Project Summary Obesity affects more than 1.4 billion adults worldwide and is a significant risk factor for chronic diseases such as hypertension, diabetes, and cardiovascular diseases. Present non-operative treatment options of obesity are woefully inadequate. Bariatric surgery is effective but invasive, costly, and associated with significant morbidity. Intragastric balloons (IGB) have been demonstrated to be effective in enabling temporary weight loss (~25-30% of excess body weight), allowing the improvement of metabolic parameters. However, IGB is a passive mechanical construct that cannot be monitored or controlled upon insertion and require endoscopy delivery. These fundamental attributes limit the reach of IGB to very selected patients as a temporary treatment or as a bridging intervention to bariatric surgery despite its effectiveness. The proposed research will overcome the fundamental limitations of IGB by creating an ingestible gastric-resident electronic-enhanced metamaterial architecture (iGEM). In stark contrast to the current strategies, iGEM can transform obesity treatment with a digital-based personalized and dynamic treatment strategy. iGEM allows the dynamic tuning of gastric restrictive effect, which can be optimized based on safety consideration, patient’s treatment goals, and the quality of life desired. For example, feedback-based control of the device distension can prevent excessive pressure point or over-inflation that may lead to ulcer formation; or to avoid intestinal obstruction due to premature disintegration. The ability to adjust gastric restrictive pressure can enhance treatment effectiveness to account for gastric accommodation. The ability to acquire sensing data can help elucidate the complex relationship between the restrictive effect of intragastric devices and treatment effectiveness. This research leverages Kong’s expertise in creating entirely 3D printable electronics and ingestible electronics, (2) Wang’s (Ph.D.) expertise in meta- materials design, and (3) Fang’s (M.D.) extensive clinical and clinical research experience in IGB usage and intragastric devices. Specifically, we will (1) develop wireless resonant-enhanced 3D printable gastric pressure sensors with a hybrid core-shell printing methodology that allow the integration of pressure sensors on a wide range of intragastric systems; (2) develop wirelessly triggered transformable active metamaterials architecture that is capable of achieving wirelessly triggered reversible structural reconfiguration, allowing the oral ingestion of the device, dynamic control of expansion to tailor gastric restriction effect and the safe excretion of the device without risk of intestinal obstruction; (3) develop and evaluate iGEM longitudinal wireless pressure sensing and triggerable volume control capability that can sustain the complex and dynamic gastric environment for a prolonged period of time (30 days). Upon completion of the proposed research, the foundation e...