REPAIR: Regenerative Electronic Patch through Advanced Intelligent Regulation

We propose Regenerative Electronic Patch through Advanced Intelligent Regulation (REPAIR) - a 3D patch of optical and electrical sensors/actuators integrated within a thin layer of ECM hydrogel that is transiently and repeatedly placed at the wound bed. Our proposed approach will provide: 1. continuous classification of wound state using minimally invasive, conformal 3D interfaces with real-time electrical and optical sensing of biochemical and biophysical markers; 2. on-demand, local synthesis, and release of biologics using optical control of cell-based “biologics production factories” safely isolated in a biologic-permeable elastomer scaffold; 3. layer-by-layer approach of applying ECM of known and controlled composition to the optoelectronically active components; 4. RNA sequencing and protein analysis of cells and neotissue at leading edge of healing wound to further characterize the wound state and correlate with measured parameters such as neurogenesis and immune cell phenotype; 5. computational modeling of the wound healing processes, including model-guided selection of reduced set of biomarkers and actuation pathways to enabled closed-loop acceleration of wound healing; and lastly 6. reinforcement learning of wound management policies from the computational wound healing models. Importantly, several key components of our approach have proven regulatory path with successful clinical translation. Several team members have extensive experience with preclinical animal models and experience with human clinical trials, which will accelerate clinical translation of our findings.