Adhesive-Free, Stretchable, and Permeable Multiplex Wound Care Platform.

The wound healing process remains a poorly understood biological mechanism. The high morbidity and mortality rates associated with chronic wounds are a critical concern to the health care industry. Although assessments and treatment options exist, these strategies have primarily relied on static wound dressings that do not consider the dynamic physicochemical microenvironment and can often create additional complications through the frequent dressing changing procedure. Inspired by the need for engineering "smart" bandages, this study resulted in a multifaceted approach to developing an adhesive-free, permeable, and multiplex sensor system. The electronic-extracellular matrix (e-ECM) platform is capable of noninvasively monitoring chemical and physical changes in real-time on a flexible, stretchable, and permeable biointegrated platform. The multiplex sensors are constructed atop a soft, thin, and microfibrous substrate of silicone to yield a conformal, adhesive-free, convective, or diffusive wound exudate flow, and passive gas transfer for increased cellular epithelization and unobstructed physical and chemical sensor monitoring at the wound site. This platform emulates the native epidermal mechanics and physical extracellular matrix architecture for intimate bio-integration. The multiple biosensor array can continuously examine inflammatory biomarker such as lactate, glucose, pH, oxygen, and wound temperature that correlates to the wound healing status. Additionally, a heating element was incorporated to maintain the optimal thermal conditions at the wound bed. The e-ECM electrochemical biosensors were tested in vitro, within phosphate-buffered saline, and ex vivo, within wound exudate. The "smart" wound bandage combines biocompatible materials, treatments, and monitoring modalities on a microfibrous platform for complex wound dynamic control and analysis.

Dietary Factors, Time of the Week, Physical Fitness and Saliva Cortisol: Their Modulatory Effect on Mental Distress and Mood.

Background: The purpose of the study was to assess the effect of diet quality and physical fitness on saliva cortisol, mood, and mental distress. These relationships were compared between a peak weekday (Wednesday) and a weekend day (Saturday) when mood may fluctuate. Methods: Forty-eight healthy college students participated in the study. Participants completed the Mood and Anxiety Symptom (MASQ) and Kessler Psychological Distress Scale 10 questionnaires on Wednesday and Saturday and recorded their diet for three days. Saliva was collected before and after a workout for cortisol extraction. Results: SA had significantly higher saliva cortisol levels post-workout but lower MASQ scores on Saturday (p < 0.05). There was a very significant association between MASQ scores on Wednesday (p = 0.005), which became less significant on Saturday. In addition, lower BMI values and high-fat consumption were associated with higher cortisol levels after exercise (p < 0.05). Conclusions: There is a strong link between dietary factors, cortisol levels, mood, and time of the week. In addition, our results suggest that saliva cortisol levels may not be directly linked to negative affect but are influenced by diet quality when mental distress exists. In addition, physical fitness may play a role in improving mood during weekends.

Upcycling Compact Discs for Flexible and Stretchable Bioelectronic Applications.

Electronic waste is a global issue brought about by the short lifespan of electronics. Viable methods to relieve the inundated disposal system by repurposing the enormous amount of electronic waste remain elusive. Inspired by the need for sustainable solutions, this study resulted in a multifaceted approach to upcycling compact discs. The once-ubiquitous plates can be transformed into stretchable and flexible biosensors. Our experiments and advanced prototypes show that effective, innovative biosensors can be developed at a low-cost. An affordable craft-based mechanical cutter allows pre-determined patterns to be scored on the recycled metal, an essential first step for producing stretchable, wearable electronics. The active metal harvested from the compact discs was inert, cytocompatible, and capable of vital biopotential measurements. Additional studies examined the material's resistive emittance, temperature sensing, real-time metabolite monitoring performance, and moisture-triggered transience. This sustainable approach for upcycling electronic waste provides an advantageous research-based waste stream that does not require cutting-edge microfabrication facilities, expensive materials, and high-caliber engineering skills.

Sweat and saliva cortisol response to stress and nutrition factors.

