Kirigami-inspired stents for sustained local delivery of therapeutics.

Implantable drug depots have the capacity to locally meet therapeutic requirements by maximizing local drug efficacy and minimizing potential systemic side effects. Tubular organs including the gastrointestinal tract, respiratory tract and vasculature all manifest with endoluminal disease. The anatomic distribution of localized drug delivery for these organs using existing therapeutic modalities is limited. Application of local depots in a circumferential and extended longitudinal fashion could transform our capacity to offer effective treatment across a range of conditions. Here we report the development and application of a kirigami-based stent platform to achieve this. The stents comprise a stretchable snake-skin-inspired kirigami shell integrated with a fluidically driven linear soft actuator. They have the capacity to deposit drug depots circumferentially and longitudinally in the tubular mucosa of the gastrointestinal tract across millimetre to multi-centimetre length scales, as well as in the vasculature and large airways. We characterize the mechanics of kirigami stents for injection, and their capacity to engage tissue in a controlled manner and deposit degradable microparticles loaded with therapeutics by evaluating these systems ex vivo and in vivo in swine. We anticipate such systems could be applied for a range of endoluminal diseases by simplifying dosing regimens while maximizing drug on-target effects through the sustained release of therapeutics and minimizing systemic side effects.

Respirators in Healthcare: Material, Design, Regulatory, Environmental, and Economic Considerations for Clinical Efficacy.

Maintaining an ample supply of personal protective equipment continues to be a challenge for the healthcare industry, especially during emergency situations and times of strain on the supply chain. Most critically, healthcare workers exposed to potential airborne hazards require sufficient respiratory protection. Respirators are the only type of personal protective equipment able to provide adequate respiratory protection. However, their ability to shield hazards depends on design, material, proper fit, and environmental conditions. As a result, not all respirators may be adequate for all scenarios. Additionally, factors including user comfort, ease of use, and cost contribute to respirator effectiveness. Therefore, a careful consideration of these parameters is essential for ensuring respiratory protection for those working in the healthcare industry. Here respirator design and material characteristics are reviewed, as well as properties of airborne hazards and potential filtration mechanisms, regulatory standards of governmental agencies, respirator efficacy in the clinical setting, attitude of healthcare personnel toward respiratory protection, and environmental and economic considerations of respirator manufacturing and distribution.

Dynamic omnidirectional adhesive microneedle system for oral macromolecular drug delivery.

Oral drug administration remains the preferred route for patients and health care providers. Delivery of macromolecules through this route remains challenging because of limitations imposed by the transport across the gastrointestinal epithelium and the dynamic and degradative environment. Here, we present the development of a delivery system that combines physical (microneedle) and nonphysical (enhancer) modes of drug delivery enhancement for a macromolecule in a large animal model. Inspired by the thorny-headed intestinal worm, we report a dynamic omnidirectional mucoadhesive microneedle system capable of prolonged gastric mucosa fixation. Moreover, we incorporate sodium N-[8-(2-hydroxybenzoyl) amino] caprylate along with semaglutide and demonstrate enhanced absorption in swine resistant to physical displacement in the gastric cavity. Meanwhile, we developed a targeted capsule system capable of deploying intact microneedle-containing systems. These systems stand to enable the delivery of a range of drugs through the generation and maintenance of a privileged region in the gastrointestinal tract.

Biodegradable ring-shaped implantable device for intravesical therapy of bladder disorders.

Intravesical instillation is an efficient drug delivery route for the local treatment of various urological conditions. Nevertheless, intravesical instillation is associated with several challenges, including pain, urological infection, and frequent clinic visits for catheterization; these difficulties support the need for a simple and easy intravesical drug delivery platform. Here, we propose a novel biodegradable intravesical device capable of long-term, local drug delivery without a retrieval procedure. The intravesical device is composed of drug encapsulating biodegradable polycaprolactone (PCL) microcapsules and connected by a bioabsorbable Polydioxanone (PDS) suture with NdFeB magnets in the end. The device is easily inserted into the bladder and forms a 'ring' shape optimized for maximal mechanical stability as informed by finite element analysis. In this study, inserted devices were retained in a swine model for 4 weeks. Using this device, we evaluated the system's capacity for delivery of lidocaine and resiquimod and demonstrated prolonged drug release. Moreover, a cost-effectiveness analysis supports device implementation compared to the standard of care. Our data support that this device can be a versatile drug delivery platform for urologic medications.

Patient and Health Care Worker Perceptions of Communication and Ability to Identify Emotion When Wearing Standard and Transparent Masks.

