A wireless, implantable bioelectronic system for monitoring urinary bladder function following surgical recovery.

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.

Materials and Device Designs for Wireless Monitoring of Temperature and Thermal Transport Properties of Wound Beds during Healing.

Chronic wounds represent a major health risk for diabetic patients. Regeneration of such wounds requires regular medical treatments over periods that can extend for several months or more. Schemes for monitoring the healing process can provide important feedback to the patient and caregiver. Although qualitative indicators such as malodor or fever can provide some indirect information, quantitative measurements of the wound bed have the potential to yield important insights. The work presented here introduces materials and engineering designs for a wireless system that captures spatio-temporal temperature and thermal transport information across the wound continuously throughout the healing process. Systematic experimental and computational studies establish the materials aspects and basic capabilities of this technology. In vivo studies reveal that both the temperature and the changes in this quantity offer information on wound status, with indications of initial exothermic reactions and mechanisms of scar tissue formation. Bioresorbable materials serve as the foundations for versions of this device that create possibilities for monitoring on and within the wound site, in a way that bypasses the risks of physical removal.

An on-demand bioresorbable neurostimulator.

Bioresorbable bioelectronics, with their natural degradation properties, hold significant potential to eliminate the need for surgical removal. Despite notable achievements, two major challenges hinder their practical application in medical settings. First, they necessitate sustainable energy solutions with biodegradable components via biosafe powering mechanisms. More importantly, reliability in their function is undermined by unpredictable device lifetimes due to the complex polymer degradation kinetics. Here, we propose an on-demand bioresorbable neurostimulator to address these issues, thus allowing for clinical operations to be manipulated using biosafe ultrasound sources. Our ultrasound-mediated transient mechanism enables (1) electrical stimulation through transcutaneous ultrasound-driven triboelectricity and (2) rapid device elimination using high-intensity ultrasound without adverse health effects. Furthermore, we perform neurophysiological analyses to show that our neurostimulator provides therapeutic benefits for both compression peripheral nerve injury and hereditary peripheral neuropathy. We anticipate that the on-demand bioresorbable neurostimulator will prove useful in the development of medical implants to treat peripheral neuropathy.

Piezoelectric and Triboelectric Nanogenerators for Enhanced Wound Healing.

Wound healing is a highly orchestrated biological process characterized by sequential phases involving inflammation, proliferation, and tissue remodeling, and the role of endogenous electrical signals in regulating these phases has been highlighted. Recently, external electrostimulation has been shown to enhance these processes by promoting cell migration, extracellular matrix formation, and growth factor release while suppressing pro-inflammatory signals and reducing the risk of infection. Among the innovative approaches, piezoelectric and triboelectric nanogenerators have emerged as the next generation of flexible and wireless electronics designed for energy harvesting and efficiently converting mechanical energy into electrical power. In this review, we discuss recent advances in the emerging field of nanogenerators for harnessing electrical stimulation to accelerate wound healing. We elucidate the fundamental mechanisms of wound healing and relevant bioelectric physiology, as well as the principles underlying each nanogenerator technology, and review their preclinical applications. In addition, we address the prominent challenges and outline the future prospects for this emerging era of electrical wound-healing devices.

A Miniaturized, Battery-Free, Wireless Wound Monitor That Predicts Wound Closure Rate Early.

Diabetic foot ulcers are chronic wounds that affect millions and increase the risk of amputation and mortality, highlighting the critical need for their early detection. Recent demonstrations of wearable sensors enable real-time wound assessment, but they rely on bulky electronics, making them difficult to interface with wounds. Herein, a miniaturized, wireless, battery-free wound monitor that measures lactate in real-time and seamlessly integrates with bandages for conformal attachment to the wound bed is introduced. Lactate is selected due to its multifaceted role in initiating healing. Studies in healthy and diabetic mice reveal distinct lactate profiles for normal and impaired healing wounds. A mathematical model based on the sensor data predicts wound closure rate within the first 3 days post-injury with ≈76% accuracy, which increases to ≈83% when pH is included. These studies underscore the significance of monitoring biomarkers during the inflammation phase, which can offer several benefits, including short-term use of wound monitors and their easy removal, resulting in lower risks of injury and infection at the wound site. Improvements in prediction accuracy can be achieved by designing mathematical models that build on multiple wound parameters such as pro-inflammatory and metabolic markers. Achieving this goal will require designing multi-analyte wound monitors.

