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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.