Improving disease prevention, diagnosis, and treatment using novel bionic technologies.

Increased human life expectancy, due in part to improvements in infant and childhood survival, more active lifestyles, in combination with higher patient expectations for better health outcomes, is leading to an extensive change in the number, type and manner in which health conditions are treated. Over the next decades as the global population rapidly progresses toward a super-aging society, meeting the long-term quality of care needs is forecast to present a major healthcare challenge. The goal is to ensure longer periods of good health, a sustained sense of well-being, with extended periods of activity, social engagement, and productivity. To accomplish these goals, multifunctionalized interfaces are an indispensable component of next generation medical technologies. The development of more sophisticated materials and devices as well as an improved understanding of human disease is forecast to revolutionize the diagnosis and treatment of conditions ranging from osteoarthritis to Alzheimer's disease and will impact disease prevention. This review examines emerging cutting-edge bionic materials, devices and technologies developed to advance disease prevention, and medical care and treatment in our elderly population including developments in smart bandages, cochlear implants, and the increasing role of artificial intelligence and nanorobotics in medicine.

Nickel foam supported porous copper oxide catalysts with noble metal-like activity for aqueous phase reactions.

Contiguous metal foams offer a multitude of advantages over conventional powders as supports for nanostructured heterogeneous catalysts; most critically a preformed 3-D porous framework ensuring full directional coverage of supported catalyst, and intrinsic ease of handling and recyclability. Nonetheless, metal foams remain comparatively underused in thermal catalysis compared to more conventional supports such as amorphous carbon, metal oxides, zeolites and more recently MOFs. Herein, we demonstrate a facile preparation of highly-reactive, robust, and easy to handle Ni foam-supported Cu-based metal catalysts. The highly sustainable synthesis requires no specialized equipment, no surfactants or additive redox reagents, uses water as solvent, and CuCl2(H2O)2 as precursor. The resulting material seeds as well-separated micro-crystalline Cu2(OH)3Cl evenly covering the Ni foam. Calcination above 400 °C transforms the Cu2(OH)3Cl to highly porous CuO. All materials display promising activity towards the reduction of 4-nitrophenol and methyl orange. Notably, our leading CuO-based material displays 4-nitrophenol reduction activity comparable with very reactive precious-metal based systems. Recyclability studies highlight the intrinsic ease of handling for the Ni foam support, and our results point to a very robust, highly recyclable catalyst system.

Polymeric Materials for Hemostatic Wound Healing.

Hemorrhage is one of the greatest threats to life on the battlefield, accounting for 50% of total deaths. Nearly 86% of combat deaths occur within the first 30 min after wounding. While external wound injuries can be treated mostly using visual inspection, abdominal or internal hemorrhages are more challenging to treat with regular hemostatic dressings because of deep wounds and points of injury that cannot be located properly. The need to treat trauma wounds from limbs, abdomen, liver, stomach, colon, spleen, arterial, venous, and/or parenchymal hemorrhage accompanied by severe bleeding requires an immediate solution that the first responders can apply to reduce rapid exsanguinations from external wounds, including in military operations. This necessitates the development of a unique, easy-to-use, FDA-approved hemostatic treatment that can deliver the agent in less than 30 s and stop bleeding within the first 1 to 2 min at the point of injury without application of manual pressure on the wounded area.

Intrarectal Xyloglucan Administration Reduces Disease Severity in the Dextran Sodium Sulfate Model of Mouse Colitis.

BACKGROUND: The pathophysiology of inflammatory bowel diseases remains poorly understood and treatment remains suboptimal for many patients. We hypothesize that the inflammatory milieu secondarily prolongs the injury and attenuates healing. We propose primary or adjuvant therapy with biocompatible adhesives to restore a barrier to protect submucosal structures, particularly stem cells. METHODS: We used the well-described mouse dextran sodium sulfate (DSS) model of colitis resembling human ulcerative colitis to test the therapeutic efficacy of intrarectal administration of the tamarind plant-derived xyloglucan (TXG) polymer adhesive which underwent extensive analytic characterization. Mice in control, DSS-only, TXG-only, and DSS + TXG groups were studied for gross (weight, blood in stool, length of colon) and multiple histologic parameters. RESULTS: Compared to DSS-only mice, TXG prevented the weight loss, occurrence of blood in the stool and colon shortening, with all those parameters not being statistically different from treatment naïve animals. Histologically, there was dramatic and highly statistically significant reduction in the total inflammatory index and protection from goblet cell loss, cellular infiltration, crypt abscess formation, epithelial erosion, granulation tissue, epithelial hyperplasia crypt irregularity and crypt loss. The TXG purity and characterization were established by nuclear magnetic resonance, infrared spectroscopy, differential scanning calorimetry, and texture analysis. CONCLUSION: The striking attenuation of disease severity by intrarectal TXG use warrants future investigations of natural bioadhesives with well-established high safety profiles, and which could potentially be derivatized to include therapeutically active moieties for local drug delivery.

