Development and assessment of hydrogel-embedded metalloporphyrin sensors for monitoring of tissue Oxygenation

Background: Continuous, objective monitoring of tissue oxygenation is crucial for early detection of ischemia and for guiding interventions in reconstructive and transplant surgery. Existing monitoring approaches are often intermittent, operator-dependent, or vulnerable to optical confounders, limiting timely recognition of vascular compromise and equitable performance across patient populations. This dissertation investigates an implantable optical biosensing platform based on hydrogel-embedded metalloporphyrins to enable real-time monitoring of tissue oxygen tension (TOT). Methods and results: Injectable sensors were engineered using a PEGDA hydrogel matrix with metalloporphyrin-based phosphorescent dyes and evaluated using fluorescence/phosphorescence lifetime approaches to provide quantitative oxygen readouts. The platform was assessed across benchtop calibration, preclinical, and ex vivo models, including flap ischemia monitoring in rodent models, quantification of perfusion changes during topical vasodilator interventions, intrahepatic oxygen monitoring during normothermic machine perfusion of liver grafts, and characterization of oxygen dynamics during ischemia–reperfusion (including post-ischemic reactive hyperoxia). Conclusions: Hydrogel-embedded metalloporphyrin sensors support minimally invasive, continuous assessment of local oxygenation with potential to detect early ischemic changes, track therapeutic modulation of perfusion, and inform organ viability assessment. The work also addresses key translational considerations by evaluating the influence of skin pigmentation and implantation depth on optical sensing performance, supporting the development of more robust and equitable monitoring tools for clinical use.