Untethered Microgrippers for Biopsy in the Upper Urinary Tract.

Untethered microrobots offer the possibility to perform medical interventions in anatomically complex and small regions in the body. Presently, it is necessary to access the upper urinary tract to diagnose and treat Upper Tract Urothelial Carcinoma (UTUC). Diagnostic and treatment challenges include ensuring adequate tissue sampling, accurately grading the disease, achieving completeness in endoscopic treatment, and consistently delivering medications to targeted sites. This work introduces microgrippers (µ-grippers) that are autonomously triggered by physiological temperature for biopsy in the upper urinary tract. The experiments demonstrated that µ-grippers can be deployed using standard ureteral catheters and maneuvered using an external magnetic field. The µ-grippers successfully biopsied tissue samples from ex vivo pig ureters, indicating that the thin-film bilayer springs' autonomous, physiologically triggered actuation exerts enough force to retrieve urinary tract tissue. The quality of these biopsy samples is sufficient for histopathological examination, including hematoxylin and eosin (H&E) and GATA3 immunohistochemical staining. Beyond biopsy applications, the µ-grippers' small size, wafer-scale fabrication, and multifunctionality suggest their potential for statistical sampling in the urinary tract. Experimental data and clinical reports underscore this potential through statistical simulations that compare the efficacy of µ-grippers with conventional tools, such as ureteroscopic forceps and baskets.

Untethered shape-changing devices in the gastrointestinal tract.

INTRODUCTION: Advances in microfabrication, automation, and computer engineering seek to revolutionize small-scale devices and machines. Emerging trends in medicine point to smart devices that emulate the motility, biosensing abilities, and intelligence of cells and pathogens that inhabit the human body. Two important characteristics of smart medical devices are the capability to be deployed in small conduits, which necessitates being untethered, and the capacity to perform mechanized functions, which requires autonomous shape-changing. AREAS COVERED: We motivate the need for untethered shape-changing devices in the gastrointestinal tract for drug delivery, diagnosis, and targeted treatment. We survey existing structures and devices designed and utilized across length scales from the macro to the sub-millimeter. These devices range from triggerable pre-stressed thin film microgrippers and spring-loaded devices to shape-memory and differentially swelling structures. EXPERT OPINION: Recent studies demonstrate that when fully enabled, tether-free and shape-changing devices, especially at sub-mm scales, could significantly advance the diagnosis and treatment of GI diseases ranging from cancer and inflammatory bowel disease (IBD) to irritable bowel syndrome (IBS) by improving treatment efficacy, reducing costs, and increasing medication compliance. We discuss the challenges and possibilities associated with ensuring safe, reliable, and autonomous operation of these smart devices.

Autonomous Untethered Microinjectors for Gastrointestinal Delivery of Insulin.

The delivery of macromolecular drugs via the gastrointestinal (GI) tract is challenging as these drugs display low stability as well as poor absorption across the intestinal epithelium. While permeation-enhancing drug delivery methods can increase the bioavailability of low molecular weight drugs, the effective delivery of high molecular weight drugs across the tight epithelial cell junctions remains a formidable challenge. Here, we describe autonomous microinjectors that are deployed in the GI tract, then efficiently penetrate the GI mucosa to deliver a macromolecular drug, insulin, to the systemic circulation. We performed in vitro studies to characterize insulin release and assess the penetration capability of microinjectors and we measured the in vivo release of insulin in live rats. We found that the microinjectors administered within the luminal GI tract could deliver insulin transmucosally to the systemic circulation at levels similar to those with intravenously administered insulin. Due to their small size, tunability in sizing and dosing, wafer-scale fabrication, and parallel, autonomous operation, we anticipate that these microinjectors will significantly advance drug delivery across the GI tract mucosa to the systemic circulation in a safe manner.

Preparation of lignosulfonate-based nanofiltration membranes with improved water desalination performance.

Pulping and papermaking generate large amounts of waste in the form of lignosulfonates which have limited valorized applications so far. Herein, we report a novel lignosulfonate-based nanofiltration membrane, prepared by using polyethylenimine (PEI) and sodium lignosulfonate (SL) via a layer-by-layer (LbL) self-assembly. As a low-cost and renewable natural polyelectrolyte, SL is selected to replace the synthetic polyelectrolyte commonly used in the conventional LbL fabrication for composite membranes. The prepared LbL (PEI/SL)7 membranes were crosslinked by glutaraldehyde (GA) to obtain (PEI/SL)7-GA membranes with compact selective layer. We characterized (PEI/SL)7 and (PEI/SL)7-GA membranes to study the chemical compositions, morphologies, and surface hydrophilicity. To improve the nanofiltration performances of the (PEI/SL)7-GA membranes for water desalination, we investigated the effects of the crosslinking time, GA concentration and the NaCl supporting electrolyte on membrane structure and performance. The optimized (PEI/SL)7-GA membrane exhibited a permeating flux up to 39.6 L/(m2·h) and a rejection of 91.7% for the MgSO4 aqueous solution 2.0 g/L concentration, showing its promising potential for water desalination. This study provides a new approach to applying the underdeveloped lignin-based biomass as green membrane materials for water treatment.

