EP-4740970-A2 - MULTI-LAYERED BIOMIMETIC OSTEOCHONDRAL IMPLANTS

EP4740970A2EP 4740970 A2EP4740970 A2EP 4740970A2EP-4740970-A2

Abstract

Provided herein are biomimetic osteochondral implants that are generally useful for the at least partial resurfacing of damaged cartilage within a joint. The implants are constructed to have a modular, layered structure in which the physical properties (e.g., stiffness and lubricity) or dimensions of each layer can be adjusted (e.g., by using the appropriate material and controlling the thickness thereof) based on the anatomy to be replaced. For example, the material and or thicknesses of the layers can be selected to approximate the physical properties and/or dimensions of cartilage (and, optionally, chondral and subchondral bone). Also provided herein are methods of treatment involving the use of said biomimetic osteochondral implants to repair an osteochondral defect in a joint.

Inventors

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

Assignees

Hyalex Orthopaedics, Inc.

Dates

Publication Date: 20260513
Application Date: 20220701

Claims (15)

A biomimetic osteochondral implant comprising: a bearing zone, a base zone configured to be attached to bone upon implantation of the implant, and a hydrophobic middle zone positioned between the bearing zone and the base zone; and wherein the bearing zone comprises a biphasic polymer, a lubricious compliant surface configured for articulation within an orthopedic joint, a non-lubricious under surface having a composition comprising less than 10% water and adapted to provide a connection to the hydrophobic middle zone, a first thickness extending between the lubricious compliant surface and the non-lubricious under surface, and a first compressive modulus with a first stiffness; the hydrophobic middle zone has a shaped first surface, a second surface, and a second thickness extending therebetween, the shaped first surface comprising a perimeter and an external face spaced within the perimeter and attached to the non-lubricious under surface of the bearing zone and forming a contact interface with the non-lubricious under surface of the bearing zone, wherein the non-lubricious under surface of the bearing zone conforms in shape to the external face, and the hydrophobic middle zone further has a second compressive modulus with a second stiffness, the second stiffness being greater than the first stiffness; and the base zone comprising a metal and having an outer base surface attached to the second surface of the hydrophobic middle zone, an inner base surface configured to attach to the bone, and a third thickness extending between the inner base surface and outer base surface, and having a third compressive modulus with a third stiffness, the third stiffness being greater than the second stiffness.
The implant of claim 1, wherein the bearing zone comprising the biphasic polymer has a water composition of at least 10% at the lubricious compliant surface.
The implant of claim 1 or 2, wherein the bearing zone comprising the biphasic polymer has a water composition gradient extending between the lubricious compliant surface and the non-lubricious under surface, the gradient comprising a first water composition at the lubricious compliant surface, a second water composition at the non-lubricious under surface, and a third water composition within a bulk of the bearing zone extending between the lubricious compliant surface and the non-lubricious under surface.
The implant of claim 3, wherein the first water composition at the lubricious compliant surface is greater than the third water composition, and the third water composition is greater than the second water composition at the non-lubricious under surface.
The implant of claim 3, wherein the bulk of the bearing zone has a water composition gradient of 20 to 45%, the first water composition at the lubricious compliant surface is 40-45%, and the second water composition at the non-lubricious under surface is less than 1%.
The implant of claim 1, wherein the bearing zone comprises urethane.
The implant of claim 1, wherein: (i) the contact interface formed between the external face and the non-lubricious under surface extends across at least 50% of the external face, at least 75% of the external face, or at least 95% of the external face; and/or (ii) the implant further comprises at least one post structure in the hydrophobic middle zone, wherein the at least one post structure comprises a plurality of posts in the hydrophobic middle zone, optionally wherein the at least one post structure is positioned at the shaped first surface or at the second surface.
The implant of any one of the foregoing claims, further comprising a central axis extending through the bearing zone, the hydrophobic middle zone and the base zone, each having an axis and being aligned coaxially along the central axis, wherein the second thickness is variable with a first height extending between the second surface and the first surface at a first position along the first surface, and a second height extending between the second surface and the first surface at a second position along the first surface.
