ADAPTIVELY CONFORMING OSTEOCHONDRAL ALLOGRAFTS FOR JOINT REPLACEMENTS

Background: Osteoarthritis (OA) is a debilitating degenerative disease that afflicts an estimated 27 million Americans age 25 and older. This disease leads to the progressive degradation of the articular layers of diarthrodial joints, significantly compromising the main function of cartilage as a load-bearing material, leading to pain and limiting activities of daily living. Though cartilage degeneration is occasionally limited to small focal areas within articular layers (~1 cm[2]), OA generally becomes symptomatic when degradation has spread over much greater surface areas (e.g., > 5 cm[2] or > 25% of the articular layer).Rationale: Currently, the primary treatment strategy for advanced osteoarthritis is artificial joint replacement. This treatment modality has proven to be highly successful, especially for total hip, knee, and shoulder replacements. However, a primary limitation of artificial joint replacements is the lifespan of the implant relative to the life expectancy of the patient. This issue is of particular concern for younger patients afflicted with post-traumatic osteoarthritis (PTOA). Osteochondral allografts, which may overcome these limitations, are not available for certain joints such as the thumb or fingers. For other joints, such as the knee and ankle, tissue banks do not have enough supplies of live allografts with dimensions and curvatures matching every patient. When a match between donor and recipient is not found within 4 weeks, the allograft is either discarded or devitalized. The ability to safely bend available osteochondral allografts to match the curvature and dimensions of the host site makes it possible to replace entire articular layers without loss of joint congruence, thereby eliminating discontinuities of the articular layer between allograft and host tissue. Better matching of osteochondral allografts also reduces waste, eliminating the need to discard or devitalize available allografts.Hypothesis and Specific Aims. The driving hypothesis of this application is that transplanted osteochondral allografts that conform better to the opposing articular surface result in better clinical outcomes than allografts that have only been size-matched for the host site. The corollary hypotheses are that (a) better conformity may be achieved by providing some measure of bending flexibility to the allograft, using streamlined tissue processing procedures to cut grooves in the bony substrate and (b) this conformity can be achieved during the transplantation procedure using a simple but effective anchoring protocol that deviates minimally from standard surgical procedures for allograft transplantation. The two primary aims of this application are to (1) develop, implement, and validate the technology for designing a suitable gridded pattern and milling grooves on the back of large human and canine osteochondral allografts and implement and refine the surgical procedure for transplanting these allografts in human and canine cadaver joints and (2) validate this technology in a canine animal model by replacing the native patellar articular layer with a grooved and bendable osteochondral allograft, or a size-matched non-grooved, non-bendable allograft to serve as a control.Study Design: Eight dogs will receive a size-matched, grooved, bendable patellar osteochondral allograft; eight additional dogs will receive a size-matched non-grooved, non-bendable patellar osteochondral allograft. Sham surgeries will be performed on contralateral knees. Dogs will be monitored for 6 months using a range of standard clinical outcome measures, histology and mechanical properties, which will be compared statistically.Impact: The short-term impact of the proposed studies will be (1) the development of a streamlined technology for cutting grooves on the bony side of large osteochondral allografts, to allow their articular layer to conform to the opposing side of the joint in which they are transplanted; (2) the development of an anchoring method used during surgery, which facilitates the bending of the osteochondral allograft while promoting osteointegration with the host tissue using a bone putty allograft; and (3) testing the effectiveness of these technologies in an animal (dog) model. The potential long-term impact will be to introduce a novel treatment modality for PTOA in younger populations, as well as other forms of arthritis, using biological replacement of entire articular layers of the afflicted joint.Topic Area: This proposal is responsive to the Peer Reviewed Medical Research Program Topic Area Post-Traumatic Osteoarthritis as well as Areas of Encouragement: (1) research toward the development of clinical practice guidelines to prevent, identify, and treat arthritis, particularly that resulting from traumatic injury, surgery, and/or infectious diseases; (2) strategies for repairing focal cartilage defects using cell-based therapies; (3) research into cell-based approaches for treatment or prevention of post-traumatic osteoarthritis; and (4) development or validation of novel and/or innovative approaches to restoring joint stability after injury.