Biomaterial Models of Ancestral Contributions to Wound Healing

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PROJECT ABSTRACT People of African ancestry are 7X more likely to develop overgrowth of scar tissue, or keloids, compared people of European ancestry. Fibrosis, chronic inflammation, and excessive scar formation is dictated by an individual’s ancestral background. Ancestry, quantified in our work through three components of self-identification, genetic ancestry, and sociocultural experiences, informs wound healing. While it is known that ancestry influences clinical wound healing, we do not understand how ancestry influences cell function or cell to cell communication in the wound response. Understanding ancestral contributions to cellular function is critical to interrogate wound healing differences. We hypothesize that ancestry informs differences in cellular response in wound healing. The overall goal of our research program is to leverage biomaterial models to interrogate ancestral contributions in wound healing. In this work, we will interrogate monocyte innate immune cells and CD34+ progenitor stem cells. Our proposed research program will answer three key questions: 1) How does ancestry influence cellular physiology? Preliminary work in our group demonstrates gene expression differences in isolated peripheral blood mononuclear cells comparing self-identified African vs. European descendants. To identify ancestral components beyond self-identification, we will interrogate genetic ancestry and sociocultural factors to quantify ancestry. To determine how each ancestral component influences cell function, we will conduct RNA sequencing and proteomic methodologies in tandem with mechanistic inhibitors to assess cell function differences in monocytes and progenitor stem cells. 2) How does ancestry influence cellular phenotype? While African ancestry is correlated with elevated scar formation, previous clinical studies do not provide mechanistic insights into cellular phenotype that occurs within wound sites. To address this limitation, we will leverage biomaterials and soluble factors to mimic wound extracellular matrix environments. To determine how ancestral components influences the cell phenotype, monocyte and progenitor stem cell responses following culture into the biomaterial microenvironments will be quantified. 3) How does ancestry correlate with the cellular response in wound healing? Wound responses necessitate cell to cell communication. We will utilize biomaterial models of cell-cell interaction and simulate wounding through oxidative stress injury. We will assess how ancestry influences cell to cell communication in these wound environments via genetic and secretome expression. This ESI-MIRA will enable my group to measure the influence of ancestry on wound healing through manipulation of biomaterial platforms. Ultimately, the vision for my lab’s research is to discern the impact of ancestry on wound healing differences and leverage biomaterial models to investigate health disparities in healing.