 2023-01-17 | Cilag Gmbh International | Staple cartridge |
USD966512S1 (en) | 2020-06-02 | 2022-10-11 | Cilag Gmbh International | Staple cartridge |
US20220031351A1 (en) | 2020-07-28 | 2022-02-03 | Cilag Gmbh International | Surgical instruments with differential articulation joint arrangements for accommodating flexible actuators |
USD1013170S1 (en) | 2020-10-29 | 2024-01-30 | Cilag Gmbh International | Surgical instrument assembly |
US11617577B2 (en) | 2020-10-29 | 2023-04-04 | Cilag Gmbh International | Surgical instrument comprising a sensor configured to sense whether an articulation drive of the surgical instrument is actuatable |
US11896217B2 (en) | 2020-10-29 | 2024-02-13 | Cilag Gmbh International | Surgical instrument comprising an articulation lock |
US11517390B2 (en) | 2020-10-29 | 2022-12-06 | Cilag Gmbh International | Surgical instrument comprising a limited travel switch |
US11844518B2 (en) | 2020-10-29 | 2023-12-19 | Cilag Gmbh International | Method for operating a surgical instrument |
US11779330B2 (en) | 2020-10-29 | 2023-10-10 | Cilag Gmbh International | Surgical instrument comprising a jaw alignment system |
US11717289B2 (en) | 2020-10-29 | 2023-08-08 | Cilag Gmbh International | Surgical instrument comprising an indicator which indicates that an articulation drive is actuatable |
US11534259B2 (en) | 2020-10-29 | 2022-12-27 | Cilag Gmbh International | Surgical instrument comprising an articulation indicator |
USD980425S1 (en) | 2020-10-29 | 2023-03-07 | Cilag Gmbh International | Surgical instrument assembly |
US11452526B2 (en) | 2020-10-29 | 2022-09-27 | Cilag Gmbh International | Surgical instrument comprising a staged voltage regulation start-up system |
US11931025B2 (en) | 2020-10-29 | 2024-03-19 | Cilag Gmbh International | Surgical instrument comprising a releasable closure drive lock |
US11653920B2 (en) | 2020-12-02 | 2023-05-23 | Cilag Gmbh International | Powered surgical instruments with communication interfaces through sterile barrier |
US11849943B2 (en) | 2020-12-02 | 2023-12-26 | Cilag Gmbh International | Surgical instrument with cartridge release mechanisms |
US11627960B2 (en) | 2020-12-02 | 2023-04-18 | Cilag Gmbh International | Powered surgical instruments with smart reload with separately attachable exteriorly mounted wiring connections |
US11678882B2 (en) | 2020-12-02 | 2023-06-20 | Cilag Gmbh International | Surgical instruments with interactive features to remedy incidental sled movements |
US11744581B2 (en) | 2020-12-02 | 2023-09-05 | Cilag Gmbh International | Powered surgical instruments with multi-phase tissue treatment |
US11944296B2 (en) | 2020-12-02 | 2024-04-02 | Cilag Gmbh International | Powered surgical instruments with external connectors |
US11890010B2 (en) | 2020-12-02 | 2024-02-06 | Cllag GmbH International | Dual-sided reinforced reload for surgical instruments |
US11737751B2 (en) | 2020-12-02 | 2023-08-29 | Cilag Gmbh International | Devices and methods of managing energy dissipated within sterile barriers of surgical instrument housings |
US11653915B2 (en) | 2020-12-02 | 2023-05-23 | Cilag Gmbh International | Surgical instruments with sled location detection and adjustment features |
US11744583B2 (en) | 2021-02-26 | 2023-09-05 | Cilag Gmbh International | Distal communication array to tune frequency of RF systems |
