Zhang Zhen, Huang Ye, Hu Xu, Mu Yulei, Zhou Huiqun, Ma Liang, Liu Bangheng, Yao Hang, Jiang Xieyuan, Wang Dong-An
Department of Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong, China.
Department of Knee Preservation Surgery at Beijing Jishuitan Hospital in Beijing, China.
Bioact Mater. 2025 Apr 22;50:364-381. doi: 10.1016/j.bioactmat.2025.04.013. eCollection 2025 Aug.
The articular osteochondral injury involves the repair of hyaline cartilage, subchondral bone plate, and cancellous bone. Due to the weak regeneration ability of chondrocytes and the complex structure of the bone-cartilage junction, there is currently no excellent repair method. The challenge of hyaline cartilage repair is to avoid fibrosis and hypertrophy, which has been solved to some extent after the advent of type II collagen scaffolds; the difficulty of the subchondral bone plate and cancellous bone repair lies in the repair of the complex transition structure of cartilage tidemark, calcified cartilage, subchondral bone plate, and cancellous bone. Inspired by developmental biology, the generation of this complex structure during development depends on endochondral ossification (ECO). ECO depends on some specific proteins, such as IHH, PTHrP, BMP, and WNT, and the receptors of these proteins. Studies have shown that polydopamine coating can promote the production of BMP and WNT proteins. We developed a type II collagen-based double-layer scaffold (Col II & Dopa-Col II) with type II collagen on the upper layer and polydopamine-coated type II collagen on the lower layer. Proteomics and RNA sequencing analysis have found that polydopamine coating can mobilize the proliferation and hypertrophy differentiation of chondrocytes, induce intra-chondral vascular nerve invasion, and promote ECO and bone remodeling by upregulating Parathyroid hormone signaling pathway, Hedgehog signaling pathway, VEGF signaling pathway, and Axon guidance. All the results indicate that Col II & Dopa-Col II can achieve hyaline cartilage and vascularized subchondral bone regeneration.
关节软骨下骨损伤涉及透明软骨、软骨下骨板和松质骨的修复。由于软骨细胞再生能力较弱且骨 - 软骨交界处结构复杂，目前尚无理想的修复方法。透明软骨修复面临的挑战是避免纤维化和肥大，II型胶原蛋白支架出现后这一问题在一定程度上得到了解决；软骨下骨板和松质骨修复的难点在于修复软骨潮标、钙化软骨、软骨下骨板和松质骨的复杂过渡结构。受发育生物学启发，发育过程中这种复杂结构的形成依赖于软骨内成骨（ECO）。ECO依赖于一些特定蛋白质，如IHH、PTHrP、BMP和WNT以及这些蛋白质的受体。研究表明，聚多巴胺涂层可促进BMP和WNT蛋白的产生。我们开发了一种基于II型胶原蛋白的双层支架（Col II & Dopa - Col II），上层为II型胶原蛋白，下层为聚多巴胺涂层的II型胶原蛋白。蛋白质组学和RNA测序分析发现，聚多巴胺涂层可动员软骨细胞的增殖和肥大分化，诱导软骨内血管神经侵入，并通过上调甲状旁腺激素信号通路、刺猬信号通路、VEGF信号通路和轴突导向来促进ECO和骨重塑。所有结果表明，Col II & Dopa - Col II可实现透明软骨和血管化软骨下骨再生。
