Release of basic fibroblast growth factor from a crosslinked glycosaminoglycan hydrogel promotes wound healing.
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.
Liu
Yanchun
Y
Department of Medicinal Chemistry, The University of Utah, Salt Lake City, UT 84108, USA.
Cai
Shenshen
S
Shu
Xiao Zheng
XZ
Shelby
Jane
J
Prestwich
Glenn D
GD
D000818:Animals; D001672:Biocompatible Materials; D002809:Chondroitin Sulfates / Q000737:chemistry; D003432:Cross-Linking Reagents; D020405:Dermis / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D004817:Epidermis / Q000502:physiology; D005109:Extracellular Matrix; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006493:Heparin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D051379:Mice; D008815:Mice, Inbred Strains; D014945:Wound Healing / Q000502:physiology*
D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006493:Heparin; D002809:Chondroitin Sulfates