优化无支架软骨细胞-胶原基细胞片用于猪全层膝关节缺损模型中透明软骨再生的研究
简介
该研究在猪膝关节全层软骨缺损模型中,采用无支架多层软骨细胞-胶原片层技术,通过纤维连接蛋白-II型胶原纳米涂层优化细胞密度与制备工艺,构建出具有良好操作性的三维移植物。结果显示,该移植物能促进透明样软骨再生并与周围组织无缝整合,显著减少纤维软骨修复,为临床软骨缺损修复提供了有转化潜力的无支架策略。
英文摘要
Traumatic articular cartilage defects remain a significant clinical challenge due to their limited intrinsic self-repair capacity, inadequate structural support, and the frequent formation of fibrocartilaginous tissue rather than hyaline cartilage. Here, we established a scaffold-free cell sheet engineering strategy to fabricate a clinically sized, multilayer chondrocyte-collagen-based implant with favorable operability. By integrating fibronectin-type II collagen (COL II) nanocoating with optimized cell seeding density and a refined fabrication process, we generated a thick, three-dimensional multilayer chondrocyte sheet with robust interlayer cohesion, abundant extracellular matrix deposition, and high expression of hyaline cartilage markers, including COL II and aggrecan. This multilayer stacking strategy overcomes the intrinsic thickness limitation of single-layer sheets and enhances cartilage-specific ECM deposition and structural continuity, yielding a tissue architecture better suited for repairing larger or deeper cartilage defects and underscoring the clinical potential of multilayer CCB cell sheets. In a porcine in vivo model of full-thickness knee cartilage defects, fibronectin-0.05 mg/mL COL II-coated multilayer sheets promoted hyaline-like cartilage regeneration and seamless integration with the surrounding native tissue, while markedly reducing fibrocartilaginous repair. Accordingly, this study defines a scalable scaffold-free chondrocyte-collagen-based platform with enhanced structural stability and hyaline chondrogenic capacity, underscoring its translational potential for the repair of traumatic articular cartilage defects.