The implant of claim 8, wherein the first height has a maximum at a position along the perimeter and the second height has a maximum at a position within the external face.
The implant of claim 9, wherein: (i) the second height is aligned co-axially with the axis of the base zone; or (ii) one or more of the bearing zone or the hydrophobic middle zone is convex, concave, plano-convex, or plano-concave, optionally wherein the implant further comprises a tapered region extending along the external face from the maximum second height toward the perimeter, such that: the first height maximum is higher than the second height maximum, and the tapered region forms a concave curve; or the first height maximum is lower than the second height maximum, and the tapered region forms a convex curve.
The implant of claim 8, wherein: (i) the perimeter includes a curved edge extending circumferentially about the central axis; (ii) the implant further comprises a ridge region comprising at least one ridge extending radially across the external face and protruding into the non-lubricious under surface; (iii) the external face includes multiple regions with differing respective radii of curvature; or (iv) the second thickness at a position along the perimeter has a boundary height of 0.01 mm to 10 mm or 0.2 mm to 5 mm, optionally wherein the bearing zone and middle zone extend axially from the outer base surface to the compliant surface over an axial length of 2 mm to 10 mm or 4 mm to 4.5 mm.
The implant of any one of the foregoing claims, wherein: (i) the perimeter encompasses an area having a width of 5 mm to 15 mm; (ii) the second stiffness is 50 MPa to 500 MPa, wherein the first stiffness is 40 MPa to 150 MPa, and wherein the third stiffness is 1.5 GPa to 11 GPa; and/or (iii) the bearing zone has a stiffness gradient extending from the non-lubricious under surface to the lubricious compliant surface of greater than or equal to 1kPa/mm.
The implant of any one of the foregoing claims, wherein: (i) the base zone comprises at least one of a polymer, a ceramic, bone, or synthetic bone; wherein the metal comprises one or more of titanium, tantalum, stainless steel, cobalt chrome, a nickel-titanium alloy, a zirconium alloy, a metal coated with plasma-sprayed titanium, a metal coated with a plasma-sprayed ceramic; and wherein the polymer comprises one or more of polyetheretherketone, polyethylene, polysulfone, or polypropylene; (ii) the inner base surface is configured to be attached to a distal femur, a proximal tibia, a patella, a condyle, a distal tibia, a distal fibia, a calcaneus, a talus, a tibiofibular joint, a proximal humerus, a labrum, a humeral head, a glenoid, a proximal femur, a pelvis, a distal humerus, a proximal ulna, a proximal radius, a distal radius, a distal ulna, a carpal, a distal metacarpal, a proximal phalanx, a metatarsal, a temporomandibular region, or a vertebra; and/or (iii) the first thickness is 1 mm to 5 mm.
The implant of any one of the foregoing claims, wherein the bearing zone includes a water-swellable interpenetrating polymer network (IPN) or semi-IPN, the base zone includes a porous metal, and the hydrophobic middle zone includes a copolymer comprising a urethane dimethacrylate monomer and a monomer selected from methyl methacrylate, acrylamide, and dimethylacrylamide.
The implant of any one of the foregoing claims, wherein: (i) the bearing zone has the ability to deform between 2% to 25% under physiological load with repeatable recovery of >70% of the deformation when said load is removed, and wherein the hydrophobic middle zone is configured to deform between 2% to 10% under physiologic load, with repeatable recovery of greater than or equal to 70% of the deformation when the physiological load is removed; (ii) the implant has the ability to deform between 5% to 20% under physiological load, with repeatable recovery of greater than or equal to 80%, or greater than or equal to 95%; and/or (iii) the implant further comprises a bonding zone extending across at least 25% of the contact interface, optionally wherein the bonding zone comprises covalent bonds.

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", the entire contents of which are incorporated herein by reference in their entirety. 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. Summary Methods of repairing articular cartilage defects and osteochondral mimetic implants and systems suitable for use in the methods are disclosed herein. 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 multilayer structure is achieved by multiple zones that are attached together by mechanical connection, chemical bonding, biological adhesion, and/or other attachment mechanisms. Mimicking properties of the cartilage or other tissue to be replaced, as closely as possible, provides benefits such as improved stress transfer from the articulating surface to subchondral bone and, in the case of one-sided repair of a joint, the preservation of the cartilage counterface. The disclosure relates, in part, to the observation that tissues respond to applied loads and the resultant stresses by remodeling. If an osteochondral implant is f