CN1947666B - In-vivo biological reactor and its application - Google Patents
In-vivo biological reactor and its application Download PDFInfo
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- CN1947666B CN1947666B CN2005100304347A CN200510030434A CN1947666B CN 1947666 B CN1947666 B CN 1947666B CN 2005100304347 A CN2005100304347 A CN 2005100304347A CN 200510030434 A CN200510030434 A CN 200510030434A CN 1947666 B CN1947666 B CN 1947666B
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Abstract
An intrabody bioreactor for the tissue-engineered organ transplantation is composed of an external powder pump system and an internal catheter system. It can be used to pump the cell culturing liquid containing the self blood serum of organ receptor, seed cells and growth factors into the transplanted organ and promote its vascularization.
Description
Technical field
The invention belongs to biomedical engineering field, be specifically related to a kind of in-vivo biological reactor and application thereof.In-vivo biological reactor of the present invention (IN-VIVO BIOREACTOR) can be kept engineered histoorgan succedaneum body and be implanted into early nutrition and promote its revascularization.
Background technology
Organizational project is an emerging biomedical high-tech subject, and its basic definition is: by cell, timbering material and (or) implantation of various bioactie agents, promote self repairing of damaged position body tissue organ.(Tissue engineering is the persuasion of the body to heal itself, through the delivery to the appropriate sites, of molecular signals, cellsand supporting structures.) Jing Dian organizational project therapeutic process comprises following step: 1) obtain all kinds of seed cells from the patient in body or allochthonous donor body, in the increase quantity of needs of subculture in vitro separately.2) utilize all kinds of degradable timbering materials (biomaterial or synthetic material), carry out plastotype, be prepared into the porous support that certain intensity is arranged by the histoorgan shape of required repairing.3) seed cell is seeded on the timbering material, makes up the cell-scaffold material composite, the In vitro culture ware is static or place bioreactor dynamically to cultivate, and promotes that seed cell sticks differentiation.4) the cell-scaffold material composite with external structure implants, and repairs the damaged tissues organ.
By above-mentioned traditional organizational project ultimate principle and method as can be known: guarantee that the early nutrition of implant and quick revascularization are the treatment key of success.There are some researches prove greater than 1mm
3Organizing promptly needs blood capillary to grow into nutrition and excretory cell metabolite are provided.Be subjected to the restriction of body regeneration capacity, the revascularization of implant is a process slowly often, and certain limit is arranged.With the tracheal replacement product is example, even have under the omentum majus parcel that enriches the revascularization ability, blood capillary is grown into by the anastomotic stoma at two ends needed for two weeks at least, and was difficult to surpass 2cm.Engineered histoorgan succedaneum is to be made up by activated seed cell to form, and is implanting very difficult survival under the environment that lacks the blood confession in early days.Revascularization has slowly limited the clinical practice of tissue engineering product greatly.
Summary of the invention
The purpose of this invention is to provide a kind of in-vivo biological reactor that can solve early stage blood confession of engineered succedaneum and quick vascularization.
Described in-vivo biological reactor is made up of external kinetic pump system and the body inner catheter two large divisions of system.External kinetic pump system comprises front pump system and rear pump system, and corresponding body inner catheter system also is divided into input pipe system and output duct system.An above-mentioned end that inputs or outputs conduit is inserted into the inside of tissue engineering tissue organ succedaneum respectively, and the other end is connected with each self-corresponding front pump or rear pump kinetic pump system.
The present invention simulates normal human's Arterial system and Venous system, front pump system and input pipe system continue nutritional solution to pump in the engineered organ succedaneum, rear pump system and output duct system then continue to get rid of the waste liquid in the engineered organ succedaneum, keep the stable of local microenvironment.The present invention can be with the regeneration induction of complete isolating external structure cell-scaffold material composite, in-vivo tissue organ in the past organizational project therapeutic scheme, and two big steps organically combine.
Described front pump system selects all kinds of infusion pump systems of clinical practice for use, for example U.S. Deltec company high capacity charge pump DeltecR300 ﹠amp; Micro 3100; The Volumetric InfusionPump of U.S. Baxter company; The Vista Basic Infusion Pump of U.S. B.Braun company; The VP series Infusion Pump of U.S. Arcomedical Infusion Ltd. company.
Described rear pump system selects all kinds of drainage systems of present clinical practice for use, as the clinical portability drainage system of the REDON of U.S. Tyko company.
Described body inner catheter system selects all kinds of implantable conduit system of present clinical practice for use, for example the implantable conduit system CliniCath PICC of U.S. Deltec company (peripherally inserted centralcatheters).
Link in all kinds of conduits of above-mentioned body inner catheter system is imbedded in subcutaneous by all kinds of implantable import systems, for example the implantable import system PORT-A-CATH of U.S. Deltec company.
