Lu Wei, Zeng Min, Liu Wenbin, Ma Tianliang, Fan Xiaolei, Li Hui, Wang Yinan, Wang Haoyi, Hu Yihe, Xie Jie
Department of Orthopedic Surgery, National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Changsha, China.
Mater Today Bio. 2023 Feb 1;19:100569. doi: 10.1016/j.mtbio.2023.100569. eCollection 2023 Apr.
The key to critical bone regeneration in tissue engineering relies on an ideal bio-scaffold coated with a controlled release of growth factors. Gelatin methacrylate (GelMA) and Hyaluronic acid methacrylate (HAMA) have been a novel topic of interest in bone regeneration while introducing appropriate nano-hydroxyapatite (nHAP) to improve its mechanical properties. And the exosomes derived from human urine-derived stem cells (human EXOs) have also been reported to promote osteogenesis in tissue engineering. The present study aimed to design a new GelMA-HAMA/nHAP composite hydrogel as a drug delivery system. The EXOs were encapsulated and slow-released in the hydrogel for better osteogenesis. The characterization of the GelMA-based hydrogel showed excellent controlled release performance and appropriate mechanical properties. The in vitro studies showed that the EXOs/GelMA-HAMA/nHAP composite hydrogel could promote the osteogenesis of bone marrow mesenchymal stem cells (BMSCs) and the angiogenesis of endothelial progenitor cells (EPCs), respectively. Meanwhile, the in vivo results confirmed that this composite hydrogel could significantly promote the defect repair of cranial bone in the rat model. In addition, we also found that EXOs/GelMA-HAMA/nHAP composite hydrogel can promote the formation of H-type vessels in the bone regeneration area, enhancing the therapeutic effect. In conclusion, our findings suggested that this controllable and biocompatible EXOs/GelMA-HAMA/nHAP composite hydrogel may effectively promote bone regeneration by coupling osteogenesis and angiogenesis.
组织工程中关键骨再生的关键在于一种理想的生物支架，该支架涂覆有可控释放的生长因子。甲基丙烯酸明胶（GelMA）和甲基丙烯酸透明质酸（HAMA）在骨再生领域一直是一个新的研究热点，同时引入适当的纳米羟基磷灰石（nHAP）以改善其力学性能。此外，据报道，源自人尿源干细胞的外泌体（人EXOs）在组织工程中也能促进骨生成。本研究旨在设计一种新型的GelMA-HAMA/nHAP复合水凝胶作为药物递送系统。将EXOs包裹在水凝胶中并缓慢释放，以更好地促进骨生成。基于GelMA的水凝胶的表征显示出优异的控释性能和适当的力学性能。体外研究表明，EXOs/GelMA-HAMA/nHAP复合水凝胶可分别促进骨髓间充质干细胞（BMSCs）的骨生成和内皮祖细胞（EPCs）的血管生成。同时，体内结果证实，这种复合水凝胶可显著促进大鼠模型颅骨缺损的修复。此外，我们还发现EXOs/GelMA-HAMA/nHAP复合水凝胶可促进骨再生区域H型血管的形成，增强治疗效果。总之，我们的研究结果表明，这种可控且生物相容的EXOs/GelMA-HAMA/nHAP复合水凝胶可能通过耦合骨生成和血管生成有效地促进骨再生。
