Engineering bioinspired pH-responsive hydrogels for smart wound repair

The growing prevalence of chronic and infected wounds represents a major clinical challenge that conventional passive dressings fail to adequately address. Bioinspired pH-responsive hydrogels have emerged as intelligent biomaterials capable of dynamically interacting with the wound microenvironment. However, the field still faces major translational barriers, with many laboratory prototypes not yet progressing to clinically or commercially established products. Unlike descriptive literature compilations, this review provides a critical analytical evaluation focused on synthesizing fundamental engineering principles and quantitative design considerations that govern smart hydrogel performance. We systematically classify pH trigger mechanisms, discuss model-based relationships among crosslinking density, mesh size, swelling behavior, and release kinetics, and delineate multifunctional synergies. Particular analytical weight is dedicated to the practical constraints of terminal sterilization, large-scale fabrication controls, and regulatory pathways. By defining a hierarchical decision framework and introducing standardized benchmarking metrics, this review aims to bridge the gap between polymer synthesis and clinical reality, offering a design-oriented framework for next-generation regenerative wound dressings.