US11751869B2 (en) | 2021-02-26 | 2023-09-12 | Cilag Gmbh International | Monitoring of multiple sensors over time to detect moving characteristics of tissue |
US11730473B2 (en) | 2021-02-26 | 2023-08-22 | Cilag Gmbh International | Monitoring of manufacturing life-cycle |
US11793514B2 (en) | 2021-02-26 | 2023-10-24 | Cilag Gmbh International | Staple cartridge comprising sensor array which may be embedded in cartridge body |
US11701113B2 (en) | 2021-02-26 | 2023-07-18 | Cilag Gmbh International | Stapling instrument comprising a separate power antenna and a data transfer antenna |
US11696757B2 (en) | 2021-02-26 | 2023-07-11 | Cilag Gmbh International | Monitoring of internal systems to detect and track cartridge motion status |
US11723657B2 (en) | 2021-02-26 | 2023-08-15 | Cilag Gmbh International | Adjustable communication based on available bandwidth and power capacity |
US11812964B2 (en) | 2021-02-26 | 2023-11-14 | Cilag Gmbh International | Staple cartridge comprising a power management circuit |
US11749877B2 (en) | 2021-02-26 | 2023-09-05 | Cilag Gmbh International | Stapling instrument comprising a signal antenna |
US11925349B2 (en) | 2021-02-26 | 2024-03-12 | Cilag Gmbh International | Adjustment to transfer parameters to improve available power |
US11826012B2 (en) | 2021-03-22 | 2023-11-28 | Cilag Gmbh International | Stapling instrument comprising a pulsed motor-driven firing rack |
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US11937816B2 (en) | 2021-10-28 | 2024-03-26 | Cilag Gmbh International | Electrical lead arrangements for surgical instruments |
Citations (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4385404A (en) * | 1980-02-21 | 1983-05-31 | J. & P. Coats, Limited | Device and method for use in the treatment of damaged articular surfaces of human joints |
US4393874A (en) * | 1982-04-26 | 1983-07-19 | Telectronics Pty. Ltd. | Bradycardia event counting and reporting pacer |
US4553272A (en) * | 1981-02-26 | 1985-11-19 | University Of Pittsburgh | Regeneration of living tissues by growth of isolated cells in porous implant and product thereof |
US4559936A (en) * | 1983-09-29 | 1985-12-24 | Hill Edward B | Bone plugging apparatus |
US4642120A (en) * | 1983-03-23 | 1987-02-10 | Ramot University Authority For Applied Research And Industrial Development Ltd. | Repair of cartilage and bones |
US4642117A (en) * | 1985-03-22 | 1987-02-10 | Collagen Corporation | Mechanically sheared collagen implant material and method |
US4649918A (en) * | 1980-09-03 | 1987-03-17 | Custom Medical Devices, Inc. | Bone core removing tool |
US4681588A (en) * | 1983-10-20 | 1987-07-21 | Vettivetpillai Ketharanathan | Biomaterial |
US4789663A (en) * | 1984-07-06 | 1988-12-06 | Collagen Corporation | Methods of bone repair using collagen |
US4846835A (en) * | 1987-06-15 | 1989-07-11 | Grande Daniel A | Technique for healing lesions in cartilage |
US4873976A (en) * | 1984-02-28 | 1989-10-17 | Schreiber Saul N | Surgical fasteners and method |
US4877020A (en) * | 1984-11-30 | 1989-10-31 | Vich Jose M O | Apparatus for bone graft |
US4904259A (en) * | 1988-04-29 | 1990-02-27 | Samuel Itay | Compositions and methods for repair of cartilage and bone |
US5019108A (en) * | 1990-02-02 | 1991-05-28 | Bertin Kim C | Modular implant |
US5041138A (en) * | 1986-11-20 | 1991-08-20 | Massachusetts Institute Of Technology | Neomorphogenesis of cartilage in vivo from cell culture |
