An impaired healing model of osteochondral defect in papain-induced arthritis

Abstract

Background: Osteochondral defects (OCD) are common in osteoarthritis (OA) and difficult to heal. Numerous tissue engineering approaches and novel biomaterials are developed to solve this challenging condition. Although most of the novel methods can successfully treat osteochondral defects in preclinical trials, their clinical application in OA patients is not satisfactory, due to a high spontaneous recovery rate of many preclinical animal models by ignoring the inflammatory environment. In this study, we developed a sustained osteochondral defect model in osteoarthritic rabbits and compared the cartilage and subchondral bone regeneration in normal and arthritic environments. Methods: Rabbits were injected with papain (1.25%) in the right knee joints (OA group), and saline in the left knee joints (Non-OA group) at day 1 and day 3. One week later a cylindrical osteochondral defect of 3.2 mm in diameter and 3 mm depth was made in the femoral patellar groove. After 16 weeks, newly regenerated cartilage and bone inside the defect were evaluated by micro-CT, histomorphology and immunohistochemistry. Results: One week after papain injection, extracellular matrix in the OA group demonstrated dramatically less safranin O staining intensity than in the non-OA group. Until 13 weeks of post-surgery, knee width remained significantly higher in the OA group than the non-OA control group. Sixteen weeks after surgery, the OA group had 11.3% lower International Cartilage Regeneration and Joint Preservation Society score and 32.5% lower O’Driscoll score than the non-OA group. There were less sulfated glycosaminoglycan and type II collagen but 74.1% more MMP-3 protein in the regenerated cartilage of the OA group compared with the non-OA group. As to the regenerated bone, bone volume fraction, trabecular thickness and trabecular number were all about 28% lower, while the bone mineral density was 26.7% higher in the OA group compared to the non-OA group. Dynamic histomorphometry parameters including percent labeled perimeter, mineral apposition rate and bone formation rate were lower in the OA group than in the non-OA group. Immunohistochemistry data showed that the OA group had 15.9% less type I collagen than the non-OA group. Conclusion: The present study successfully established a non-self-healing osteochondral defect rabbit model in papain-induced OA, which was well simulating the clinical feature and pathology. In addition, we confirmed that both cartilage and subchondral bone regeneration were further impaired in arthritic environment. The translational potential of this article: The present study provides an osteochondral defect in a small osteoarthritic model. This non-self-healing model and the evaluation protocol could be used to evaluate the efficacy and study the mechanism of newly developed biomaterials or tissue engineering methods preclinically; as methods tested in reliable preclinical models are expected to achieve improved success rate when tested clinically for treatment of OCD in OA patients.

Keywords

• Impaired healing
• Osteochondral defect
• Papain-induced osteoarthritis