Natural proteins-derived asymmetric porous conduit for peripheral nerve regeneration

Abstract

Artificial nerve guidance conduits (NGCs) have been developed by using various biomaterials for bridging relatively long nerve defects. Though integrating neurotrophic factors with these NGCs could improve the nerve repair effects, their uncontrolled degradation and roundly random administration still restrict complete nerve regeneration. Herein, a novel silk fibroin (SF)-derived NGC with internal-facing inverse opal structures is presented, achieving the local neurotrophic factor delivery and effective nerve regeneration. The resultant NGC is confirmed with excellent biocompatibility and suitable biodegradability, as well as satisfactory mechanical performance to bridge nerve defects. Significantly, benefiting from an asymmetric structure with inverse opal porous nanostructures inside walls and hybrid hydrogel outside walls, such NGC can spatially restrict the distribution of loading factors, thus enhancing the curative efficacy. By implanting in a sciatic nerve injury rat model with a long segment defect, it is demonstrated that the drug-loaded conduit presented a similar performance to autograft, which can facilitate axons growth and remyelination, thereby promoting nerve regeneration. These results indicate a great potential of such a novel design for peripheral nerve repair applications.