US5062845A (en) * | 1989-05-10 | 1991-11-05 | Spine-Tech, Inc. | Method of making an intervertebral reamer |
US5067964A (en) * | 1989-12-13 | 1991-11-26 | Stryker Corporation | Articular surface repair |
US5092883A (en) * | 1988-12-28 | 1992-03-03 | Eppley Barry L | Method for promoting soft connective tissue growth and repair in mammals |
US5116374A (en) * | 1989-03-02 | 1992-05-26 | Regen Corporation | Prosthetic meniscus |
US5158574A (en) * | 1987-07-20 | 1992-10-27 | Regen Corporation | Prosthetic meniscus |
US5201745A (en) * | 1988-03-15 | 1993-04-13 | Imedex | Visceral surgery patch |
US5206023A (en) * | 1991-01-31 | 1993-04-27 | Robert F. Shaw | Method and compositions for the treatment and repair of defects or lesions in cartilage |
US5206028A (en) * | 1991-02-11 | 1993-04-27 | Li Shu Tung | Dense collagen membrane matrices for medical uses |
US5246441A (en) * | 1989-09-08 | 1993-09-21 | Linvatec Corporation | Bioabsorbable tack for joining bodily tissue |
US5258043A (en) * | 1987-07-20 | 1993-11-02 | Regen Corporation | Method for making a prosthetic intervertebral disc |
US5259835A (en) * | 1991-08-29 | 1993-11-09 | Tri-Point Medical L.P. | Wound closure means and method using flowable adhesive |
US5306311A (en) * | 1987-07-20 | 1994-04-26 | Regen Corporation | Prosthetic articular cartilage |
US5344459A (en) * | 1991-12-03 | 1994-09-06 | Swartz Stephen J | Arthroscopically implantable prosthesis |
US5354283A (en) * | 1994-01-07 | 1994-10-11 | Little Rapids Corporation | Trocar retention apparatus |
US5403338A (en) * | 1992-01-21 | 1995-04-04 | Scanlan International, Inc. | Punch for opening passages between two compartments |
US5423858A (en) * | 1993-09-30 | 1995-06-13 | United States Surgical Corporation | Septoplasty fasteners and device for applying same |
US5470911A (en) * | 1988-11-21 | 1995-11-28 | Collagen Corporation | Glycosaminoglycan-synthetic polymer conjugates |
US5544552A (en) * | 1993-01-04 | 1996-08-13 | Axel Kirsch | Tool for setting a fastening nail |
US5567806A (en) * | 1991-08-02 | 1996-10-22 | Abdul-Malak; Nabil | Collagen crosslinked with a crosslinking agent for the manufacture of a suturable, biocompatible slowresorbing membrane, and such a membrane |
US5569252A (en) * | 1994-09-27 | 1996-10-29 | Justin; Daniel F. | Device for repairing a meniscal tear in a knee and method |
US5658343A (en) * | 1994-07-11 | 1997-08-19 | Sulzer Medizinaltechnik Ag | Areal implant |
US5713374A (en) * | 1995-02-10 | 1998-02-03 | The Hospital For Joint Diseases Orthopaedic Institute | Fixation method for the attachment of wound repair materials to cartilage defects |
US5736372A (en) * | 1986-11-20 | 1998-04-07 | Massachusetts Institute Of Technology | Biodegradable synthetic polymeric fibrous matrix containing chondrocyte for in vivo production of a cartilaginous structure |
US5759190A (en) * | 1996-08-30 | 1998-06-02 | Vts Holdings Limited | Method and kit for autologous transplantation |
US5769899A (en) * | 1994-08-12 | 1998-06-23 | Matrix Biotechnologies, Inc. | Cartilage repair unit |
US5837278A (en) * | 1994-01-06 | 1998-11-17 | Ed Geistlich Sohne Ag Fur Chemische Industrie | Resorbable collagen membrane for use in guided tissue regeneration |
US5853746A (en) * | 1991-01-31 | 1998-12-29 | Robert Francis Shaw | Methods and compositions for the treatment and repair of defects or lesions in cartilage or bone using functional barrier |
