Treatment of osteochondral (OC) defects is still an immense challenge in clinic due to lack of satisfactory strategy to simultaneously regenerate both cartilage and subchondral bone. Herein, we propose an effective bottom-up strategy by developing a type of multifunctional chitosan-based nanocomposite microgels as the building blocks to repair OC defects. The microgels are biocompatible, and biodegradable, and have a hierarchical nanofibrous structure, mimicking the structural feature of extracellular matrix (ECM) to facilitate cell attachment and proliferation. Additionally, β-tricalcium phosphate (β-TCP) nanoparticles are incorporated in the microgels not only to promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), but also to facilitate the loading of transforming growth factor beta 1 (TGF-β1). For reconstructing OC defects, pure microgels are implanted at the bottom layer of the OC defects in rat knee joints to promote osteogenesis, while the microgels loaded with TGF-β1 are implanted at the top layer of the OC defects to promote cartilage regeneration. This modular microgel system results in simultaneous regeneration of cartilage and subchondral bone in OC defects, which is expected as a promising way for repairing other complex tissue defects in the field of tissue engineering.

中文翻译：

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用于重建骨软骨缺损的多功能壳聚糖纳米复合微凝胶

由于缺乏同时再生软骨和软骨下骨的令人满意的策略，骨软骨（OC）缺陷的治疗在临床上仍然是一个巨大的挑战。在此，我们提出了一种有效的自下而上的策略，开发一种基于多功能壳聚糖的纳米复合微凝胶作为修复OC缺陷的构建块。该微凝胶具有生物相容性、可生物降解性，并具有分层纳米纤维结构，模仿细胞外基质（ECM）的结构特征，以促进细胞附着和增殖。此外，微凝胶中掺入β-磷酸三钙（β-TCP）纳米颗粒不仅可以促进骨髓间充质干细胞（BMSC）的成骨分化，而且还可以促进转化生长因子β1（TGF-β1）的负载）。为了重建OC缺损，将纯微凝胶植入大鼠膝关节OC缺损的底层以促进成骨，而负载TGF-β1的微凝胶则植入OC缺损的顶层以促进软骨再生。这种模块化微凝胶系统可实现 OC 缺损中软骨和软骨下骨的同步再生，这有望成为组织工程领域修复其他复杂组织缺损的一种有前景的方法。