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EP-4362856-B1 - MULTI-LAYERED BIOMIMETIC OSTEOCHONDRAL IMPLANTS

EP4362856B1EP 4362856 B1EP4362856 B1EP 4362856B1EP-4362856-B1

Inventors

  • FRYMAN, JAMES, CRAIG
  • HAWKINS, MICHAEL, E.
  • SAHNEY, MIRA
  • MYUNG, DAVID

Dates

Publication Date
20260506
Application Date
20220701

Claims (15)

  1. A biomimetic osteochondral implant (100) comprising: a bearing zone (102), a base zone (112) configured to be attached to bone upon implantation of the implant (100), and a hydrophobic middle zone (106) positioned between the bearing zone (102) and the base zone (112); and wherein the bearing zone (102) comprises a compliant surface (104) configured for articulation within an orthopedic joint, an under surface (105), a first thickness (103) extending between the compliant surface (104) and the under surface (105), and a first compressive modulus with a first stiffness, wherein the bearing zone (102) comprises a biphasic polymer, the biphasic polymer has a water composition gradient between the compliant surface (104) and the under surface (105), the gradient comprising a water composition at the compliant surface (104), a water composition at the under surface (105), and a bulk water composition extending between the compliant surface (104) and the under surface (105), and the bulk water composition has a gradient of 20 to 45%; the middle zone (106) has a shaped first surface (108), a second surface (109), and a second thickness (107) extending therebetween, the shaped first surface (108) comprising a perimeter (110) and an external surface (111) spaced within the perimeter (110) and attached to the under surface (105) of the bearing zone (102), wherein the under surface (105) of the bearing zone (102) conforms in shape to the external surface (111), and the middle zone (106) further has a second compressive modulus with a second stiffness, the second stiffness being greater than the first stiffness; and the base zone (112) has an outer base surface (114) attached to the second surface (109) of the middle zone (106), an inner base surface (115) configured to attach to the bone, and a third thickness (113) extending between the inner base surface (115) and outer base surface (114), and having a third compressive modulus with a third stiffness, the third stiffness being greater than the second stiffness.
  2. The implant of claim 1, wherein the biphasic polymer has a water composition of at least 10%, at least 20% or at least 30%.
  3. The implant of claim 1 or 2, wherein the water composition at the compliant surface (104) is greater than the bulk water composition, and the bulk water composition is greater than the water composition at the under surface (105).
  4. The implant of claim 3, wherein the water composition at the under surface (105) is less than 1%.
  5. The implant of any one of claims 1 to 4, wherein the water composition at the compliant surface (104) is 40-45%, and the bulk water composition gradient is 27-41%.
  6. The implant of any of the foregoing claims, wherein the compliant surface (104) is lubricious.
  7. The implant of any of the foregoing claims, wherein the under surface (105) is non-lubricious.
  8. The implant of claim 6 or 7, wherein the bearing zone (102) comprises urethane.
  9. The implant of any of the foregoing claims, comprising a contact interface formed between the external surface (111) and the under surface (105) and extending across at least 50%, at least 75% or at least 95% of the external surface (111).
  10. The implant of any of claims 1 to 9, wherein the middle zone (106), or the bearing zone (102), or both comprise a separate polymer network.
  11. The implant of claim 10, wherein the bearing zone (102) and the middle zone (106) are joined together via chemical bonding or mechanical bonding, optionally wherein the bearing zone (102) and the middle zone (106) are joined together via covalent bonding, non-covalent bonding, or polymeric entanglement.
  12. The implant of any of the foregoing claims, wherein the second stiffness is 50 MPa to 500 MPa.
  13. The implant of claim 12, wherein the first stiffness is 40 MPa to 150 MPa, and the third stiffness is 1.5 GPa to 11 GPa.
  14. The implant of any of the foregoing claims, the bearing zone (102) having a stiffness gradient extending from the under surface (105) to the compliant surface (104) of greater than or equal to 1kPa/mm.
  15. The implant of any of the foregoing claims, wherein the bearing zone (102) includes a water-swellable interpenetrating polymer network (IPN) or semi-IPN, the base zone (112) includes a porous metal, and the middle zone (106) includes a copolymer comprising a urethane dimethacrylate monomer and a monomer selected from methyl methacrylate, acrylamide, and dimethylacrylamide.

