The In Vivo Performance of Osteochondral Allografts in the Goat Is Diminished With Extended Storage and Decreased Cartilage Cellularity

Abstract

Background: Currently, osteochondral allografts (OCA) are typically used after 4°C storage for prolonged durations (15-43 days), which compromises chondrocyte viability, especially at the articular surface. The long-term in vivo performance of these fresh-stored allografts, in association with variable cellularity, is unknown. Purpose: To determine the effect of 4°C storage duration (14, 28 days) versus the best (fresh) and worst (frozen) conditions of chondrocyte viability on structure, composition, and function of cartilage in the goat and the association of retrieved chondrocyte cellularity with those tissue properties. Study Design: Controlled laboratory study. Methods: The effect of allograft storage on in vivo repair outcomes was determined for OCA transplanted into 15 recipient goats and analyzed at 12 months. Repair outcomes were assessed by examining cartilage structure (gross, histopathology), composition (cellularity by depth, matrix fixed charge), and biomechanical function (stiffness). Relationships between cellularity and structural scores, matrix fixed charge, and stiffness were assessed by linear regression. Results: Repair outcomes in 4°C-stored OCA were similar after 14 and 28 days of storage, and both were inferior to fresh OCA and were accompanied by diminished cellularity at the surface, matrix fixed charge, and histopathological structure. Overall, cellularity by depth and matrix fixed charge in cartilage of fresh OCA were similar to nonoperated controls. However, cellularity at the articular surface and matrix fixed charge in 4°C-stored OCA were lower than fresh, by ~55% (95% confidence interval [CI], 32%-76%) and ~20% (CI, 9%-30%), respectively. In frozen OCA, cellularity and matrix fixed charge were lower than 4°C-stored OCA, by ~93% (CI, 88%-99%) and ~22% (CI, 10%-35%), respectively. Cellularity correlated negatively with cartilage health indices, including structural scores, and positively with matrix fixed charge and stiffness. Conclusion: Reduced cellularity at the articular surface, resulting from 4°C storage, was associated with variable long-term outcomes versus consistently good repair by fresh allografts. Cellularity at the articular surface was an important index of biological performance. Clinical Relevance: Normal chondrocyte density in vivo, especially in the superficial region of cartilage, is important for maintaining long-term cartilage function and matrix content. In human cartilage, containing cells at ~3 to 5 times lower density than goat, repair outcomes may be related to absolute minimum number of cells rather than density.