Abstract
<jats:p>Gastrointestinal anastomotic leakage (AL) remains a life-threatening complication following gastrointestinal surgery, where outcomes critically depend on timely diagnosis. Current diagnostic strategies rely on periodic sampling and resource-intensive analysis in centralized laboratories. Here, we present a sterilizable, time-integrating hydrogel sensor platform for continuous, infrastructure-free monitoring of the patient's postoperative drain fluid. We introduce enzyme-responsive macromolecular networks for semi-quantitative bedside assessment of leak-associated digestive enzymes. The sensors retain functionality following lyophilization and ethylene oxide sterilization, enabling long-term storage and scalable deployment around the world. In a Swiss clinical cohort of 56 patients, including 19 with gastrointestinal anastomotic leakage, the sensor detected amylase-associated leaks two days (median) prior to clinical diagnosis with a sensitivity of 78% (95% CI 55-91) and a specificity of 95% (95% CI 82-99). The prospective validation in an independent cohort of 37 patients in Colombia, including seven patients with leaks, demonstrated 100% sensitivity (95% CI 64.6-100) and a 100% negative predictive value (95% CI 87.9-100.0), with sensor activation preceding standard clinical diagnosis by a median of five days. By converting episodic biochemical measurements into continuous, cumulative visual records, this infrastructure-free material platform enables close-meshed postoperative monitoring and may facilitate earlier recognition of anastomotic leakage across diverse healthcare settings.</jats:p>