Synthetic Cartilage-Capped, Regenerative Osteochondral Plugs to Heal Osteochondral Defects - ABSTRACT Osteochondral defects (OCDs) – localized damage to the cartilage and subchondral bone of a joint – often lead to pain, loss of joint function, and osteoarthritis. This work seeks to develop a superior treatment (versus autografting, allografting, and partial resurfacing implants) to treat OCDs of knees and other joints. Proposed is a bioprosthetic implant – a “cartilage-capped, regenerative osteochondral plug (CC-ROP)” - that combines a permanent synthetic resurfacing cartilage cap and a biodegradable bone regenerative base. The cartilage cap will be prepared from a biostable, ultra-tough hydrogel, circumventing the low regeneration potential of cartilage tissue and providing immediate matching of the strength, stiffness, hydration, lubricity, and wear-resistance of native cartilage. The underlying biodegradable scaffold base will promote new bone formation to anchor the cartilage cap. The CC-ROP’s autograft-sized, cylindrical geometry will allow for implantation with existing surgical techniques. To promote healing and functionality, both the cartilage cap and osseous scaffold base will be designed to also support integration with adjacent tissue. Cartilage cap: Synthetic, biostable cartilage replacements (e.g., UHMWPE) lack the combined biomechanical properties of native cartilage, and do not provide critical integration to adjacent tissue. Thus, CC-ROP’s cartilage cap will be prepared with a new electrostatic, double network (DN) hydrogel that has been shown by the team to mimic the stiffness, strength, and lubrication of native articular cartilage. Poration at the perimeter of the cap and a bioactive polydopamine coating will encourage in-growth of adjacent tissue. Osseous scaffold base: The base will be formed with a biodegradable, templated semi-interpenetrating polymer network (semi-IPN) PCL:PLLA scaffold that the team has shown supports hBMSC osteogenesis in vitro, as well as neotissue formation and integration in vivo. CC-ROP: To evaluate their potential to heal OCDs, CC-ROPs will be evaluated in terms of metrics of cartilage resurfacing and integration, as well as osseous tissue regeneration and integration. Prof. Melissa Grunlan (PI) will lead all efforts in Aims 1-2 related to the fabrication of the CC-ROPs. Prof. Mariah Hahn (Co-I) will lead in vitro cell culture studies (Aim 1) to evaluate hBMSC behavior on the osseous scaffolds as well as the potential for chondrocytic invasion into the cartilage cap and immunoreactivity of potential cap wear debris. In Aim 2, the in vivo performance of the CC-ROPs in a rabbit femoral condyle OCD model will be assessed. Prof. Brian Saunders (Co-I) will lead subcutaneous biocompatibility studies (in rats) and OCD studies (in rabbits) in terms of histology and micro-CT. Prof. Michael Moreno will lead efforts to test the biomechanical properties of the explanted rabbit knees and controls. A veterinary pathologist, Prof. Roy Pool (consultant), will read and score histology slides (Aim 2). Dr. Patrick McCulloch (consultant), an orthopedic surgeon, will provide guidance.
