Tailoring mechanical properties of hydrogels for wound repair from perspectives of simulating cellular microenvironment

Wound repair remains a major challenge in clinical practice. Wounds are often characterized by abnormal stiffness, altered viscoelasticity, and abnormal tension, which can impair cellular repair functions. While hydrogels are promising candidates due to their biocompatibility and tunable properties, conventional designs often function as passive barriers, lacking the capacity to actively correct the hostile mechanical microenvironment. Consequently, there is a pressing need to develop hydrogels that not only retain their excellent biocompatibility but also actively restore physiological mechanical cues. This review summarizes strategies for regulating the mechanical properties of hydrogels and explores the molecular mechanisms through which mechanical changes in wounds influence the repair process. It further discusses the design principles of various types of mechanically biomimetic hydrogels developed in recent years, along with their therapeutic applications in treating challenging wounds such as deep tissue injuries and diabetic ulcers. Through a systematic analysis of hydrogel mechanical design strategies and their underlying mechanisms, this article aims to offer a comprehensive framework and specific design principles to guide the development of next-generation mechanically biomimetic hydrogels for wound-healing applications.