Materials and Design Approaches for a Fully Bioresorbable, Electrically Conductive and Mechanically Compliant Cardiac Patch Technology.

Myocardial infarction (MI) is one of the leading causes of death and disability. Recently developed cardiac patches provide mechanical support and additional conductive paths to promote electrical signal propagation in the MI area to synchronize cardiac excitation and contraction. Cardiac patches based on conductive polymers offer attractive features; however, the modest levels of elasticity and high impedance interfaces limit their mechanical and electrical performance. These structures also operate as permanent implants, even in cases where their utility is limited to the healing period of tissue damaged by the MI. The work presented here introduces a highly conductive cardiac patch that combines bioresorbable metals and polymers together in a hybrid material structure configured in a thin serpentine geometry that yields elastic mechanical properties. Finite element analysis guides optimized choices of layouts in these systems. Regular and synchronous contraction of human induced pluripotent stem cell-derived cardiomyocytes on the cardiac patch and ex vivo studies offer insights into the essential properties and the bio-interface. These results provide additional options in the design of cardiac patches to treat MI and other cardiac disorders.

Bioresorbable, wireless, and battery-free system for electrotherapy and impedance sensing at wound sites.

Chronic wounds, particularly those associated with diabetes mellitus, represent a growing threat to public health, with additional notable economic impacts. Inflammation associated with these wounds leads to abnormalities in endogenous electrical signals that impede the migration of keratinocytes needed to support the healing process. This observation motivates the treatment of chronic wounds with electrical stimulation therapy, but practical engineering challenges, difficulties in removing stimulation hardware from the wound site, and absence of means to monitor the healing process create barriers to widespread clinical use. Here, we demonstrate a miniaturized wireless, battery-free bioresorbable electrotherapy system that overcomes these challenges. Studies based on a splinted diabetic mouse wound model confirm the efficacy for accelerated wound closure by guiding epithelial migration, modulating inflammation, and promoting vasculogenesis. Changes in the impedance provide means for tracking the healing process. The results demonstrate a simple and effective platform for wound site electrotherapy.

Biodegradable, three-dimensional colorimetric fliers for environmental monitoring.

Recently reported winged microelectronic systems offer passive flight mechanisms as a dispersal strategy for purposes in environmental monitoring, population surveillance, pathogen tracking, and other applications. Initial studies indicate potential for technologies of this type, but advances in structural and responsive materials and in aerodynamically optimized geometries are necessary to improve the functionality and expand the modes of operation. Here, we introduce environmentally degradable materials as the basis of 3D fliers that allow remote, colorimetric assessments of multiple environmental parameters-pH, heavy metal concentrations, and ultraviolet exposure, along with humidity levels and temperature. Experimental and theoretical investigations of the aerodynamics of these systems reveal design considerations that include not only the geometries of the structures but also their mass distributions across a range of bioinspired designs. Preliminary field studies that rely on drones for deployment and for remote colorimetric analysis by machine learning interpretation of digital images illustrate scenarios for practical use.

A bioresorbable peripheral nerve stimulator for electronic pain block.