Cortisol is a biomarker for stress monitoring; however, the biomedical and clinical relevance is still controversial due to the complexity of cortisol secretion mechanisms and their circadian cycles as well as environmental factors that affect physiological cortisol level, which include individual mood and dietary intake. To further investigate this multifaceted relationship, a human pilot study examined cortisol concentration in sweat and saliva samples collected from 48 college-aged participants during aerobic exercise sessions along with mental distress and nutrition surveys. Enzyme-linked immunosorbent assays determined highly significant differences between apocrine-dominant sweat (AP), saliva before exercise (SBE), and saliva after exercise (SAE) cortisol concentration (AP-SBE: p = 0.0017, AP-SAE: p = 0.0102). A significantly greater AP cortisol concentration was detected in males compared to females (p = 0.0559), and significant SAE cortisol concentration differences were also recorded between recreational athletes and non-athletes (p = 0.044). However, Kessler 10 Psychological Distress Scale (K10) scores, an examination administered to deduce overall wellness, provided no significant differences between males and females or athletes and non-athletes in distress levels, which statistically signifies a direct relationship to cortisol was not present. For further analysis, dietary intake from all participants was considered to investigate whether a multiplexed association was prevalent between nutrition, mood, and cortisol release. Significant positive correlations between AP cortisol, SAE cortisol, K10 scores, and fat intake among female participants and athletes were discovered. The various machine learning algorithms utilized the extensive connections between dietary intake, overall well-being, sex factors, athletic activity, and cortisol concentrations in various biofluids to predict K10 scores. Indeed, the understanding of physiochemical stress response and the associations between studied factors can advance algorithm developments for cortisol biosensing systems to mitigate stress-based illnesses and improve an individual's quality of life.

Stress Monitoring and Recent Advancements in Wearable Biosensors.

The stress response allows the body to overcome obstacles and prepare for threats, but sustained levels of stress can damage one's health. Stress has long been measured through physical tests and questionnaires that rely primarily on user-inputted data, which can be subjective and inaccurate. To quantify the amount of stress that the body is experiencing biologically, analytical detection of biomarkers associated with the stress response recently have been developed. Novel stress sensing devices focus on cortisol sweat sensing as a part of wearable, flexible devices. These devices promise a real-time, continuous collection of stress data that can be used in clinical diagnoses or for personal stress monitoring and mediation.

Highly Conductive Collagen by Low-Temperature Atomic Layer Deposition of Platinum.

In modern biomaterial-based electronics, conductive and flexible biomaterials are gaining increasing attention for their wide range of applications in biomedical and wearable electronics industries. The ecofriendly, biodegradable, and self-resorbable nature of these materials makes them an excellent choice in fabricating green and transient electronics. Surface functionalization of these biomaterials is required to cater to the need of designing electronics based on these substrate materials. In this work, a low-temperature atomic layer deposition (ALD) process of platinum (Pt) is presented to deposit a conductive thin film on collagen biomaterials, for the first time. Surface characterization revealed that a very thin ALD-deposited seed layer of TiO2 on the collagen surface prior to Pt deposition is an alternative for achieving a better nucleation and 100% surface coverage of ultrathin Pt on collagen surfaces. The presence of a pure metallic Pt thin film was confirmed from surface chemical characterization. Electrical characterization proved the existence of a continuous and conductive Pt thin film (∼27.8 ± 1.4 nm) on collagen with a resistivity of 295 ± 30 µΩ cm, which occurred because of the virtue of TiO2. Analysis of its electronic structures showed that the presence of metastable state due to the presence of TiO2 enables electrons to easily flow from valence into conductive bands. As a result, this turned collagen into a flexible conductive biomaterial.

Comparison of Colorimetric Analyses to Determine Cortisol in Human Sweat.

