The effect of local hyperglycemia on skin cells in vitro and on wound healing in euglycemic rats

Multiple previous studies have established that high systemic blood glucose concentration impairs skin wound healing. However, the effects of local hyperglycemia on wound healing are not well defined. Comprehensive animal studies and in vitro studies using both fibroblasts and keratinocytes are lacking.Primary keratinocytes and fibroblasts were isolated from discarded human tissue, cultured under different concentrations of glucose, and the effect on cell function was examined. In addition, a rat full-thickness wound model was used to topically treat the wounds with different glucose concentrations and the effect on wound closure and re-epithelialization was investigated over time.The cell viability experiments indicated that both keratinocytes and fibroblasts endure high glucose well and concentrations under 26 mM did not have a remarkable effect on their viability over time. Moderate addition of glucose (10 mM) boosted fibroblast proliferation (6-fold) but did not have an effect on keratinocyte proliferation. In both keratinocytes and fibroblasts, glucose inhibited their migration and already the addition of 5.6-mM glucose had an inhibitory effect. In vivo experiments showed that full-thickness wounds treated with topical glucose had impaired wound closure and lower re-epithelialization rate in comparison to nontreated control wounds. The results also showed that higher glucose concentrations inhibited wound healing more efficiently.In conclusion, our study indicates that high glucose inhibits both keratinocyte and fibroblast migration as well as wound healing in vivo in a concentration dependent manner.