Targeting the neuro-immune-skin axis: Advanced functional biomaterials for intelligent wound management and regeneration.

Chronic skin wounds and inflammatory skin diseases remain major clinical challenges because conventional dressings cannot dynamically respond to wound microenvironment changes. The emerging neuro-immune-skin axis concept highlights bidirectional communication between peripheral neurons and cutaneous immune cells mediated by neuropeptides, neurotransmitters, and cytokines, offering a new framework for advanced wound management. Unlike previous reviews that focus separately on neuroimmunology or wound biomaterials, this review integrates the two through the neuro-immune-skin axis. We systematically summarize the key molecular and cellular events of this triadic interplay, emphasizing how neural signals (e.g., substance P, CGRP) regulate immune cells and how immune mediators reciprocally affect neural and skin cells, while dissecting feedback loops. We then summarize recent biomaterial advances targeting this axis, including closed-loop regulatory approaches like neuro-immune crosstalk modulation, oxidative stress management, and pathology-triggered drug release, along with their applications in disease models. These materials are shifting from passive coverage to active intervention, steering wound healing toward neuroimmune-coordinated regeneration. Future integration of AI-assisted design, organoid-on-chip platforms, and smart closed-loop dressings may help overcome translational hurdles in biosafety, scalable manufacturing, and standardized evaluation.