Gastrointestinal-resident, shape-changing microdevices extend drug release in vivo.

Extended-release gastrointestinal (GI) luminal delivery substantially increases the ease of administration of drugs and consequently the adherence to therapeutic regimens. However, because of clearance by intrinsic GI motility, device gastroretention and extended drug release over a prolonged duration are very challenging. Here, we report that GI parasite-inspired active mechanochemical therapeutic grippers, or theragrippers, can reside within the GI tract of live animals for 24 hours by autonomously latching onto the mucosal tissue. We also observe a notable sixfold increase in the elimination half-life using theragripper-mediated delivery of a model analgesic ketorolac tromethamine. These results provide first-in-class evidence that shape-changing and self-latching microdevices enhance the efficacy of extended drug delivery.

3D Printing of an In Situ Grown MOF Hydrogel with Tunable Mechanical Properties.

Due to their precisely modifiable microporosity and chemical functionality, Metal-Organic Frameworks (MOFs) have revolutionized catalysis, separations, gas storage, drug delivery, and sensors. However, because of their rigid and brittle powder morphology, it is challenging to build customizable MOF shapes with tunable mechanical properties. Here, we describe a new three-dimensional (3D) printing approach to create stretchable and tough MOF hydrogel structures with tunable mechanical properties. We formulate a printable ink by combining prepolymers of a versatile double network (DN) hydrogel of acrylamide and alginate, a shear-thinning agent, and MOF ligands. Importantly, by simultaneous cross-linking of alginate and in situ growth of the HKUST-1 using copper ions, we are able to create composites with high MOF dispersity in the DN hydrogel matrix with high pore accessibility. We extensively characterize the inks and uncover parameters to tune modulus, strength, and toughness of the 3D prints. We also demonstrate the excellent performance of the MOF hydrogels for dye absorption. Our approach incorporates all of the advantageous attributes of 3D printing while offering a rational approach to merge stretchable hydrogels and MOFs, and our findings are of broad relevance to wearables, implantable and flexible sensors, chemical separations, and soft robotics.

Extraction of Polysaccharide from Dendrobium nobile Lindl. by Subcritical Water Extraction.

Subcritical water extraction (SWE) uses hot compressed water as an effective solvent for both polar and nonpolar compounds and has been developed as an environmentally benign extraction technology for natural materials. Polysaccharides as one of the main ingredients in Dendrobium plants showed obvious biological activity. Thus, SWE of polysaccharides obtained from Dendrobium nobile Lindl. was investigated in this work. The response surface methodology (RSM) was combined with a Box-Behnken design to evaluate the influence that the three independent variables had on the response. The optimal extraction conditions (determined via RSM) were 129.83 °C extraction temperature, 16.71 min extraction time, and 1.12 MPa extraction pressure. The maximum predicted polysaccharide yield was 20.67%, which corresponded well with the experiential extraction (21.88%). The polysaccharides obtained from either the stirring extraction, refluxing extraction, ultrasound extraction, or SWE methods were compared, and the extraction processes were modeled. The molecular weight, monosaccharide composition, and antioxidative activities of the polysaccharides were analyzed.

Dual-Gel 4D Printing of Bioinspired Tubes.

The distribution of periodic patterns of materials with radial or bilateral symmetry is a universal natural design principle. Among the many biological forms, tubular shapes are a common motif in many organisms, and they are also important for bioimplants and soft robots. However, the simple design principle of strategic placement of 3D printed segments of swelling and nonswelling materials to achieve widely different functionalities is yet to be demonstrated. Here, we report the design, fabrication, and characterization of segmented 3D printed gel tubes composed of an active thermally responsive swelling gel (poly N-isopropylacrylamide) and a passive thermally nonresponsive gel (polyacrylamide). Using finite element simulations and experiments, we report a variety of shape changes including uniaxial elongation, radial expansion, bending, and gripping based on two gels. Actualization and characterization of thermally induced shape changes are of key importance to robotics and biomedical engineering. Our studies present rational approaches to engineer complex parameters with a high level of customization and tunability for additive manufacturing of dynamic gel structures.