WO2009052208A2 - Knee joint prosthesis and hyaluronate compositions and systems useful for osteoarthritis - Google Patents

Abstract

A medical device and systems can be customized to generate a prosthesis useful for knee joint repair, replacement and augmentation. The invention discloses joint lubricant, particularly hyaluronate compositions and methods for treatment of osteoarthritis.

Description

KNEE JOINT PROSTHESIS AND HYALURONATE COMPOSITIONS AND SYSTEMS USEFUL FOR OSTEOARTHRITIS

Cross-reference to Related Applications

[0001] The application claims the priority benefits of U.S. Utility Application No. 11/974,538 filed October 15, 2007, which claimed priority of U.S. Provisional Application No. 60/852,885 filed October 19, 2006, and U.S. Provisional Application No. 60/919,305 filed March 20, 2007.

Field of the Invention

[0002] The present invention is generally related to therapies for treating a joint or other body parts of a patient. More particularly, the present invention is related to a medical device, hyaluronic compositions, and systems for use with osteoarthritis or joint pain, replacement and augmentation.

Background of the Invention

[0003] The knee is very complex and includes many components with many functions. The knee problems may be related to meniscus, pain, cartilage, shock absorption, synovial fluids, articular cartilage, ligaments/tendons and/or preserving normal biomechanics. Available therapy currently includes chronic synovial lubrication, acute synovial lubrication, meniscal protection, meniscal augmentation, partial meniscal replacement, total meniscal replacement, and partial or total knee prosthesis.

[0004] The menisci arc crescents roughly triangular in cross section, covering one-half to two thirds of the articular surface of the corresponding tibial plateau. The outer rims of the menisci are convex and attached to the knee joint capsule. The inner edges are concave, thin and free. The anatomy of menisci and knee joints can be found in any anatomy book, for example, Gray's Anatomy of the Human Body, 20^th edition, New York (Bartleby.com 2000).

[0005] The menisci extend the superior tibial surface, improving its congruency with the femoral condyles. Both menisci are fibrocartilaginous and wedge shaped in the

078376-011300v1 236,323,216 Λ coronal plane. The medial meniscus is crescent shaped, and the lateral meniscus is more circular. The superior portions of the menisci are concave, enabling effective articulation with their respective convex condyles, whereas the inferior surfaces are flat to conform to the tibial plateaus. Anterior and posterior meniscal horns attach to the intercondylar eminence of the tibial plateau. The coronary ligaments provide peripheral attachments between the tibial plateau and the perimeter of both menisci. The medial meniscus is also attached to the medial collateral ligament, which limits its mobility. The lateral meniscus is connected to the femur via the anterior and posterior meniscofemoral ligaments, which can tension its posterior horn anteriorly and medially with increasing knee flexion. The transverse ligament provides a connection between the anterior aspects of both menisci. The increased stability provided by the ligamentous attachments prevents the menisci from being extruded out of the joint during compression.

[0006] The knee joint is innervated by the posterior articular branch of the posterior tibial nerve and the terminal branches of the obturator and femoral nerves. Nerve fibers generally penetrate the joint capsule, along with the vascular supply and service the substance of the menisci.

[0007] Vascular supply is crucial to meniscal healing. The medial, lateral, and middle geniculate arteries, which branch off the popliteal artery, provide the major vascularization to the inferior and superior aspects of each meniscus. Only 10% to 30% of the peripheral medial meniscus border and 10% to 25% of the lateral meniscus border receive direct blood supply. The remaining portion of each meniscus receives nourishment only from the synovial fluid via diffusion or mechanical pumping. The latter mechanism derives from intermittent compression of the tissue during function. Mechanical pumping through joint flexion may be essential for continued nutrition.

[0008] The major meniscal functions are to distribute stress across the knee during weight bearing, provide shock absorption, serve as secondary joint stabilizers, provide articular cartilage nutrition and lubrication, facilitate joint gliding, prevent Superextension, and protect the joint margins. During knee flexion, the femoral condyles glide posteriorly on the tibial plateau in conjunction with tibial internal rotation. The lateral meniscus

078376-011300v1 286,323,276 O undergoes twice the anteroposterior translation of the medial meniscus during knee flexion.

[0009] Type I collagen fibers provide the primary meniscal structural scaffolding; this predominance of Type I collagen is one of the major differences between the menisci and hyaline, or articular, cartilage, which is composed of predominantly Type Il collagen. Three collagen fiber layers are specifically arranged to convert compressive loads into circumferential or "hoop" stresses. In the superficial layer, the fibers travel radially, serving as "ties" that resist shearing or splitting. In the middle layer, the fibers run parallel or circumferentially to resist hoop stress during weight bearing. Lastly, there is a deep layer of collagen bundles that are aligned parallel to the periphery.

[0010] Heatley reported that repair of incisions in the central part of the meniscus on rabbits has demonstrated after surgical excision of the peripheral rim (J bone Joint Surg 1980; 62-B:397-402). Healing took place via a highly cellular but relatively avascular fibrous tissue stroma which proliferated from the synovial margin and invaded along the cut edge of the meniscus. Suturing facilitated this healing process by providing stability and possibly by supplying bridges for synovial cells to migrate onto the meniscus.

[0011] U.S. Pat. No. 4,919,667 issued on April 24, 1990, entire contents of which are incorporated herein by reference, discloses a soft tissue implant in the form of a meniscus cartilage replacement for a patient. Appropriately shaped top and bottom layers sandwich therebetween at least one intermediate felted layer. A resilient bonding material coats the layers and holds same in a laminated condition. The top layer is contoured, to provide a wedge shaped cross section and a contoured three dimensional shape. A fabric member is bonded to the thickened edge of the laminant and is porous to invite ingrowth of patient tissue to anchor the implant eventually in place.

[0012] U.S. Pat. No. 5,067,964 issued on November 26, 1991, entire contents of which are incorporated herein by reference, discloses an articular cartilage repair piece to substitute for a cut-out piece of damaged articular cartilage on a bone in an articulated joint. The repair piece includes a backing layer of non-woven, felted fibrous material which is conformable to flat and curved surfaces.

078376-011300v1 286,323,216 [0013] U.S. Pat. No. 5,092,894 issued on March 3, 1992, entire contents of which are incorporated herein by reference, discloses a meniscus prosthetic device replacing natural components of a condylar joint. The body of the device is of biocompatible, deformable, flexible and resilient material for bearing compressive loads and for translating the loads to tensile stress. The tail of the device is also biocompatible material and extends as a continuation of the body from a first end to a second end of the body. The tail provides a continuous loop circuit for the propagation of hoop tensile stresses from the body, and provides stabilization of the knee joint and proprioceptive feedback. The prosthesis is implanted in a human knee in a position to take the place of a naturally occurring meniscus between the femoral coadyle and the corresponding tibia, and the tail is placed into contact with bone associated with the knee.

[0014] U.S. Pat. No. 5,158,574 issued on October 27, 1992, entire contents of which are incorporated herein by reference, discloses a prosthetic meniscus implanted in a human knee where it can act as a scaffold for regrowth of native meniscal tissues. The meniscus comprises a dry, porous, matrix of biocompatible and bioresorbable fibers, at least a portion of which may be crosslinked. The fibers include natural polymers, analogs, or mixtures thereof. The matrix is adapted to have in vivo an outer surface contour substantially the same as that of a natural meniscus. With this configuration, the matrix establishes an at least partially bioresorbable scaffold adapted for ingrowth of meniscal ftbrochondrocytes.

[0015] U.S. Pat. No. 5,344,459 issued on September 6, 1994, entire contents of which are incorporated herein by reference, discloses a prosthetic device which is arthroscopically implantable into a joint. The device has a ring or a pair of rings sized and shaped to fit within the joint. The ring or rings are comprised of a polymeric substance and may contain one or more compartments which are inflatable or expandable with air, a liquid or a semi-solid, through an arthroscope coupling means.

[0016] U.S. Pat. No. 6,046,379 issued on April 4, 2000, entire contents of which are incorporated herein by reference, discloses an article of manufacture comprising a substantially non-immunogenic knee meniscal xenograft for implantation into humans. The invention further provides methods for preparing a knee meniscal xenograft by

078376-011300v1 286,323,216 A removing at least a portion of a meniscus from a non-human animal to provide a xenograft; washing the xenograft in saline and alcohol; and subjecting the xenograft to at least one treatment selected from the group consisting of exposure to ultraviolet radiation, immersion in alcohol, ozonation, and freeze/thaw cycling.

[0017] U.S. Pat. No. 5,171 ,322 issued on December 15, 1992, entire contents of which are incorporated herein by reference, discloses a meniscus prosthetic device including a body and a tail. The body is of biocompatible, deformable, flexible and resilient material for bearing compressive loads and for translating the loads to tensile stress. The tail is also biocompatible material and extends as a continuation of the body from a first end to a second end of the body. The tail provides a continuous loop circuit for the propagation of tensile (hoop) stresses from the body, and provides stabilization of the knee joint and proprioceptive feedback.

[0018] U.S. Pat. No. 5,807,303 issued on September 15, 1998, entire contents of which are incorporated herein by reference, discloses a device for relieving synovial fluid pressure in a capsule surrounding a body joint including a valve for placement in the capsule surrounding the joint for regulating passage of synovial fluid from the capsule. The valve can include a valve housing defining a passage between an interior and exterior of the capsule and a valve member disposed within the valve housing for regulating synovial fluid pressure within the capsule by permitting synovial fluid to drain from the capsule when a predetermined synovial fluid pressure is exceeded. The valve housing can be secured to the capsule with inlet and outlet flanges disposed at opposite ends of the housing and, additionally, by use of openings formed in the outlet flange to allow passage of sutures and to promote integral tissue fixation over time.

[0019] U.S. Pat. No. 6,005,161 issued on December 21 , 1999, entire contents of which are incorporated herein by reference, discloses a biodegradable device for facilitating healing of structural voids in bone, cartilage as well as soft tissue in the most preferred form including a porous macrostructure made from a biodegradable polymer and a chemotactic ground substance in the form of an ROD attachment moiety of fibronectin formed as a porous microstructure. For repair of articular cartilage, harvested precursor cells are secured to the biodegradable carrier which is shaped for press fitting

078376-011300v1286,323,216 z_> into the articular cartilage lesion. In the most preferred form, biological modifiers such as transforming growth factor 13 and basic fibroblastic growth factor is incorporated in the biodegradable device to mediate cellular activity and regulate cellular functions.

[0020] U.S. Pat. No. 6,132,468 issued on October 17, 2000, entire contents of which are incorporated herein by reference, discloses a flexible scaffold envelope which can be used to replace damaged cartilage. Designed for use in arthroscopic surgery, the envelope is sufficiently flexible to allow it to be rolled up or folded and inserted into a knee joint via a small skin incision. After the envelope is inserted into the joint, it is unfolded, positioned properly, and anchored and cemented to a bone surface. After anchoring, the envelope is filled via an inlet tube with a polymeric substance that will set and solidify at body temperature. During filling and setting, the surgeon can manipulate the exterior shape of the scaffold envelope, to ensure that the implant will have a proper final shape after the polymer has cured into fully solidified form.

[0021] U.S. Pat. No. 6,176,880 issued on January 23, 2001, entire contents of which are incorporated herein by reference, discloses a reconstructive structure for a cartilaginous element having a plurality of superimposed layers of intestinal submucosa tissue compressed and secured together and shaped to provide a reconstructive structure having the anatomical shape of the cartilaginous element to be reconstructed is described. The method of forming the reconstructive structure includes superimposing the planar layers of the intestinal submucosa tissue, securing the layers to form a multi-layered structure and cutting the resulting multi-layered structure to the desired shape.

[0022] U.S. Pat. No. 6,352,558 issued on March 5, 2002, entire contents of which are incorporated herein by reference, discloses a method of promoting regeneration of surface cartilage of a joint including the steps of forming punctures in a subchondral plate of an area of the joint to be treated, covering the puncture and the area to be treated with a chondrocyte-free patch made of a sheet of collagen membrane material without adding chondrocytes to the area to be treated, fixing the patch over the area to he treated, and allowing the area to be treated to regenerate cartilage without adding chondrocytes to the area to be treated,

078376-011300v1 286,323,216 β [0023] U.S. Pat. No. 6,530,956 issued on March 11 , 2003, entire contents of which are incorporated herein by reference, discloses a load-sharing resorbable scaffold used to help transplanted chondrocytes or other cells generate new cartilage in a damaged joint such as a knee, hip, or shoulder. These scaffolds use two distinct matrix materials. One is a relatively stiff matrix material, designed to withstand and resist a compressive articulating load placed on the joint during the convalescent period, shortly after surgery. The second material comprises a more open and porous matrix, designed to promote maximal rapid generation of new cartilage. The scaffold would support the membrane with a degree of stiffness and resiliency that allows the membrane to mimic a healthy cartilage surface.

[0024] U.S. Pat. No. 6,629,997 issued on October 7, 2003, entire contents of which are incorporated herein by reference, discloses a device for surgical implantation to replace damaged tissue in a joint (such as a meniscus in a knee) that is created from a hydrogel that is reinforced by a three-dimensional flexible fibrous mesh. In a meniscal implant, the mesh is exposed at one or more locations around the periphery, to provide anchoring attachments that can be sutured, pinned, or otherwise securely affixed to tissue that surrounds the implant. Articulating surfaces which will rub and slide against cartilage should be coated with a hydrogel layer that is completely smooth and nonabrasive, and made of a material that remains constantly wet.

[0025] U.S. Pat. No. 6,800,298 issued on October 5, 2004, entire contents of which are incorporated herein by reference, discloses fluid compositions containing a dextran- based hydrogel with lipids that provides enhanced theological and tribological properties of such a fluid. Phospholipids are particularly useful in dextran-based compositions for synovial fluid. One phospholipid that can be used advantageously in synovial fluid is dipaimitoyl phosphatidylcholine.