Local electrical stimulation of peripheral nerves can block the propagation of action potentials, as an attractive alternative to pharmacological agents for the treatment of acute pain. Traditional hardware for such purposes, however, involves interfaces that can damage nerve tissue and, when used for temporary pain relief, that impose costs and risks due to requirements for surgical extraction after a period of need. Here, we introduce a bioresorbable nerve stimulator that enables electrical nerve block and associated pain mitigation without these drawbacks. This platform combines a collection of bioresorbable materials in architectures that support stable blocking with minimal adverse mechanical, electrical, or biochemical effects. Optimized designs ensure that the device disappears harmlessly in the body after a desired period of use. Studies in live animal models illustrate capabilities for complete nerve block and other key features of the technology. In certain clinically relevant scenarios, such approaches may reduce or eliminate the need for use of highly addictive drugs such as opioids.

Acute Liver Failure Secondary to Hepatic Infiltration of Malignant Melanoma.

Acute liver failure due to malignant melanoma is uncommon. We presents a case of acute liver failure secondary to hepatic infiltration of a malignant melanoma. An 86-year-old man was admitted with elevated liver enzymes and an increased lactate dehydrogenase level. His condition progressed to acute liver failure, but the etiology of liver failure was unclear. Esophagogastroduodenoscopy was performed to evaluate dyspepsia, which showed signs indicative of malignant melanoma. Based on the endoscopy findings and elevated liver enzyme levels, liver biopsy was performed to confirm the presence of malignant melanoma. Hepatic infiltration of malignant melanoma was observed histologically. However, massive and diffuse liver metastasis is very rare and difficult to identify on imaging studies. If the etiology of liver failure is unclear, diffuse metastatic melanoma infiltration should be considered as differential diagnosis. Early liver biopsy can help to clarify the diagnosis.

A Skin-Interfaced, Miniaturized Microfluidic Analysis and Delivery System for Colorimetric Measurements of Nutrients in Sweat and Supply of Vitamins Through the Skin.

Nutrients play critical roles in maintaining core physiological functions and in preventing diseases. Technologies for delivering these nutrients and for monitoring their concentrations can help to ensure proper nutritional balance. Eccrine sweat is a potentially attractive class of biofluid for monitoring purposes due to the ability to capture sweat easily and noninvasively from nearly any region of the body using skin-integrated microfluidic technologies. Here, a miniaturized system of this type is presented that allows simple, rapid colorimetric assessments of the concentrations of multiple essential nutrients in sweat, simultaneously and without any supporting electronics - vitamin C, calcium, zinc, and iron. A transdermal patch integrated directly with the microfluidics supports passive, sustained delivery of these species to the body throughout a period of wear. Comparisons of measurement results to those from traditional lab analysis methods demonstrate the accuracy and reliability of this platform. On-body tests with human subjects reveal correlations between the time dynamics of concentrations of these nutrients in sweat and those of the corresponding concentrations in blood. Studies conducted before and after consuming certain foods and beverages highlight practical capabilities in monitoring nutritional balance, with strong potential to serve as a basis for guiding personalized dietary choices.

Skin-Integrated Devices with Soft, Holey Architectures for Wireless Physiological Monitoring, With Applications in the Neonatal Intensive Care Unit.

Continuous monitoring of vital signs is an essential aspect of operations in neonatal and pediatric intensive care units (NICUs and PICUs), of particular importance to extremely premature and/or critically ill patients. Current approaches require multiple sensors taped to the skin and connected via hard-wired interfaces to external data acquisition electronics. The adhesives can cause iatrogenic injuries to fragile, underdeveloped skin, and the wires can complicate even the most routine tasks in patient care. Here, materials strategies and design concepts are introduced that significantly improve these platforms through the use of optimized materials, open (i.e., "holey") layouts and precurved designs. These schemes 1) reduce the stresses at the skin interface, 2) facilitate release of interfacial moisture from transepidermal water loss, 3) allow visual inspection of the skin for rashes or other forms of irritation, 4) enable triggered reduction of adhesion to reduce the probability for injuries that can result from device removal. A combination of systematic benchtop testing and computational modeling identifies the essential mechanisms and key considerations. Demonstrations on adult volunteers and on a neonate in an operating NICUs illustrate a broad range of capabilities in continuous, clinical-grade monitoring of conventional vital signs, and unconventional indicators of health status.

