Impaired wound healing increases the risks of infection and the development of chronic wounds, which can lead to significant morbidity and decreased quality of life, as well as increased healthcare costs. For people with additional risk factors for chronic wounds, such as aging, diabetes, and obesity, the failure of a wound to heal properly can be especially dangerous and may lead to amputation and even death. Current therapeutic approaches for wound healing are often inadequate because they do not address the underlying causes of impaired healing. If a wound is not healing properly because of poor blood flow, simply applying a bandage or topical antibiotic will not solve the problem. Regenerative medicine strategies, such as the use of stem cells, growth factors, and scaffolds, have the potential to revolutionize the treatment of acute and chronic wounds by promoting the body's natural healing processes and improving tissue regeneration. Angiogenesis, the formation of new blood vessels, is essential for tissue repair and regeneration. Acute inflammation plays a crucial role in the initial stages of wound healing, however chronic inflammation can impede wound healing. Therefore, it is crucial to develop therapies that can modulate these processes in a precise and controlled manner to promote optimal wound healing. However, the complexity of the interactions between cells, matrix, and microenvironment during wound healing hampers the development of effective biomaterials for wound repair. Experiments proposed here will investigate VEGFR signaling in engineered models of wound healing. Specific Aim 1 will use a novel engineered biopolymer to dissect the role of VEGFR1, a poorly understood growth factor receptor in both endothelial cells, which contribute to blood vessel formation, and macrophages, which are involved in tissue repair and inflammation. Specific Aim 2 will examine the biochemical events that contribute to cell-cell crosstalk between endothelial cells and macrophages. Embedded in both aims is demonstration of the potential of elastin-like polymers to be a supportive and instructive biomaterial for tissue engineering and regenerative medicine. This proposal uses the powerful dual approach of biomaterials development and characterization as both an end goal for clinical translation and a biotechnological tool for unraveling the intricacies of cell signaling events.