Intestinal retentive systems - recent advances and emerging approaches.

Intestinal retentive devices (IRDs) are devices designed to anchor within the lumen of the intestines for long-term residence in the gastrointestinal tract. IRDs can enable impactful medical device technologies including sustained oral drug delivery systems, indwelling sensors, or real-time diagnostics. The design and testing of IRDs present a myriad of challenges, including precise deployment of the device at desired intestinal locations, secure anchoring within the gastrointestinal tract to allow for natural function, and safe removal of the IRD at user-defined times. Advancing the state-of-the-art of IRD is an interdisciplinary effort that requires innovations such as new materials, novel anchoring mechanisms, and medical device design with consistent input from clinical practitioners and end-users. This perspective briefly reviews the current state-of-the-art for IRDs and charts a path forward to inform the design of future concepts. Specifically, this article will highlight materials, retention mechanisms, and test beds to measure the efficacy of IRDs and their mechanisms. Finally, potential synergies between IRD and other medical device technologies are presented to identify future opportunities.

Edible Origami Actuators Using Gelatin-Based Bioplastics.

The potential of ingestible medical devices can be greatly enhanced through the use of smart structures made from stimuli-responsive materials. While hydration is a convenient stimulus for inducing shape changes in biomaterials, finding robust materials that can achieve rapid actuation, facile manufacturability, and biocompatibility suitable for ingestible medical devices poses practical challenges. Hydration is a convenient stimulus to induce shape changes in smart biomaterials; however, there are many practical challenges to identifying materials that can achieve rapid actuation and facile manufacturability while satisfying constraints associated with biocompatibility requirements and mechanical properties that are suitable for ingestible medical devices. Herein, we illustrate the formulation and processability of a moisture-responsive genipin-crosslinked gelatin bioplastic system, which can be processed into complex three-dimensional shapes. Mechanical characterization of bioplastic samples showed Young's Modulus values as high as 1845 MPa and toughness values up to 52 MJ/m3, using only food-safe ingredients. Custom molds and UV-laser processing enabled the fabrication of centimeter-scale structures with over 150 independent actuating joints. These self-actuating structures soften and unfold in response to surrounding moisture, eliminating the need for additional stimuli or actuating elements.

Villi Inspired Mechanical Interlocking for Intestinal Retentive Devices.

Intestinal retentive devices have applications ranging from sustained oral drug delivery systems to indwelling ingestible medical devices. Current strategies to retain devices in the small intestine primarily focus on chemical anchoring using mucoadhesives or mechanical coupling using expandable devices or structures that pierce the intestinal epithelium. Here, the feasibility of intestinal retention using devices containing villi-inspired structures that mechanically interlock with natural villi of the small intestine is evaluated. First the viability of mechanical interlocking as an intestinal retention strategy is estimated by estimating the resistance to peristaltic shear between simulated natural villi and devices with various micropost geometries and parameters. Simulations are validated in vitro by fabricating micropost array patches via multistep replica molding and performing lap-shear tests to evaluate the interlocking performance of the fabricated microposts with artificial villi. Finally, the optimal material and design parameters of the patches that can successfully achieve retention in vivo are predicted. This study represents a proof-of-concept for the viability of micropost-villi mechanical interlocking strategy to develop nonpenetrative multifunctional intestinal retentive devices for the future.

Gelatin-Based Ingestible Impedance Sensor to Evaluate Gastrointestinal Epithelial Barriers.

Low-profile and transient ingestible electronic capsules for diagnostics and therapeutics can replace widely used yet invasive procedures such as endoscopies. Several gastrointestinal diseases such as reflux disease, Crohn's disease, irritable bowel syndrome, and eosinophilic esophagitis result in increased intercellular dilation in epithelial barriers. Currently, the primary method of diagnosing and monitoring epithelial barrier integrity is via endoscopic tissue biopsies followed by histological imaging. Here, a gelatin-based ingestible electronic capsule that can monitor epithelial barriers via electrochemical impedance measurements is proposed. Toward this end, material-specific transfer printing methodologies to manufacture soft-gelatin-based electronics, an in vitro synthetic disease model to validate impedance-based sensing, and tests of capsules using ex vivo using porcine esophageal tissue are described. The technologies described herein can advance next generation of oral diagnostic devices that reduce invasiveness and improve convenience for patients.

Hysteresis-free and high sensitivity strain sensing of ionically conductive hydrogels.

Hydrogels are promising materials for soft and implantable strain sensors owing to their large compliance (E<100 kPa) and significant extensibility (εmax >500%) compared to other polymer networks. Further, hydrogels can be functionalized to seamlessly integrate with many types of tissues. However, most current methods attempt to imbue additional electronic functionality to structural hydrogel materials by incorporating fillers with orthogonal properties such as electronic or mixed ionic conduction. Although composite strategies may improve performance or facilitate heterogeneous integration with downstream hardware, composites complicate the path for regulatory approval and may compromise the otherwise compelling properties of the underlying structural material. Here we report hydrogel strain sensors composed of genipin-crosslinked gelatin and dopamine-functionalized poly(ethylene glycol) for in vivo monitoring of cardiac function. By measuring their impedance only in their resistive regime (>10 kHz), hysteresis is reduced and the resulting gauge factor is increased by ~50x to 1.02±0.05 and 1.46±0.05 from approximately 0.03-0.05 for PEG-Dopa and genipin-crosslinked gelatin respectively. Adhesion and in vivo biocompatibility are studied to support implementation of strain sensors for monitoring cardiac output in porcine models. Impedance-based strain sensing in the kilohertz regime simplifies the piezoresistive behavior of these materials and expands the range of hydrogel-based strain sensors.