Abstract
In this 12-month long, preclinical large animal study using a canine model, we report that engineered osteochondral grafts (comprised of allogeneic chondrocyte-seeded hydrogels with the capacity for sustained release of the corticosteroid dexamethasone [DEX], cultured to functional mechanical properties, and incorporated over porous titanium bases), can successfully repair damaged cartilage. DEX release from within engineered cartilage was hypothesized to improve initial cartilage repair by modulating the local inflammatory environment, which was also associated with suppressed degenerative changes exhibited by menisci and synovium. We note that not all histological and clinical outcomes at an intermediary time point of three months paralleled 12-month outcomes, which emphasizes the importance of in vivo studies in valid preclinical models that incorporate clinically relevant follow-up durations. Together, our study demonstrates that engineered cartilage fabricated under the conditions reported herein can repair full-thickness cartilage defects and promote synovial joint health and function.
Impact Statement
Osteochondral defect repair and functional outcome measures associated with engineered osteochondral constructs largely resembled those associated with the positive control-osteochondral allografts. Further, meniscus and synovium pathology observed in joints treated with dexamethasone (DEX)-free constructs was mitigated by the incorporation of corticosteroid-loaded microspheres. The findings suggest that while mechanically competent engineered osteochondral grafts can restore the articular surface and joint function, the addition of sustained DEX delivery can promote overall joint health presumably by modulating local inflammation, thereby providing a potential alternative to current clinical options such as osteochondral allograft transplantation.
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