E.R.M. Balog
University of New England,
United States
Keywords: VEGF, signaling, cells, wound healing, biomaterials, biopolymer
Summary:
Despite recent innovation in regenerative medicine approaches to support and accelerate cutaneous wound healing, there remains a critical need for improved predictability and reproducibility to achieve full clinical utility. To meet this need, mounting evidence suggests that the next generation of wound-healing therapeutic biomaterials must directly engage the macrophage response to enhance healthy revascularization. In tissue engineering models, the influence of the immune response on angiogenesis remains poorly understood. VEGF homolog VEGF-B and its receptor VEGFR1 are implicated in wound healing, but evidence for their roles has been confusing. Depending on the experiment, VEGF-B may be pro- or anti-angiogenic. In macrophages, VEGFR1 is highly expressed and thought to mediate recruitment to injured tissues. Novel scientific approaches are necessary to resolve the multifaceted roles of VEGFR1 and develop its therapeutic potential. Recently, we developed a stimuli-responsive elastin-like polymer (ELP) fused to a VEGF-B type ligand mimetic peptide, termed R1B (VEGFR1 Binding)-ELP. ELPs retain the mechanical, cytocompatibility, and self-assembly properties of native elastin while being precisely sequence-tunable through genetic engineering, allowing site-specific chemistry and incorporation of bioactive motifs. ELPylated peptides have increased half-lives in biological media and can be processed into polymeric materials such as nano/microparticles, modified surfaces, and hydrogels. In this talk, I will present our recent results showing the effects of R1B-ELP treatment on vascular endothelial cell survival and macrophage recruitment in a mouse model of wound healing. Our results suggest that administration of R1B-ELP post-incision accelerates recovery from wound pain, offering an opportunity for a biomaterials-based approach to dissecting the pleiotropic roles of VEGFR1 in pain signaling. Related, R1B-ELP also localizes to the kidney when injected intravenously in mice, with early data suggesting that it may be protective against toxin-induced kidney injury. I will discuss the potential of the mammalian kidney as a model to gain insight into wound healing and as a physiological testbed for advancing engineered biomaterials.