The dura mater is an essential barrier to protect the brain tissue and the dural defects caused by accidents can lead to serious complications. Various materials have been applied to dural repair, but it remains a challenge to perfectly match the structure and properties of the natural dura mater. Small intestinal submucosa has been developed for dural repair because of its excellent biocompatibility and biological activity, but its application is tremendously limited by the rapid degradation rate. Chitosan has also been broadly investigated in tissue repair, but the traditional chitosan hydrogels exhibit poor mechanical properties. A nanofiber chitosan hydrogel can be constructed based on an alkaline solvent, which is equipped with surprisingly high strength. Therefore, based on the bilayer structure of the natural dura mater, a biomimetic hierarchical small intestinal submucosa–chitosan sponge/chitosan hydrogel scaffold with a micro/nano structure was fabricated, which possessed a microporous structure in the upper sponge and a nanofiber structure in the lower hydrogel. The degradation rate was remarkably reduced compared with that of the small intestinal submucosa in the enzymatic degradation experiment in vitro. Meanwhile, the chitosan nanofibers brought high mechanical strength to the bilayer scaffold. Moreover, the hierarchical micro/nano structure and the active factors in the small intestinal submucosa have a fantastic effect on promoting the proliferation of fibroblasts and vascular endothelial cells. The bilayer scaffold showed good histocompatibility in the experiment of in vitro subcutaneous implantation in rats. Thus, the biomimetic hierarchical small intestinal submucosa–chitosan sponge/chitosan hydrogel scaffold with micro/nano structure simulates the structure of the natural dura mater and possesses properties with excellent performance, which has high practical value for dural repair.

中文翻译：

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用于硬脑膜修复的具有微/纳米结构的仿生分层小肠黏膜下层-壳聚糖海绵/壳聚糖水凝胶支架

硬脑膜是保护脑组织的重要屏障，意外造成的硬脑膜缺损会导致严重的并发症。各种材料已应用于硬脑膜修复，但完美匹配天然硬脑膜的结构和特性仍然是一项挑战。小肠黏膜下层因其优异的生物相容性和生物活性而被开发用于硬脑膜修复，但其应用受到快速降解速度的极大限制。壳聚糖在组织修复中也得到了广泛的研究，但传统的壳聚糖水凝胶表现出较差的机械性能。可以基于碱性溶剂构建纳米纤维壳聚糖水凝胶，其具有惊人的高强度。因此，基于天然硬脑膜的双层结构，制备了具有微/纳米结构的仿生分层小肠粘膜下层-壳聚糖海绵/壳聚糖水凝胶支架，其在上部海绵中具有微孔结构，在下部水凝胶中具有纳米纤维结构。酶促降解实验与小肠黏膜下层相比降解率明显降低体外。同时，壳聚糖纳米纤维为双层支架带来了高机械强度。此外，小肠黏膜下层的分层微/纳米结构和活性因子对促进成纤维细胞和血管内皮细胞的增殖具有极好的作用。该双层支架在大鼠体外皮下植入实验中表现出良好的组织相容性。因此，具有微/纳米结构的仿生分层小肠粘膜下层-壳聚糖海绵/壳聚糖水凝胶支架模拟了天然硬脑膜的结构，具有优异的性能，对硬脑膜修复具有很高的实用价值。