Articular cartilage (AC) injury repair has always been a difficult problem for clinicians and researchers. Recently, a promising therapy based on mesenchymal stem cells (MSCs) has been developed for the regeneration of cartilage defects. As endogenous articular stem cells, synovial MSCs (SMSCs) possess strong chondrogenic differentiation ability and articular specificity. In this study, a cartilage regenerative system was developed based on a chitosan (CS) hydrogel/3D-printed poly(ε‐caprolactone) (PCL) hybrid containing SMSCs and recruiting tetrahedral framework nucleic acid (TFNA) injected into the articular cavity. TFNA, which is a promising DNA nanomaterial for improving the regenerative microenvironment, could be taken up into SMSCs and promoted the proliferation and chondrogenic differentiation of SMSCs. CS, as a cationic polysaccharide, can bind to DNA through electrostatic action and recruit free TFNA after articular cavity injection in vivo. The 3D-printed PCL scaffold provided basic mechanical support, and TFNA provided a good microenvironment for the proliferation and chondrogenic differentiation of the delivered SMSCs and promoted cartilage regeneration, thus greatly improving the repair of cartilage defects. In conclusion, this study confirmed that a CS hydrogel/3D-printed PCL hybrid scaffold containing SMSCs could be a promising strategy for cartilage regeneration based on chitosan-directed TFNA recruitment and TFNA-enhanced cell proliferation and chondrogenesis.

关节软骨 (AC) 损伤修复一直是临床医生和研究人员面临的难题。最近，已经开发出一种基于间充质干细胞 (MSCs) 的有前景的疗法，用于软骨缺损的再生。作为内源性关节干细胞，滑膜间充质干细胞（SMSCs）具有很强的成软骨分化能力和关节特异性。在这项研究中，基于壳聚糖 (CS) 水凝胶 / 3D 打印聚 (ε-己内酯) (PCL) 混合体开发了一种软骨再生系统，该混合物含有 SMSCs 并募集注射到关节腔中的四面体框架核酸 (TFNA)。TFNA 是一种用于改善再生微环境的有前途的 DNA 纳米材料，可以被吸收到 SMSCs 中并促进 SMSCs 的增殖和软骨分化。CS，作为一种阳离子多糖，可以通过静电作用与 DNA 结合并在体内关节腔注射后募集游离的 TFNA。3D打印的PCL支架提供了基本的机械支撑，TFNA为输送的SMSCs的增殖和软骨分化提供了良好的微环境，促进了软骨再生，从而大大提高了软骨缺损的修复。总之，这项研究证实，基于壳聚糖导向的 TFNA 募集和 TFNA 增强的细胞增殖和软骨形成，含有 SMSC 的 CS 水凝胶/3D 打印 PCL 混合支架可能是一种很有前景的软骨再生策略。TFNA为递送的SMSCs的增殖和成软骨分化提供了良好的微环境，促进了软骨再生，从而大大改善了软骨缺损的修复。总之，这项研究证实，基于壳聚糖导向的 TFNA 募集和 TFNA 增强的细胞增殖和软骨形成，含有 SMSC 的 CS 水凝胶/3D 打印 PCL 混合支架可能是一种很有前景的软骨再生策略。TFNA为递送的SMSCs的增殖和成软骨分化提供了良好的微环境，促进了软骨再生，从而大大改善了软骨缺损的修复。总之，这项研究证实，基于壳聚糖导向的 TFNA 募集和 TFNA 增强的细胞增殖和软骨形成，含有 SMSC 的 CS 水凝胶/3D 打印 PCL 混合支架可能是一种很有前景的软骨再生策略。