Wang Wanshun, Chen Hu, Xiao Jiacong, Luo Dan, Hou Yonghui, Zhan Jiheng, Hou Yu, Li Xing, Yang Huili, Chen Shudong, Lin Dingkun
The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China.
Department of Orthopedic Surgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong, China.
Mater Today Bio. 2024 Nov 26;29:101369. doi: 10.1016/j.mtbio.2024.101369. eCollection 2024 Dec.
Bone is a richly innervated and vascularized tissue, whereas nerve-vascular network reconstruction was often ignored in biomaterial design, resulting in delayed or incomplete bone healing. Inspired by the bone injury microenvironments, here we report a controllable drug delivery strategy using a pH and reactive oxygen species (ROS) dual-response injectable hydrogel. Based on the dynamic borate ester bond covalent crosslinking, nano-hydroxyapatite (HA) and curculigoside (CCG) are integrated into PVA/TSPBA (PT) to construct a responsive injectable hydrogel (PTHC), which scavenges excessive ROS from the injury microenvironment and responsively releases HA and CCG, providing favorable homeostasis and sustained release drug delivery system for bone repair. Additionally, PTHC hydrogel can alleviate ROS-mediated intracellular oxidative and exhibit multiple biological activities of angiogenesis, neurogenesis, and osteogenesis. Furthermore, it reconstructs the microvascular network, accelerates sensory nerve repair, secretes neurotransmitters and bioactive factors, and improves neuro-vascularized bone regeneration. This multi-bioactive injectable hydrogel system offers a promising advance in therapeutic materials for bone repair.
骨是一种神经和血管丰富的组织，然而在生物材料设计中，神经血管网络重建常常被忽视，导致骨愈合延迟或不完全。受骨损伤微环境的启发，在此我们报道一种使用pH和活性氧（ROS）双响应可注射水凝胶的可控药物递送策略。基于动态硼酸酯键共价交联，将纳米羟基磷灰石（HA）和仙茅苷（CCG）整合到聚乙烯醇/三（4-磺酸钠苯基）硼酸酯（PT）中，构建一种响应性可注射水凝胶（PTHC），其可清除损伤微环境中的过量ROS，并响应性释放HA和CCG，为骨修复提供有利的内环境稳定和持续释放的药物递送系统。此外，PTHC水凝胶可减轻ROS介导的细胞内氧化，并表现出血管生成、神经发生和成骨的多种生物学活性。此外，它可重建微血管网络，加速感觉神经修复，分泌神经递质和生物活性因子，并改善神经血管化骨再生。这种具有多种生物活性的可注射水凝胶系统为骨修复治疗材料提供了有前景的进展。
