Tailoring the Wound Microenvironment: Programmable Hydrogel Fibers for Adaptive Tissue Repair

Abstract Wound healing and tissue reconstruction following a skin defect, particularly the restoration of full skin function and appearance, remain a major clinical challenge. Traditional hydrogel dressings face limitations in mechanical strength, poor permeability, and a lack of multifunctionality, making them inadequate for meeting the dynamic demands of the wound healing process. Fibrous hydrogels offer a compelling alternative by combining the high-water content and biocompatibility of hydrogels with the anisotropic structure and design flexibility of fibers, allowing them to closely mimic native tissue architecture. In this review, we introduce a three-tier framework based on structural, functional, and responsive programmability to systematically classify and evaluate programmable hydrogel fibers for wound healing. Recent advances in structural design strategies, functionalization approaches, and biomedical applications are summarized. Notably, this review uniquely integrates structural design, functional strategies, and translational potential within a unified programmability framework, while critically examining current limitations and challenges in clinical translation. Despite these obstacles, hydrogel fibers hold considerable promise for personalized tissue engineering and functional regeneration.