049 Lactate Controls Vascular Development in Wound Healing

INTRODUCTION: High concentrations of lactate approx. 10 mM are characteristic of wound healing. We have previously shown that lactate instigates release of VEGF from macrophages and endothelial cells. Our present study uses an in vivo murine Matrigel model to study how lactate enhances vascular development and repair. METHODS: Matrigel is a reconstituted basement membrane complex, a liquid at 4 degree C. When injected subcutaneously, it reconstitutes as a gel. 30 mgs of finely divided polylactate polymer (DL-lactide-co-glycolide) was mixed with 1cc of Matrigel, and 2 injections were made into the dorsum of each of 60 (average 7/group), 6-month-old Swiss Webster mice. The gel implants were harvested at 3, 6, 9, 11 and 16 days post injection, and were fixed in buffered formalin or frozen. Cell migration and vascular development were assessed using H&E, anti-CD31 and anti-MAC3 antibody stainings for leukocytes, fibroblasts, endothelial cells, and macrophages. Cells and vessels were quantified microscopically. RESULTS: Control implants (without polylactate) developed little or no inflammation or angiogenesis. Polylactated implants developed highly significant number of endothelial cells and recognizable vessels at 6 and 9 days. At 11 and 16 days, sizeable vessels with surrounding connective tissue were found. Though a moderate inflammation occurred in the lactate groups, no foreign body reaction was seen. Larger implants of high molecular weight instigated little inflammation and few vessels. CONCLUSION: Slowly released lactate leads to the formation of new vessels. Our results provide support for further clinical applications of lactate polymer in wounds. NIH/NIGMS Trauma Training Grant