Battery-free, wireless soft sensors for continuous multi-site measurements of pressure and temperature from patients at risk for pressure injuries.

Capabilities for continuous monitoring of pressures and temperatures at critical skin interfaces can help to guide care strategies that minimize the potential for pressure injuries in hospitalized patients or in individuals confined to the bed. This paper introduces a soft, skin-mountable class of sensor system for this purpose. The design includes a pressure-responsive element based on membrane deflection and a battery-free, wireless mode of operation capable of multi-site measurements at strategic locations across the body. Such devices yield continuous, simultaneous readings of pressure and temperature in a sequential readout scheme from a pair of primary antennas mounted under the bedding and connected to a wireless reader and a multiplexer located at the bedside. Experimental evaluation of the sensor and the complete system includes benchtop measurements and numerical simulations of the key features. Clinical trials involving two hemiplegic patients and a tetraplegic patient demonstrate the feasibility, functionality and long-term stability of this technology in operating hospital settings.

Self-rechargeable cardiac pacemaker system with triboelectric nanogenerators.

Self-powered implantable devices have the potential to extend device operation time inside the body and reduce the necessity for high-risk repeated surgery. Without the technological innovation of in vivo energy harvesters driven by biomechanical energy, energy harvesters are insufficient and inconvenient to power titanium-packaged implantable medical devices. Here, we report on a commercial coin battery-sized high-performance inertia-driven triboelectric nanogenerator (I-TENG) based on body motion and gravity. We demonstrate that the enclosed five-stacked I-TENG converts mechanical energy into electricity at 4.9 µW/cm3 (root-mean-square output). In a preclinical test, we show that the device successfully harvests energy using real-time output voltage data monitored via Bluetooth and demonstrate the ability to charge a lithium-ion battery. Furthermore, we successfully integrate a cardiac pacemaker with the I-TENG, and confirm the ventricle pacing and sensing operation mode of the self-rechargeable cardiac pacemaker system. This proof-of-concept device may lead to the development of new self-rechargeable implantable medical devices.

Differential cardiopulmonary monitoring system for artifact-canceled physiological tracking of athletes, workers, and COVID-19 patients.

Soft, skin-integrated electronic sensors can provide continuous measurements of diverse physiological parameters, with broad relevance to the future of human health care. Motion artifacts can, however, corrupt the recorded signals, particularly those associated with mechanical signatures of cardiopulmonary processes. Design strategies introduced here address this limitation through differential operation of a matched, time-synchronized pair of high-bandwidth accelerometers located on parts of the anatomy that exhibit strong spatial gradients in motion characteristics. When mounted at a location that spans the suprasternal notch and the sternal manubrium, these dual-sensing devices allow measurements of heart rate and sounds, respiratory activities, body temperature, body orientation, and activity level, along with swallowing, coughing, talking, and related processes, without sensitivity to ambient conditions during routine daily activities, vigorous exercises, intense manual labor, and even swimming. Deployments on patients with COVID-19 allow clinical-grade ambulatory monitoring of the key symptoms of the disease even during rehabilitation protocols.

Transparent, Compliant 3D Mesostructures for Precise Evaluation of Mechanical Characteristics of Organoids.