[0026] U.S. Pat. No. 6,893,463 issued on May 17, 2005, entire contents of which are incorporated herein by reference, discloses an implantable knee prosthesis including a two-piece body having a substantially elliptical shape in plane and including a first piece and a second piece. The first piece is a tibial piece including a tibial surface. The

078376-011300v1 286,323,276 7 second piece is a femoral piece including a femoral surface. The first piece and the second piece are mutually slidably engageable and separable.

[0027] U.S. Pat. No. 6,905,514 issued on June 14, 2005, entire contents of which are incorporated herein by reference, discloses a replacement device for resurfacing a joint surface of a femur. The custom replacement device is designed to substantially fit the trochlear groove surface of an individual femur. Thereby creating a "customized" replacement device for that individual femur and maintaining the original kinematics of the joint. The top surface is designed so as to maintain centrally directed tracking of the patella perpendicular to the plane established by the distal end of the femoral condyles and aligned with the center of the femoral head.

[0028] U.S. Pat. No. 6,960,617 issued on November 1 , 2005, entire contents of which are incorporated herein by reference, discloses hydrogels having improved elasticity and mechanical strength properties by subjecting a hydrogel formulation containing a strengthening agent to chemical or physical crossliπking conditions subsequent to initial gel formation. Superporous hydrogels having improved elasticity and mechanical strength properties are similarly obtained whenever the hydrogel formulation is provided with a foaming agent. Interpenetrating networks of polymer chains comprised of primary polymer and strengthening polymer are thereby formed. The primary polymer affords capillary-based water sorption properties while the strengthening polymer imparts significantly enhanced mechanical strength and elasticity to the hydrogel or superporous hydrogel. Suitable strengthening agents can be natural or synthetic polymers, polyelectrolytes, or neutral, hydrophilic polymers.

[0029] U.S. Pat. No. 6,994,730 issued on February 7, 2006, entire contents of which are incorporated herein by reference, discloses a method for resurfacing a joint capsule having cartilage and meniscal surfaces such as a knee joint including resecting a central portion of the joint cartilage on one joint member such as the tibia while leaving a meniscal rim attached to the peripheral joint capsule. A cavity is then formed in the bone underlying the central portion of the joint surface such as the lateral tibial surface. A resurfacing implant is then coupled, by cementing for example, to the cavity. A soft

078376-011300v1 286,323,276 g prosthetic meniscal implant is then coupled to the remaining meniscal ring such as by suturing.

[0030] U.S. Pat. No. 7,008.635 issued on March 7, 2006, entire contents of which are incorporated herein by reference, discloses hydrogels intended for orthopedic applications with a hydrogel formulation which has high strength, toughness, a suitable mechanical modulus and low equilibrium hydration. It may have controlled porosity or degradation time, it can be made to polymerize in situ with high adherence to target tissue or surfaces. A preferred formulation for forming such gels comprises 40 to 80% by weight of a low-molecular weight polar monomer and 30 to 10% of a hydrophiiic macromeric crosslinker.

[0031] U.S. Pat. No. 7,060,074 issued on June 13, 2006, entire contents of which are incorporated herein by reference, discloses instrumentation for use in minimally invasive unicompartmental knee replacement including a tibial cutting guide for establishing a planar surface along a tibia! plateau and a tibial stylus having an anatomic contour for controlling the depth of the planar surface along the tibial plateau. The instrumentation further comprises a posterior resection block for preparing a posterior femoral resection, with a forward portion of the posterior resection block having a configuration corresponding to the configuration of a prosthetic femoral component. Instrumentation comprising a resection block and a resurfacing guide are provided for surgically preparing a femoral condyle to receive a prosthetic femoral component. The instrumentation further includes a resurfacing guide and a resurfacing instrument for resurfacing a femoral condyle to a controlled depth.

[0032] U.S. Application publication No. 2002/0127264 published on September 12, 2002, entire contents of which are incorporated herein by reference, discloses a method and system for the creation or modification of the wear surface of orthopedic joints, involving the preparation and use of one or more partially or fully preformed and procured components, adapted for insertion and placement into the body and at the joint site. In a preferred embodiment, component(s) can be partially cured and generally formed ex vivo and further formed in vivo at the joint site to enhance conformance and improve long-term performance. In another embodiment, a preformed balloon or

078376-011300v1 286,323,216 g composite material can be inserted into the joint site and filled with a flowable biomaterial in situ to conform to the joint site.

[0033] U.S. Application publication No. 2004/0133275 published on July 8. 2004, entire contents of which are incorporated herein by reference, discloses a permanent nonresorbable implant allowing surgical replacement of cartilage in articulating joints, using a hydrogel material (such as a synthetic polyacrylonitrile polymer) reinforced by a flexible fibrous matrix. Articulating hydrogel surface(s) are chemically treated to provide a negative electrical charge that emulates the negative charge of natural cartilage, and also can be treated with halogenating, cross-linking, or other chemical agents for greater strength.

[0034] U.S. Application publication No. 2004/0195727 published on October 7, 2004, entire contents of which are incorporated herein by reference, discloses a method of making a lubricious polyacrylonitrile knee meniscus implant of a predetermined form and the resulting product.

[0035] U.S. Application publication No. 2004/0267371 published on December 30,

2004, entire contents of which are incorporated herein by reference, discloses a prosthetic tibial component for a prosthetic total knee joint, that comprises two constructs, one being a metal base construct that engages the bone and the other being a polyethylene bearing construct that attaches to the metal base construct and articulates with a femoral prosthetic component on the opposing side of the joint. The metal base construct is composed of two different metals, one of which engages the bone surface and the other of which engages the polyethylene bearing construct. The first metal (i.e., the one that engages the bone surface) is selected so as to provide a superior bone-engaging face, while the second metal (i.e., the one that engages the polyethylene bearing construct) is selected so as to provide a superior polyethylene- engaging face.

[0036] U.S. Application publication No. 2005/0043808 published on February 24,

2005, entire contents of which are incorporated herein by reference, discloses a method and related composition and apparatus for repairing a tissue site. The method involves the use of a curable polyurethane biomaterial composition having a plurality of parts

078376-011300v1 286,323,216 ■] Q adapted to be mixed at the time of use in order to provide a flowable composition and to initiate cure. The flowable composition can be delivered using minimally invasive means to a tissue site and there fully cured provide a permanent and biocompatible prosthesis for repair of the tissue site. Further provided are a mold apparatus, e.g., in the form of a balloon or tubular cavity, for receiving a biomaterial composition, and a method for delivering and filling the mold apparatus with a curable composition in situ to provide a prosthesis for tissue repair.

[0037] U.S. Application publication No. 2005/0055101 published on March 10, 2005, entire contents of which are incorporated herein by reference, discloses an endoprosthesis having improved self-lubrication mechanisms, the ability to filter the particles from the debris produced by the moving parts, and a new viscoelastic behavior under loading which reduce the transmitted forces. This has been achieved with the use of compressible materials and mechanisms between the fixed hearing and the tibial component, allowing the endoprosthesis to have compressibility under loading, which allows it also to receive or create chambers with an exit to the surface articulating with the femoral condyles.

[0038] U.S. Application publication No. 2006/0178497 published on August 10, 2006, entire contents of which are incorporated herein by reference, discloses implantable devices that include biocompatible polyurethane materials. In particular, the disclosed polyurethane materials can maintain desired elastomeric characteristics while exhibiting thermoset-like behavior and can exhibit improved characteristics so as to be suitable in load-bearing applications such as in artificial joints, including total joint replacement applications.

[0039] Oka and his associates reported that polyvinyl alcohol hydrogel (PVA-H), "a rubber-like gel", shows its usefulness as an artificial articular cartilage (Prot. Inst. Mech Eng 2000;214:59-68). As compared to polyethylene (PE), the PVA-H had a thicker fluid film under higher pressures than polyethylene (PE) did, and PVA-11 had a better damping effect and better wear factor. The artificial articular cartilage made from PVA-H could be attached to the underlying bone using a composite osteochondral device made

078376-011300v1 286,323,216 -| -j from titanium fibre mesh. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh.

[0040] Hyaluronic acid and hyaluronates (HA's), such as Synvisc, Hyalgan, Supartz, Orthovisc, Neovisc, EuflexxalNullexxz, Duroiane, Fermathron, Suplaysn, are available for injection into joint spaces to provide additional lubrication and treat pain associated with osteoarthritis. HA's in solution are very viscous and therefore the amount of HA per injection (about 2.0 ml) is limited by viscosity. Although injections appear to be effective, these products require multiple injections (usually 3-5) and the effectiveness lasts only for 3-6 months. The present technology is to increase molecular weight of the HA or to crosslink the HA to retard its degradation and clearance from the joint space.

[0041] Hence, repairing or replacing a torn meniscus with a meniscus wafer or other prosthetic is suggested as a useful system to address joint pain. The current invention also discloses devices, methods, formulations, and instruments comprising proprietary systems and ways to make same.

Summary of the Invention

[0042] A prosthetic useful for addressing osteoarthritis uses hyaluronate compositions to increase the duration of effectiveness in lubrication and pain reduction, and to reduce the number of injections required, is taught in terms of creating the same.

[0043] Using prosthetics for osteoarthritis with hyaluronate compositions improves the effectiveness (i.e. reduce the coefficient of friction) in lubrication and pain reduction, and provides a system which can have applicability in joints with relatively healthy (and therefore stiffer) cartilage as wel! as older and degenerated (and therefore softer) cartilage.

[0044] The present invention does so by increasing the residence time (half life) of the injected HA in the joint space; improving/supplementing the lubrication efficacy of HA in the joint space; and/or increasing the amount of HA per the injection.

[0045] In accordance with embodiments of the present invention, the instant prosthetics provide a support structure around the circumference of the meniscus in a patient configured like a collar around a neck ("meniscal collar"), wherein the support

078376-0? 1300v1 286,323,216 <| 2 structure comprises a body with an exterior surface characterized with enhanced boundary lubrication properties, the body being durable and abrasiveless that is made of biocompatible material selected from the group consisting of PVA hydrogel, elastomers, polypropylene, polyethylene, PEEK, and metals.

[0046] Some aspects of the invention provide a device for meniscal augmentation using meniscal bulking agents to increase the volume of the meniscus either by injection or other filling means. The bulking agent may include biodegradable or nonbiodegradable hydrogels, crosslinkable hydrogels having a higher molecular weight than those of pre-crosslinkcd hydrogels, and the solidifiable hydrogels having a higher viscosity index than those of pre-administered hydrogels. The bulking agent may also include the scaffold, scaffold material or scaffoldable biomaterial with cell seeding, ingrowth and regeneration capabilities. In one aspect, the mesenchymal stem cells or regenerative cells are included in the product formulation of the bulking agent. Further, some aspects of the invention provide a device useful for cartilage augmentation for increasing the volume of the cartilage by injection, substitution or grafting. The system taught is applied using imaging guidance or arthroscopically under direct viewing.

[0047J Some aspects of the invention provide a system comprising meniscal wafer, a generally planar construct, to fit between the tibial plateau/meniscus and the femoral condyle. In one embodiment, a meniscal wafer is an implant adapted to encourage tissue healing and/or mitigate pain. In one embodiment, the meniscal wafer comprises a surface antistick agent or characterized with boundary lubrication configured to reduce physical adhesion. In another embodiment, the meniscal wafer comprises an impregnated/entrapped chemical marker that is leachable or exposable as a warning after a predefined thickness of the wafer is worn out.

[0048] Some aspects of the invention provide a composite meniscus comprising a multiple component or layer structure that serves as a replacement meniscus. Components may be selected from the group consisting of metals (stainless steel, NiTi, titanium, porous titanium, and the like), lubricious polymers (PE₁ crosslinked PE. PP, and the like), shape memory material (polymer and metal), biodegradable polymers (PLA, PVA, PGA, PU and the like), hydrogels or hydrophilic (PVA hydrogel,

078376-011300v1 286,323,216 -j 3 polyacrylamide, and the like), and reinforcing support (porous substrate, woven fibers, filaments, and the like). Layer configurations may be selected from the group consisting of sliding layer, transition layer, ingrowth layer, backing layer, and combinations thereof. The materials and constructions disclosed herein also apply to the wafer. As disclosed herein, a meniscal wafer differs from a replacement meniscus by (1) generally being thinner and (2) attaching to or abutting the meniscus vs. the tibia or tibial cartilage.

[0049] Some aspects of the invention provide a condyle cap sized and configured to cover the femoral condoyle, the condyle cap fitting like a cap (e.g. a form fitting knit hat) over the condylar cartilage or bone. Further, some aspects of the invention provide an articular bumper sized and configured as a cap covering the tibial plateau that either may cover the meniscus or includes a replacement meniscus.

[0050] Some aspects of the invention provide a method for manufacturing a customized anatomic implant by applying data from modern imaging modalities such as CAT and MRI to create custom implants (or tooling to manufacturing implants) with surfaces that match the anatomy and the retained natural surface.

[0051] Some aspects of the invention provide a synovial lubricant comprising phospholipids selected from the group consisting of phosphoglycerides, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol, phosphatidyl serine, diphosphatidyl glycerol, and the like.

[0052] Some aspects of the invention provide a material or a surface of the device that preferentially attracts and/or adsorbs SAPL, the surface comprising a lipid or fatty surface. In one embodiment of placing a functional phospholipid coating on a device, one may prepare the surface (e.g. plasma etch or chemically treat the surface of the device), and then expose the surface to a reactable phospholipid, such as a phosphorylcholine which contains an additional acrylic double bond, or a reactable acrylate polymer with phospholipid side chains. The phospholipid is chemically, covalently bonded to the surface of the device and to itself.