US5902741A (en) * | 1986-04-18 | 1999-05-11 | Advanced Tissue Sciences, Inc. | Three-dimensional cartilage cultures |
US5932459A (en) * | 1995-10-20 | 1999-08-03 | Sittinger; Michael | Artificial tissues, methods for the production and the use thereof |
US5989269A (en) * | 1996-08-30 | 1999-11-23 | Vts Holdings L.L.C. | Method, instruments and kit for autologous transplantation |
US6007539A (en) * | 1996-01-17 | 1999-12-28 | Axel Kirsch | Fastening nail |
US6080194A (en) * | 1995-02-10 | 2000-06-27 | The Hospital For Joint Disease Orthopaedic Institute | Multi-stage collagen-based template or implant for use in the repair of cartilage lesions |
US6132463A (en) * | 1995-05-19 | 2000-10-17 | Etex Corporation | Cell seeding of ceramic compositions |
US6187053B1 (en) * | 1996-11-16 | 2001-02-13 | Will Minuth | Process for producing a natural implant |
Family Cites Families (48)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US542A (en) * | 1837-12-29 | Machine for ti-ibeshing and cleaning g-rain | ||
US2670519A (en) * | 1951-10-24 | 1954-03-02 | Charles F Recklitis | Drainage tube with clot extractor |
US3989049A (en) * | 1973-07-30 | 1976-11-02 | In Bae Yoon | Method of applying an elastic ring to an anatomical tubular structure |
US4374523A (en) * | 1974-10-29 | 1983-02-22 | Yoon In B | Occlusion ring applicator |
US4174715A (en) * | 1977-03-28 | 1979-11-20 | Hasson Harrith M | Multi-pronged laparoscopy forceps |
CH632923A5 (en) * | 1978-10-06 | 1982-11-15 | Sulzer Ag | Implant for partial replacement of a sliding surface of a human joint |
US4393872A (en) * | 1980-05-27 | 1983-07-19 | Eder Instrument Co., Inc. | Aspirating surgical forceps |
US4611594A (en) * | 1984-04-11 | 1986-09-16 | Northwestern University | Medical instrument for containment and removal of calculi |
US4620327A (en) | 1984-07-05 | 1986-11-04 | Caplan Arnold I | Process of adapting soluble bone protein for use in stimulating osteoinduction |
US4657020A (en) * | 1985-07-10 | 1987-04-14 | Jayco Pharmaceuticals | Method of using a foreign object protector hood |
GB8705985D0 (en) | 1987-03-13 | 1987-04-15 | Geistlich Soehne Ag | Dressings |
CA1329089C (en) * | 1987-09-02 | 1994-05-03 | Russell Warren | Surgical fastener |
NZ226170A (en) | 1987-09-18 | 1990-07-26 | Ethicon Inc | Stable freeze-dried pharmaceutical composition containing epidermal growth factor |
CA1339083C (en) | 1987-11-13 | 1997-07-29 | Steven R. Jefferies | Bone repair material and delayed drug delivery system |
JP2820415B2 (en) | 1988-03-14 | 1998-11-05 | ティーエイチエム・バイオメディカル・インコーポレイテッド | Biodegradable and osteogenic graft bone graft substitute composition |
US4975526A (en) | 1989-02-23 | 1990-12-04 | Creative Biomolecules, Inc. | Bone collagen matrix for zenogenic implants |
US5108436A (en) | 1988-09-29 | 1992-04-28 | Collagen Corporation | Implant fixation |
IE61346B1 (en) | 1988-11-02 | 1994-11-02 | Genentech Inc | A permeable material to fit around the teeth or gums of a mammal |
US5162430A (en) | 1988-11-21 | 1992-11-10 | Collagen Corporation | Collagen-polymer conjugates |
WO1990009783A1 (en) | 1989-02-22 | 1990-09-07 | Massachusetts Institute Of Technology | Delivery system for controlled release of bioactive factors |
AU5654990A (en) | 1989-04-28 | 1990-11-29 | Brigham And Women's Hospital | Novel materials and methods for guided tissue regeneration |