Colorimetric analysis, which relies on a chemical reaction to facilitate a change in visible color, is a great strategy for detecting cortisol, which is necessary to diagnose and manage the wide variety of diseases related to the hormone, because it is simple in design, inexpensive, and reliable as a standard cortisol analysis technique. In this study, four different colorimetric cortisol analyses that use various chromogens, which include sulfuric acid, Porter-Silber reagent, Prussian blue, and blue tetrazolium, are studied. Modifications to the classic Porter-Silber method are made by increasing the carbon content of the alcohol and adding gold nanoparticles, which result in a twofold increase in reaction rate and a slight decrease in the limit of detection (LoD). After a comparison of the reaction rate, LoD, dynamic range, characteristic peaks, and color stability of all methods, blue tetrazolium demonstrates a low LoD (97 ng/mL), broad dynamic range (0.05-2 µg/mL), and quick reaction rate (color development as fast as 10 min), which are well within the requirements for human biofluids. Cortisol in artificial saliva and sweat and in human sweat was determined while confirming that no excipients or other biomarkers interfered with the reactions. Twenty-one human sweat samples were tested using blue tetrazolium and revealed a significant difference between male and female apocrine cortisol concentrations and showed a highly significant difference between apocrine and eccrine cortisol concentrations. Colorimetric methods of cortisol can compete with existing electrochemical sensors because of their similar accuracy and detection range in certain wearable biosensor applications. The simplicity of colorimetric methods advances potential applications in skin-interfaced bio-electronics and point-of-care devices.

Skin-inspired, open mesh electrochemical sensors for lactate and oxygen monitoring.

Research in wearable electronics has paved the way for next-generation technology, sought to create point-of-care biosensors that combine chemical sensing on a biocompatible platform with a broad range of applications in human health monitoring. Despite significant progress, the microspatial mechanical mismatch and fluid-impermeable interface presented between skin and the electronics create adscititious problems in device lamination, conformality, and long-term monitoring. Herein, we engineered a skin-inspired, deterministically patterned, electrochemical biosensor that can be fully integrated with the curvilinear surface of the human body, while mechanically adapting to the natural stresses applied to the skin and allowing the mass transfer of gas and fluids. In particular, we developed mechanically-compliant lattice-structured biosensors for the continuous evaluation of lactate and oxygen. Systematic studies of the sensor performance were evaluated with variations in polymeric membranes and its ability to withstand commonplace harsh, multiaxial stresses.

Wearable Technology for Chronic Wound Monitoring: Current Dressings, Advancements, and Future Prospects.

Chronic non-healing wounds challenge tissue regeneration and impair infection regulation for patients afflicted with this condition. Next generation wound care technology capable of in situ physiological surveillance which can diagnose wound parameters, treat various chronic wound symptoms, and reduce infection at the wound noninvasively with the use of a closed loop therapeutic system would provide patients with an improved standard of care and an accelerated wound repair mechanism. The indicating biomarkers specific to chronic wounds include blood pressure, temperature, oxygen, pH, lactate, glucose, interleukin-6 (IL-6), and infection status. A wound monitoring device would help decrease prolonged hospitalization, multiple doctors' visits, and the expensive lab testing associated with the diagnosis and treatment of chronic wounds. A device capable of monitoring the wound status and stimulating the healing process is highly desirable. In this review, we discuss the impaired physiological states of chronic wounds and explain the current treatment methods. Specifically, we focus on improvements in materials, platforms, fabrication methods for wearable devices, and quantitative analysis of various biomarkers vital to wound healing progress.

Super-Absorbent Polymer Valves and Colorimetric Chemistries for Time-Sequenced Discrete Sampling and Chloride Analysis of Sweat via Skin-Mounted Soft Microfluidics.

This paper introduces super absorbent polymer valves and colorimetric sensing reagents as enabling components of soft, skin-mounted microfluidic devices designed to capture, store, and chemically analyze sweat released from eccrine glands. The valving technology enables robust means for guiding the flow of sweat from an inlet location into a collection of isolated reservoirs, in a well-defined sequence. Analysis in these reservoirs involves a color responsive indicator of chloride concentration with a formulation tailored to offer stable operation with sensitivity optimized for the relevant physiological range. Evaluations on human subjects with comparisons against ex situ analysis illustrate the practical utility of these advances.

