Fibronectin functional domains coupled to hyaluronan stimulate adult human dermal fibroblast responses critical for wound healing.
Fibronectin (FN) facilitates dermal fibroblast migration during normal wound healing. Proteolytic degradation of FN in chronic wounds hampers healing. Previously, three FN functional domains (FNfd) have been shown to be sufficient for optimal adult human dermal fibroblast migration. Here we report the development of an acellular hydrogel matrix comprised of the FNfds coupled to a hyaluronan (HA) backbone to stimulate wound repair. Employing Michael-type addition, the cysteine- tagged FNfds were first coupled to a homobifunctional PEG derivative. Thereafter, these PEG derivative FNfd solutions, containing bifunctional PEG-derivative crosslinker were coupled to thiol-modified HA (HA-DTPH) to obtain a crosslinked hydrogel matrix. When evaluated in vitro, these acellular hydrogels were completely cytocompatible. While spreading and proliferation of adult human dermal fibroblasts plateaued at higher FNfd bulk densities, their rapid and robust migration followed a typical bell-shaped response. When implanted in porcine cutaneous wounds, these acellular matrices, besides being completely biocompatible, induced rapid and en masse recruitment of stromal fibroblasts that was not observed with RGD-tethered or unmodified hydrogels. Such constructs might be of great benefit in clinical settings where rapid formation of new tissue is needed.
Department of Biomedical Engineering, SUNY at Stony Brook, Stony Brook, New York 11794-8165, USA.
Kaustabh
K
Ghosh
Xiang-Dong
XD
Ren
Xiao Zheng
XZ
Shu
Glenn D
GD
Prestwich
Richard A F
RA
Clark
D000328:Adult; D000818:Animals; D001672:Biocompatible Materials; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005353:Fibronectins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D020100:Hydrogels; D008422:Materials Testing; D015394:Molecular Structure; D011092:Polyethylene Glycols; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000293:injuries; D034421:Sus scrofa; D023822:Tissue Engineering; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D001672:Biocompatible Materials; D005353:Fibronectins; D020100:Hydrogels; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid