Hydrogel-based neural engineering for skin wound healing

Neuro-driven skin regeneration represents an emerging paradigm in wound healing that integrates peripheral nerve repair with functional skin restoration. Hydrogels serve as versatile platforms for supporting such dual tissue regeneration, owing to their biocompatibility, tunable physicochemical properties, and ability to mimic the extracellular matrix. Recent advances have enabled the development of multifunctional hydrogels that combine biophysical and biochemical cues-including conductive materials, bioactive molecules, and exosomes-to create healing microenvironments that promote nerve growth, angiogenesis, and tissue repair, particularly in challenging conditions such as diabetic ulcers and chronic wounds. This review examines the molecular mechanisms underlying neural regulation of wound healing, focusing on sensory neuron-derived factors, neuro-immune crosstalk, neurovascular integration, and the emerging role of neurogenic exosomes as central signaling hubs. Furthermore, design principles for hydrogel materials-including natural, synthetic, and composite systems-are explored alongside smart responsive hydrogels that adapt to dynamic wound environments, thereby enabling controlled therapeutic delivery. Current trends integrating wearable bioelectronics, artificial intelligence (AI), and bioengineered scaffolds are discussed in the context of real-time monitoring and personalized therapy. While neurogenic hydrogels show significant promise for clinical translation, their development requires rigorous preclinical validation and well-designed human trials. Beyond skin regeneration, these materials hold potential for nerve repair, bone healing, and cardiac tissue engineering, highlighting their versatility as therapeutic solutions across diverse physiological systems. Future efforts should focus on leveraging AI to optimize hydrogel formulations, advancing stem cell-based therapies, and establishing standardized metrics for treatment efficacy.