Adaptively Conforming Osteochondral Allografts for Joint Replacements

This proposal is responsive to the Peer Reviewed Medical Research Program Topic Area Post-Traumatic Osteoarthritis as well as a number of the 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.

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). Currently, the primary treatment strategy for advanced OA 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).

A promising biological alternative to artificial joint replacements has emerged over the last two decades, whereby fresh osteochondral (bone and cartilage) allografts (OCA), harvested from human donors and preserved live for up to a few (4 to 6) weeks in tissue banks, are used to fill large defects, or even replace an entire portion of an articular layer. Osteochondral allograft transplantation has demonstrated favorable outcomes, particularly in the knee, but also in the ankle and preliminarily in the shoulder. To date, OCA transplantation has been considered to be primarily a salvaging procedure, with only a few tens of thousands performed yearly in the U.S., although some investigators have advocated it as a standard treatment modality. One of the greatest obstacles to widespread use of OCA transplantation is the difficulty in matching the size and curvature of donor OCA with the recipient's joint anatomy, especially in the context of the limited, weeks-long shelf life of fresh allografts.

Our research idea is to develop a practical methodology for adaptively bending osteochondral allografts during transplantation surgery, such that their articular surface conforms to the anatomy of the recipient's joint. This will be achieved by milling grooves on the bony side of large allografts, in a grid pattern, whose depth just meets the zone of calcified cartilage. Since cartilage is a soft tissue, these grooves will make it possible to bend the OCA to either increase or decrease its local curvature, without damaging cartilage or compromising cell viability in the fresh allograft. Groove milling will be performed a priori by the tissue bank in a predetermined pattern, using standard sterile procedures employed in tissue preprocessing. The grooved OCA will be shipped in a sealed bag, in the same manner as other allografts, ready for use in the operating room. Bending will be performed in situ during surgery, with the OCA freshly transplanted while locally applied spots of bone cement are still malleable, by articulating the joint back and forth against the opposing articular layer. Upon setting of the bone cement, more permanent anchors may be used, such as headless compression screws. To eliminate gaps between the bent OCA and the recipient bony side and promote better bony integration where bone cement is not used, a demineralized bone putty allograft may also be applied.

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. As with any technology, the failure or success of a procedure depends significantly on the simplicity and feasibility of each step in its application. This proposal addresses those technical steps and culminates in a well-controlled animal study that will clearly support or reject the driving hypothesis.