1516 Genetic mouse models and a new pro-lymphangiogenic treatment approach reveal beneficial effects of lymphatic vessel activation in cutaneous wound healing

Chronic wounds represent a major medical challenge. While the essential role of blood vessel growth and function in wound healing has been thoroughly studied, lymphatic vessels remained unclear. Full-thickness excisional were made wildtype mice, transgenic mice with an increased number cutaneous (K14-VEGF-C expressing lymphangiogenic factor VEGF-C skin), that lack skin (K14-sVEGFR3 soluble form VEGF receptor 3 is expressed on endothelium). Also, was studied diabetic (db/db) treated i.v. newly developed recombinant F8-VEGF-C fusion protein, targeting protein specifically to via binding EDA fibronectin splice variant which upregulated wounded skin, or control (F8-SIP). In lymphangiogenesis first detected at edge within granulation tissue between 7- 10-days post-wounding. This significantly K14-VEGF-C mice. contrast, completely absent K14-sVEGFR3 associated delayed closure expression inflammatory markers, as evaluated by immunofluorescence RNAseq. Similarly, systemic treatment VEGFR3 blocking antibody prevented lymphangiogenesis. db/dbmice, enabled targeted delivery wounds, resulting enhanced lymphangiogenesis, accelerated re-epithelialization, reduction inflammation, increase myofibroblast density collagen type I deposition. These results indicate activation improves quality suggesting potential new strategy promote chronic wounds.