Understanding the role of anesthesia in perioperative organ injury via wireless soft implants - PROJECT SUMMARY/ABSTRACT Perioperative organ injury (POI) is a major contributor to morbidity and mortality in surgical patients, impacting multiple organs, including the heart, lungs, kidneys, liver, and gastrointestinal system. Perioperative acute kidney injury (AKI), for instance, occurs in 2% – 18% of patients and 22% – 57% of intensive care patients, accounts for 30% – 40% of total AKI cases in the United States, and increases hospitalization costs by up to 70%. Despite substantial advances in anesthesiology, POI remains largely unpredictable, with treatment still limited to organ- supportive care. While hypoperfusion and inflammation are recognized as the pathophysiological hallmarks of POI, current understandings are still broad and inadequate. In particular, anesthesia is a crucial factor in the pathophysiology of POI, but its specific roles remain to be clarified. Suboptimal anesthesia is known to impair organ function, but certain anesthetics, via preconditioning and postconditioning procedures, have been reported to offer protective effects against ischemia-reperfusion injury, a leading cause of POI. This ambiguity is largely due to the lack of advanced monitoring techniques capable of continuously and comprehensively tracking the pathogenic processes of POI to yield robust interpretations. The overall vision of this research program is to elucidate the pathophysiology of POI and the role of anesthesia therein by pioneering the development of a wireless, soft implant for continuous and comprehensive tracking of organ physiology and biochemistry. The goals for the next five years include: 1) Develop a wireless, battery-free soft implant with a protruding micronee- dle sensor array for spatiotemporal probing of organs, using a 3D-printing based manufacturing process to achieve 3D sensor configuration and fully biocompatible materials to minimize immune response. 2) Develop sensors on microneedle tips for monitoring hypoperfusion (oxygen and lactate), inflammation (interleukin-1β, interleukin-6, and tumor necrosis factor-α), and organ injury (neutrophil gelatinase-associated lipocalin), with a focus on achieving direct in vivo electrochemical detection of biomarkers and stable chronic recordings for at least 7 days post-operation. 3) Use the integrated implant to investigate the harmful effects of anesthetics at various dosages and the protective effects of different anesthetic preconditioning and postconditioning protocols in rat models. This project is significant because it seeks to decode the role of anesthesia in the complex patho- physiology of POI, offering potential insights that could inform clinical anesthesiology practices. This project is innovative because it pioneers the development of a wireless, soft implant capable of spatiotemporally tracking important organ biochemical markers over extended periods.
