Biomaterial Models of Ancestral Contributions to Wound Healing

Univ Of Maryland, College Park, College Park MD

Investigators

Abstract

The goals of this project focus on understanding how ancestry affects tissue repair following wounding. Current models do not adequately account for components of ancestry that influence this healing. A greater understanding of how ancestry affects wound healing should reveal mechanisms undermining effective tissue repair. This understanding may lead to more personalized therapeutics for people impacted by tissue regeneration complications. Different cell populations contribute to defects in tissue regeneration. We seek to examine how genetic and self-reported ancestry impact cellular responses underlying wound healing. Our work employs dermal fibroblasts that facilitate the recovery of skin following injury. We also focus on monocytes and macrophages, immune cells involved in cellular signaling and tissue recovery following injury. Monocyte and macrophage function is shaped by hormonal signaling, the surrounding extracellular matrix, and communication with fibroblasts. To investigate the contribution of different genetic and self-reported ancestry to influencing monocyte/macrophage function, we leveraging a PEG (poly (ethylene glycol)) hydrogel model that mimics extracellular environments. This hydrogel model captures communication between cell types by incorporating both macrophages and dermal fibroblasts. The cellular response to oxidative stress is then used as a model of wounding. We will further investigate the role of hormone signaling by examining the macrophage response to gonadal hormones, a critical component of assessing cellular physiology. We hypothesize that these components of ancestry impact monocyte and macrophage responses important for cellular function and cell-to-cell communication during tissue repair, and these impacts can be elucidated using biomaterial models. Our research program will investigate this hypothesis by answering three central questions: 1) How does ancestry influence cellular physiology? 2) How does ancestry influence cellular phenotype? 3) How does ancestry correlate with cellular responses in wound healing?