A Glucose-Responsive Cannula for Automated and Electronics-Free Insulin Delivery.

Automated delivery of insulin based on continuous glucose monitoring is revolutionizing the way insulin-dependent diabetes is treated. However, challenges remain for the widespread adoption of these systems, including the requirement of a separate glucose sensor, sophisticated electronics and algorithms, and the need for significant user input to operate these costly therapies. Herein, a user-centric glucose-responsive cannula is reported for electronics-free insulin delivery. The cannula-made from a tough, elastomer-hydrogel hybrid membrane formed through a one-pot solvent exchange method-changes permeability to release insulin rapidly upon physiologically relevant varying glucose levels, providing simple and automated insulin delivery with no additional hardware or software. Two prototypes of the cannula are evaluated in insulin-deficient diabetic mice. The first cannula-an ends-sealed, subcutaneously inserted prototype-normalizes blood glucose levels for 3 d and controls postprandial glucose levels. The second, more translational version-a cannula with the distal end sealed and the proximal end connected to a transcutaneous injection port-likewise demonstrates tight, 3-d regulation of blood glucose levels when refilled twice daily. This proof-of-concept study may aid in the development of "smart" cannulas and next-generation insulin therapies at a reduced burden-of-care toll and cost to end-users.

A Broad-Spectrum Antimicrobial and Antiviral Membrane Inactivates SARS-CoV-2 in Minutes.

SARS-CoV-2, the virus that caused the COVID-19 pandemic, can remain viable and infectious on surfaces for days, posing a potential risk for fomite transmission. Liquid-based disinfectants, such as chlorine-based ones, have played an indispensable role in decontaminating surfaces but they do not provide prolonged protection from recontamination. Here a safe, inexpensive, and scalable membrane with covalently immobilized chlorine, large surface area, and fast wetting that exhibits long-lasting, exceptional killing efficacy against a broad spectrum of bacteria and viruses is reported. The membrane achieves a more than 6 log reduction within several minutes against all five bacterial strains tested, including gram-positive, gram-negative, and drug-resistant ones as well as a clinical bacterial cocktail. The membrane also efficiently deactivated nonenveloped and enveloped viruses in minutes. In particular, a 5.17 log reduction is achieved against SARS-CoV-2 after only 10 min of contact with the membrane. This membrane may be used on high-touch surfaces in healthcare and other public facilities or in air filters and personal protective equipment to provide continuous protection and minimize transmission risks.

A Zwitterionic Polyurethane Nanoporous Device with Low Foreign-Body Response for Islet Encapsulation.

Encapsulation of insulin-producing cells is a promising strategy for treatment of type 1 diabetes. However, engineering an encapsulation device that is both safe (i.e., no cell escape and no breakage) and functional (i.e., low foreign-body response (FBR) and high mass transfer) remains a challenge. Here, a family of zwitterionic polyurethanes (ZPU) with sulfobetaine groups in the polymer backbone is developed, which are fabricated into encapsulation devices with tunable nanoporous structures via electrospinning. The ZPU encapsulation device is hydrophilic and fouling-resistant, exhibits robust mechanical properties, and prevents cell escape while still allowing efficient mass transfer. The ZPU device also induces a much lower FBR or cellular overgrowth upon intraperitoneal implantation in C57BL/6 mice for up to 6 months compared to devices made of similar polyurethane without the zwitterionic modification. The therapeutic potential of the ZPU device is shown for islet encapsulation and diabetes correction in mice for ≈3 months is demonstrated. As a proof of concept, the scalability and retrievability of the ZPU device in pigs and dogs are further demonstrated. Collectively, these attributes make ZPU devices attractive candidates for cell encapsulation therapies.

Local Immunomodulatory Strategies to Prevent Allo-Rejection in Transplantation of Insulin-Producing Cells.

Islet transplantation has shown promise as a curative therapy for type 1 diabetes (T1D). However, the side effects of systemic immunosuppression and limited long-term viability of engrafted islets, together with the scarcity of donor organs, highlight an urgent need for the development of new, improved, and safer cell-replacement strategies. Induction of local immunotolerance to prevent allo-rejection against islets and stem cell derived ß cells has the potential to improve graft function and broaden the applicability of cellular therapy while minimizing adverse effects of systemic immunosuppression. In this mini review, recent developments in non-encapsulation, local immunomodulatory approaches for T1D cell replacement therapies, including islet/ß cell modification, immunomodulatory biomaterial platforms, and co-transplantation of immunomodulatory cells are discussed. Key advantages and remaining challenges in translating such technologies to clinical settings are identified. Although many of the studies discussed are preliminary, the growing interest in the field has led to the exploration of new combinatorial strategies involving cellular engineering, immunotherapy, and novel biomaterials. Such interdisciplinary research will undoubtedly accelerate the development of therapies that can benefit the whole T1D population.

Hydrogels in Emerging Technologies for Type 1 Diabetes.

