ABSTRACT
Impaired wound healing remains an important clinical problem. Treatment with systemic Adriamycin (doxorubicin) is known to impair wound healing in patients, and it has been used to produce animal models of impaired healing. The results of previous studies have shown that local treatment of incisions in normal rats with transforming growth factor beta (TGF-beta) or epidermal growth factor (EGF) stimulated early increases in tensile strength of surgical incisions in normal rats. We investigated the effects of locally applied, biosynthetic TGF-beta or EGF on the tensile strength of standardized incisions in rats treated with Adriamycin. Systemic Adriamycin treatment (8 milligrams per kilogram) produced significant decreases in wound tear strength (WTS) and wound tear energy (WTE) when compared with that of normal rats at seven and ten days (p less than 0.01). A single dose of TGF-beta (2 micrograms) in a collagen vehicle stimulated a reversal of this wound healing impairment at ten days (p less than 0.05), returning the WTS and WTE to near normal levels. A single dose of EGF (50 micrograms) in hyaluronic acid failed to increase tensile strength, probably because of formulation of EGF in a vehicle that does not prolong its release in incisions. These results suggest that exogenous growth factors may be clinically useful in stimulating healing in incisions in healing impaired conditions.
Subject(s)
Doxorubicin/pharmacology , Transforming Growth Factors/pharmacology , Wound Healing/drug effects , Animals , Epidermal Growth Factor/pharmacology , Male , Premedication , Rats , Rats, Inbred Strains , Surgical Wound Dehiscence/prevention & control , Tensile Strength/drug effectsABSTRACT
The ability of surgeons to accelerate wound healing through pharmacologic intervention is limited. The effects of locally applied, biosynthetic human epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) on tensile strength of experimental incisions were investigated. A single dose of EGF in saline failed to increase tensile strength over controls. Thus, EGF was incorporated into multilamellar liposomes, which prolonged the exposure of incisions to EGF (p less than 0.001). A single dose of EGF in multilamellar liposomes produced a 200% increase in wound tensile strength over controls between 7 and 14 days (p less than 0.05). Light and electron microscopy of the wounds revealed increased collagen formation and fibroblast proliferation. A single dose of TGB-beta in a collagen vehicle stimulated a 51% increase in wound tensile strength at 9 days (p less than 0.01). We conclude that addition of EGF and TGF-beta in appropriate vehicles stimulates early transient increases in wound tensile strength in normal rats.
