Recent Advances in Dynamic Schiff Base Hydrogels for Advanced Skin Regeneration

Abstract

Severe dermal injuries present significant clinical challenges due to delayed healing, infection, and fibrotic scarring. While hydrogels provide three-dimensional matrices that mimic the extracellular matrix (ECM), conventional statically crosslinked systems fail to replicate the dynamic viscoelasticity of native tissue. Schiff base hydrogels, crosslinked via reversible covalent imine bonds, address this limitation by exhibiting stress relaxation, shear-thinning injectability, and autonomous self-healing under physiological conditions. At the cellular level, these dynamic biophysical properties modulate integrin-mediated focal adhesion dynamics and YAP/TAZ nuclear translocation, directing stem cell spreading, migration, and lineage specification. In vivo studies demonstrate that Schiff base matrices enhance cell retention within the wound bed, promote re-epithelialization, and drive CD31/CD34-mediated neovascularization in chronic and ischemic wound models. Furthermore, tuning the hydrolysis kinetics of the dynamic imine linkages synchronizes matrix degradation with endogenous tissue ingrowth, facilitating organized collagen deposition and functional tissue restoration. Integrating dynamic covalent networks with bioactive signaling molecules provides a robust strategy for advanced skin regeneration.