Engineering Silk Fibroin-Based Biomaterials for Neural Repair

Neurological injuries remain a major clinical challenge due to the limited regenerative capacity of neural tissue, the persistence of inhibitory post-injury microenvironments, and the lack of biomaterials capable of simultaneously providing structural support and biological instruction. Growing evidence highlights that biomaterial-mediated modulation of the neural microenvironment is essential for effective neural regeneration and functional recovery. Silk fibroin (SF), a naturally derived protein biomaterial, has attracted growing interest in neural repair owing to its tunable mechanical properties, controllable degradation, structural anisotropy, and versatile modification potential. Beyond serving as passive scaffolds, SF-based biomaterials actively regulate axonal guidance, neural and glial cell behavior, and neuroinflammatory responses. This review systematically summarizes the physicochemical properties and modification strategies of SF, elucidates the underlying mechanisms by which SF-based materials promote neural repair, and discusses diverse SF-based material formats, including hydrogels, scaffolds, patches, nanofibers, and nerve conduits. Representative applications in peripheral nerve injury and central nervous system disorders, such as spinal cord injury, traumatic brain injury, cerebral palsy, ischemic stroke, and Parkinson's disease, are highlighted. Finally, current challenges and future perspectives of SF-based neural biomaterials are discussed, with an emphasis on guiding the rational design and clinical translation of next-generation neural repair strategies.