Scar formation and improper wound healing has a considerable impact on the health and wellbeing of many people. In this project, we want to improve wound healing by modulating angiogenesis, which is the formation of new blood vessels. Angiogenesis plays an important role in wound healing, but too much angiogenesis can cause hypertrophic scar and keloid formation. We believe that an angiogenesis modulating treatment will prevent excessive angiogenesis. Importantly, this treatment should not completely block angiogenesis, but moderate the angiogenic response. TIE2 expressing macrophages (TEMs) may form ideal targets for such a treatment, as these macrophages are involved in all steps of the angiogenic cascade, from initial angiogenesis to vascular maturation. To investigate the potential of TEMs to normalize angiogenesis, we will investigate how different subpopulations of TEMs are important in each of the specific steps during the angiogenic cascade. Next, we will investigate if the balance of the TIE2 ligands, angiopoietin-1 and angiopoietin-2 affects the impact of TEMs on angiogenesis. These studies will be performed using the chick chorioallantoic membrane model of angiogenesis and we will use a macrophage specific TIE-knockdown model in mice to validate our findings. Finally, we will investigate whether TEMs are also important in exuberant granulation tissue in equine
wounds, which is a promising model for chronic wound healing in humans.