[0053] One aspect of the invention provides a material for prosthetic articular surface that has high affinity to adsorb SAPL or SAPL-like surfactant. Another aspect of

078376-011300v1 286,323,216 -J 4 this invention provides for this affinity to absorb SAPL to be incorporated into the bearing/lubricating surface of any of the devices described herein.

[0054] Some aspects of the invention provide a particuiate-containing synovial lubricant that is specifically designed to overcome some of the limitations of fluids such as HA, wherein the preferred size range is about 50-150 microns with 50-100 microns considered normal desired size. The particles could he made of any biodegradable polymer, such as PLA or other hydrogei. The particles could be less than 6OA (shore durometer scale) hardness.

Brief Description of the Drawings

[0055] Additional objects and features of the present invention will become more apparent and the invention itself will he best understood from the following Detailed Description of Exemplary Embodiments, when read with reference to the accompanying drawings.

[0056] FIG. 1 shows a system useful for emplacement of an inserted meniscal liner according to the principles of the present invention.

[0057] FIG. 2 shows placement of a meniscal liner using sutures.

[0058] FIG. 3 shows a system for emplacement of a meniscal liner implant using a delivery cannula.

[0059] FIG. 4 shows a system with a meniscal liner emplaced without use of an insertion cannula.

[0060] FIGS. 5A-5D show placement of a meniscal implant. [0061] FIG. 6 shows a combined meniscal-tibial implant.

[0062] FIGS. 7A-7B shows an exemplary meniscal liner and an exemplary combined meniscal-tibial liner.

[0063] FIG. 8 shows a prototype of meniscus replacement. [0064] FIGS. 9A-9C shows meniscus liner variations. [0065] FIG. 10 shows a condylar cover.

078376-011300v1 286,323,216 15 [0066] FIG. 11 shows a flowchart for manufacturing a custom anatomic implant. [0067] FIG. 12 shows load transmission in a meniscal collar.

[0068] FIG. 13 shows a meniscal prosthesis with: (A) layer configuration; and (B) structure configuration.

[0069] FIG. 14 shows a process of repetitive surface coating on an artificial cartilage.

[0070] FIG. 15 shows an illustration of a composite meniscus.

[0071] FIG. 16 shows one embodiment of a cone/frustum sliding layer construct.

[0072] FIG. 17 shows a semi-lunar meniscus having a support collar and an inner collar.

[0073] FIG. 18 shows a meniscus liner having prongs or anchors. [0074] FIG. 19 shows a meniscus liner having screw or nail like anchors.

[0075] FIG. 20 shows magnetic unloading mechanism of a joint by configuring a femur having plural curved magnets which follow the arc of the femoral condyle.

Detailed Description of Exemplary Embodiments

[0076] The preferred embodiments of the present invention described below relate particularly to medical devices and systems that can be used to replace joints. Joints are the place where two bones meet. All of our bones, except for one (the hyoid bone in our neck), form a joint with another bone. Joints hold our hones together and allow our rigid skeleton to move. While the description sets forth various embodiment specific details, it will be appreciated that the description is illustrative only and should not be construed in any way as limiting the invention. Furthermore, various applications of the invention, and modifications thereto, which may occur to those who are skilled in the art, are also encompassed by the general concepts described below.

[0077] To better describe the invention, some terms are defined herein as follows. "Meniscal collar" in this invention is meant to refer to a support structure around the circumference of the meniscus like a collar around a neck. "Meniscal augmentation" (or "meniscal bulking agent") in this invention is meant to refer to a process of increasing

078376-011300v1 286,323,216 -| Q the volume of the meniscus either by injection or other means. "Meniscai liner" ("meniscal wafer" or "joint interface sheet") in this invention is meant to refer to a generally planar construct that fits between the tibial plateau/meniscus and the femoral condyle. Meniscal liners are implants adapted to encourage tissue healing and/or mitigate pain. The terms meniscal liner, meniscal wafer or joint interface sheet can refer to devices that (1) cover the meniscus (only), (2) cover the tibial plateau (only) or (3) cover both. "Composite meniscus" in this invention is meant to refer to a multiple component or layer structure that serves as a replacement meniscus. "Condyle cap" in this invention is meant to refer to a prosthesis covering the femoral condoyle, fitting like a cap (hat) over the condylar cartilage or hone. "Cartilage augmentation" in this invention is meant to refer to a process of increasing the volume of the cartilage by substitution or grafting. "Articular bumper" is meant to refer to a cap covering the tibial plateau that may either cover the meniscus or include a replacement meniscus. Most of our joints are "synovial joints". They are movable joints containing a lubricating liquid called synovial fluid. Synovial joints are predominant in our limbs where mobility is important. Ligaments help provide their stability and muscles contract to produce movement.

[0078] The knee includes many components (such as the bones, the cartilage, the meniscus, and others) with many functions, including the weight bearing, flexing, and walking. Femoral and tibial condyles are the hard bones underlying the gliding surfaces of the joint. Cartilage (articular hyaline) covers the bearing surfaces of the bone and forms the primary bearing surfaces in a healthy joint. Meniscus is a secondary bearing surface between the femora! and tibial cartilages, is a cushioning layer and is a contoured surface to help guide the joint as it flexes.

[0079] The bone joint includes medial and lateral compartments that essentially create two separate, though not independent, bearing surfaces. Synovial fluid serves to lubricate, and in some cases, nourish the tissue and surfaces of the joint.

[0080] A ligament is a short band of tough fibrous connective tissue composed mainly of long, stringy collagen fibres. Ligaments connect bones to other bones to form a joint. Capsular ligaments are part of the articular capsule that surrounds synovial joints. They

078376-011300V1286,323,216 γj act as mechanical reinforcements. Extra-capsular ligaments join bones together and provide joint stability. Ligaments are sli⁹htly elastic; when under tension, they gradually lengthen, '[his is one reason why dislocated joints must be set as quickly as possible: if the ligaments lengthen too much, then the joint will be weakened, becoming prone to future dislocations. Athletes, gymnasts, dancers, and martial artists perform stretching exercises to lengthen their ligaments, making their joints suppler. Some ligaments limit the mobility of articulations, or prevent certain movements altogether.

[0081] FIG. 11 shows a flowchart for manufacturing a custom anatomic implant. This method can optionally be enhanced by use of a replaceable or regeneratable bearing surface.

[0082] One significant aspect of knee joint procedures is the criticality of the alignment of the bearing surfaces as well as the quality of their attachment to underlying structures. This can be of particular interest with customized implants manufactured from imaging. Similarly externally manufactured surface implants must align with the existing structures they are designed to overlay. Systems to either artificially create or naturally identify landmarks during both imaging/design and implantation are necessary, methods and/or structures for aligning the bones and other anatomic structures may also be appropriate,

[0083] Osteotomy is an accepted treatment for knee problems. In this case, a cut is made in a hone (usually the tibia) to allow the angle of the knee joint (e.g., the tibial plateau) to be adjusted with appropriate joint alignment. The principle can be applied to other approaches, for example, the meniscal liner described herein can have varying thickness (e.g., thicker on the medial side) to readjust the angle of the joint and its bearing surfaces (see FIG. 9). This could also be applied to a knee prosthesis such as a uni-knee where the side of the knee which was not replaced may show wear, thereby providing an opportunity for improved function by (1) reducing the height of the uni-knee or (2) increasing the height of the opposite side by the insertion of a spacer (for example a meniscus liner). In both these cases, aligning the joint to distribute load over both the lateral and medial side of the joint will improve joint Function/longevity and/or reducing pain.

078376-011300V1 286,323,216 -] 3 [0084] FIGS. 9A-9C shows meniscal wafer variations. One aspect of the invention (FIG. 9A) relates to a meniscal wafer with optional tibial plateau cover. This example of the meniscal wafer is shown including a tibia! plateau cover. It is shown as having no special attachment means and is intended for a free-floating application. However, it could be sutured or adhesively bonded in place. Exemplary prototypes of this configuration have been assembled using 2 mm thick hydrogel adhesively bonded to a 0.5 mm thick relatively rigid polymer backing layer. In this case, the polymer backing layer was formed using vacuum forming techniques as known in the art.

[0085] Another aspect of the invention (FIG. 9B) relates to a meniscal wafer with optional meniscal retaining wing. This example of the meniscal wafer is shown including tibial plateau cover and a retention wing to extend the backing layer so it curves over and around the outer circumference of the meniscus. Though this example shows the retention wing around the entire circumference of the meniscus, partial retention wings may be also clinically indicated in certain situations. Exemplary prototypes of this configuration have been assembled from vacuum formed polymers of varying thicknesses and durometers as well as structures as described.

[0086] A third aspect of the invention (FIG. 9C) relates to a meniscal wafer with optional tibial attachment wing. This example of the meniscal wafer is shown including tibial plateau cover and a retention wing to extend the backing layer so it curves over the meniscus and extends down where it can be attached directly to the tibia (for reference, U.S. Pat. No. 4,502,161 "Prosthetic meniscus for the repair of joints" issued to Wall on 03-05-1985),

Exemplary prototypes of this configuration have been assembled as described.

[0087] One issue relating to meniscus treatment is the understanding of the process of meniscal degradation and sensitivity of imaging methodologies for detection of meniscal degradation.

[0088] In general the peripheral border of each meniscus is thick, convex, and attached to the inside capsule of the joint. The opposite border tapers to a thin free edge. The proximal surfaces of the menisci are concave and in contact with the condyles of the femur. The distal surfaces are flat and rest on the head of the tibia.

078376-011300v1 286,323,216 -j g [0089] The medial meniscus (MM) is somewhat semicircular in form and is approximately 3.5 cm in length in the anteroposterior direction and considerably wider posteriorly than it is anteriorly. The anterior horn of the medial meniscus is attached to the tibial plateau in the area of the anterior intercondylar fossa in front of the anterior cruciate ligaments. The posterior fibers of the anterior horn attachment merge with the transverse ligament, which connects the anterior horns of the medial and lateral meniscus. The posterior horn of the medial meniscus is firmly attached to the posterior intercondylar fossa of the tibia between the attachments of the lateral meniscus. The periphery of the media! meniscus is attached to the joint capsule throughout its length. At its mid-point, the MM is more firmly attached to the femur and tibia though a condensation in the joint capsule known as the deep medial collateral ligament (MCL).

[0090] On the other hand, the lateral meniscus (LM) is almost circular and covers a larger portion of the tibial articular surface than the MM. It is approximately the same width from front to back. The anterior horn of the LM is attached to the tibia in front of the intercondylar eminence and behind the attachment of the ACL, with which it partially blends. The posterior horn of the LM is attached behind the intercondylar eminence of the tibia in front of the posterior end of the MM. There is no attachment of the LM to the lateral collateral ligament (LCL) but there is a loose peripheral attachment. The posterior horn of the LM is also attached to the femur by means of the meniscofemoral ligament.

[0091] The meniscofemoral ligament is an accessory ligament of the knee. During knee flexion, the meniscofemoral ligament pulls the posterior horn of the LM anteriorly, increasing the congruity between the meniscotibial socket and the lateral femoral condyle.

[0092] It has been demonstrated that for meniscus lesions to heal, the lesion must communicate with the peripheral blood supply. After injury within the peripheral vascular zone, a clot forms rich in inflammatory cells. This is a fibrin scaffold that eventually gets filled with cellular fibrovascular scar tissue that glues wound edges together. It becomes continuous with normal meniscus.

[0093] The extraceliular matrix of menisci is composed primarily of the fibrous elements, collagen and elastin, the proteoglycans, the non-collagenous matrix proteins,

078376-011300v1 286,323,216 20 and water with dissolved solutes. The water content of menisci is about 74%. The dry meniscus is composed of about 75% collagen. 8% - 13% non-collagenous proteins and 1% hexosamine. Collagen fibers dominate both the morphology and composition of the meniscus. Fibers are critical for the relationship of structure and function of the tissue. The tissue called fibrocartilage because of the dominance of collagen fibers. This is apparent both at gross inspection and microscopic inspection of the tissue. The non- fibrous proteoglycans are also important for structure and function but also to the metabolism of the menisci.

[0094] The combination of low compressive stiffness and low permeability suggests that the menisci, as structures, should function as highly efficient shock absorbers. Since the combined mass of the menisci is much greater than that of the articular cartilage bearing load across the femoromeniscotibial articulation it is likely that most of the mechanical shocks generated in the knee joint by the loading is absorbed by the menisci. The deformation nature of the menisci with this low compressive {and shear) stiffness and permeability show them to distribute load well in the knee.

[0095] The strong ligaments, (cruciates and collaterals) menisci and capsule, and the musculature constitute the primary stabilizers of the knee. These structures and muscles around the knee constitute a complete biomechanical system in which the tibia can move with respect to the femur in many planes, yet also support the high loads (more than 5 times body weight) commonly found in the joint during daily activities.

[0096] Congruency is important in load transmission through the femoromeniscotibial articulation. It has been reported that the meniscus bears 50-80% of the compressive load of the knee joint. It was reported that removal of 15-34% of the meniscus increases contact pressure by more than 350%. The meniscal collar is a minimally invasive implant device intended to augment the function of the meniscus. The basic idea is a "collar" or rim placed around one or both of the menisci. One embodiment is shown in FIG. 12 for illustration. Lateral collar 611 , and medial collar 613 are shown with meniscus having diagonal lines the first sub-view being a restraining or compressive collar, the second sub-view being the load bearing collar and the third sub-view being the partial replacement collar with arrows showing fore vectors, as discussed.