Above-mentioned front pump system connects syringe needles by all kinds of implantable import systems, and the PORT-A-CATH Needles of U.S. Deltec company for example and is imbedded in subcutaneous implantable import system and is connected, thereby is connected with input pipe system in the body.
Above-mentioned rear pump system connects syringe needles by all kinds of implantable import systems, and the PORT-A-CATH Needles of U.S. Deltec company for example and is imbedded in subcutaneous implantable import system and is connected, thereby is connected with output duct system in the body.
Described engineered organ succedaneum comprises the engineered product of all clinical practices, for example: tissue-engineered bone, engineered trachea, tissue engineered esophageal, engineered liver or engineered bladder.
The present invention has following advantage:
1. by continuing and stably pumping into the survival that cell nutrient solution is kept engineered succedaneum internal seeds cell, guarantee the function replacement effect of succedaneum.
2. can in nutritional solution, add corresponding seed cell simultaneously, replace dead seed cell, guarantee the stable persistence of succedaneum function replacement in order to upgrade.
3. owing to increasing at any time and upgrading seed cell, alleviated of the requirement of organizational project succedaneum external structure to seed cell quantity.Can significantly shorten the external structure required time, greatly expand the clinical practice indication.As can be earlier in emergency operation simple implant frame material, the cultivation seed cell of drawing materials simultaneously continues input and upgrades seed cell by in-vivo biological reactor again during the emergency treatment post-operative recovery.
4. can in nutritional solution, add corresponding all kinds of somatomedin assurance simultaneously and promote the seed cell directed differentiation.Particularly after utilizing all kinds of stem cell to implant,, need keep suitable microenvironment and guarantee that it is to the direction differentiation of estimating owing to himself have multidirectional differentiation capability as seed cell.Traditional method utilizes the transgenic cell localized sustained to secrete corresponding somatomedin more, but its technical sophistication, cost height, and the influence that is subjected to the moral controversy uncertainty.
5. can in nutritional solution, add corresponding all kinds of somatomedin simultaneously and promote the revascularization of organizational project organ succedaneum.Revascularization is a complex physical repair process, needs the various kinds of cell factor to continue the synergism of coordinating.Can accuracy controlling all kinds of somatomedin effect frequency and intensity by in-vivo biological reactor, better simulate normal physiological processes.
Description of drawings
Fig. 1 is the engineered bone substitute timbering material structural representation of embodiment 1.
A wherein: be this engineered bone substitute timbering material vertical view, be shown as 6 * 6 centimeters square.The yellow input and output conduit system that shows, the inner and perpendicular hole of input and output conduit system of red display succedaneum, purpose is to enlarge input perfusion scope to greatest extent;
B: for parallel with the input and output conduit system, this engineered bone substitute timbering material side view shows that its thickness is 1 centimeter.Little figure shown in its right side arrow has shown that succedaneum inside is porous cellular tissue, and hole diameter is 200 microns;
C: for vertical with the input and output conduit system, this engineered bone substitute timbering material side view;
D: be the miter angle side view, the green part that shows that the input and output conduit system is connected with implantable import system.
The specific embodiment
Embodiment 1: tissue-engineered bone connects in-vivo biological reactor:
The present invention further specifies technical scheme of the present invention and effect by following embodiment, but does not therefore limit technical scheme of the present invention and effect.
1. structure in-vivo biological reactor:
Select the high capacity charge pump DeltecR300 ﹠amp of U.S. Deltec company for use; Micro 3100 is as the front pump system in the external kinetic pump system.
Select for use the clinical portability drainage system of the REDON of U.S. Tyko company as the rear pump system in the external kinetic pump system.
Select for use the CliniCathR PolyFlowR of U.S. Deltec company single-lumen polyurethane conduit as body inner catheter system.One end is imbedded and is implanted the intravital organizational project bone substitute of patient inside, the other end be imbedded in the subcutaneous implantable import system PORT-A-CATH of U.S. Deltec company and link to each other.
The implantable import system of U.S. Deltec company connects syringe needle PORT-A-CATH Needles, and external kinetic pump system is linked to each other with body inner catheter system.
2, make up tissue-engineered bone:
Press the known method extraction and, make seed cell at amplification in vitro bone marrow interstital stem cell (mesenchymal stem cellsMSCs); (LangeC, Schroeder J.High-potential humanmesenchymal stem cells.Stem Cell Dev.2005 Feb; 14 (1): 70-80)
Make up engineered bone holder material by shown in the figure (1).This support is made of degradation material, simulation normal person bone structure, the cladding material porosity is less, therefore rigidity is similar to cortical bone more greatly, the inner layer material porosity is bigger, and rigidity is little, but helps the seed cell tactophily, simulating normal spongiosa bone characteristics, is that body inner catheter system reserves tubular space in inner spongy bone district.
