3D-Printed Gastric Resident Electronics

Abstract

Long-term implantation of biomedical electronics into the human body enables advanced diagnostic and therapeutic functionalities. However, most long-term resident electronics devices require invasive procedures for implantation as well as a specialized receiver for communication. Here, a gastric resident electronic (GRE) system that leverages the anatomical space offered by the gastric environment to enable residence of an orally delivered platform of such devices within the human body is presented. The GRE is capable of directly interfacing with portable consumer personal electronics through Bluetooth, a widely adopted wireless protocol. In contrast to the passive day-long gastric residence achieved with prior ingestible electronics, advancement in multimaterial prototyping enables the GRE to reside in the hostile gastric environment for a maximum of 36 d and maintain ≈15 d of wireless electronics communications as evidenced by the studies in a porcine model. Indeed, the synergistic integration of reconfigurable gastric-residence structure, drug release modules, and wireless electronics could ultimately enable the next-generation remote diagnostic and automated therapeutic strategies.

Keywords: 3D printing; biomedical devices; gastric resident devices; gastric resident electronics; ingestible electronics.

Figure 1

3D-printed gastric resident electronics (GRE) for biomedical applications. Illustration describes the 3D-printed GRE concept: A) patient-specific multimaterial 3D printing of GRE. B) GRE is designed to be delivered orally (1), reside in the stomach for weeks (2), and finally break up (3) pass through the pylorus and be excreted from the gastric space. C) Specifically, the GRE can be compressed into a capsule-size dosage form. D) The expansion of the device enables gastric residence and allows long-term remote communication with personal device. E) Ultimately, the disintegration of the device allows the safe passage of the device from the gastric space. F) GRE is directly compatible with personal devices, such as a smart phone, empowering the users to communicate and control the long-residence device without a specialized equipment. G) This enables a seamless interconnection with other wireless electronics peripherals, wearable devices, and biomedical implants, allowing a real-time feedback-based automated treatment or responsive medication. The interconnection of GRE with the digital cloud via personal electronics could ultimately enable the next generation of digital medical interventions. H) Computer-aided design models of the gastric-resident electronics device showing the (i) gastric resident architecture; (ii) integration of electronics and power system for communications and control; (iii) personalized drug delivery modules. Inset shows the cross section of the design demonstrating the integration of a Bluetooth wireless-microcontroller, antenna, batteries, and drug delivery modules. I) Optical photograph shows the dimension of a fabricated device. J) X-ray image shows the deployed GRE in a porcine stomach.

Figure 2

3D-printed multimaterial gastric-residence architecture prototype (GRA) and electronics (GRE). A) Schematic of the computer-aided design model of the 3D-printed multimaterial architecture. Left inset image shows the optical photograph of a 3D-printed multimaterial GRA and right inset is an X-ray image indicating the relative location of metal probes embedded in the GRA of the in vivo gastric residence study. B) High-speed camera imaging series showing the expansion of 3D-printed architecture (i) before, (ii) during, and (iii) after expansion. C) X-ray image shows the gastric residence of a control prototype demonstrating the maximum gastric residence of 4 d without a gastric residence architecture. D) In contrast, GRA permits gastric residence for up to 24 d, as shown in the X-ray image. The structure will subsequently disintegrate by detachment. First, one of the GRA arm is detached, as indicated by the metal probes at day 27. (The top inset image shows the detached arm that has been passed to the intestinal region, while the remaining structure stays in the gastric space.) Second, at day 30, both GRA arms are detached, allowing the GRA to pass between day 31 and day 33. E) GRE exhibited a similar disintegration as GRA where at day 24, one of the prototypes began to lose one of the gastric residence structure, before both gastric residence arms are detached. F) In another GRE, a maximum gastric residence of 36 d was achieved. G) Statistical comparison of device residence period of a structure without GRA (control), GRA prototype, and ultimately GRE, demonstrating the effectiveness of GRA in prolonging gastric residence.

Figure 3

Wireless performance and lifetime of gastric-residence electronics. A) Average received signal strength indicator (RSSI) of seven devices measured with a smart phone. Inset shows an X-ray image of the integrated electronics at the GRE with three major components. B) The RSSI measured from GRE in a porcine stomach. The distance is measured relative to the abdominal surface of the pig. The in vivo measurements are repeated in three orthogonal directions. Inset shows the stability of RSSI measured at fixed location. C) GRE bilateral wireless communications from the gastric space: the change of temperature measured from GRE delivered to the porcine stomach, demonstrating the ability to perform bilateral wireless Blue-tooth interconnection between the device in the gastric space and a smart phone. D) Prolonging GRE lifetime: the optimization of communication protocol and power sources enable the maximum device lifetime of 20.1 d when configured to perform temperature measurement at an hourly interval. Inset shows bar charts demonstrate the average lifetime of GRE when maintained at three different modes of operation. The graph shows the in vitro experimental data of temperature measured when the device is left in a convection oven maintained at 37 °C over 19.5 d.

Figure 4

Drug delivery and remote sensing with gastric-residence electronics. A) The cumulative release of doxycycline in a controlled released poly(ε-caprolactone) matrix formulation (red dots and blue line), in comparison to the release profile of 20 mg in tablet form (blue stars and black line) and delayed released tablet (purple diamond and green line). B) The cumulative release of levonorgestrel from a 3D-printed formulation over one week, demonstrating the ability to integrate GRE with a controlled delivery platform. Inset shows the 3D printing of levonorgestrel into the defined drug wells. C) in vivo long-residence performance of GRE: The graph shows the measured received signal strength indicator (RSSI) of a GRE deployed in a porcine stomach of a pig from tablets attached to the walls of the cage over 15.3 d. Inset shows an X-ray image of the GRE (yellow circled) inside the stomach at the day the device is deployed. D) in vivo long-residence physiological parameter sensing with GRE: a direct, real-time core-temperature measurement with a tablet attached on the wall of the cage over 17 d. Inset shows the integrity of the GRE on day 15, demonstrating the robustness of the GRE to withstand the hostile gastric environment for weeks.