078376-O11300v1 286,323,216 21 [0097] The meniscal collar (MC) can be placed in an open procedure, arthroscopically using a percutaneous procedure, or a combination thereof. In a percutaneous approach, a guidewire would be passed around the meniscus and then the MC could be pulled into position by the wire or, with an appropriate lumen incorporated into the MC, pushed over the wire into position. FIG. 1 shows positioning of an inserted meniscal liner. Though the technique shown in FIG. 1 is for positioning a menisca] liner, the similar technique can also be used in positioning a meniscal collar.

[0098] The MC can be constructed from metal such as stainless steel or tantalum, a lubricious polymer such as polyethylene (PE) or crosslinked polyethylene or from a lubricating hydrogel such as polyvinyl alcohol. The MC could optionally have reinforcing mesh or wire or load transmitting wire or a removable wire that could be placed in a lumen such as a guidewire lumen. The MC could also be constructed, wholly, in combination or in part, from a shape memory and/or biodegradable polymer such as those described in U.S. Pat. No. 6,720,402 and U.S. Pat. No. 6,160,084, entire contents of both are incorporated herein by reference.

[0099] The MC could have a variety of cross-section shapes including round, oblong or custom shapes to mimic the load hearing surfaces of the meniscus. The MC could be a single continuous shape or change over the perimeter of the meniscus. The MC could be smooth, contoured, or notched. Notched construction can facilitate flexing of the MC if constructed by a more rigid polymer.

[00100] An MC could be constructed in many configurations, such as a lateral medial construct, a combined heart construct, or a combined pretzel construct.

[00101] Various shapes can accomplish certain goals such as avoiding the cruciate ligaments or transmit greater forces (the "pretzel" shape as shown above can have legs that can be locked and/or tightened). These means to effect locking and/or tightening can be optionally reversible and could use structures such as a ratchet similar to that used in a "zip-tie", a series of balls with one or more mating sockets or other means well know in the fastener art.

07δ376-011300v1 286,323,216 22 [00102] The meniscal collar may function directly (by providing a load bearing surface) or indirectly (by deforming and/or containing) to supplement the meniscus so it can better support loads. Or the meniscal collar may function both in combination.

[00103] One issue related to the use of a meniscal collar is the fact that meniscal innervation and vasculature is on its periphery. MC design should optionally incorporate means such as cushioning (e.g., a hydrogel lining) or dimensioning (e.g.. sizing to avoid constant pressure on the meniscus) to avoid pain and/or ischemia. Reinforcing of the MC can be, for example, NiTi, stainless steel, other rigid polymers, or shape memory material. Additionally the capsule of the knee joint surrounds the meniscus (as well as the rest of the joint). Though in most clinical situations the meniscal collar would be placed within the joint capsule, if clinically indicated, certain configurations of a meniscal collar (not the pretzel) could be placed on the exterior surface of the capsule.

[00104] The MC design and shapes could be asymmetric in the support of the knee and could work in extension, flexion or both. The MC can be "free floating" or attached to the tibial and/or the meniscus. The MC could be constructed of layered material where some layers are optimized for their lubricious load bearing (for example, PE) while other layers could be used for cushioning (e.g., a hydrogel or polyurethane). Attachment can be using fasteners or ingrowth where a portion of the device in contact with the tibial plateau can be, for example, sintered porous tantalum.

[00105] Meniscal Wafer/Liner

[00106] Sonic special characteristics of one example of the proposed meniscal wafer of the present invention are shown below: (1) a PVA (polyvinyl alcohol) backing plate with appropriate hydrogels (for example, a PVA hydrogel ) such that when wet, the hydrogels are very slippery and the hydrogels provide good cushioning; (2) the meniscal wafer might have an attachment wing (in some cases); (3) the meniscal wafer might have a crescent-shaped NiTi reinforcement (or reinforced by other material, configuration, or composite characteristics) around the periphery of the hydrogel; (4) the thickness of the meniscal wafer could be at least 1 mm, preferably 3 mm or more; (5) the backing plate is material that can be manufactured as an integral or chemically compatible (for bonding) to the hydrogel with desired mechanical integrity and

078376-011300v1 286,323,216 23 properties. FIG. 8 shows a combined meniscal-tibial implant whereas FIGS. 7A-7B shows an exemplary meniscal liner and an exemplary combined meniscal-tibial liner of the present invention. The meniscal-tibial implant is herein meant to be the same as the replacement meniscus with combined meniscus-tibia. For illustration, FIGS. 5 and 6 show the three variations of the meniscal. tibial and combined liners.

[00107] A meniscal wafer/liner of this construction can be constructed of materials with flexibility to allow implantation through a small skin incision. By ways of illustration. FIGS. 5B-5D and 6B-6D show placement of a meniscal liner, where FIGS. 5A and 6A show the corresponding anatomy with no implant. Sutures, or a wing if included in the device, can be grasped from another port or incision and used to pull the device through the skin and into position in the knee. FIG. 2 shows attachment of a meniscal liner using sutures. A meniscus liner can also be inserted with a delivery catheter (see FIG. 3) or without use of an insertion cannula (see FIG. 4).

Example No. 1 Meniscal Wafer Manufacturing

[00108] A meniscal wafer (MW) is a medical device implanted via an arthroscope into the knee joint space (see FIG. 1) to act as a support and bearing wear surface between the femoral condyle and the meniscus/tibial plateau. It is for (1) use in partial or total meniscectomy to supplement or provide meniscus function and articulating surface (to minimize joint degradation). (2) use in place of partial or total meniscectomy (to delay joint degradation), (3) use after arthroscopic clean-up of osteoarthritis (GA) joint to provide fresh articulating surface and improve biomechanics (to delay total knee replacement, for example), and/or (4) to adjust the alignment of the joint though height supplementation. Meniscal wafers can be used on the medial, lateral or both sides of one or both joints. Meniscal wafers can (i) cover the meniscus (only), (ii) cover the tibial plateau (only) or (iii) cover both. FIG. 5 (B-D) shows placement of a meniscal wafer.

[00109] The manufactured meniscal wafer has at least one of the following attributes: [00110] Permanent, non-biodegradable device with a functional lifetime of 3-F years;

[00111] Non-fixed or floating design, limited in movement by mechanical/physical means, such as a passive stopper configuration at a periphery of the meniscal wafer;

078376O11300V1 286,323,216 24 [00112] Medial, lateral and dual compartment designs for various indications/presentations; able to be trimmed (or malleable) by physicians;

[00113] Materials can be polymeric (e.g. crystalline PVA, crosslinked PU, PEEK, UHMW PE) or a soft metal (e.g. Ti, non-ferrous, alloy). Reinforcing mesh (e.g. carbon fiber) may be required for tear strength or combinations of the above;

[00114] Lubricious materials (e.g. hydrogel or surfactant) or coating on device surface by adsorption, chemical bonding (e.g. phospholipids) or ion implantation (sputtering); sterilization by ETO, HbO₂, or radiation (gamma or e-beam); and shelf life of about 2 years or more.

[00115] FIG. 7B shows a combined meniscal/tibial liner for reference.

[00116] The meniscal wafer or liner may need to be well attached, particularly to resist shear forces. The anatomy might make it difficult to secure at the perimeter. One approach is to have a prong or interlocking fiber filled backing, like Velcro that will stick to tissue when implanted as one approach for anchoring purposes. An ingrowth encouraging material as described above (e.g. sintered porous tantalum) may be appropriate if, in a specific clinical condition, it is desirable to fix the device to the tibial plateau. The attachment means can be over all or part of the area of the meniscal wafer (MW). Alternately, the meniscal wafer may be sutured to the meniscus (see FIG. 2).

[00117] It is possible that a sheet would fragment, probably painfully, when it fails. Fiber reinforced sheet may require replacement before it wears to the reinforcing layer which will be abrasive. A sheet constructed from metal may fail too and would probably accelerate cartilage degradation. It may be desirable for a meniscal wafer to have the property of degradation-on-demand or other means described herein to facilitate device removal. This may comprise a step of injecting a medically compatible solvent, for example DMSO, into the knee that will quickly degrade the implant (but preserve the surrounding tissue) so it can be removed by flushing.

[00118] Active electronic detection could be built in for detection of incipient failure. One example is to incorporate radiopaque and/or MRI readable layers so device thickness and/or wear can be seen at a routine doctor visit (for example, with

078376-011300v1 286,323,216 25 ferromagnetic tags) or wear releases something easily (and painlessly) detectable, for example, methylene blue which turns urine blue.

[00119] In the past, porous material made of an aromatic polyurethane were successfully used for meniscal reconstruction in dogs. An aliphatic PU network, synthesized by crosslinking poly(e-caprolactone) and 1 ,4-trans-cyclohexane diisocyanate with glycerol, was used (Biomaterial, September 1995). Dislocation caused by tearing out of the sutures was found to be a problem because the tear resistance of the material was relatively low. Meniscal prosthesis turned out to induce fibrocartilage upon implantation, and degeneration of articular cartilage was less severe than after meniscectomy.

[00120] In the following embodiment, simple layers are shown with a porous, woven or filamentous layer for ingrowth (see FIG. I3B). Sintered porous materials such as tantalum are well known in the art. They are created by compressing and bonding the particles so there are a series of connected voids (or open pores) between the particles. The size of the voids are related to the size and shape of the particles as well as the processing (sintering) parameters.

[00121] By ways of illustration, an exemplary meniscal liner and an exemplary combined meniscal-tibial liner have been shown in FIG. 7A and FlG. 7B.

Lubricating Fluid

[00122] The synovium (synovial membrane) generates and contains the synovial fluid. The inner membrane of synovial joints is called the synovial membrane, which secrets synovial fluid into the joint cavity. This fluid forms a thin layer (approximately 50 micrometers) at the surface of cartilage, but also seeps into the articular cartilage filling any empty space. The fluid within articular cartilage effectively serves as a synovial fluid reserve. During normal movement, the synovial fluid held within the cartilage is squeezed out mechanically (so-called weeping lubrication) to maintain a layer of fluid on the cartilage surface. There is about 3.5 ml of synovial fluid bathes the knee joint. Some lubricant or lubricant component is adsorbed by the articular cartilage and then released under pressure.

078376-011300v1 286,323, 216 26 [00123] Lubrication may be categorized as hydrodynamic lubrication, elasto- hydrodynamic lubrication, transition from hydrodynamic to elasto-hydrodynamic to boundary lubrication, and boundary lubrication. Any substance acting as a boundary lubricant must first be adsorbed or otherwise bound to the surface before it can impart solid-to-solid boundary lubrication. The stronger the binding and the more cohesive the adsorbed lining, the better is the lubrication and resistance to wear under load. Synovial fluid is believed to act as a vehicle for transporting the boundary lubricant to its site of adsorption. Hyaluronic acid is often injected into joints to provide "visco- supplementation", which would enhance hydrodynamic lubrication in nonload-bearing joints and other joints when not subjected to load. Basically, it possesses no load- bearing capability unless surface-active phospholipid (SAPL) or equivalent is incorporated.

[00124] Some aspects of the invention relate to a meniscal device comprising a support structure around circumference of a meniscus in a patient, wherein the support structure comprises a body with an exterior surface characterized with enhanced boundary lubrication, the body being made of biocompatible material selected from the group consisting of PVA hydrogel, elastomers, polypropylene, polyethylene, PEEK, and metals. In one embodiment, the device comprises a meniscal collar device, a meniscal wafer device, a meniscal liner device and the like.

[00125] In one preferred embodiment, the enhanced boundary lubrication comprises means for attracting or adsorbing a surface-active phospholipid, for coating a functional phospholipid on the device, and for coating a reactable acrylate polymer with phospholipid side chains.

[00126] One group of substances much used in the physical sciences as boundary lubricants for transforming hydrophilic subphases to hydrophobic surfaces are surfactants. Moreover, SAPL, known as a surfactant in the lung, is present in the SF of normal joints in appreciable quantities. These small molecules bind to amino acid groups that comprise the protein chains in proteoglycans such as lubricin. The lipid content of cartilage amounts to 0.3 to 4% and lipid is composed of three basic components: cholesterol, triglycerides, and phospholipids. The first two predominate in

078376-011300v1 286,323,216 27 most sites in which fat is located in the body. In the normal joint and in the lung, the major component (about 60%) is phospholipid, whereas a major sub-fraction of phospholipid is phosphatidylcholine.

100127] Some aspects of the invention relate to a material or a surface of the device that preferentially attracts and/or adsorbs SAPL, comprising a lipid or fatty surface. In one embodiment of placing a functional phospholipid coating on a device, one must prepare the surface (e.g. plasma etch or chemically treat the surface of the device), and then expose the surface to a reactable phospholipid, such as a phosphorylcholine which contains an additional acrylic double bond, or a reactable acrylate polymer with phospholipid side chains. The phosphatidylserine could also be used. The phospholipid must be chemically, covalently bonded to the surface of the device and to itself. Without a good covalent bonding, the coating will nib off. Hydrophilic coatings are applied in the same manner to the device surface.

[00128] Phospholipids (PL's) are naturally present in blood, plasma, serum, etc. A mixed protein layer is deposited on a device's surface within minutes to hours after body contact. PL's will adsorb on the surface of a device soon after deposition of the protein layer. Investigators have dip coated PL's from solution onto an artificial surface and then exposed the device to blood or plasma to get an even richer PL layer. However, this coating will not be sturdy enough for a wear surface.

[00129] The capability of SAPL to act as a boundary lubricant was first recognized in the thoracic cavity, in which frictionless sliding of the lungs is needed to reduce the work of breathing. SAPL also acts as a release (antistick) agent. If two normal articular surfaces are clamped together, they do not stick. However, if the SAPL lining (the outermost phospholipid zone) of the articular cartilage is removed by a lipid solvent, then they would stick. Some aspects of the invention relate to a meniscal wafer, meniscal liner or a meniscal implant that comprises a surface antistick agent or characterized with boundary lubrication configured to reduce physical adhesion. Thus, a nonstick lining of SAPI.-like surfactant would prevent adhesive wear of the device of the invention.

