Biomimetic hydrogel design for programmable ECM and tissue regeneration.

Abstract

Successful functional tissue regeneration demands biomaterials that can recapitulate the dynamic structural, mechanical, and biochemical properties of native extracellular matrices (ECMs). Conventional biomaterials fall short in this regard. Biomimetic hydrogels serve as a transformative paradigm rather than simple scaffolds, evolving from structural mimics to actively programmable platforms for cell guidance. This review first dissects the design principles for hydrogels to mimic key ECM features, including biochemical composition, spatiotemporal microenvironment, and tunable mechanical properties. It then illustrates how these biologically inspired principles contribute to advanced functions such as strong adhesion, self-healing, adaptive lubrication, and intelligent responsiveness. We further discuss how these integrated properties overcome tissue-specific regeneration challenges in osteochondral defects, nerve injuries, and chronic wounds, establishing a function-driven design framework that links material performance to clinical efficacy. Finally, we propose a development roadmap for next-generation intelligent hydrogels. We highlight the importance of constructing systems with closed-loop feedback to enable dynamic adaptation to the changing microenvironment. The translation of such intelligent systems via scalable fabrication and strict validation represents a critical research direction. This review summarizes recent progress and provides a conceptual framework for developing biomimetic hydrogels into interactive therapeutic agents that synergize with tissue regeneration.