Biomechanical and immunological contributions to osteochondral allograft transplantation outcomes
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Osteochondral allograft (OCA) transplantation offers a reliable option for treating complex articular injuries in multiple joints, but treatment failure rates remain a concern. Lack of functional integration of OCAs is a primary mechanism of failure. Although post-transplantation biomechanics have been implicated as a primary culprit in treatment failures, the relationships among mechanical and biological factors that contribute to treatment success versus failure have not been fully characterized. Based on the unique capabilities and benefits of OCA transplantation for a large and growing patient population, studies that comprehensively assess and correlate cellular, histological, biomechanical, immunological, and patient-reported outcome measures are needed in order to fill this knowledge gap and meet the increasing clinical need. This dissertation presents a body of work consisting of in silico, ex vivo, and in vitro experiments to characterize key biomechanical and immunological contributions to OCA integration and functional survival. From our results, significant changes in joint space loading after OCA transplantation due to geometric differences between the patient and host were noted. Optimization of graft biomechanics is required to accommodate such stress changes and avoid premature graft failure. Subchondral bone drilling, aimed at facilitating integration, has not been evaluated biomechanically. In silico modeling showed that small diameter holes effectively optimize integration potential without sacrificing graft integrity and should be used in clinic rather than fewer large drill holes. In addition, pulse lavage can reduce bioburden and improve OCA outcomes, as our ex vivo and in vitro experiments suggest that residual donor bone marrow elements may stimulate immune responses leading to graft failure. The success of OCA transplantation is multifactorial, and future research should target understanding failure mechanisms, identify prognostic techniques, and develop solutions to enhance the efficacy of OCA transplantation, biomechanically and immunologically.
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Ph. D.