078376-011300V1286,323,216 28 [00130] One aspect of the invention provides a material for prosthetic articular surface that has high affinity to adsorb SAPL like surfactant. Another aspect of this invention provides for this affinity to absorb SAPL to be incorporated into the bearing/lubricating surface of any of the devices described herein.

[00131] It is speculated that changes in synovial fluid properties accelerate meniscal degradation. The purpose of lubricating the joint is to relieve pain, not to mask pain. Synovial fluid can be classified into normal, non-inflammatory, inflammatory, septic and hemorrhagic fluids. Osteoarthritis and trauma are in the non-inflammatory class. Rheumatoid arthritis is inflammatory whereas trauma can also be hemorrhagic.

[00132] Joints such as the knee are bathed in lubricating synovial fluid. If additional synovial fluid could be directed into the space within the meniscus between the condyle and tibial plateau, improved lubrication could be achieved. Similarly, if the synovial fluid can be maintained in and around the surface of the meniscus and/or between the cartilage of the femoral condyle and tibial plateau during gait, improved lubrication could be achieved. Similarly, if the synovial fluid in the meniscus (between the condyle and the tibial plateau) could be pressurized, force would be applied to separate and reduce the friction between the condyle and tibial plateau (as with pressurized "air" bearings). And thereby, the same effect as improved lubrication can be achieved.

[00133] The lubrication of the knee joints provided by synovial fluid is necessary for joint function and longevity. It has been reported that the lubricating ability of synovial fluid can change due to or in response to, e.g., acute injury or arthritis. Hyaluronic acid (HA) is used clinically to improve the lubricating ability of synovial fluid. However, its effectiveness and length of action (time wise) has been questioned or is not as long as desired. Burdick et al. in U.S. Application publication No. 2005/0164981 and U.S. Pat. No. 6.800,298 proposed a combination of a dextran hydrogel and a phospholipid.

[00134] Some aspects of the invention relate to a particulate synovial lubricant that is specifically designed to overcome some of the limitations of fluids such as HA which have very limited half lives when injected into joints. The invention is unique in that (1) it recognizes that one aspect of creating an artificial lubricant, can be the criticality of particle size for function and longevity; (2) it provides for material specifically different

073376-011300v1 286,323, 216 29 fluid than dextran and phospholipid; and (3) it defines preferred material parameters. For size consideration, particles should he greater than 10 microns to avoid macrophage phagocytosis and greater than 30-40 microns to avoid particles escaping into the capillaries or other vasculature. As mentioned herein, the typical SAPL lubricating layer is approximately 50 microns.

[00135] It is suggested that large particle sizes (100 microns) may keep an artificial lubricant out of the bursae. The bursae are synovial fluid filled sacs which form a lubricating interface between soft tissue and bone; e.g. between the patellar tendon and the underlying bone. Bursae occur at sites of shearing in subcutaneous tissue or between deeper tissues such as muscle groups and Fascia. Many bursae develop during growth but new or adventitious bursae can occur at sites of occupational friction. The preferred size range is 50-150 microns with 50-100 microns considered normal desired size.

[00136] For materials consideration, though longevity of treatment is desirable it is expected that any such lubricant would have a limited life and therefore safe biodegradation to allow re-treatment is desirable. An example of a possible material is poly(lactic acid) (PLA) or derivative, a well known material which is (1) biodegradable (with control over degradation rate by compounding); (2) available/processible as a solid particle, a hollow particle or a hydrogel; (3) available in different forces with controllable hardness; and (4) readily accepting other materials attached/grafted or otherwise incorporated.

[00137] In one embodiment, the configuration is a central (3-D) core with attached long chain (-D) hydrophilic molecules. Alternatively, these attached long chain molecules could he lipids, e.g. SAPL's, other PL's or hydrophilic molecules. The material composite core and long chains would have effective particle sizes in the desired range. This is another advantage of PLA in that it can be made into particles of various sizes, for example PLA particles of <0.2 micron have been reported. This combined with the added long chain hydrophilic or lipophilic molecules would allow manufacture of particles in the desired size range.

078376-011300v1 286,323,216 30 [00138] A lubricant works by reducing friction between bearing surfaces in the knee. The bearing surfaces of greatest interest are the femoral condyles and the tibial plateau/meniscus. The lubricant can function as a thin film (such as when walking) or in a static squeezed flat mode (such as when initiating motion after standing still) certain properties of an optimal lubricant will address each and/or both of these situations. It would not be desirable for any particles present between bearing surface to be harder than the bearing surfaces since this could cause the hard particles to dig into or score the bearing, surfaces under load. This would suggest that the particles should be less than the 6OA (shore durometer scale) hardness for healthy cartilage. If used with damaged or degraded cartilage, the material with lower durometers may be indicated.

[00139] This lubricant which is composed of (a) particles, (b) long water or lipid trapping chain, and (c) a carrier fluid, saline or preferably or an inert water soluble gel with the viscosity and osmolarity of synovial fluid, will behave as (and in fact is) a non-Newtonian fluid.. This will help to address the needs of static and dynamic lubrication in that (i) the particle will help to keep a small separation space between bearing surfaces under static loading; (ii) long chains will trap water or lipids which, in combination with the long chains, will create a lubricity layer for dynamic motion; and (iii) the carrier will assist with injection of the lubricant, and in the case of inflammation, can help restore synovial fluid viscosity.

[00140] One aspect of a lubricant is that it functions when in place between load bearing layers. In other words, this is between the femoral condyle and the meniscus and tibial plateau. Herein the improvement of lubrication by pumping lubricant into this portion of the joint has been discussed. It would alternately and/or additionally be desirable to attract, and possibly attach, lubricating molecules/particles to the bearing surfaces of the joint whether natural and/or artificial, It could be desirable to have the bearing surface had an inherent attraction to the particles. This could be accomplished, for example, by having the surfaces and the lubricating molecules/particles being of opposite charge. In the case of an artificial bearing surface a magnetic bearing surface could attract ferrous, or otherwise magnetically susceptible, lubricating. It is possible that these effects could be externally controlled by the application of external magnetic field or be intrinsic properties of the materials. These attractive effects can be used

078376-011300V1286,323,216 3-J alone or in combination with chemical bonding, for example as described herein applying to SAPL or other PL lubricants.

[00141] Similarly, it would be possible to create particles of materials which mimic the properties of the bearing layer itself. This could create a self-healing and/or self lubricating bearing surface where the combination of the loading and tracking of the surfaces and the deposition and entrapment of new material could mimic the living cartilage. Surface coating can be repeated by a repeat application of artificial cartilage or lubricant particles circulating in the SF (as shown in FIG. 14). Circulating cartilage particles 800, and bound artificial cartilage particles are attracted at surface 803 and active surface 813, bearing layer base 812, and bone layer 811 are shown.

[00142] Materials for this could include the PIA or PVA hydrogel and other materials, including the particulate lubricant described herein. The PVA, or other hydrogel, could optionally be treated as described herein to create a lipid attracting volume. Particles for this application could be the same size as the lubricant described above or could be larger depending upon the clinical situation. The receptive bearing layer base could be natural cartilage or an artificial material as described herein. Optionally have an increased surface roughness or other treatment to increase the adherence of the particles to the surface. Artificial cartilage materials could mimic the properties of natural cartilage and have, for example, durometer of 30A - 6OA; a SF lubricated static friction of 0.20 - 0.40 (or 0.10 - 0.100); and a SF lubricated dynamic friction of 0.03 - 0.05 (or 0.01 - 0.010).

Composite Meniscus

[00143] The meniscal replacement shown herein is one embodiment of a composite meniscus. Current replacement menisci are homogenous. The basic composite meniscus can have 2, 3, 4 or more layer/components as shown below.

[00144] Materials can be selected or optimized for their specific function. The bearing layer should be durable (resist shear forces) and be lubricious. Crosslinked HDPE is one example of a material candidate for this layer. This layer can be further coated to improve its lubricity with a hydrophilic or lipophilic coating, e.g. a SAPL absorbing or adsorptive coating.

078376-011300v1 286,323,216 32 [00145] FIG. 8 shows a replacement Meniscus, with optional tibial plateau cover. This example of the replacement meniscus is shown including a tibial plateau cover. A soft meniscal portion is molded from a polymer of appropriate durometer. It can be optionally reinforced in a uni, bi or triaxial manner to resist flex and/or prevent tearing or fragmentation. This can be accomplished using fibers and or metal reinforcing bands or wires. This is then optionally attached to a backing plate for mounting and interfacing with the tibial plateau. The replacement meniscus can be attached to the backing plate along all or a portion of its circumference. In certain clinical situations, the "horns" of the meniscus are not bonded to the backing plate to allow flexing during gait. The backing plate can be attached to the tibial plateau using screw type fasteners, adhesives or other means know in the art.

[00146] Exemplary prototypes of this configuration have been assembled using a molded 50A silicone rubber adhesively bonded to a 0.25 mm thick metal backing layer. The area of the tibial cover included a layer of a fiber reinforced lubricious fluoropolymer. Though not included on these particular prototypes, a hydrogel coating for the silicone layer was also avai fable.

[00147] The lateral restraint would be to stabilize the knee as it bends and this component would be expected to have been selected for controlled resistance to deflection. High density polyethylene (HDPE) or a fiber reinforced medium density polyethylene (MDPE) are examples of the types of materials which could be used for this application. The cushioning layer would be selected for its ability to deform under load and absorb shocks; a low density polyethylene (LDPE) or PE/EVA blend could be appropriate for this layer.

[00148] The mounting layer would be selected for rigidity to facilitate interlocking (e.g., with a dovetail) with the optional separable tibial base (e.g., SS or Ti) and for its ability to be bonded to and integrated with the other components (e.g., HDPE). The mounting layer could also include means such as fiber reinforcement to facilitate attachment, and resist pull out by sutures or other means such as darts or anchors The materials described are all polyethylene, for purposes of illustration. The materials can be thermally bonded together and the bearing layer is the material often used in knee

078376-011300v1 286,323,216 33 prostheses. Alternate materials may be selected from a variety of sources: biodegradable (e.g., PIA, PVA, PGA, PU and the like), hydrogels or hydrophilic (e.g., PVA hydrogel, polyacrylamide, and the Like), scaffold for cell growth (e.g., PU₁ collagen, and the like) and metals such as porous Tantalum, SS and NiTi or the like. The material can combine the above properties and/or components and/or materials to achieve the desired device useful life and properties.

[00149] A Meniscal liner or cartilage prosthesis, e.g., a meniscal or condylar prosthesis, consisting of multiple layers (see FIG. I3A through 14) is illustrated in an exemplary embodiment with three layers as shown here: FIG. 13B shows porous 666, woven over and under fibers 667 and filamentous materials as described herein.

[00150] 1. Backing layer a. For mounting to the bone/cartilage surface i. (Optionally) to hold the device in place e.g., by ingrowth into a porous surface as described herein ii, (Optionally) to allow motion relative to the bone/cartilage surface iii. (Optionally) to incorporate barbs, screws, cement or other means to hold the backing layer to the bone/cartilage iv. (Optionally) to incorporate reinforcement to facilitate attachment using sutures, darts, anchors et al. b. For lateral support (resistance to wrinkling due to lateral forces) c. As a "last line of protection" of the bone/cartilage surface i. (Optionally) stronger and/or lower wear than the other layers may compromise properties which prevent damage to mating surface for increased strength iii. Ideally, if exposed by wear of the other surfaces, to function and be lubricious with natural synovial fluid;

[00151] 2. Transition layer 812 To provide a transition between the backing and sliding layers i. Optionally (1) to be of intermediate wear and/or strength; (2) to incorporate a wear indicator; (3) to be formed from a material with mechanical properties identical to the sliding layer; (4) to be formed from the same material as the sliding layer modified/adjusted to have different mechanical properties To have properties that will induce little or no damage to its mating surface May compromise properties which prevent damage to mating surface for increased strength When exposed by wear of the sliding surface, to function and be lubricious with natural synovial fluid To provide cushioning i. May resist deformation more (or less) than the sliding layer;

07B376-011300v1 286,323,2« 34 [00152] 3. Sliding interface layer 813 to provide a low wear low friction sliding surface In the case of the meniscus to allow the femoral condyle to slide to function and compatible with natural synovial fluid iii. (Optionally) to incorporate a wear indicator to have properties that will NOT damage its mating surface to provide cushioning.

[00153] An exemplary combined meniscal-tibial liner is shown in FIG. 7B which applies some of the above-identified specifications.

[00154] In the following embodiment, simple layers are shown in FIG. 16, namely sliding layer 714, transition layer 713, backing layer 712 and bone or cartilage layer 711.

[00155] In the above cone/frustum embodiment the sliding layer can be radiopaque or MRI opaque. With lucent transition and backing layers when the device is viewed from above, and when the opaque layer is worn away, lucent circles become visible or more visible. The location of the circles will indicate the location of the wear while the diameter of the circles will indicate the degree of wear. Wear past the depth of the cones will be visible as a widening non-opaque area. This can alternately or additionally be accomplished by using colorants if wear detection by direct (arthroscopic) vision is desired.

[00156] Double sided devices for placement between cartilage surfaces (e.g. one embodiment of a meniscus liner) can he created similarly using, for example, a 5-layer structure: 1. sliding layer; 2. transition layer; 3. backing layer; transition layer; and 5. sliding layer.