US6413511B1 (en) | 1990-12-20 | 2002-07-02 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Cartilage alterations by administering to joints chondrocytes comprising a heterologous polynucleotide |
US5190561A (en) * | 1991-01-23 | 1993-03-02 | Surgical Innovations, Inc. | Tissue and organ extractor |
US5147378A (en) * | 1991-03-05 | 1992-09-15 | Harold Markham | Grapsing forceps |
SE9101853D0 (en) | 1991-06-17 | 1991-06-17 | Jonas Wadstroem | IMPROVED TISSUE ASHESIVE |
US5270300A (en) | 1991-09-06 | 1993-12-14 | Robert Francis Shaw | Methods and compositions for the treatment and repair of defects or lesions in cartilage or bone |
US5308327A (en) * | 1991-11-25 | 1994-05-03 | Advanced Surgical Inc. | Self-deployed inflatable retractor |
US5326357A (en) | 1992-03-18 | 1994-07-05 | Mount Sinai Hospital Corporation | Reconstituted cartridge tissue |
AU4543193A (en) | 1992-06-22 | 1994-01-24 | Henry E. Young | Scar inhibitory factor and use thereof |
WO1994009118A1 (en) | 1992-10-13 | 1994-04-28 | The General Hospital Corporation | Immortalized human chondrocytes |
WO1994015533A2 (en) * | 1993-01-18 | 1994-07-21 | John Crowe | Endoscope forceps |
CA2130295A1 (en) | 1993-08-26 | 1995-02-27 | Richard A. Berg | Ionically crosslinked glycosaminoglycan gels for soft tissue augmentation and drug delivery |
CA2142209A1 (en) | 1994-03-29 | 1995-09-30 | George H. Chu | Collagen implants having improved tensile properties |
WO1995030742A1 (en) | 1994-05-05 | 1995-11-16 | Genzyme Corporation | Methods and compositions for the repair of articular cartilage defects in mammals |
CA2196213A1 (en) | 1994-07-28 | 1996-02-08 | Ivan Vesely | Bioprosthetic implants and method of making and using same |
JPH0856951A (en) * | 1994-08-25 | 1996-03-05 | Olympus Optical Co Ltd | Clamping forceps for endoscope |
DE4425456A1 (en) | 1994-09-07 | 1996-03-21 | Matthias Dr Med Honl | Bone saw for concentric cylindrical or part spherical cuts |
GB9721585D0 (en) | 1997-10-10 | 1997-12-10 | Geistlich Soehne Ag | Chemical product |
GB9503492D0 (en) | 1995-02-22 | 1995-04-12 | Ed Geistlich S Hne A G F R Che | Chemical product |
US5842477A (en) * | 1996-02-21 | 1998-12-01 | Advanced Tissue Sciences, Inc. | Method for repairing cartilage |
DE19654884C2 (en) | 1996-03-04 | 1999-07-29 | Kirsch Axel | Molded body |
ATE250666T1 (en) * | 1996-06-04 | 2003-10-15 | Sulzer Orthopedics Ltd | METHOD FOR PRODUCING CARTILAGE TISSUE AND IMPLANTS |
JP2001505330A (en) * | 1996-08-22 | 2001-04-17 | ルノー・アンド・オスピー・スピーチ・プロダクツ・ナームローゼ・ベンノートシャープ | Method and apparatus for providing word breaks in a text stream |
EP0842670A1 (en) | 1996-11-13 | 1998-05-20 | Katsunari Nishihara | Biomedical materials |
DE19648876C2 (en) | 1996-11-16 | 1999-10-07 | Will Minuth | Method of making a natural implant |
AU6654598A (en) | 1997-02-13 | 1998-09-08 | Benedict, James A. | Implantable collagen-containing putty material |
US6383195B1 (en) * | 1998-04-13 | 2002-05-07 | Endoline, Inc. | Laparoscopic specimen removal apparatus |
JP2000037388A (en) * | 1998-05-20 | 2000-02-08 | Osamu Yoshida | Organ housing bag and organ housing bag inserter |
-
1999
- 1999-08-16 AU AU56222/99A patent/AU771701B2/en not_active Ceased
- 1999-08-16 NZ NZ526523A patent/NZ526523A/en not_active IP Right Cessation
- 1999-08-16 SG SG200300186A patent/SG115519A1/en unknown
- 1999-08-16 CA CA2338909A patent/CA2338909C/en not_active Expired - Fee Related
