Tang Guoke, Zhu Liang, Wang Weiheng, Zuo Dongqing, Shi Changgui, Yu Xiaojie, Chen Rui
Department of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai, China.
Department of Orthopedics, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
Front Chem. 2022 Aug 17;10:977419. doi: 10.3389/fchem.2022.977419. eCollection 2022.
Development of artificial bone substitutes mimicking the extracellular matrix is a promising strategy for bone repair and regeneration. In views of the actual requirement of biomechanics, biodegradability, and bioactivity, herein, a double-network (DN) hydrogel was constructed by interspersing a methacrylated gelatin (GelMA) network into alendronate (ALN)-modified oxidized alginate (OSA) network via Schiff base reaction and photo-crosslinking process to promote bone regeneration. This GelMA@OSA-ALN DN hydrogel possessed favorable network and pores, good biocompatibility, and enhanced biomechanics. Notably, the introduction of Schiff base furnished the ND hydrogel scaffold with pH-responsive biodegradation and sustained ALN drug release delivery, which could provide effective bioactivity, upregulate osteogenesis-related genes, and promote the cell viability, growth, proliferation, and osteogenesis differentiation for bone regeneration. Therefore, we provide a new insight to develop functional DN hydrogel scaffold toward governing the on-demand drug release and achieving the stem cell therapy, which will be developed into the minimally invasive gelling system to prolong local delivery of bisphosphonates for the bone-related diseases.
开发模仿细胞外基质的人工骨替代物是一种很有前景的骨修复和再生策略。鉴于生物力学、生物可降解性和生物活性的实际需求，在此，通过席夫碱反应和光交联过程，将甲基丙烯酸化明胶（GelMA）网络穿插到阿仑膦酸盐（ALN）修饰的氧化海藻酸盐（OSA）网络中，构建了一种双网络（DN）水凝胶，以促进骨再生。这种GelMA@OSA-ALN DN水凝胶具有良好的网络和孔隙、良好的生物相容性以及增强的生物力学性能。值得注意的是，席夫碱的引入为ND水凝胶支架提供了pH响应性生物降解和持续的ALN药物释放递送，这可以提供有效的生物活性，上调成骨相关基因，并促进细胞活力、生长、增殖和成骨分化以实现骨再生。因此，我们为开发功能性DN水凝胶支架以控制按需药物释放和实现干细胞治疗提供了新的见解，该支架将被开发成微创凝胶系统，以延长双膦酸盐在骨相关疾病中的局部递送。