[00157] In the above exemplary embodiment, the materials for the device could be as follows:

[00158] 1. Backing layer a. Crystalline Polyvinyl Alcohol Transition layer a. A PVA hydrogel, slightly stiffer than the PVA-PVP of the sliding layer 3. Sliding layer a. PVA- PVP As described by Katta et al (Bioengineering Conference, 2004. Proceedings of the IEEE 30th Annual Northeast, Publication Date: 17-18 April 2004. pp.142- 143) i. Including an MRI-opaque ferromagnetic additive.

[00159] An exemplary meniscal liner is shown in FIG. 7A which applies some or all of the above-identified specifications.

078376-011300v1 286,323,216 35 [00160] In another embodiment, the backing layer can be or can mate with a bone interface layer that allows total or partial relative motion of the meniscal layers relative to the bone interface layers. An example of this could be a metal tibial cover with a multilayer meniscus anchored to the tibial cover at its lateral or mid portion while the horns of the meniscal layers are allowed to flex and/or move as the joint extends and flexes. In this case, the metal layer not covered by the semi-lunar shaped meniscal prosthesis would be covered with a stationary lubricious low wear surface (e.g. a phospholipid coating or a multilayer structure as defined herein). Metal backings can optionally be attached or use ingrowth for anchoring as previously described herein.

100161] In these or other embodiments (and other types of meniscal prostheses or meniscal wafer/liner type devices), as an alternative or in addition to anchoring as described herein, the flexing and deformation of the horns or periphery of a device may be controlled by inclusion of a "C" or "0" shaped collar incorporated in the periphery of the device. These support collars can also provide tension on the device to resist lateral forces. These collars can be metal (e.g. NiTi or SS) or a polymer (e.g. PEEK) or a metal polymer combination.

[00162] If an inner collar is used (as shown in FIG. 17) it must be configured not to create high spots or stress concentrations when impinged by the mating joint surface (if in the area of joint surface). Namely, support collar 702, is connected to optional innercollar 701 and semi-lunar meniscus 703.

[00163] Kobayashi and associates reported that artificial meniscus replacement using PVA hydrogel can supplement the meniscus function 2 years after implantation (Biomaterials 2005;26:3243-3248). Neither wear, dislocation, nor breakage of the PVA hydrogel meniscus implant (90 % water content) was observed. They also proposed a composite meniscus of PVA hydrogel and the tissue inducing polymer binding to surrounding peri-meniscus area.

Meniscus Liner Anchoring

[00164] An implanted ML NA₁ will be exposed to both normal (perpendicular to the plane of the ML) and lateral (in the plane of the ML) forces. While normal forces would tend to compress the ML between the femoral condyle and the meniscus/tibial plateau,

078376-011300v1 286,323,216 ^Q lateral forces can induce lateral or sliding (or gliding) motion of the ML relative to the meniscus/tibial plateau. Note that in some clinical conditions, the ML is intended to remain stationary relative to the meniscus/tibial plateau while the femoral condyle slides over the surface of the ML. To prevent lateral motion of the ML relative to the meniscus/tibial plateau there are a number of structures which can be employed as follows:

[00165] (1) Prongs/anchors — Prongs or anchors extending out of the plane of the ML where they can (i) extend into the cartilage/meniscus, (ii) extend through the cartilage into the tibial plateau (TP) as shown in FIG. 18, where meniscal liner 44 is shown above meniscus and forces shown with arrow.

[00166] Optionally the anchors can be angled to improve their resistance to lateral forces/motion. Forces will be primarily front to back but they can/will also be side to side.

[00167] (2) Ingrowth — tissue ingrowth is a well known method for establishing an implant. A porous metal such as sintered Tantalum or a felt type material or other tissue ingrowth material may be secured to the meniscal/TP side of the ML or the ML material itself may be configured to encourage ingrowth, optionally chemical means such as growth factors or autologotts blood clot may be used. Optionally the meniscus/TP may be prepared to encourage ingrowth by being pierced/scored or other equivalent means to the point of bleeding to provide clots (blood cells, endothelial growth factors, platelet derived growth factors, other growth factors, and fibrin etc.) and a healing response to encourage ingrowth.

[00168] (3) Screw/Nail/Anchors - In some cases, a 2-stage anchoring process may be desirable. In this case, the meniscus/TP is prepared by the placement of one or more primary anchors to which the ML is thus attached (see FIG. 19). This attachment can be with a peg or socket or other means known in the art. Those skilled in the art understand that meniscus collar 46 replaces ML of Fig. 18.

[00169] The primary anchor can screw or by other means be secured in the TP and/or meniscal. Note that forces on the primary anchor will, for the most part, be lateral and front to back in particular, and the anchor should he optimized for resistance to front to

076376-011300v1 266,323,216 37 back lateral motion. An example of this could be something similar to an arrowhead with blade surrounding a socket. In this case, the broad side of the arrowhead would be oriented to resist front to back motion. Use of individual pegs to resist lateral motion of a meniscal liner can have additional benefits by allowing or (by using a concave or concave shape) encouraging separation between the liner and the underlining tissue. The combination of this separation and the motion/compression due to gait and joint flexion and elongation can effectively improve circulation of synovial fluid by pumping the synovial fluid under the device to the living cartilage.

[00170] One aspect of an ML type implant is that it would be subject to wear and may fail mechanically as a result of wear and/or the stresses imposed by norma! and/or athletic activities. Since it is likely that an ML would have a finite useful life it is desirable that as the implant nears the end of its life it is not subject to catastrophic failure in the event, it is not removed prior to the end of its useful (undamaged) life. For the purposes of this discussion, we would grade some primary failure modes as follows: device fragmentation (worst), splitting or tearing (bad), or thinninufwearing through (most desirable failure mode).

[00171] Cast or extruded polymeric sheets can be prone to fragmentation as a failure mode. This can be reduced by the inclusion of fibers as reinforcement. Fiber reinforcement can be accomplished, for example, by adding chopped fibers, woven strands, or layered strands. Inclusion of chopped fibers in a polymer matrix can reduce and/or delay failure but the failure mode of this type of reinforcement can still be fragmentation, Woven fabric incorporated into and/or coated by a polymer can be the most resistant to fragmentation; however, the over and under nature of the fabric weave can be abrasive once the overlying polymer has worn away. This can be minimized by selecting fibers which are softer than the condyle cartilage which will be sliding over the weave fibers. Layers of parallel fibers will be likely to be weaker than a woven fabric when used in a polymer composite construction as an ML. However, if the top layer of fibers is aligned with the primary motion of the condyle over the TP, exposed fibers will be less likely to abrade the cartilage.

078376-011300V1 286,323,216 38 [00172] In clinical situations, material selection and the ability to detect the progress of wear of an ML will be factors in determining the appropriate structure/reinforcing of an ML. Further, detection of the wear progression or wear on an implant before failure or before wear becomes detrimental to the patient can be desirable, The defining parameter of an ML is its height or thickness. The thickness of an ML defines the height (or separation) of the knee joints. As the ML wears, it would be expected that the thickness and height would be reduced. Though significant height change can be detected using known imaging techniques (e.g., MRI), greater precision could be desirable. For example, in the case of a fabric reinforced ML, it would be desirable to know when a certain thickness of polymer remained above the fabric. This could be accomplished by creating a layered polymer above the fabric where for example radiopaque and radioiucent layers of 0.5 mm could be alternated. Similarly, ferromagnetic particles could he used to create such a structure that could be visualized using an MRI.

[00173] Another alternative would be to have a radiopaque or Ferro-opaque layer 0.5 mm above the fabric in which case the distance between the opaque layer and the bone vs. the known preoperative distance corresponding to the articular cartilage would indicate the wear limit had been reached. Please note that the strategies can be used in many scenarios, in addition to the fabric reinforced polymers. Another approach would be to have a layer or defined zone of the material subject to wear been impregnated with a chemical marker. This chemical marker would be compatible and inert in that it could have no effect on the body means of detection and could be by a routine blood test or other diagnostic means.

[00174] One embodiment of this type of detector could be a material such as methylene blue, a well known medical dye. This material has been known to turn urine blue when ingested. If impregnation and wear does not release sufficient material to be detected, then marker material can be deposited in a small pocket or reservoir in the implant which will be released by wear.

[00175] One other aspect of an implant relating to wear is the issue of replacement. Removal of an implant can be a problemic part of the replacement procedure. The idea

078376-011300v1 286,323,216 39 of degrade-on-demand (DOD) is that, when a naturally wearing or degrading implant should be removed, the materials would allow quick and easy replacement by accelerating the wear/degradation by causing the device to rapidly degrade to allow reabsorbance and/or removal (for example, by flushing).

[00176] For example, an ML may be constructed of a polymer which is soluble in DMSO at body temperature. When wear is detected, the knee joint may be flushed with DMSO until the ML degrades and is flushed out of the knee joint by the flush fluid (DMSO). This can then allow immediate replacement of the ML. Similarly, anchors used to retain the ML in place may be soluble in DMSO or sonic other biocompatible solvent. This would facilitate release of the ML from its attachment to speed up or case removal. Another aspect of degradation on demand could be automatic degradation. This could be an embodiment of a multilayer construction as described herein. In this case, for example, an inner layer made of gelatin or some other rapidly dissolving material would be surrounded and sealed by a water impervious layer which could then be combined with a primary outer layer composed of a hydrogel. The inner layers could provide bulk and/or support to the softer outer layer which will be of low friction and the primary load bearing interface layer. Wear of the device through the water impervious layer would allow water to attack the gelatin layer and a rapid decrease in the size and stiffness of the device. Though this may be a painful means of informing the patient that it is time to remove/replace the device, its removal will be simplified by the dissolution of the inner layer.

Magnetic Unloading and/or Alignment

[00177] The knee joints bear the weight of the body and have transient loading more than double the body static weight. The weight translates to normal forces on the bearing surfaces of the joint. Reducing these normal forces can reduce the load, and therefore the wear of the joint. It is suggested herein that opposing magnets placed in or on the femoral condyle and tibial plateau could be used to reduce these normal forces. Since it is desirable for this force reduction to occur during gait and not only when standing, it is preferable that this magnetic opposition occurs while the joint flexes or extends.

078376-011300v1 286,323,216 4Q [00178] The following options include both means to preserve and/or replace the bearing surfaces of the joint. In the case of replacement of the bearing surfaces (e.g., in a total knee replacement) all or part of the femoral and tibial components which are anchored to the bone are typically metal and could include and/or be constructed from or include magnetic materials. For example, rare earth magnets could be used with both components having like poles (e.g.. negative) facing each other. If it is desired to unload the joint while preserving the bearing surfaces of the knee, the mechanism as shown in FIG. 20 can be applied.

[00179] In this case, the femur has two or more curved magnets which follow the arc of motion of the femoral condyle as it slides along the tibial plateau.

[00180] Opposing bones in the tibia, shown here as opposing pairs, can be straight or curved depending upon clinical requirements. Though the opposing magnets are intended to provide a reduction in the upward normal forces, geometric relationships can be selected to include lateral force vectors to help stabilize the joint.

[00181] It is understood that lateral forces can be used to stabilize a joint. These forces can. by their orientation, help to align the path of the elongation and flexion of the knee. Thought the rods should be parallel to each other for proper tracking they can be angled to the left or right from the natural axis of the relative (e.g. femoral vs. tibial) bending of the joint. In certain clinical situations, it may be desirable to change this relative angle. The gentle magnetic bias imposed by these off axis magnets can result in a reorientation of the relative bending angle.

[00182] In other clinical situations, it may be desirable to adjust the left-right (inside- outside) angle of the joint. Use of magnets on one (not both) sides of the knee would result in biasing forces which could result in realignment of the side to side tracking of the knee.

Meniscal Allografting

[00183] One aspect of the partial meniscectomy, particularly in the case of an acute injury to a young patient, is that the tissue removed is basically healthy. During the partial meniscectomy procedure, the tissue can he collected, prepared and then

078376-011300v1 286,323,216 4^ reimplanted into the meniscus as an allograft. Collection could be performed using an arthroscopic shaver (which will result in relatively small chunks) or other methods can be used to remove the tissue block.

Other Aspect-Custom Condyle Caps

[00184] The custom condyle cap (CCC) is based upon the concept of covering the existing surface(s) at the femoral condyle with a custom made form fitting prosthesis. One example is a half red blood cell shape that covers the condyle to relieve pain. For simplicity, the following examples would model the condyle as a hemisphere. The CCC is a customized anatomic implant. The CCC may be made of a metal, such as NiTi as follows: (a) image the condyle or condyles; (b) create male & female tools; (c) stamp and clamp a sheet of metal between the tools; (d) trim the sheet as appropriate (this step may precede step c above); (e) if integral retainer tabs are included with design, position tabs in their final intended position; (0 heat the metal sheet and tools above the transition temperature (about 1000⁰F) to the austenitic phase; (g) after an appropriate time at the desired temperature, remove CCC from tools and cool below the metal austenitic/martinesetic transition temperature of about 9O⁰F (Note: the metal NiTi is selected to achieve this austenitic/martinestic transition temperature); (h) reform the CCC to be optimal for the desired surgical procedure for implantation/attachment; (i) maintain CCC below the transition temperature until implantation; and 0) implant and allow CCC to achieve its final shape on the face of the femoral condyle. Note that with shape memory CCCs, it is critical that the CCC be maintained at temperature until positioned for attachment to the condyle and maintained in position until shape change is complete.. At any stage, generally after (e) or (h), the metal can be coated on one or both sides with an appropriate polymer (e.g. a PE or Fiuoropolyment or a hydrogel) or other coating. If applied after (f) or (g) and before 0) it must have sufficient flexibility deformability to accommodate the shape change at step (j). If applied before step (f), the coating must withstand the processing temperature and have the flex ibility/deformability previously mentioned. If applied in-situ using attraction deposition as mentioned herein, the metal should be made receptive/attractive to the coating.