- 1999-08-16 MX MXPA01001460A patent/MXPA01001460A/en not_active IP Right Cessation
- 1999-08-16 TR TR2002/00088T patent/TR200200088T2/en unknown
- 1999-08-16 SK SK193-2001A patent/SK1932001A3/en unknown
- 1999-08-16 TR TR2002/00089T patent/TR200200089T2/en unknown
- 1999-08-16 HU HU0103133A patent/HU224279B1/en not_active IP Right Cessation
- 1999-08-16 JP JP2000564680A patent/JP2002522168A/en active Pending
- 1999-08-16 KR KR1020017001941A patent/KR20010082172A/en not_active Application Discontinuation
- 1999-08-16 YU YU12201A patent/YU12201A/en unknown
- 1999-08-16 WO PCT/EP1999/005993 patent/WO2000009179A2/en not_active Application Discontinuation
- 1999-08-16 BR BR9912913-2A patent/BR9912913A/en not_active Application Discontinuation
- 1999-08-16 CZ CZ2001442A patent/CZ2001442A3/en unknown
- 1999-08-16 KR KR10-2004-7012698A patent/KR20040077968A/en not_active Application Discontinuation
- 1999-08-16 IL IL14130899A patent/IL141308A0/en active IP Right Grant
- 1999-08-16 NZ NZ509565A patent/NZ509565A/en not_active IP Right Cessation
- 1999-08-16 TR TR2001/00482T patent/TR200100482T2/en unknown
- 1999-08-16 CN CN99812041A patent/CN1323228A/en active Pending
- 1999-08-16 KR KR10-2004-7012696A patent/KR20040081798A/en not_active Application Discontinuation
- 1999-08-16 PL PL99346653A patent/PL346653A1/en unknown
- 1999-08-16 EP EP99942872A patent/EP1104313A2/en not_active Withdrawn
-
2001
- 2001-01-29 NO NO20010482A patent/NO20010482L/en not_active Application Discontinuation
- 2001-02-07 IL IL141308A patent/IL141308A/en not_active IP Right Cessation
- 2001-05-17 US US09/859,370 patent/US6866668B2/en not_active Expired - Fee Related
-
2004
- 2004-06-25 AU AU2004202874A patent/AU2004202874A1/en not_active Abandoned
-
2005
- 2005-02-03 US US11/050,523 patent/US20050129668A1/en not_active Abandoned
Patent Citations (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4385404A (en) * | 1980-02-21 | 1983-05-31 | J. & P. Coats, Limited | Device and method for use in the treatment of damaged articular surfaces of human joints |
US4649918A (en) * | 1980-09-03 | 1987-03-17 | Custom Medical Devices, Inc. | Bone core removing tool |
US4553272A (en) * | 1981-02-26 | 1985-11-19 | University Of Pittsburgh | Regeneration of living tissues by growth of isolated cells in porous implant and product thereof |
US4393874A (en) * | 1982-04-26 | 1983-07-19 | Telectronics Pty. Ltd. | Bradycardia event counting and reporting pacer |
US4642120A (en) * | 1983-03-23 | 1987-02-10 | Ramot University Authority For Applied Research And Industrial Development Ltd. | Repair of cartilage and bones |
US4559936A (en) * | 1983-09-29 | 1985-12-24 | Hill Edward B | Bone plugging apparatus |
US4681588A (en) * | 1983-10-20 | 1987-07-21 | Vettivetpillai Ketharanathan | Biomaterial |
US4873976A (en) * | 1984-02-28 | 1989-10-17 | Schreiber Saul N | Surgical fasteners and method |
US4789663A (en) * | 1984-07-06 | 1988-12-06 | Collagen Corporation | Methods of bone repair using collagen |
US4877020A (en) * | 1984-11-30 | 1989-10-31 | Vich Jose M O | Apparatus for bone graft |
US4642117A (en) * | 1985-03-22 | 1987-02-10 | Collagen Corporation | Mechanically sheared collagen implant material and method |
US5902741A (en) * | 1986-04-18 | 1999-05-11 | Advanced Tissue Sciences, Inc. | Three-dimensional cartilage cultures |
