Cai Zhengwei, Saiding Qimanguli, Cheng Liang, Zhang Liucheng, Wang Zhen, Wang Fei, Chen Xinliang, Chen Gang, Deng Lianfu, Cui Wenguo
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China.
Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, 1518 North Huancheng Road, Jiaxing, 314000, China.
Bioact Mater. 2021 May 11;6(12):4506-4516. doi: 10.1016/j.bioactmat.2021.04.039. eCollection 2021 Dec.
Soft tissue remodeling is a sophisticated process that sequentially provides dynamic biological signals to guide cell behavior. However, capturing these signals within hydrogel and directing over time has still been unrealized owing to the poor comprehension of physiological processes. Here, a bio-mimicking hydrogel is designed via thiol-ene click reaction to capture the early physical signal triggered by inflammation, and the chemical signals provided with chemokine and natural adhesion sites, which guaranteed the precise soft tissue remodeling. This bio-mimicking hydrogel efficiently facilitated cell anchoring, migration, and invasion in the 3D matrix due to the permissive space and the interaction with integrin receptors. Besides, the covalently grafted chemokine-like peptide is optimal for colonization and functional differentiation of endothelial cells through a HIF-1α dependent signal pathway. Furthermore, the early polarization of macrophages, collagen deposition and angiogenesis in rat acute wound model, and the increased blood perfusion in mouse skin flap model have confirmed that the bio-mimicking hydrogel realized precise soft tissue remodeling and opens new avenues for the phased repair of different tissues such as nerve, myocardium, and even bone.
软组织重塑是一个复杂的过程,它依次提供动态生物信号以指导细胞行为。然而,由于对生理过程的理解不足,在水凝胶中捕获这些信号并随时间进行引导仍未实现。在此,通过硫醇-烯点击反应设计了一种仿生水凝胶,以捕获由炎症触发的早期物理信号,以及由趋化因子和天然粘附位点提供的化学信号,这保证了精确的软组织重塑。由于宽松的空间以及与整合素受体的相互作用,这种仿生水凝胶有效地促进了细胞在三维基质中的锚定、迁移和侵袭。此外,通过HIF-1α依赖性信号通路,共价接枝的趋化因子样肽对于内皮细胞的定植和功能分化是最佳的。此外,大鼠急性伤口模型中巨噬细胞的早期极化、胶原沉积和血管生成,以及小鼠皮瓣模型中血液灌注的增加,均证实了这种仿生水凝胶实现了精确的软组织重塑,并为神经、心肌甚至骨骼等不同组织的阶段性修复开辟了新途径。