Abstract
Knee cartilage does not regenerate spontaneously after injury, and a gold standard regenerative treatment algorithm has not been established. This study demonstrates preclinical safety and efficacy of scaffold-free, human juvenile cartilage-derived-chondrocyte (JCC) sheets produced from routine surgical discards using thermo-responsive cultureware. JCCs exhibit stable and high growth potential in vitro over passage 10, supporting possibilities for scale-up to mass production for commercialization. JCC sheets contain highly viable, densely packed cells, show no anchorage-independent cell growth, express mesenchymal surface markers, and lack MHC II expression. In nude rat focal osteochondral defect models, stable neocartilage formation was observed at 4 weeks by JCC sheet transplantation without abnormal tissue growth over 24 weeks in contrast to the nontreatment group showing no spontaneous cartilage repair. Regenerated cartilage was safranin-O positive, contained type II collagen, aggrecan, and human vimentin, and lacked type I collagen, indicating that the hyaline-like neocartilage formed originates from transplanted JCC sheets rather than host-derived cells. This study demonstrates the safety of JCC sheets and stable hyaline cartilage formation with engineered JCC sheets utilizing a sustainable tissue supply. Cost-benefit and scaling issues for sheet fabrication and use support feasibility of this JCC sheet strategy in clinical cartilage repair.
Highlights
Articular cartilage plays an essential role in reducing friction in joint motion and mitigating joint load stress
Focal cartilage defects have been identified as a potent risk factor for early osteoarthritic disease[2,3], and restoring cartilage integrity is considered to be a key means of preventing or delaying the reduction in patient quality of life associated with osteoarthritis development[4,5]
Autologous chondrocyte implantation (ACI) sacrifices native patient cartilage and has significant preparation costs that proportionally increase with increasing patient treatment numbers
Summary
Articular cartilage plays an essential role in reducing friction in joint motion and mitigating joint load stress. The post-traumatic repair capacity of cartilage is limited[1]. Focal cartilage defects have been identified as a potent risk factor for early osteoarthritic disease[2,3], and restoring cartilage integrity is considered to be a key means of preventing or delaying the reduction in patient quality of life associated with osteoarthritis development[4,5]. Autologous and allogeneic osteochondral grafts have been applied as mosaicplasty, bulk grafts, and particulated cartilage[6] to replace damaged cartilage. Allogeneic grafts have limited supply, treatable lesion location, and area restricts graft options, and the limited duration of bulk osteochondral allograft (OCA) transplantation viability makes the timing of surgical treatment difficult[7]. In many cases, fibrocartilage is often reported following chondral repair techniques
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