PDGF and FGF reverse the healing impairment in protein-malnourished diabetic mice

Growth factors have been shown to improve healing in impaired models but not after malnutrition. The effects of growth factors on altered tissue repair caused by malnutrition were examined.

Nondiabetic and diabetic mice fed a 1% protein diet received full-thickness skin wounds. Wounds were treated topically with vehicle, platelet-derived growth factor (PDGF, 10 micrograms) or basic fibroblast growth factor (bFGF, 1 microgram), for 5 days.

Malnourished animals developed significantly impaired wound closure. PDGF or bFGF did not enhance closure in nondiabetic C57BL/KsJ-db/m mice, whether fed normal or restricted diets. The same treatment regimen was effective in reversing the delayed wound closure in their genetically diabetic C57BL/KsJ-db/db littermates. 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 21. Protein-depleted diabetic wounds had significantly decreased cellularity and granulation tissue formation. These deficiencies were reversed with growth factor treatment.

Despite the lack of effects in nondiabetic animals, growth factors improve healing in diabetic mice with restricted protein intake. The differential effects may result from different healing mechanisms: nondiabetic animals heal mainly by contraction; diabetic animals require granulation tissue formation and reepithelialization.