Treatment of Articular Cartilage Defects in the Goat with Frozen Versus Fresh Osteochondral Allografts: Effects on Cartilage Stiffness, Zonal Composition, and Structure at Six Months

The repair of articular defects with use of osteochondral allografts ideally restores the structure, function, and biology of the cartilage surface. Allograft efficacy may be dependent on sufficient chondrocyte metabolism to preserve cartilage homeostasis and prevent degeneration. Fresh osteochondral allografts are typically implanted with high chondrocyte viability, and retrieved grafts have contained viable chondrocytes up to twenty-nine years after implantation1-5. In contrast, frozen osteochondral allografts, used for massive oncologic joint reconstructions, have low chondrocyte viability at implantation, and grafts retrieved at approximately one to five years contain acellular and often degenerate cartilage6,7. Attempts at future improvements in the application of osteochondral allografts would benefit from an understanding of how the allograft implantation state affects defect repair efficacy and the mechanisms of cartilage maintenance with the best (fresh) and worst (frozen) conditions of cartilage within allografts. Animal models allow for a systematic and temporal evaluation of cartilage repair and remodeling. Data obtained from human allograft retrievals are skewed toward poor outcomes, since analysis is performed on “failed” cases, where revision or conversion to total joint arthroplasty was required5,8,9. Clinical evaluations based on patient satisfaction and often limited by availability for long-term follow-up are not sensitive to early stage degeneration. Intradisciplinary and multiscale analyses of cartilage repair in animal models may elucidate the types of tissue changes that are indicative of early stage degeneration and may provide insight into the time course of cartilage remodeling and/or deterioration. Results from such animal models suggest that postoperative time is an important determinant of the quality of cartilage repair. Frozen allografts appear grossly normal and similar to fresh allografts at short postoperative durations of as long as three months10-13, and then they appear discolored and roughened, often exposing subchondral bone, at eleven to twelve months12-15. In contrast, cartilage of fresh allografts remains grossly normal for as long as twelve months, with only mild degenerative changes14-16. Gross observations are paralleled by histopathologic changes, including reduced (for frozen) and maintained (for fresh) safranin-O staining intensity10-21. Cartilage cellularity and load-bearing function have been analyzed in relatively few studies. Qualitatively, frozen allografts appear acellular by three months, compared with fresh allografts, which contain viable cells for as long as twelve months12-16. When compared with that in the nonoperative control knees, the confined compressive stiffness of the operatively treated knees was slightly reduced in the fresh allograft areas, and markedly reduced in the frozen allograft areas with increasing postoperative duration12,13,15,19,20. The reduction of cartilage load-bearing function was associated with proteoglycan content15; however, other determinants of cartilage stiffness have not been investigated. Rapid indentation testing of cartilage, which is sensitive to structural measures of cartilage degeneration22, may be useful to elucidate mechanisms of allograft deterioration or maintenance. Large-animal studies with frozen or fresh allografts at moderate time points (between three and eleven months) are needed to understand the progression of articular cartilage deterioration. The hypothesis of this study was that the state of the allograft at implantation affects its performance after six months in vivo. The specific aim was to determine the effect of allograft treatment (frozen or fresh) on the properties of articular cartilage from retrieved osteochondral allografts at six months in the goat model by assessing cartilage function, zonal composition, and structure. The results of this study suggest that the use of a systematic approach as discussed in this paper, including a detailed baseline analysis at six months, may aid in the evaluation of in vivo cartilage restoration.