Type 1 diabetes therapies that afford tighter glycemic control in a more manageable and painless manner for patients has remained a central focus of next-generation diabetes therapies. In many of these emerging technologies, namely, self-regulated insulin delivery and cell replacement therapies, hydrogels are employed to mitigate some of the most long-standing challenges. In this Review, we summarize recent developments in the use of hydrogels for both insulin delivery and insulin-producing cell therapies for type 1 diabetes management. We first outline perspectives in glucose sensitive hydrogels for smart insulin delivery, pH sensitive polymeric hydrogels for oral insulin delivery, and other physiochemical signals used to trigger insulin release from hydrogels. We, then, investigate the use of hydrogels in the encapsulation of insulin secreting cells with a special emphasis on hydrogels designed to mitigate the foreign body response, provide a suitable extracellular microenvironment, and improve mass transfer through oxygen supplementation and vascularization. Evaluations of limitations and promising directions for future research are also considered. Continuing interdisciplinary and collaborative research efforts will be required to produce hydrogels with instructive biochemical microenvironments necessary to address the enduring challenges of emerging type 1 diabetes therapies.

Stimuli-Responsive Insulin Delivery Devices.

The development of new diabetes treatment strategies has garnered much interest given that conventional management therapies for type 1 diabetes fail to provide optimal glycemic control while creating a high burden of self-care to patients. Stimuli-responsive, "closed-loop" systems are particularly attractive due to their ability to mimic dynamic ß cell function by releasing insulin in response to fluctuating glucose levels in real-time and with minimal patient discomfort. In this short review, we focus on stimuli-responsive, reservoir-based insulin delivery devices. We explore and evaluate systems that are either physiologically or externally triggered. While obstacles remain before such technologies can be translated to clinical settings, further optimization of delivery systems forebodes that these technologies will have a tremendous impact on type 1 diabetes treatment.

Specialty Tough Hydrogels and Their Biomedical Applications.

Hydrogels have long been explored as attractive materials for biomedical applications given their outstanding biocompatibility, high water content, and versatile fabrication platforms into materials with different physiochemical properties and geometries. Nonetheless, conventional hydrogels suffer from weak mechanical properties, restricting their use in persistent load-bearing applications often required of materials used in medical settings. Thus, the fabrication of mechanically robust hydrogels that can prolong the lifetime of clinically suitable materials under uncompromising in vivo conditions is of great interest. This review focuses on design considerations and strategies to construct such tough hydrogels. Several promising advances in the proposed use of specialty tough hydrogels for soft actuators, drug delivery vehicles, adhesives, coatings, and in tissue engineering settings are highlighted. While challenges remain before these specialty tough hydrogels will be deemed translationally acceptable for clinical applications, promising preliminary results undoubtedly spur great hope in the potential impact this embryonic research field can have on the biomedical community.

Theory and reported practice in EFL literacy instruction: EFL teachers' perceptions about classroom practices.

Acquiring literacy in English as a foreign language (EFL) is important for language development. However, many students enter middle school without adequate EFL literacy skills. This may indicate a gap between EFL literacy instruction theory and the classroom practice that is occurring in elementary school classrooms. The aim of this study was to explore the components of EFL literacy instruction as perceived by teachers. The study investigated whether perceptions of classroom practices are theoretically based, thus shedding light on the gap between EFL literacy theory and practice. The participants were 167 EFL elementary school teachers, who submitted anonymous online questionnaires regarding their reported EFL teaching in year one, two, three, four, and five of elementary school. The research was based on the five pillars of literacy instruction for English as a first language (National Reading Panel, 2000) and additional EFL components (August & Shanahan, 2006). Results of this study showed that EFL teachers expressed views that may indicate a gap between teachers' practices and most cutting-edge research. The study concluded that providing EFL elementary school teachers with theoretical knowledge may lead to more productive literacy programs and may improve classroom practices.

Conformal Hydrogel Coatings on Catheters To Reduce Biofouling.

Reducing biofouling while increasing lubricity of inserted medical catheters is highly desirable to improve their comfort, safety, and long-term use. We report here a simple method to create thin (∼30 µm) conformal lubricating hydrogel coatings on catheters. The key to this method is a three-step process including shape-forming, gradient cross-linking, and swell-peeling (we label this method as SGS). First, we took advantage of the fast gelation of agar to form a hydrogel layer conformal to catheters; then, we performed a surface-bound UV cross-linking of acrylamide mixed in agar in open air, purposely allowing gradual oxygen inhibition of free radicals to generate a gradient of cross-linking density across the hydrogel layer; and finally, we caused the hydrogel to swell to let the non-cross-linked/loosely attached hydrogel fall off, leaving behind a surface-bound, thin, and mostly uniform hydrogel coating. This method also allowed easy incorporation of different polymerizable monomers to obtain multifunctionality. For example, incorporating an antifouling, zwitterionic moiety sulfobetaine in the hydrogel reduced both in vitro protein adsorption and in vivo foreign-body response in mice. The addition of a biocidal N-halamine monomer to the hydrogel coating deactivated both Staphylococcus aureus ( S. aureus) and Escherichia coli ( E. coli) O157:H7 within 30 min of contact and reduced biofilm formation by 90% compared to those of uncoated commercial catheters when challenged with S. aureus for 3 days. The lubricating, antibiofouling hydrogel coating may bring clinical benefits in the use of urinary and venous catheters as well as other types of medical devices.