Repair of Porcine Articular Osteochondral Defects

Introduction: Our previous study showed that porcine articular osteochondral defects at non-weight bearing area could be repaired by autologous induced bone marrow stromal cells (BMSCs) and scaffold, which provided the direct evidence that BMSCs could differentiate into chondrocytes and osteoblasts respectively in different local environment . This study tests the possibility of repairing porcine articular defect at weight-bearing area using autologous BMSCs and observes the long-term results. Methods: Bone marrows were harvested from 24 hybrid pigs to isolate BMSCs. BMSCs were in vitro expanded and either induced with dexamethasone and transforming growth factor-ß1(TGF-ß1) or noninduced. Collagen II and aggrecan expressions were examined with immunohistochemistry and RT-PCR. Both induced and non-induced BMSCs were respectively seeded on a scaffold composed of polyglycolic acid (PGA) and polylactic acid (PLA), and co-cultured for 1 week before implantation. Total 4 osteochondral defects (8mm in diameter) were created at medial and external condyles of femur on both knee joints. Defects were repaired with induced BMSC-PGA/PLA constructs as group A or with non-induced BMSC-PGA/PLA constructs as group B, with scaffold alone (group C) or non-treated (group D) as controls. Eight animals were sacrificed at each time point of 3, 6 and 18 months postimplantation. Gross observation, histology, glycosaminoglycan (GAG) quantification and biomechanical tests were applied to analyze the results. Results: Strong expression of type II collagen and aggrecan was observed in induced BMSCs, while no or low expression was oberved in non-induced cells. In both groups, cells attached well to the PGA/PLA scaffold and produced abundant extracellular matrices when observed with scanning electron microscope. In groups A and B, gross observation and histology showed that most of the defects were completely repaired by tissue engineered hyaline cartilage and cancellous bone when examined at all time points, except that the central areas of some defects (4/8) of group B showed immature cartilage tissue at 3 months. At 18 months, the defects in both groups A and B showed no distinct interface between the repaired tissue and the adjacent normal tissue, with a normal epiphyseal structure between the repaired cartilage and the subchondral bone. No repair or only fibrous tissue were observed in groups C and D at all time points except for partial repair by fibrocartilage in 2 samples of group C at 18 months. Besides, the compressive moduli of groups A and B showed no statistical difference and reached 56.2% and 49.3% of normal amount at 3 months, 84.6% and 81.4% at 6 months and 91.7% and 90.0% at 18 months respectively. In addition, high levels of GAG contents in engineered cartilage of both groups A and B were found at time points of 6 and 18 months, which were not significantly different from those of normal contents. Conclusion: Both induced and non-induced BMSCs can repair articular osteochondral defects at weight bearing area with stable longterm results, indicating that articular microenvironment is more important than in vitro induction for BMSC differentiation in vivo. Reference: [1] Guangdong ZHOU, Lei CUI, Wei LIU, Yilin CAO. Repair of porcine articular cartilage full-thickness defect with autologous bone marrow stromal cells. The 49th annual meeting of orthopaedic research society. Oral presentation (#165). 2003 Feb. New Orleans, USA.