PDGF AND FGF REVERSE THE HEALING IMPAIRMENT IN PROTEIN-MALNOURISHED DIABETIC MICE

Background. Growth factors have been shown to improve healing in impai red models but not after malnutrition. The effects of growth factors o n altered tissue repair caused by malnutrition were examined. Methods. Nondiabetic and diabetic mice fed a 1 % protein diet received full-th ickness skin wounds. Wounds were treated topically with vehicle, plate let-derived growth factor (PDGF, 10 mug) or basic fibroblast growth fa ctor (bFGF, 1 mug), for 5 days. Results. Malnourished animals develope d significantly impaired wound closure. PDGF or bFGF did not enhance c losure in nondiabetic C57BL/KsJ-db/m mice, whether fed normal or restr icted diets. The same treatment regimen was effective in reversing the delayed wound closure in their genetically diabetic C57BL/KsJ-db/db l ittermates. The growth factors significantly enhanced tissue repair in diabetic mice fed a 1 % protein diet starting as early as day 15 and continuing until day 2 1. Protein-depleted diabetic wounds had signifi cantly decreased cellularity and granulation tissue formation. These d eficiencies were reversed with growth factor treatment. Conclusions. D espite the lack of effects in nondiabetic animals, growth factors impr ove healing in diabetic mice with restricted protein intake. The diffe rential effects may result from different healing mechanisms: nondiabe tic animals heal mainly by contraction; diabetic animals require granu lation tissue formation and reepithelialization.