US5041138A (en) * | 1986-11-20 | 1991-08-20 | Massachusetts Institute Of Technology | Neomorphogenesis of cartilage in vivo from cell culture |
US5736372A (en) * | 1986-11-20 | 1998-04-07 | Massachusetts Institute Of Technology | Biodegradable synthetic polymeric fibrous matrix containing chondrocyte for in vivo production of a cartilaginous structure |
US4846835A (en) * | 1987-06-15 | 1989-07-11 | Grande Daniel A | Technique for healing lesions in cartilage |
US5158574A (en) * | 1987-07-20 | 1992-10-27 | Regen Corporation | Prosthetic meniscus |
US5258043A (en) * | 1987-07-20 | 1993-11-02 | Regen Corporation | Method for making a prosthetic intervertebral disc |
US5306311A (en) * | 1987-07-20 | 1994-04-26 | Regen Corporation | Prosthetic articular cartilage |
US5201745A (en) * | 1988-03-15 | 1993-04-13 | Imedex | Visceral surgery patch |
US4904259A (en) * | 1988-04-29 | 1990-02-27 | Samuel Itay | Compositions and methods for repair of cartilage and bone |
US5470911A (en) * | 1988-11-21 | 1995-11-28 | Collagen Corporation | Glycosaminoglycan-synthetic polymer conjugates |
US5092883A (en) * | 1988-12-28 | 1992-03-03 | Eppley Barry L | Method for promoting soft connective tissue growth and repair in mammals |
US5116374A (en) * | 1989-03-02 | 1992-05-26 | Regen Corporation | Prosthetic meniscus |
US5062845A (en) * | 1989-05-10 | 1991-11-05 | Spine-Tech, Inc. | Method of making an intervertebral reamer |
US5246441A (en) * | 1989-09-08 | 1993-09-21 | Linvatec Corporation | Bioabsorbable tack for joining bodily tissue |
US5067964A (en) * | 1989-12-13 | 1991-11-26 | Stryker Corporation | Articular surface repair |
US5019108A (en) * | 1990-02-02 | 1991-05-28 | Bertin Kim C | Modular implant |
US5206023A (en) * | 1991-01-31 | 1993-04-27 | Robert F. Shaw | Method and compositions for the treatment and repair of defects or lesions in cartilage |
US5853746A (en) * | 1991-01-31 | 1998-12-29 | Robert Francis Shaw | Methods and compositions for the treatment and repair of defects or lesions in cartilage or bone using functional barrier |
US5206028A (en) * | 1991-02-11 | 1993-04-27 | Li Shu Tung | Dense collagen membrane matrices for medical uses |
US5567806A (en) * | 1991-08-02 | 1996-10-22 | Abdul-Malak; Nabil | Collagen crosslinked with a crosslinking agent for the manufacture of a suturable, biocompatible slowresorbing membrane, and such a membrane |
US5445597A (en) * | 1991-08-29 | 1995-08-29 | Tri-Point Medical L.P. | Wound closure means using flowable adhesive |
US5259835A (en) * | 1991-08-29 | 1993-11-09 | Tri-Point Medical L.P. | Wound closure means and method using flowable adhesive |
US5344459A (en) * | 1991-12-03 | 1994-09-06 | Swartz Stephen J | Arthroscopically implantable prosthesis |
US5403338A (en) * | 1992-01-21 | 1995-04-04 | Scanlan International, Inc. | Punch for opening passages between two compartments |
US5544552A (en) * | 1993-01-04 | 1996-08-13 | Axel Kirsch | Tool for setting a fastening nail |
US5423858A (en) * | 1993-09-30 | 1995-06-13 | United States Surgical Corporation | Septoplasty fasteners and device for applying same |
US5837278A (en) * | 1994-01-06 | 1998-11-17 | Ed Geistlich Sohne Ag Fur Chemische Industrie | Resorbable collagen membrane for use in guided tissue regeneration |
US5354283A (en) * | 1994-01-07 | 1994-10-11 | Little Rapids Corporation | Trocar retention apparatus |
US5658343A (en) * | 1994-07-11 | 1997-08-19 | Sulzer Medizinaltechnik Ag | Areal implant |