Recently developed methods for transforming 2D patterns of thin-film materials into 3D mesostructures create many interesting opportunities in microsystems design. A growing area of interest is in multifunctional thermal, electrical, chemical, and optical interfaces to biological tissues, particularly 3D multicellular, millimeter-scale constructs, such as spheroids, assembloids, and organoids. Herein, examples of 3D mechanical interfaces are presented, in which thin ribbons of parylene-C form the basis of transparent, highly compliant frameworks that can be reversibly opened and closed to capture, envelop, and mechanically restrain fragile 3D tissues in a gentle, nondestructive manner, for precise measurements of viscoelastic properties using techniques in nanoindentation. Finite element analysis serves as a design tool to guide selection of geometries and material parameters for shape-matching 3D architectures tailored to organoids of interest. These computational approaches also quantitate all aspects of deformations during the processes of opening and closing the structures and of forces imparted by them onto the surfaces of enclosed soft tissues. Studies of cerebral organoids by nanoindentation show effective Young's moduli in the range from 1.5 to 2.5 kPa depending on the age of the organoid. This collection of results suggests broad utility of compliant 3D mesostructures in noninvasive mechanical measurements of millimeter-scale, soft biological tissues.

Three-dimensional, multifunctional neural interfaces for cortical spheroids and engineered assembloids.

Three-dimensional (3D), submillimeter-scale constructs of neural cells, known as cortical spheroids, are of rapidly growing importance in biological research because these systems reproduce complex features of the brain in vitro. Despite their great potential for studies of neurodevelopment and neurological disease modeling, 3D living objects cannot be studied easily using conventional approaches to neuromodulation, sensing, and manipulation. Here, we introduce classes of microfabricated 3D frameworks as compliant, multifunctional neural interfaces to spheroids and to assembloids. Electrical, optical, chemical, and thermal interfaces to cortical spheroids demonstrate some of the capabilities. Complex architectures and high-resolution features highlight the design versatility. Detailed studies of the spreading of coordinated bursting events across the surface of an isolated cortical spheroid and of the cascade of processes associated with formation and regrowth of bridging tissues across a pair of such spheroids represent two of the many opportunities in basic neuroscience research enabled by these platforms.

Bioresorbable Metals for Biomedical Applications: From Mechanical Components to Electronic Devices.

Bioresorbable metals and metal alloys are of growing interest for myriad uses in temporary biomedical implants. Examples range from structural elements as stents, screws, and scaffolds to electronic components as sensors, electrical stimulators, and programmable fluidics. The associated physical forms span mechanically machined bulk parts to lithographically patterned conductive traces, across a diversity of metals and alloys based on magnesium, zinc, iron, tungsten, and others. The result is a rich set of opportunities in healthcare materials science and engineering. This review article summarizes recent advances in this area, starting with an historical perspective followed by a discussion of materials options, considerations in biocompatibility, and device applications. Highlights are in system level bioresorbable electronic platforms that support functions as diagnostics and therapeutics in the context of specific, temporary clinical needs. A concluding section highlights challenges and emerging research directions.

MPRO: A Professionalism Curriculum to Enhance the Professional Identity Formation of University Premedical Students.

Limited opportunities exist for university premedical students to gain exposure to the realities of clinical practice through physician shadowing or through a formal curriculum. Medical Professionalism and Observership utilizes didactics, reflective writing, small- and large- group discussions, and clinical observerships to enhance the process of professional identity formation during a critical developmental window of late- adolescence. The pilot semester included a sample of 135 students, all in their sophomore, junior, or senior years of study at Rice University. Students were selected through an application process and paired with physicians at Houston Methodist Hospital based on specialty preference and availability. Students were required to participate in biweekly lectures and discussions and to submit a weekly reflection on topics discussed in the course and their shadowing experiences. Student evaluations were administered to survey changes in students' knowledge and perceptions of the curriculum. Selected reflections were read for evidence of professional identity formation. Lectures increased students' exposure to core competencies within the medical profession and influenced their desire to become physicians. Reflective writings demonstrated integration of these core competencies into the professional identity of students. Structured reflection and didactics, when coupled with physician shadowing, appear to promote integration of the values, beliefs, and attitudes of medical professionalism. Future studies should seek to demonstrate how such a curriculum affects professional identity formation through established measures, and to assess whether such a curriculum may influence students' preparedness for medical training and practice as they progress along their careers.