Acidic fibroblast growth factor accelerates dermal wound healing in diabetic mice.
Acidic fibroblast growth factor (aFGF) is a potent mitogenic and chemotactic agent for vascular endothelial cells, dermal fibroblasts, and epidermal keratinocytes, the principal cellular constituents of skin. To explore its potential to heal chronic dermal wounds, we applied pure recombinant human aFGF topically to full-thickness excisional injuries in healing-impaired genetically diabetic mice. Transformation of the nonlinear percent initial wound areas as a function of time to linear rates of tissue ingrowth from the original wound edges showed that aFGF increased wound closure in a dose-dependent manner. Optimal 3-micrograms/cm2 doses of aFGF nearly tripled the linear rate of healing. The median time to complete closure decreased from 46 d in vehicle-treated wounds to only 16 d in those treated with aFGF. Histomorphometric analyses established that aFGF increased granulation tissue formation and reepithelialization throughout healing. Vehicle- and aFGF-treated wounds appeared to be histologically equivalent by the time of closure. Therefore, aFGF has potential therapeutic applications for promoting healing of dermal ulcers, especially in healing-impaired individuals.
Mellin
T N
TN
Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey, USA.
Cashen
D E
DE
Ronan
J J
JJ
Murphy
B S
BS
DiSalvo
J
J
Thomas
K A
KA
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000378:metabolism; D013268:Stimulation, Chemical; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000188:drug therapy / Q000473:pathology
D011994:Recombinant Proteins; D016220:Fibroblast Growth Factor 1; D004247:DNA