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新捕获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特征的细胞外基质模拟支架，以满足硬脑膜修复的多种需求。具有各向异性拓扑结构和优化的化学信号的内表面可以协调成纤维细胞的伸长和双极化，并保持由下调的 α-平滑肌肌动蛋白表达所指示的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，验证了拓扑和化学线索触发的整合素β1和Yes相关蛋白分子信号传导活动，为潜在机制提供证据。在兔椎板切除模型中进一步验证了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，如此生产的异质纤维支架可以再现天然硬脑膜的微观结构和功能。