Shuaiwu Chen, Yuqi Cao, Yuanbo Wang, Chenggang Liu
Nerve injuries pose a significant clinical challenge in both the central and peripheral nervous systems, which often lead to permanent functional deficits. Nerve tissue engineering offers a promising path forward, and gelatin methacryloyl (GelMA) hydrogels have emerged as a powerful and versatile platform in this endeavor. Derived from natural collagen, GelMA possesses inherent biocompatibility and cell-adhesive properties, while its photocrosslinkable nature allows for the precise tuning of its mechanical stiffness, degradation rate, and porous architecture to recapitulate the native neural microenvironment. This review comprehensively elucidates the evolution of GelMA from a passive physical support to an active and instructive biomaterial. We explore a wide array of functionalization strategies, including the incorporation of therapeutic cells, the sustained delivery of neurotrophic factors, and the integration of conductive materials to guide regeneration. Furthermore, we discuss the development of advanced stimuli-responsive systems and the application of 3D bioprinting to fabricate anatomically complex nerve guidance conduits. Ultimately, this work establishes GelMA as a pivotal technology for developing the next generation of intelligent and clinically translatable strategies for nerve repair.Impact StatementThis review highlights the transformative potential of gelatin methacryloyl (GelMA) hydrogels in nerve tissue engineering. By comprehensively analyzing advanced functionalization strategies and "smart" stimuli-responsive systems that adapt to pathological microenvironments, this work underscores the capacity of GelMA to overcome critical barriers in neural repair. We detail how these versatile scaffolds can be engineered for precise drug delivery, electrical conductivity, and gene editing. These insights provide a roadmap for developing next-generation, autonomous biomaterials, paving the way for personalized clinical solutions that significantly enhance functional recovery in patients with severe neuronal injuries.