078376-011300v1 286,323,216 42 [00185] FIG. 10 shows a condylar cap with a lubricious bearing surface and surfaces on the side to hold the cap in place. Though this example of the condylar cap is intended to represent a custom anatomically designed specifically fit on this individual patient's anatomy, it could be also a standard implant placed on a prepared surface. In this example, a 3-layer structure is employed with a flexible middle land a top sliding layers limited to the load bearing regions of the device. The backing layer has additional material which extends around the femoral condyle to retain the device in place. Optionally additional fastenings and/or adhesives can be used to hold the device in place.

[00186] Use of a shape change material for a CCC is exemplary. Stainless steel, titanium or other materials (alloy with suitable fabrication techniques) can be used. Materials used for CCCs may have an impact on surgical procedures. Flexible or shape changing implants may allow implantation through a smaller incision or even arthroscopically. NiTi can be used to make a superelastic CCC also. The concept of a custom cap of this invention may apply to other implant caps beyond the standardized shaped and sized condylar caps.

[00187] One aspect of the CCC is that it is ideally of a relatively thin thickness or cross- section. Another aspect is that it requires little or no removal of bone. Cartilage overlying the condyle is optionally or non-optionally removed. The CCC designs can include coating and/or layer(s) which would simulate or substitute for the cartilage. This artificial cartilage may be designed to be replaceable. It can be PE, crosslinked PE, hydrogel or other suitable material. This artificial cartilage layer can also optionally include self- healing capability as described above.

[00188] In an extremely superelastic CCC, the CCC may he formed and then rolled into a cylinder which can be passed through an arthroscopic portal into the knee. The CCC then would unroll and be positioned accordingly. The procedure/method as outlined should include the step of preparing the condyle or condyles for receiving the CCC implant. CCC design may also include spikes or pegs to attach them to the femur and prevent shifting or slipping. Cement or other adhesives can also be used.

078376-011300v1 286,323,216 43 [00189] Tibial/meniscal cover devices (for medial or lateral compartment menisci) may be constructed as an artificial cartilage covered metal plate over the tibia/meniscus with wings for attachment. In one embodiment, the backing should be directly over the tibia and include a total meniscus replacement. In another embodiment, the above-identified plate is without wings. If needed, the mounting of the cover device is on or very close to the tibial face, possibly under the meniscus replacement. Similarly, a condyle cover may be consisted of a tin backing plate with wings for attachment to an artificial cartilage sliding surface.

[00190] One of the advantages that may be achieved with a custom constructed implant is the minimization or elimination of cutting notches in the bone to position the implant. Absent notches cut in the bone or in a situation where an implant is designed and/or constructed using an anatomy dependent notch which may be defined (but not formed) at a procedure other than the procedure in which the implant is placed, other methods and apparatus are needed.

[00191] Markers would prefer to be biodegradable or removable. This can be accomplished by having an opening in the bottom of the marker into which a hydrogel or barbed removal tool can be placed. In one embodiment, the removal tool is part of the frame used for the second procedure (not the first) so removal at the frame removes the marker.

[00192] Three markers can have the advantage of surrounding the limb.

[00193] Two line type markers can accept and restrain elongated pines that can allow the use of a guide frame that does not need to surround the limbs. The above shows the most basic frame where it is used only to accurately localize and relocalize the limbs. Additional arms or beams attached to the frame can be used to guide placement of an implant or cutting a notch in a base.

[00194] The meniscus bears a great deal of the load which is borne by the knee. Replacement menisci have had mixed result while arthroscopic procedures on the meniscus are effective. In an effort to preserve and supplement the performance of the meniscus, the idea of injecting materials into tissue to augment the appearance or function of tissue is well known. U.S. Pat. No. 6,390,096 is an example of where a

078376-011300V1 286,323,216 44 needle is used to implant a solid prosthesis into the palate to alter the mechanical response of the palate to air flow.

[00195] Implant material can be relatively rigid or soft and springy as would be a hydrogel which will cyclically absorb and expel fluid due to changes in external stress. This would duplicate the performance of natural cartilage. Elastomers such as silicone or polyurethane may also be useful in this application. One advantage of this type of implant is that it maintains the meniscus tissue as the bearing material in contact with cartilage and bone. Optionally, the hulking implant can be a growth encouraging scaffold which would facilitate growth and regeneration of meniscal cells. Optionally, the building implant can be biodegradable.

[00196] The idea of the meniscal liner (ML₁ also referred to herein as meniscal wafer MW) is more akin to the concept of placing a sleeve within an existing bearing liner. A sleeve type liner placed over the existing meniscus and/or tibial plateau could achieve multiple objectives: (1) It can isolate the meniscus from tear inducing shear stresses; (2) ft can provide a fresh smooth lubricious bearing surface; (3) It can optionally add height to the joint by adjusting the thickness at the liner; and (4) It can optionally adjust or modify the shape/configuration of the bearing surface of the joint.

[00197] The ML can be constructed in a number of manners. One example would be to make a positive mold of the meniscus from CAT or MRI data. This mold could then be used with standard vacuum form equipment. After forming, the liner could be trimmed and optionally modified, coated and/or otherwise prepared for implantation before sterilization. The liner could be made from many materials (some of the following can be thermoformed: PE, PP, acrylic, PU et al., biodegradable materials such as PLA, PGA etc). The ML can also be used as an adjunct to a meniscal tissue engineering procedure. In this case, the ML is used to provide a bearing surface for the joint while a paste graft, collagen (or other) scaffold or other collagen regenerating procedure is performed. In some cases, an ML made from a biodegradable material would he used for this application. In some cases, an ML made from or coated with a hydrogel material would be used for this application.

078376-011300v1 286,323,216 45 [00198] The ML can be a totally separate component or can be integrated with the graft/scaffold/collagen. In certain clinical situations, a key of the use of the ML can be that it protects a regenerating meniscus. It should be noted that though described as being specific to the knee, the devices and methods might apply to other joints, such as hip and shoulder.

[00199] The meniscal liner can optionally include a liner that covers the tibial plateau in addition to the meniscus. Optionally the ML can be porous to allow passage of synovial fluids. Optionally the ML can be made from a hydrogel and/or lipophilic material where the trapped/absorbed water or lipids could improve the lubricity of the ML surface. A mock up meniscal liner was prepared using 0.5 mm PP and a dental thermoforming machine. The ML was trimmed and removed from a meniscus mold. A plastic knee model was then reassembled with the ML in place. Prototypes were also constructed using hydrogel layers of varying thicknesses on the PP backing layer. In bench-top experiments, the knee articulated appropriately with the polypropylene and PP/Hydrogel ML mock-up sheets in place. The bearing surfaces at the knee include the condyles (their articular cartilage lining), the meniscus and the tibial plateau.

[00200] The surfaces can he improved in a number of manners using a number of technologies/techniques that differ from improvement of their lubricating synovial fluid. The surfaces could be improved by: (1) making them smoother and harder (to reduce friction and resist wear and damage); (2) making them more lubricious (to reduce friction); (3) making them softer to avoid damage to the natural surfaces; and (4) making them tougher (to resist tears and other damage). The surface improvement could be accomplished by: (1) attaching a material or lubricant directly to the cartilage using a chemical bond; (2) attaching the material or lubricant directly to the cartilage using a photo activated bond; (3) attaching the material or lubricant to the cartilage using a carrier material; (4) attaching an intermediate material to the cartilage which will scavenge and bond active particles, moieties or ingredient circulating in the synovial fluid; and (5) placing an active particles, moiety/molecule in the synovial fluid where it is absorbed by the cartilage.

078376-011300V1 286,323,216 4β [00201] Long chain hyclrophilic or 3-D hyclrogel materials may be other candidates for a lubricious coating material. Coating of interpenetrating and/or crosslinking long chains may serve to protect the area and isolate the meniscus from tear-inducing shear stresses while similar coatings may be optimized for hardness and/or load distribution. In many situations, it would be desirable for these coatings to be porous to some degree to allow nutrients and other active agents from the synovial fluid to penetrate to the cartilage underlying the coating.

[00202] One method for surface coating the joints could include steps: removing the synovial fluid (SF), replacing the SF with another fluid, drying the interior of the joint, applying a first agent, applying a second agent, applying activity energy (e.g., light, UV light, RF energy), applying a third agent, rinsing the joint and replacing the SF. One aspect of the invention relates to activated coating active components of the synovial fluid, such as SAN.. and the like, onto a joint or onto implantable devices (such as a meniscal liner, meniscal wafer, meniscal collar, composite meniscus, condyle cap, cartilage cap. articular bumper, meniscal hulking agent, and the like). The following prior art is incorporated herein by reference: U.S. Pat. No. 4,722,906 issued on February 2, 1988, U.S. Pat. No. 5,512,320 issued on April 30, 1996, and U.S. Pat. No. 6,077,698 issued on June 20, 2000.

[00203] Meniscus augmentation is a subset of the idea of cartilage augmentation (CA). Augmenting or bulking (these terms are used interchangeably) agents can be: (a) rigid, elastorneric, porous; (b) biostable or biodegradable (used interchangeably with the term bioresorbable); (c) coated, impregnated or seeded with cells or bioactive agents; (d) biological materials such as cells (e.g., cartilage cells) from the patient or other sources; or (e) combinations thereof [0247] The bulking agent can be biocompatible and/or serves as a scaffold for the growth and regeneration of cells/tissue. To scaffold, a material must have a combination of surfaces and voids. The voids should communicate as in an open cell form or a matrix of round pellets. The scaffold could be a combination e.g., particles of open cell foam. Scaffold material should be compatible with the cells which are desired to colonize the scaffold and regenerate the desired tissue. Hyrdogels can be used as scaffolds and can act in a manner similar to an open

078376-011300V1 286,323,216 47 cell foam. In addition to compatibility, it can he desirable in some situations to encourage this colonization and regeneration.

[00204] Cartilage, articular and meniscal, are intermediate tissues softer than bone but harder than soft tissue such as muscle. Furthermore, both the meniscus and most articular cartilage (e.g., that overlying the femoral condyle) are attached on one side to bone. In the knee and other joints, one or more of the non-attached surfaces are lubricated bearing surfaces. These cartilaginous tissues also are compressible and serve to cushion loads transmitted within and through the joint. Furthermore, some cartilage, in particular the meniscus, is known to be prone to tearing and other mechanical failure.

Biomaterials for Meniscal Liner

[00205] Biomaterials for implantable knee devices, wafer, liner, meniscal/tibial cover, condylar cover may include:

[00206] (1) Core material: (a) High Modulus (>300,000 psi) *Metals - ferrous/non- ferrous metals, metal alloys (stainless steels, cobalt steels, cobalt chromium alloys, Nitinol) *Ceramics - zirconium *Polymers - polysulfones, poiycarhonates, polyesters, epoxies, PEEK, polyirnides Moderate Modulus (50,000 - 300,000 psi) ^*Po!ymers - nylons, polyurethanes, polypropylenes, polyethylenes, polyesters, polyureas, polyacrylates, polyvinyl alcohol, polymer blends, natural polymers (collagen)

[00207] (2) Optional Reinforcement: (woven or non-woven) Polyester fibers Carbon fibers.

[00208] C3) Optional Lubricious Surface Coating: [00209] Hydrogels - polyacrylates, PVP, PEO [00210] Lipids - phospholipids (phosphatidyl choline) [00211] Protein - tribonectins, glycoproteins

[00212] There are many biocompatible polymers, such as PVA, polyurethanes, polyolefins, that can meet requirements for the core of the device, (e.g., shore hardness of 70A to 6OD, or a compressive modulus about 400 kPa). It is noted that the materials

078376-011300v1 236,323,216 43 challenge is in the wear/friction surface against the natural tissues. Without causing tissue degradation, the device must stand up to the repeated frictional forces in the knee joint, and give acceptable wear with minimal particulate generation. A tough, wear resistant, lubricious surface is needed.

HA Microparticles

[00213] Microparticles can be made by known techniques such as spray evaporation, precipitation, emulsification and filtration, or grinding. Particle size needs to be >10 p, preferably >25 p to minimize inflammation and diffusive leaching. A preferred range is 50-100Ou.. In some clinical situations, this preferred range could be 100-200 .t. High molecular weight of the HA is preferred and MW should be at least 500,000. In some clinical situations MW >1 , 000,000 or even >10,000,000 may be indicated. Bacterial sourced HA may be preferred to minimize pathogenic contamination and allergic reactions. Since the HA particle is soluble, it will initially become hydrated and soft, thereby further acting as a cushioning agent within the joint space.

[00214] HA particles can form in-situ from a liquid injection. Methods for self agglutination of this type have been described by Bell et al. Alternately, HA can be bound Or otherwise attached to a molecule which will aggregate into particles in situ.

[00215] Water soluble radiopaque agents (RO) such as metrizainide may be added to the composition to allow visualization upon injection to insure the target joint space is successfully treated. RD ingredient could alternately be biodegradable and/or MRl visible. MRI visible agents can be, for example ferromagnetic. RO ingredients, such as gadolinium complexes, could alternately enhance MRI visibility. RO agents can be optionally incorporated in particles and/or bound to HA molecules. RU agents can optionally be excretable through the kidneys such as diatrizoate meglumine.

[00216] Dissolution rates can be adjusted. Rates can be decreased with larger particle sizes or incorporation of additives to retard dissolution, such as lactic and/or glycolic acid polymers. PEG, collagen, gelatin, etc. Use of the free HA acid or the partial salt of HA (sodium, calcium, ferric) or cross-linking may also decrease dissolution times. Other methods e.g. cross-linking can also be used to control the dissolution of HA. Cross- linking is an example of a method that is known to effect the hardness (durometer) and

078376-011300v1 286,323,216 49 durability of materials. Cross-inking can be induced, for example, chemically or by radiation.

