The Reversal of an Adriamycin® Induced Healing Impairment with Chemoattractants and Growth Factors

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Abstract
Rats treated with 8 mg/kg Adriamycin intravenously 4 days prior to chamber implantation develop impaired wound healing in a wound chamber model. In this study, the effects on healing of supplemental platelet derived growth factor (PDGF), transforming growth factor-.beta. (TGF-.beta.), epidermal growth factor (EGF), and insulin were evaluated in chambers extracted from Adriamycin-treated rats 10 and 20 days after implantation. The effects of individual factors, combinations of factors, and different concentrations of TGF-.beta. were evaluated. The parameters evaluated included collagen content, protein content, cellular proliferation rate, chamber histology, and collagen types. Supplemental TGF-.beta. alone reversed much of the healing deficit noted. A minimum concentration of 100 ng/ml TGF-.beta. was required to significantly reverse this deficit. PDGF and EGF alone had no effect. Addition of PDGF and TGF-.beta. in combination stimulated a significantly higher level of collagen deposit than TGF-.beta. alone. Addition of EGF in combination with PDGF and TGF-.beta. restored collagen deposition to 86% of normal. No synergism was seen between TGF-.beta. and EGF unless PDGF was also present. These data suggest that growth factors contained in platelets may play key roles in initiating the wound healing response and may have clinical utility in healing deficit states.