Biomaterial-assisted neuralization strategies for tissue engineering applications

In recent years, a large number of biomaterial-based strategies have been developed for tissue repair and regeneration. Despite these advances, achieving functional recovery of regenerated tissues remains a significant challenge, primarily because of insufficient attention to neuromodulation. This review provides a comprehensive analysis of biomaterial-assisted neuralization approaches aimed at repairing damaged tissues and restoring physiological function. We elucidate the mechanisms underlying neuralized tissue repair through four key aspects: the neural response following tissue injury or lesion, neurogenic inflammation and immune modulation, neurovascular coupling effects, and the effects of neuromodulation on stem cell behavior. Notably, smart-responsive and electroactive biomaterials have facilitated neuralization, thereby improving functional integration. Furthermore, this review highlights novel advances in biomaterial-assisted neuralization strategies for tissue engineering. The discussion is organized around four key perspectives: establishing structural and mechanical foundations conducive to neural regeneration, designing delivery systems for neural modulation, constructing microenvironments for electrophysiological regulation, and developing smart responsive biomaterials that facilitate neuralization. By examining current challenges and future directions, we provide innovative perspectives for the development of next-generation biomaterials to advance regenerative medicine.