[00217] HA an be formed into particles of various durometer hardnesses. In most clinical situations it will be desirable that the HA particles be softer (with lower durometer numbers) than the cartilage to avoid damaging the cartilage. Bae et al., have published data indicating the durometer of young healthy cartilage can be on the order of 60 Shore A while the durometer of older or unhealthy cartilage can be on the order of 30 Shore A. The preferred durometer of the HA particles would range from 10 Shore A to 50 Shore A depending upon the clinical situation. This invention also includes a method by which the durometer of the cartilage will be measured, and a HA particle durometer selected based upon the durometer of the cartilage.

[00218] Therapeutic medications, such as steroids, growth factors, etc., can also be incorporated into the HA particle. Lubrication enhancers, such as proteins, e.g., lubricin or phospholipids, e.g., dipalmitoyl phosphatidylcholine may also be incorporated in the formulation. For example, Pasquali-Ranchetti et al. have described methods by which HA and PL's can be combined.

Table t

Volumes and Weights for a Single Injection of HA Microparticles The ingredients are: A B C

HA (sodium salt) 100 100 100 mg

Polymer (control release) 0 100 200 mg

Particles weight 100 200 300 mg

Saline (phosphate buffer) to 2.0 to 2.0 to 2.0 ml

Particles volume 0.125 0.174 0.236 nil

Number particles 240,000 333,000 452,000

[00219] Assuming a density of about 0.8 g/ml for the HA and about 1.5 g/ml for the polymer (po!y(lactic-glycolic acid)), the densities for the solid microparticles would he 0.8 for composition A, 1.15 for composition B and 1.27 for composition C. (Density may be decreased somewhat due to the production method for the microparticle.)

078376-011300v1 286,323,216 gQ [00220] Since density is equal to g/mi, the volume that the microparticles occupy would be 0.125 ml for composition A. (1.174 ml for composition B, and 0.236 ml for composition C. Particle size has no significant effect on total volume of the suspension. By calculation, each 100 p.m microparticle sphere occupies 0.522 x 10^"6 cc.

[00221] The amount (if any) of the polymer for control release depends on solubility of the HA (sodium salt or free acid), HA particle size, and how it was made, as well as the selection of the control release polymer. For example, poiyglycolic acid dissolves in vivo over a period of weeks; polylactic acid dissolves over several months.

[00222] There is a limit on how much solids can be injected in 2.0 nil of fluid, probably about 400 mg. An injection volume of 2.5 ml could hold up to 500 mg.

[00223] Hydrated particle hardness will also depend on selection of the HA and polymeric ingredients.

[00224] Joint toxicity due to the presence of microparticles may be addressed by injection of the microparticle depot into a "safe" joint space, such as bursa.

Subcutaneous Depot

[00225] Implant HA in a manner similar to a subcutaneous bleb or where the injected agent (liquid and/or solid) is injected directly into tissue where it creates space rather than into an existing space or potential space as a slow release subcutaneous depot to increase concentrations.

[00226] Use of the suprapatellar fat pads as a location for an injected intracutaneous depot. Just above the patella and right behind the quadriceps tendon is the anterior suprapatellar fat pad. Just anterior to the femur is the prefemoral fat pad. Unlike the anterior suprapatellar fat pad, which is relatively constant in shape and size, this fat pad is quite variable in size, and may appear either fairly flat or quite plump. Extending up between these two fat pads is the suprapatellar bursa, an extension of the knee joint space.

The Suprapatellar Bursa as a Depot

[00227] These two fat pads can usually be seen on a lateral plain film. Usually the suprapatellar bursa is only a potential space, and contains very little fluid. In this case,

078376-011300v1 286,323,216 5-) the two fat pads are separated by less than 5 mm. If a suprapatellar effusion is present, the two fat pads are pushed apart by the effusion. If the distance separating them is 5 mm or greater, we consider this sufficient evidence to diagnose a knee effusion on plain film

[00228] The bursa could be the location of an injectable depot. With a 5-10 mm depth, a length of 30-40 mm and a width of 20-30 min the volume of such a depot could be 3-12 CC.

Refillable Reservoir or Depot

[00229] As known in the art, both reservoir and contents distribution and distribution rate control the HA release. Optionally with a port that is local (e.g. on reservoir) or remote (e.g. with a fill tube connecting to the reservoir). Optionally, the reservoir can be expandable and be delivered through a relatively small diameter cannula (e.g. a silicone structure similar to the balloon described in U.S. Pat. No. 4,213,461 which can inflate to many times (e.g. 8-1Ox) their formed diameter.

Compositions:

[00230] 1. Agent - HA: sodium salt, partial salt or other cation, 1 MM-F molecular weight Solvent - biocompatible, water soluble: DMSO, ethyl lactate, EtOH/water, acetone/water

[00231] 3. Polymeric Encapsulant - soluble in solvent, insoluble in water/tissues to form suitable precipitate; biocompatible itself and its degradation products; dissolves/degrades within 4-12 weeks: PLGA, PLA₁ PGA, PEG, PCL, copolymers, terpolymers and mixtures of the preceding, PHB, PHBV, zein. Optimum concentrations of the ingredients, mole ratios and molecular weights (2-10 k-Daltons) of the polymer to be determined,

[00232] PLGA is soluble in DMSO and will form a precipitate depot for proteins (J. Control. Release, (1995) Vol. 33, no. 1 . p189-195). A composition consisting of PLGA with HA in DMSO may work as an injectable depot for HA viscosupplementation.

[00233] Viscosupplementation with HA Microparticles Supplemental information

073376-011300V1 286,323,216 52 [00234] Slow or controlled release of substances, such as drugs, from solubie/degradable inicropartiele depots has been known and developed since the late 1970's. There exists a well developed technological and patent base. Medical products include: Pharmacia & Upjohn's Depo-Provera (progesterone with PEG, IM injection), TAP's Lupron Depot (leuprolide in PLA microspheres, IM injection), Chiron's Depocyt (cytarabine in liposomes, CSF injection).

[00235] Results from intra-articular injection of microparticles have been published within the last seven years. These have dealt with site specific release of drugs, such as paciitaxel, hydrocortisone and NTHE's, to treat osteoarthritis. Results have been generally favorable, with claims of hiocompatibility of the microparticles within the joint cavity.

[00236] Note that small molecule (drug) release is diffusion controlled through the microcapsules, which disappear after the drug is released. We are dealing with a different mechanism in rnicroparticle viscosupplementation, which is particle dissolution or degradation controlled, since we have a macromolecule (HA) to release.

[00237] 3. The most favored encapsulants are poly(alpha esters), such as PLA, PGA and PLGA copolymers; poly(hydroxyalkanoates), such as PI-IB and PHBV copolymers; polylactones, such as PCL; and various polyethylene glycols). HA has been reported as an encapsulant also.

[00238] 4. The following patent applications were particularly valuable: U.S. Application publication 2006/0148755 from Genzyme is of special interest - a single 6 ml (vs. 2 ml) injection of HA, good for 6 months; U.S. Application publication 2005/0123593 from .1&7 describes intra-articular delivery of HA in liposomes (phosphatidylcholine) for extended release of HA; U.S. Application publication 2005/0227911 from SoluBest discloses naπoparticles of starch with HA, forming an inclusion complex, for delivery of HA; U.S. Application publication 2006/0140988 claims compositions and methods for an injectable depot using an emulsion of biodegradable (PLGA) particles for sustained delivery of HA for viscosupplementation, a solvent and surfactant are required.

[00239] Exemplary Viscosupplementation Depots e.g., Polymer/Solvent and Compositions of Hyaluronic Acid.

078376-011300v1 286,323,216 53 [00240] Polymer/Solvent Compositions: To obtain a composition that models an injectable liquid, which solidifies upon contact with an aqueous environment, it is suggested a process of solidification by precipitation with 8 grams ethylene vinyl alcohol copolymer (Aldrich #414107-100) and 110 grams dimethyl sulfoxide (Aldrich #154938- 500); (110 g = 100 ml).

[00241] The polymer dissolves at room temperature (or -5O⁰C) with stirring within a few hours. Store all items in sealed containers, in a dry, cool place.

[00242] If a denser precipitate solid is required, use 12 g of copolymer; for a less dense precipitate solid, use 6 g of copolymer. If radio-opacity is needed, add 40 g of tantalum powder (Aldrich #262846-100) to the polymer solution and vigorously shake to disperse the powder.

[00243] Hyaluronic Acid Compositions: To obtain a depot for feasibility that will slowly dissolve in vivo and yield hyaluronic acid (HA), it is suggested as follows. This is equivalent to the current treatment, a total of 4 weekly injections - 100 mg of HA. 0.1 g HA sodium salt (Sigma or other choice; rooster or bacterial source). 0.3 g polyethylene glycol) or PEG (Aldrich #202436-250 rapid dissolution, or #202452250 slower dissolution in vivo)

[00244] Coaxial depot injection could be used to provide multiple layers such that the outer layers (which will have greater surface area than inner layers) disseminate HA at a slower rate than the internal layers thereby releasing HA at a near constant rate. This could be accomplished e.g. with a constant concentration of HA and a faster dissolving/degrading carrier on the inner layer or an inner layer with a higher HA concentration. Some aspects of the invention relate to a method for treatment of osteoarthritis of a patient, the method comprising injecting a suspension of HA microparticles into a joint space of the patient, wherein the microparticles have a hardness number less than the hardness number of a cartilage within the joint space, wherein the microparticles have plural concentric layers and plural concentric compartments separated by the layers, each compartment being filled with the HA, wherein an outer layer of the concentric layers is configured with a higher degradation rate than a second degradation rate of an inner layer.

078376-011300v1 286,323,216 54 Composite Depot

[00245] One concern about injectable solvent carrier depots could be related to depot migration as depot size decreases over time. Various means can be combined with an injectable depot to physically contain and/or stabilize the depot over its life as it dissolves/degrades, such as Inject into open cell foam where the depot invades and fills the open cells and the struts reinforce the injected material.

[00246] Coaxial injection over a suture or other filament Injection into a membrane or other potential space enclosing bladder (porous to fluids and HA or with ports to allow fluid exchange). For example, a thin permeable silicone balloon inflated as the depot material is injected

[00247] All of the above support materials could be optionally degradable with similar or longer degradation times relative to the depot material.

Depot Anchors

[00248] One concern about depots could be related to the potential for depot migration. Depots could be anchors using well known means such as t-tags, sutures, clips or the like. The coaxially injected over suture depot, as well as other depots, could be anchored by barbed sutures. The barbed suture can be especially useful with the injectable depot as a single needle stick can easily anchor and deploy the depot. This can also be accomplished with a t-tag or other type of barbed anchor et al.

[00249] From the foregoing, it should now be appreciated that a meniscal implant and other medical devices for treating knee joint has been disclosed. Furthermore, hyaluronate compositions lubricant and methods for treatment of osteoarthritis were also disclosed. While the invention has been described with reference to a specific embodiment, the description is illustrative of the invention and is not to be construed as limiting the invention. Various modifications and applications may occur to those skilled in the art without departing from the true spirit and scope of the invention as described by the appended claims.

078376-011300v1 286,323,216 55

Claims

What is claimed is;

1. A meniscal device comprising a support structure around circumference of a meniscus in a patient, wherein the support structure comprises a body with an exterior surface characterized with enhanced boundary lubrication, the body being made of biocompatible material selected from the group consisting of PVA hydrogel, elastomers, polypropylene, polyethylene, PEEK, and metals.

2. The device of claim 1, wherein said device comprises a meniscal collar device.

3. The device of claim 1 , wherein said device comprises a meniscal wafer device.

4. The device of claim 1 , wherein said enhanced boundary lubrication comprises means for attracting or adsorbing a surface-active phospholipid.

5. The device of claim 1 , wherein said enhanced boundary lubrication comprises means for coating a functional phospholipid on said device.

6. The device of claim 1 , wherein said enhanced boundary lubrication comprises means for coating a reactable phospholipid of phosphorylcholine.

7. The device of claim 1 , wherein said enhanced boundary lubrication comprises means for coating a reactable acrylate polymer with phospholipid side chains.

8. A system for menisical augmentation comprising, in combination: a meniscal bulking agent; an injection mechanism for administering the meniscal bulking agent; and imagery from at least one viewing appliance selected from the group of direct arthroscopic equipment and guidance imaging apparatus.

9. The system of claim 8, further comprising at biodegradable hydrogel.

078376-011300v1 286,323,216 §Q

10. The system of claim 8, wherein said meniscal bulking agent comprising a cross-linkable hydrogel with a first molecular weight and a second molecular weight higher than said first molecular weight.

11. The system of claim 8, wherein the bulking agent further comprises a scaffold seeded with autologons cells.

12. A process for making a prosthetic comprising: injecting lyophilized HA microparticles into a space; forming a reconstituted space filing device where said microparticles reform an HA microparticle structure further comprising plural concentrate layers and compartments separated by said layers, each compartment being filled with said HA, wherein an outer layer of said concentric layers is configured with a higher degraduation rate than a second degradation rate of an inner layer.

13. A product, by the process of claim 12, further comprising steroid nanoparticles.

14. In a prosthetic for converting compressive loads into circumferential stresses, the improvement comprising, in combination: said prosthetic having at least three layers for interfacing between a bone surface, and an active surface including a load bearing layer base.

15. A manufacturing methodology for customized anatomic implants, comprising in combination: determining if an implant is clinically indicated; imaging a joint area using a multiple place methodology; determining an appropriate implant fabrication method; and fabricating at least one of directly, by a cast form or mold and by a CAD/CAD form; and completing the process by sterilizing the resulting product; whereby an implant is completed and useful for emplacement.

078376-011300v1 286,323,216 57