Needle-shaped ultrathin piezoelectric microsystem for guided tissue targeting via mechanical sensing.

Needles for percutaneous biopsies of tumour tissue can be guided by ultrasound or computed tomography. However, despite best imaging practices and operator experience, high rates of inadequate tissue sampling, especially for small lesions, are common. Here, we introduce a needle-shaped ultrathin piezoelectric microsystem that can be injected or mounted directly onto conventional biopsy needles and used to distinguish abnormal tissue during the capture of biopsy samples, through quantitative real-time measurements of variations in tissue modulus. Using well-characterized synthetic soft materials, explanted tissues and animal models, we establish experimentally and theoretically the fundamental operating principles of the microsystem, as well as key considerations in materials choices and device designs. Through systematic tests on human livers with cancerous lesions, we demonstrate that the piezoelectric microsystem provides quantitative agreement with magnetic resonance elastography, the clinical gold standard for the measurement of tissue modulus. The piezoelectric microsystem provides a foundation for the design of tools for the rapid, modulus-based characterization of tissues.

Chemical Sensing Systems that Utilize Soft Electronics on Thin Elastomeric Substrates with Open Cellular Designs.

A collection of materials and device architectures are introduced for thin, stretchable arrays of ion sensors that mount on open cellular substrates to facilitate solution exchange for use in biointegrated electronics. The results include integration strategies and studies of fundamental characteristics in chemical sensing and mechanical response. The latter involves experimental measurements and theoretical simulations that establish important considerations in the design of low modulus, stretchable properties in cellular substrates, and in the realization of advanced capabilities in spatiotemporal mapping of chemicals' gradients. As the chemical composition of extracellular fluids contains valuable information related to biological function, the concepts introduced here have potential utility across a range of skin- and internal-organ-integrated electronics where soft mechanics, fluidic permeability, and advanced chemical sensing capabilities are key requirements.

A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat.

Capabilities in health monitoring enabled by capture and quantitative chemical analysis of sweat could complement, or potentially obviate the need for, approaches based on sporadic assessment of blood samples. Established sweat monitoring technologies use simple fabric swatches and are limited to basic analysis in controlled laboratory or hospital settings. We present a collection of materials and device designs for soft, flexible, and stretchable microfluidic systems, including embodiments that integrate wireless communication electronics, which can intimately and robustly bond to the surface of the skin without chemical and mechanical irritation. This integration defines access points for a small set of sweat glands such that perspiration spontaneously initiates routing of sweat through a microfluidic network and set of reservoirs. Embedded chemical analyses respond in colorimetric fashion to markers such as chloride and hydronium ions, glucose, and lactate. Wireless interfaces to digital image capture hardware serve as a means for quantitation. Human studies demonstrated the functionality of this microfluidic device during fitness cycling in a controlled environment and during long-distance bicycle racing in arid, outdoor conditions. The results include quantitative values for sweat rate, total sweat loss, pH, and concentration of chloride and lactate.

Ultrathin Injectable Sensors of Temperature, Thermal Conductivity, and Heat Capacity for Cardiac Ablation Monitoring.

Knowledge of the distributions of temperature in cardiac tissue during and after ablation is important in advancing a basic understanding of this process, and for improving its efficacy in treating arrhythmias. Technologies that enable real-time temperature detection and thermal characterization in the transmural direction can help to predict the depths and sizes of lesion that form. Herein, materials and designs for an injectable device platform that supports precision sensors of temperature and thermal transport properties distributed along the length of an ultrathin and flexible needle-type polymer substrate are introduced. The resulting system can insert into the myocardial tissue, in a minimally invasive manner, to monitor both radiofrequency ablation and cryoablation, in a manner that has no measurable effects on the natural mechanical motions of the heart. The measurement results exhibit excellent agreement with thermal simulations, thereby providing improved insights into lesion transmurality.

Fabrication of nitric oxide-releasing porous polyurethane membranes-coated needle-type implantable glucose biosensors.

