Release of basic fibroblast growth factor from a crosslinked glycosaminoglycan hydrogel promotes wound healing

Abstract

We describe synthetic extracellular matrix (sECM) hydrogel films composed of co‐crosslinked thiolated derivatives of chondroitin 6‐sulfate (CS) and heparin (HP) for controlled‐release delivery of basic fibroblast growth factor (bFGF) to full‐thickness wounds in genetically diabetic (db/db) mice. In this model for chronic wound repair, full‐thickness wounds were treated with CS, CS‐bFGF, or CS‐HP‐bFGF films. At 2 and 4 weeks postinjury, wound closure and formation of the new epidermis and dermis were determined. Both CS and CS‐HP hydrogel films accelerated wound repair, even without bFGF. Addition of bFGF to CS films showed partial dose‐dependent acceleration of wound repair. Importantly, addition of bFGF to co‐crosslinked CS‐HP sECM films showed a dramatic bFGF dose‐dependent acceleration of wound healing, as well as improved dermis formation and vascularization. Compared with 27% wound closure in 2 weeks in the controls, 89% wound closure was observed for mice treated with the CS‐HP‐bFGF films. The synthetic CS‐HP sECM films mimic the chemistry and biology of heparan sulfate proteoglycans, and may have clinical potential for topical delivery of growth factors to patients with compromised wound healing.