A biomimetic hierarchical small intestinal submucosa-chitosan sponge/chitosan hydrogel scaffold with a micro/nano structure for dural repair.

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.