The active release of pharmaceutical agents and the use of porous sensor membranes represent the two most promising strategies for addressing the poor tissue biocompatibility of implantable glucose biosensors. Herein, we describe the combination of these approaches to create nitric oxide (NO)-releasing porous fiber mat-modified sensor membranes. An electrospinning method was used to directly modify needle-type glucose biosensors with the NO donor-loaded fibers. The resulting NO-releasing fiber mat (540 ± 139 nm fiber diameter, 94.1 ± 3.7% porosity) released ~100 nmol of NO per mg of polyurethane over 6 h while maintaining a porous structure without leaching of the NO donor, even in serum. The porous fiber membrane did not influence the analytical performance of the biosensor when ≤50 µm thick.

Nitric oxide-releasing silica nanoparticle-doped polyurethane electrospun fibers.

Electrospun polyurethane fibers doped with nitric oxide (NO)-releasing silica particles are presented as novel macromolecular scaffolds with prolonged NO-release and high porosity. Fiber diameter (119-614 nm) and mechanical strength (1.7-34.5 MPa of modulus) were varied by altering polyurethane type and concentration, as well as the NO-releasing particle composition, size, and concentration. The resulting NO-releasing electrospun nanofibers exhibited ~83% porosity with flexible plastic or elastomeric behavior. The use of N-diazeniumdiolate- or S-nitrosothiol-modified particles yielded scaffolds exhibiting a wide range of NO release totals and durations (7.5 nmol mg(-1)-0.12 µmol mg(-1) and 7 h to 2 weeks, respectively). The application of NO-releasing porous materials as coatings for subcutaneous implants may improve tissue biocompatibility by mitigating the foreign body response and promoting cell integration.

The effect of nitric oxide surface flux on the foreign body response to subcutaneous implants.

Although the release of nitric oxide (NO) from biomaterials has been shown to reduce the foreign body response (FBR), the optimal NO release kinetics and doses remain unknown. Herein, polyurethane-coated wire substrates with varying NO release properties were implanted into porcine subcutaneous tissue for 3, 7, 21 and 42 d. Histological analysis revealed that materials with short NO release durations (i.e., 24 h) were insufficient to reduce the collagen capsule thickness at 3 and 6 weeks, whereas implants with longer release durations (i.e., 3 and 14 d) and greater NO payloads significantly reduced the collagen encapsulation at both 3 and 6 weeks. The acute inflammatory response was mitigated most notably by systems with the longest duration and greatest dose of NO release, supporting the notion that these properties are most critical in circumventing the FBR for subcutaneous biomedical applications (e.g., glucose sensors).

Local delivery of nitric oxide: targeted delivery of therapeutics to bone and connective tissues.

Non-invasive treatment of injuries and disorders affecting bone and connective tissue remains a significant challenge facing the medical community. A treatment route that has recently been proposed is nitric oxide (NO) therapy. Nitric oxide plays several important roles in physiology with many conditions lacking adequate levels of NO. As NO is a radical, localized delivery via NO donors is essential to promoting biological activity. Herein, we review current literature related to therapeutic NO delivery in the treatment of bone, skin and tendon repair.

Glucose sensor membranes for mitigating the foreign body response.

Continuous glucose monitoring devices remain limited in their duration of use due to difficulties presented by the foreign body response (FBR), which impairs sensor functionality immediately following implantation via biofouling and leukocyte infiltration. The FBR persists through the life of the implant, culminating with fibrous encapsulation and isolation from normal tissue. These issues have led researchers to develop strategies to mitigate the FBR and improve tissue integration. Studies have often focused on abating the FBR using various outer coatings, thereby changing the chemical or physical characteristics of the sensor surface. While such strategies have led to some success, they have failed to fully integrate the sensor into surrounding tissue. To further address biocompatibility, researchers have designed coatings capable of actively releasing biological agents (e.g., vascular endothelial growth factor, dexamethasone, and nitric oxide) to direct the FBR to induce tissue integration. Active release approaches have proven promising and, when combined with biocompatible coating materials, may ultimately improve the in vivo lifetime of subcutaneous glucose biosensors. This article focuses on strategies currently under development for mitigating the FBR.