Carboxymethyl chitosan microspheres structurally reinforce silk fibroin hydrogels for integrated aesthetic and functional soft tissue repair

Achieving concurrent aesthetic volume contouring and physiological healing remains a major hurdle in soft tissue reconstruction. While conventional hydrogels hold potential for soft tissue reconstruction, their clinical application is limited by insufficient mechanical durability for aesthetic volume contouring and a lack of bioactive signals for physiological healing. We engineered a structurally reinforced hydrogel (SFCC) where zinc crosslinked carboxymethyl chitosan microspheres bind to a thermal induced silk fibroin network, driving the formation of a coarsened fibrillar architecture. The microsphere reinforced fibrillar architecture facilitates the sustained release of zinc ions and endows the SFCC hydrogel with a significantly elevated storage modulus, superior antioxidant capacity, and robust angiogenic properties. In a rabbit intradermal implantation model, SFCC successfully activated dermal hair follicle regeneration, upregulated the expression of CD31 and Ki67, promoted collagen fiber deposition and enhanced cellular proliferation. Notably, SFCC decreased the Col I/Col III ratio by approximately 1.56-fold compared to the silk fibroin hydrogel. In a rat chronic burn model, SFCC accelerated healing by promoting macrophage polarization from the M1 to the M2 and stimulating fibronectin expression to orchestrate dermal epidermal junction reconstruction. The engineered SFCC hydrogel shows immense promise in integrated skin reconstruction, offering considerable potential to advance soft tissue repair therapies.