Press the described method inoculation of document seed cell to the biodegradable stent material, make up engineered bone substitute.(Takahashi?Y，Yamamoto?M.Osteogenic?differentia-tion?of?mesenchymal?stemcells?in?biodegradable?sponges?composed?of?gelatin?and?beta-tricalciumphosphate.Biomaterials.2005?Jun；26(17)：3587-96)
3, input pipe system and output duct system one end are inserted engineered bone substitute inside respectively, the other end is free.
Press the described method implanting tissue of document through engineering approaches bone substitute.With input pipe system and output duct system free-end be connected with implantable import system PORT-A-CATH (U.S. Deltec company) bury subcutaneous.(WarnkePH，Springer?IN.The?mechanical?integrity?of?in?vivo?engineered?heterotopicbone.Biomaterials.2005?Aug?22)
Connect syringe needle PORT-A-CATH Needles (U.S. Deltec company) by implantable import system input pipe system and output duct system are connected to front pump system and rear pump system.
With culture fluid DMEM, it contains the receptor autoserum, seed cell, bone morphogenetic protein(BMP)-2 (bonemorphogenetic protein-2, BMP-2), vascular endothelial cell growth factor (vascular endothelial cellgrowth factor, VEGF), (basic fibroblast growth factor bFGF), continues to pump into in-vivo tissue through engineering approaches bone substitute by the front pump system through the input pipe system to fibroblast growth factor.Wherein each somatomedin concentration is adjusted according to actual needs.
In-vivo tissue through engineering approaches bone substitute contains products of cellular metabolism, and the waste liquid of timbering material catabolite is continued to pump by the rear pump system through the output duct system.
After three months, engineered bone substitute revascularization is finished substantially, can stop external kinetic pump system, and little otch takes out implantable import system PORT-A-CATH and extracts body inner catheter system.
Claims (7)
1. in-vivo biological reactor, it is characterized in that forming by external kinetic pump system and body inner catheter system, described external kinetic pump system comprises front pump system and rear pump system, described body inner catheter system comprises input pipe system and output duct system, one end of above-mentioned input and output conduit is inserted into the inside of tissue engineering tissue organ succedaneum respectively, the other end and corresponding front pump or the connection of rear pump kinetic pump system; Described input pipe is connected with the front pump system, and output duct is connected with the rear pump system.
2. in-vivo biological reactor according to claim 1 is characterized in that described front pump system selects all kinds of infusion pump systems of clinical practice for use.
3. in-vivo biological reactor according to claim 1 is characterized in that described rear pump system is clinical portability drainage system.
4. in-vivo biological reactor according to claim 1 is characterized in that described body inner catheter system and is imbedded in subcutaneous implantable import system and is connected.
5. according to claim 1 or 2 or 4 described in-vivo biological reactors, it is characterized in that described front pump system connects syringe needles by all kinds of implantable import systems, with be imbedded in subcutaneous implantable import system and be connected, thereby be connected with input pipe system in the body.
6. according to claim 1 or 2 or 4 described in-vivo biological reactors, it is characterized in that described rear pump system connects syringe needles by all kinds of implantable import systems, with be imbedded in subcutaneous implantable import system and be connected, thereby be connected with output duct system in the body.
7. in-vivo biological reactor according to claim 1 is characterized in that described engineered organ succedaneum is: tissue-engineered bone, engineered trachea, tissue engineered esophageal, engineered liver or engineered bladder.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2005100304347A CN1947666B (en) | 2005-10-12 | 2005-10-12 | In-vivo biological reactor and its application |
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| CN2005100304347A CN1947666B (en) | 2005-10-12 | 2005-10-12 | In-vivo biological reactor and its application |
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| CN1947666A CN1947666A (en) | 2007-04-18 |
| CN1947666B true CN1947666B (en) | 2011-09-14 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103537002A (en) * | 2013-10-29 | 2014-01-29 | 同济大学附属上海市肺科医院 | In-vivo biological generator |
| CN104188738B (en) * | 2014-08-14 | 2018-04-27 | 卢建熙 | Multifunctional body in-seam generator |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4242459A (en) * | 1978-11-02 | 1980-12-30 | Chick William L | Cell culture device |
| US5011472A (en) * | 1988-09-06 | 1991-04-30 | Brown University Research Foundation | Implantable delivery system for biological factors |
| US6875605B1 (en) * | 2002-08-21 | 2005-04-05 | Florida State University Research Foundation, Inc. | Modular cell culture bioreactor and associated methods |
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2005
- 2005-10-12 CN CN2005100304347A patent/CN1947666B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4242459A (en) * | 1978-11-02 | 1980-12-30 | Chick William L | Cell culture device |
| US5011472A (en) * | 1988-09-06 | 1991-04-30 | Brown University Research Foundation | Implantable delivery system for biological factors |
| US6875605B1 (en) * | 2002-08-21 | 2005-04-05 | Florida State University Research Foundation, Inc. | Modular cell culture bioreactor and associated methods |
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