Description

Cross Reference to Related Applications This application claims priority to and benefit of U.S. Patent Application No. 17/365,135, filed on July 1, 2021, and entitled "MULTI-LAYERED BIOMIMETIC OSTEOCHONDRAL IMPLANTS AND METHODS OF USING THEREOF". Background Many different injuries or constant stress can wear down articular cartilage, the gliding surfaces of a joint. Cartilage lesions, particularly in weight-bearing joints, often fail to heal on their own and can be associated with pain, loss of joint function, and long-term complications such as osteoarthritis. In the United States, 1.2 million patients per year are diagnosed with a knee cartilage lesion, while only 550,000 patients per year receive knee cartilage repair surgery. Still, there is a significant satisfaction gap of patients diagnosed with cartilage injury, who decline current surgical standard-of-care due to poor outcomes and long rehabilitation - more than 30% of micro-fracture surgeries fail. Furthermore, osteochondral injuries are considered by some to be not just naturally but also therapeutically irreversible with current treatment parameters. Inferior repair commonly occurs, with stable regeneration of hyaline cartilage being a rare outcome. Accordingly, unmet needs in cartilage lesion repair include improved joint function and pain-reduction, higher effectiveness of intervention, faster return to weight-bearing and normal activities, shorter rehabilitation time, long-term implant effectiveness, applicability to a wide range of patients and variety of lesions, repair by a single surgery, and rapid surgeon adoption of an effective technique. Some tissue regeneration techniques for cartilage defects range from simple micro-fracture techniques (drilling a multitude of holes through the cartilage defect into subchondral bone) to multistep cartilage transplantation procedures. Regenerative approaches have several shortcomings. For example, they require a long recovery period before allowing the patient to return to full weight-bearing and activity levels, results are highly variable based on individual patient factors such as age and body-mass-index, and they are generally unsuitable for middle-aged or older patients due to poor ability to regenerate hyaline cartilage, often resulting in production of fibro-cartilage having inferior properties. Furthermore, regenerative approaches have not demonstrated any viable method for successful interfacing or anchoring of regenerated cartilage with bone. Many attempts have been made at chondral regeneration and repair or osteo regeneration and repair but have not addressed the osteochondral complex which is relevant to positive clinical outcomes. Additionally, even for those patients with initial benefits, long term results are often elusive. Availability of tissue supply, high costs and the need for multiple surgical procedures are all additional challenges for regenerative approaches. The shortcomings of tissue regeneration techniques have prompted investigations into the use of synthetic implants. While synthetic materials such as metals and most polymers are generally more durable than the cartilage, they fail to mimic the properties of the native tissue closely enough, and tend to adversely influence the health of the surrounding tissue and damage the opposing cartilage surface under articulation, thereby limiting the lifetime of such implants and hastening failure of the opposing cartilage surface. Other materials fail because they have tear strength that is too low and weak mechanical properties, as compared with cartilage, and often are unable to be properly fixed to the patient's bone in a way that can provide a stable long-term solution. Accordingly, there is a need for new osteochondral implants with improved properties and techniques of repairing focal cartilage defects. US 2010/010114 A1 describes a composition of matter comprising a water-swellable interpenetrating polymer network (IPN) or semi-IPN including a hydrophobic thermoset or thermoplastic polymer and an ionic polymer, articles made from such composition and methods of using such articles. Also described is a process for producing a water-swellable IPN or semi-IPN from a hydrophobic thermoset or thermoplastic polymer including the steps of placing an ionizable monomer solution in contact with a solid form of the hydrophobic thermoset or thermoplastic polymer; diffusing the ionizable monomer solution into the hydrophobic thermoset or thermoplastic polymer; and polymerizing the ionizable monomers to form a ionic polymer inside the hydrophobic thermoset or thermoplastic polymer, thereby forming the IPN or semi-IPN. Summary The present invention is defined by claim 1. Provided herein are biomimetic osteochondral implants that are multilayered constructs that, through the thickness thereof, mimic the properties (e.g., stiffness) of articular cartilage and, in some implementations, the underlying subchondral bone. The underlying multil