Reprogramming cells for repair of chronic wounds

Regenerating soft tissue is critical for adequate healing after injury across many tissue types, but often does not occur due to inadequate microenvironmental cues. There remains an unmet clinical need to heal chronic wounds, and similar problems exist are ubiquitous across many wound types including: dysregulation of inflammatory processes and insufficient signal from regenerative factors. We propose a research program dedicated to deepening our understanding of chronic wounds and developing translational treatments that centers around four basic questions about reprogramming cellular responses in wound microenvironments: i) how do T-cell phenotypes contribute to inflammatory dysregulation?, ii) can T-cells be reprogrammed to mitigate inflammation and resolve injury?, iii) how does dynamic secretion of alarmin proteins impact healing?, and iv) can we reprogram cellular responses to alarmins to respond with regenerative factors. We know that multiple types of T cells are involved in healing wounds, but it is not clear how they interact and directly influence healing or if reprogramming inflammatory T cells to regulatory ones could improve healing. Furthermore, we know that alarmins play a critical role in clearing pathogens and debris, but it is suspected that overexpression of alarmins contributes to inflammatory dysregulation and non-healing. We hypothesize that a synthetic biology approach could enable more precisely dissecting this biology and yield responsive cell therapies that target chronic wounds for regeneration. Proposed herein we harness two models of chronic wound healing i) diabetic skin wounds and ii) the foreign body response to implants, and we use these models to probe fundamentals of cellular responses to injury and develop improved regenerative therapies. Project Number: 1R35GM162195-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Aaron Morris | Institution: UNIVERSITY OF MICHIGAN AT ANN ARBOR, ANN ARBOR, MI | Award Amount: $409,941 | Activity Code: R35 | Study Section: Special Emphasis Panel[ZRG1 MCST-Q (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11267753