US5769899A (en) * | 1994-08-12 | 1998-06-23 | Matrix Biotechnologies, Inc. | Cartilage repair unit |
US5569252A (en) * | 1994-09-27 | 1996-10-29 | Justin; Daniel F. | Device for repairing a meniscal tear in a knee and method |
US5713374A (en) * | 1995-02-10 | 1998-02-03 | The Hospital For Joint Diseases Orthopaedic Institute | Fixation method for the attachment of wound repair materials to cartilage defects |
US6080194A (en) * | 1995-02-10 | 2000-06-27 | The Hospital For Joint Disease Orthopaedic Institute | Multi-stage collagen-based template or implant for use in the repair of cartilage lesions |
US6132463A (en) * | 1995-05-19 | 2000-10-17 | Etex Corporation | Cell seeding of ceramic compositions |
US5932459A (en) * | 1995-10-20 | 1999-08-03 | Sittinger; Michael | Artificial tissues, methods for the production and the use thereof |
US6143501A (en) * | 1995-10-20 | 2000-11-07 | Sittinger; Michael | Artificial tissues, methods for the production and the use thereof |
US6007539A (en) * | 1996-01-17 | 1999-12-28 | Axel Kirsch | Fastening nail |
US5759190A (en) * | 1996-08-30 | 1998-06-02 | Vts Holdings Limited | Method and kit for autologous transplantation |
US5989269A (en) * | 1996-08-30 | 1999-11-23 | Vts Holdings L.L.C. | Method, instruments and kit for autologous transplantation |
US6187053B1 (en) * | 1996-11-16 | 2001-02-13 | Will Minuth | Process for producing a natural implant |
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
USRE42208E1 (en) | 2003-04-29 | 2011-03-08 | Musculoskeletal Transplant Foundation | Glue for cartilage repair |
USRE43258E1 (en) | 2003-04-29 | 2012-03-20 | Musculoskeletal Transplant Foundation | Glue for cartilage repair |
US7901457B2 (en) | 2003-05-16 | 2011-03-08 | Musculoskeletal Transplant Foundation | Cartilage allograft plug |
US8221500B2 (en) | 2003-05-16 | 2012-07-17 | Musculoskeletal Transplant Foundation | Cartilage allograft plug |
US8292968B2 (en) | 2004-10-12 | 2012-10-23 | Musculoskeletal Transplant Foundation | Cancellous constructs, cartilage particles and combinations of cancellous constructs and cartilage particles |
US7815926B2 (en) | 2005-07-11 | 2010-10-19 | Musculoskeletal Transplant Foundation | Implant for articular cartilage repair |
US20090214614A1 (en) * | 2005-09-02 | 2009-08-27 | Interface Biotech A/S | Method for Cell Implantation |
US9701940B2 (en) | 2005-09-19 | 2017-07-11 | Histogenics Corporation | Cell-support matrix having narrowly defined uniformly vertically and non-randomly organized porosity and pore density and a method for preparation thereof |
US7837740B2 (en) | 2007-01-24 | 2010-11-23 | Musculoskeletal Transplant Foundation | Two piece cancellous construct for cartilage repair |
US8906110B2 (en) | 2007-01-24 | 2014-12-09 | Musculoskeletal Transplant Foundation | Two piece cancellous construct for cartilage repair |
US8435551B2 (en) | 2007-03-06 | 2013-05-07 | Musculoskeletal Transplant Foundation | Cancellous construct with support ring for repair of osteochondral defects |
US8109935B2 (en) | 2009-05-15 | 2012-02-07 | Musculoskeletal Transplant Foundation | Implant inserter device |
US10077420B2 (en) | 2014-12-02 | 2018-09-18 | Histogenics Corporation | Cell and tissue culture container |
US11555172B2 (en) | 2014-12-02 | 2023-01-17 | Ocugen, Inc. | Cell and tissue culture container |
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