Qualitative histological evaluation of photooxidized bovine osteochondral grafts in rabbits: a pilot study.

Photooxidation is a treatment that can render tissue less immunogenic and resistant to enzymatic degradation, while maintaining the mechanical properties of the material. The purpose of this study was to histologically examine the biocompatibility of photooxidized bovine osteochondral grafts when implanted into the rabbit. Two holes were drilled into the patellar groove of the rabbit knee. Photooxidized bovine osteochondral grafts were implanted into the holes. As a control, 1 surgically created hole in each rabbit was left to heal naturally. The animals were killed after 12 weeks. Histological analysis of the control sites indicated that fibrocartilage had begun to regenerate in the defect. Analysis of the grafts revealed a chronic, nonspecific inflammatory reaction. Active remodeling was observed in the graft bone, with "bridging" between host and graft bone evident. The articulating surface and majority of the graft cartilage remained undamaged. In a few instances, however, there was an inflammatory response to the base of the graft cartilage, near the subchondral plate. The surface of the graft cartilage was covered by a thin layer of fibrous tissue, and no viable chondrocytes were present. In most cases, there was no fusion between host and graft cartilage. The results from this study suggest that, while a biological reaction to the grafts occurred, the bone portion of the graft appeared to be in the process of remodeling, and the majority of the graft cartilage, most significantly the articulating surface, remained intact. Photooxidized osteochondral grafts show promise for use in the repair of osteochondral defects.

Immunogenicity of unprocessed and photooxidized bovine and human osteochondral grafts in collagen-sensitive mice.

BACKGROUND: Autologous and allogeneic osteochondral grafts have been used to repair damaged or diseased cartilage. There are drawbacks to both of these methods, however. Another possible source for osteochondral grafting is photooxidized xenograft scaffolds. The purpose of this study was to evaluate the adaptive immune response to unprocessed and photooxidized xenogeneic osteochondral grafts in a collagen-sensitive mouse model. METHODS: Unprocessed and photooxidized bovine and human osteochondral grafts were used. The grafts were implanted subcutaneously in collagen-sensitive DBA/1LacJ mice for four or twelve weeks. ELISPOT assays were conducted with spleen cells to evaluate the number of collagen-specific T cells that produce IL-2, IL-4, IL-5 or IFN-gamma. Serum was collected and ELISA assays were performed to determine the titers of collagen-specific and total IgG, IgG1, IgG2a, or IgM antibodies. Histology was conducted on the retrieved osteochondral grafts. RESULTS: Results indicated that, with respect to adaptive T cell immunity, the photooxidized bovine grafts, unprocessed human grafts and photooxidized human grafts did not induce a significant response to collagen. The unprocessed bovine grafts, however, were slightly more immunogenic, inducing a weak immune response. With respect to antibody production, the bovine grafts were less immunogenic than the human grafts. Bovine collagen-specific IgG antibodies were not induced by these grafts, but production of IgM after twelve weeks was observed with both the unprocessed and photooxidized bovine grafts. In contrast, photooxidized human osteochondral grafts induced IgG1 and IgG2a antibodies, while the unprocessed human grafts did not. Pre-existing human collagen-specific IgM antibodies were present in all mice, including sham-operated negative controls that did not receive an implant. Histological analysis revealed some degree of fibrous encapsulation and inflammatory infiltrations in both bovine and human implants, whether unprocessed or photooxidized. CONCLUSION: Both bovine and human cartilage grafts showed weak, but clear immunogenicity in the DBA/1LacJ mice, indicating that immunogenic collagen was still contained in the grafts, even after cleaning and photooxidation. The process of photooxidation is still important in osteochondral grafting, since it stabilizes the surface of the cartilage by cross-linking the collagen fibers, and allows for immediate load bearing and joint resurfacing.