Xu Yun, Shi Guodong, Tang Jincheng, Cheng Ruoyu, Shen Xiaofeng, Gu Yong, Wu Liang, Xi Kun, Zhao Yihong, Cui Wenguo, Chen Liang
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 708 Renmin Road, Suzhou, Jiangsu 215006, P.R. China.
Departments of Pain Rehabilitation and Orthopaedic Surgery, Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Shanghai 201500, P.R. China.
Sci Adv. 2020 Nov 25;6(48). doi: 10.1126/sciadv.abc2036. Print 2020 Nov.
Current homogeneous bioscaffolds could hardly recapture the regenerative microenvironment of extracellular matrix. Inspired by the peculiar nature of dura matter, we developed an extracellular matrix-mimicking scaffold with biomimetic heterogeneous features so as to fit the multiple needs in dura mater repairing. The inner surface endowed with anisotropic topology and optimized chemical cues could orchestrate the elongation and bipolarization of fibroblasts and preserve the quiescent phenotype of fibroblasts indicated by down-regulated α-smooth muscle actin expression. The outer surface could suppress the fibrotic activity of myofibroblasts via increased microfiber density. Furthermore, integrin β1 and Yes-associated protein molecule signaling activities triggered by topological and chemical cues were verified, providing evidence for a potential mechanism. The capability of the scaffold in simultaneously promoting dura regeneration and inhibiting epidural fibrosis was further verified in a rabbit laminectomy model. Hence, the so-produced heterogeneous fibrous scaffold could reproduce the microstructure and function of natural dura.
目前的均质生物支架很难重现细胞外基质的再生微环境。受硬脑膜特殊性质的启发，我们开发了一种具有仿生异质性特征的细胞外基质模拟支架，以满足硬脑膜修复中的多种需求。具有各向异性拓扑结构和优化化学信号的内表面可以协调成纤维细胞的伸长和双极化，并通过下调α-平滑肌肌动蛋白表达来维持成纤维细胞的静止表型。外表面可以通过增加微纤维密度来抑制肌成纤维细胞的纤维化活性。此外，还验证了由拓扑和化学信号触发的整合素β1和Yes相关蛋白分子信号活性，为潜在机制提供了证据。在兔椎板切除模型中进一步验证了该支架同时促进硬脑膜再生和抑制硬膜外纤维化的能力。因此，所制备的异质纤维支架可以重现天然硬脑膜的微观结构和功能。
