Intra-articular Delivery of Recombinant Interleukin-1 Receptor Antagonist Protein (Anakinra) Enhances Graft Function in a Porcine Model of Osteochondral Repair

BACKGROUND: Osteochondral autografts may be subject to suboptimal healing and graft degeneration due to surgical insult and the inflammatory environment of an injured joint. PURPOSE/HYPOTHESIS: The purpose of this study was to alleviate the negative effect of this inflammatory milieu on the healing of osteochondral grafts by treating operative joints with interleukin-1 receptor antagonist (IL-1ra; Anakinra) in a porcine model. It was hypothesized that such treatment would reduce markers of inflammation and lead to improved implant structural and functional outcomes. STUDY DESIGN: Controlled laboratory study. METHODS: The authors performed an osteochondral autograft transfer (OAT) procedure on the weightbearing surface of the medial femoral condyle of adult Yucatan minipigs. Beginning 1 week after surgery, a subset of animals received an intra-articular injection of 8 mg Anakinra in the operative stifle on a weekly basis for 4 weeks. At the 5-week endpoint, mechanical testing of the cartilage was performed, synovium and osteochondral specimens were analyzed histologically using semiquantitative scoring systems, and subchondral bone was analyzed via micro-computed tomography. RESULTS: IL-1ra-treated joints showed significantly less histological evidence of synovial inflammation. Autografts from treated joints showed better retention of mechanical properties and better histological scores. CONCLUSION: Results indicate that intra-articular IL-1ra administration after surgery significantly improves graft structure and function and dramatically enhances healing. CLINICAL RELEVANCE: This study demonstrates that local provision of adjuvant anti-inflammatory therapeutics after OAT may enhance healing and protect graft integrity. This not only has implications for current clinical practice of osteochondral autograft (and allograft) procedures but also may allow expanded indications for advanced biological repair in a greater number of patients.