Importance: Adoption of mask wearing in response to the COVID-19 pandemic alters daily communication. Objective: To assess communication barriers associated with mask wearing in patient-clinician interactions and individuals who are deaf and hard of hearing. Design, Setting, and Participants: This pilot cross-sectional survey study included the general population, health care workers, and health care workers who are deaf or hard of hearing in the United States. Volunteers were sampled via an opt-in survey panel and nonrandomized convenience sampling. The general population survey was conducted between January 5 and January 8, 2021. The health care worker surveys were conducted between December 3, 2020, and January 3, 2021. Respondents viewed 2 short videos of a study author wearing both a standard and transparent N95 mask and answered questions regarding mask use, communication, preference, and fit. Surveys took 15 to 20 minutes to complete. Main Outcomes and Measures: Participants' perceptions were assessed surrounding the use of both mask types related to communication and the ability to express emotions. Results: The national survey consisted of 1000 participants (mean [SD] age, 48.7 [18.5] years; 496 [49.6%] women) with a response rate of 92.25%. The survey of general health care workers consisted of 123 participants (mean [SD] age, 49.5 [9.0] years; 84 [68.3%] women), with a response rate of 11.14%. The survey of health care workers who are deaf or hard of hearing consisted of 45 participants (mean [SD] age, 54.5 [9.0] years; 30 [66.7%] women) with a response rate of 23.95%. After viewing a video demonstrating a study author wearing a transparent N95 mask, 781 (78.1%) in the general population, 109 general health care workers (88.6%), and 38 health care workers who are deaf or hard of hearing (84.4%) were able to identify the emotion being expressed, in contrast with 201 (20.1%), 25 (20.5%), and 11 (24.4%) for the standard opaque N95 mask. In the general population, 450 (45.0%) felt positively about interacting with a health care worker wearing a transparent mask; 76 general health care workers (61.8%) and 37 health care workers who are deaf or hard of hearing (82.2%) felt positively about wearing a transparent mask to communicate with patients. Conclusions and Relevance: The findings of this study suggest that transparent masks could help improve communication during the COVID-19 pandemic, particularly for individuals who are deaf and hard of hearing.

Personalized Radiation Attenuating Materials for Gastrointestinal Mucosal Protection.

Cancer patients undergoing therapeutic radiation routinely develop injury of the adjacent gastrointestinal (GI) tract mucosa due to treatment. To reduce radiation dose to critical GI structures including the rectum and oral mucosa, 3D-printed GI radioprotective devices composed of high-Z materials are generated from patient CT scans. In a radiation proctitis rat model, a significant reduction in crypt injury is demonstrated with the device compared to without (p < 0.0087). Optimal device placement for radiation attenuation is further confirmed in a swine model. Dosimetric modeling in oral cavity cancer patients demonstrates a 30% radiation dose reduction to the normal buccal mucosa and a 15.2% dose reduction in the rectum for prostate cancer patients with the radioprotectant material in place compared to without. Finally, it is found that the rectal radioprotectant device is more cost-effective compared to a hydrogel rectal spacer. Taken together, these data suggest that personalized radioprotectant devices may be used to reduce GI tissue injury in cancer patients undergoing therapeutic radiation.

Implantable system for chronotherapy.

Diurnal variation in enzymes, hormones, and other biological mediators has long been recognized in mammalian physiology. Developments in pharmacobiology over the past few decades have shown that timing drug delivery can enhance drug efficacy. Here, we report the development of a battery-free, refillable, subcutaneous, and trocar-compatible implantable system that facilitates chronotherapy by enabling tight control over the timing of drug administration in response to external mechanical actuation. The external wearable system is coupled to a mobile app to facilitate control over dosing time. Using this system, we show the efficacy of bromocriptine on glycemic control in a diabetic rat model. We also demonstrate that antihypertensives can be delivered through this device, which could have clinical applications given the recognized diurnal variation of hypertension-related complications. We anticipate that implants capable of chronotherapy will have a substantial impact on our capacity to enhance treatment effectiveness for a broad range of chronic conditions.

Temperature-responsive biometamaterials for gastrointestinal applications.

We hypothesized that ingested warm fluids could act as triggers for biomedical devices. We investigated heat dissipation throughout the upper gastrointestinal (GI) tract by administering warm (55°C) water to pigs and identified two zones in which thermal actuation could be applied: esophageal (actuation through warm water ingestion) and extra-esophageal (protected from ingestion of warm liquids and actuatable by endoscopically administered warm fluids). Inspired by a blooming flower, we developed a capsule-sized esophageal system that deploys using elastomeric elements and then recovers its original shape in response to thermal triggering of shape-memory nitinol springs by ingestion of warm water. Degradable millineedles incorporated into the system could deliver model molecules to the esophagus. For the extra-esophageal compartment, we developed a highly flexible macrostructure (mechanical metamaterial) that deforms into a cylindrical shape to safely pass through the esophagus and deploys into a fenestrated spherical shape in the stomach, capable of residing safely in the gastric cavity for weeks. The macrostructure uses thermoresponsive elements that dissociate when triggered with the endoscopic application of warm (55°C) water, allowing safe passage of the components through the GI tract. Our gastric-resident platform acts as a gram-level long-lasting drug delivery dosage form, releasing small-molecule drugs for 2 weeks. We anticipate that temperature-triggered systems could usher the development of the next generation of stents, drug delivery, and sensing systems housed in the GI tract.

Endoscopically Injectable Shear-Thinning Hydrogels Facilitating Polyp Removal.

Submucosal elevation, the process of instilling material in the submucosal space for separation of the surface mucosa and deeper muscularis layer, is a significant aspect of the endoscopic mucosal resection of large lesions performed to facilitate lesion removal and maximize safety. Submucosal injection, when applied, has historically been performed with normal saline, though this is limited by its rapid dissipation; solutions ideally need to be easily injectable, biocompatible, and provide a long-lasting submucosal cushion with a desirable height. Here, reported is a new set of materials, endoscopically injectable shear-thinning hydrogels, meeting these requirements because of their biocompatible components and ability to form a solid hydrogel upon injection. These findings are supported by evaluation in a large animal model and ultimately demonstrate the potential of these shear-thinning hydrogels to serve as efficient submucosal injection fluids for cushion development. Given these unique characteristics, their broad application in mucosal resection techniques is anticipated.

3D-Printed Gastric Resident Electronics.

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.