Multimodal Sensing with a Three-Dimensional Piezoresistive Structure.

Sensors that reproduce the complex characteristics of cutaneous receptors in the skin have important potential in the context of artificial systems for controlled interactions with the physical environment. Multimodal responses with high sensitivity and wide dynamic range are essential for many such applications. This report introduces a simple, three-dimensional type of microelectromechanical sensor that incorporates monocrystalline silicon nanomembranes as piezoresistive elements in a configuration that enables separate, simultaneous measurements of multiple mechanical stimuli, such as normal force, shear force, and bending, along with temperature. The technology provides high sensitivity measurements with millisecond response times, as supported by quantitative simulations. The fabrication and assembly processes allow scalable production of interconnected arrays of such devices with capabilities in spatiotemporal mapping. Integration with wireless data recording and transmission electronics allows operation with standard consumer devices.

A wireless closed-loop system for optogenetic peripheral neuromodulation.

The fast-growing field of bioelectronic medicine aims to develop engineered systems that can relieve clinical conditions by stimulating the peripheral nervous system1-5. This type of technology relies largely on electrical stimulation to provide neuromodulation of organ function or pain. One example is sacral nerve stimulation to treat overactive bladder, urinary incontinence and interstitial cystitis (also known as bladder pain syndrome)4,6,7. Conventional, continuous stimulation protocols, however, can cause discomfort and pain, particularly when treating symptoms that can be intermittent (for example, sudden urinary urgency)8. Direct physical coupling of electrodes to the nerve can lead to injury and inflammation9-11. Furthermore, typical therapeutic stimulators target large nerve bundles that innervate multiple structures, resulting in a lack of organ specificity. Here we introduce a miniaturized bio-optoelectronic implant that avoids these limitations by using (1) an optical stimulation interface that exploits microscale inorganic light-emitting diodes to activate opsins; (2) a soft, high-precision biophysical sensor system that allows continuous measurements of organ function; and (3) a control module and data analytics approach that enables coordinated, closed-loop operation of the system to eliminate pathological behaviours as they occur in real-time. In the example reported here, a soft strain gauge yields real-time information on bladder function in a rat model. Data algorithms identify pathological behaviour, and automated, closed-loop optogenetic neuromodulation of bladder sensory afferents normalizes bladder function. This all-optical scheme for neuromodulation offers chronic stability and the potential to stimulate specific cell types.

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.

Advanced approaches for quantitative characterization of thermal transport properties in soft materials using thin, conformable resistive sensors.

Noninvasive methods for precise characterization of the thermal properties of soft biological tissues such as the skin can yield vital details about physiological health status including at critical intervals during recovery following skin injury. Here, we introduce quantitative measurement and characterization methods that allow rapid, accurate determination of the thermal conductivity of soft materials using thin, skin-like resistive sensor platforms. Systematic evaluations of skin at eight different locations and of six different synthetic skin-mimicking materials across sensor sizes, measurement times, and surface geometries (planar, highly curvilinear) validate simple scaling laws for data interpretation and parameter extraction. As an example of the possibilities, changes in the thermal properties of skin (volar forearm) can be monitored during recovery from exposure to ultraviolet radiation (sunburn) and to stressors associated with localized heating and cooling. More generally, the results described here facilitate rapid, non-invasive thermal measurements on broad classes of biological and non-biological soft materials.

Optogenetic silencing of nociceptive primary afferents reduces evoked and ongoing bladder pain.

Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) suffer from chronic pain that severely affects quality of life. Although the underlying pathophysiology is not well understood, inhibition of bladder sensory afferents temporarily relieves pain. Here, we explored the possibility that optogenetic inhibition of nociceptive sensory afferents could be used to modulate bladder pain. The light-activated inhibitory proton pump Archaerhodopsin (Arch) was expressed under control of the sensory neuron-specific sodium channel (sns) gene to selectively silence these neurons. Optically silencing nociceptive sensory afferents significantly blunted the evoked visceromotor response to bladder distension and led to small but significant changes in bladder function. To study of the role of nociceptive sensory afferents in freely behaving mice, we developed a fully implantable, flexible, wirelessly powered optoelectronic system for the long-term manipulation of bladder afferent expressed opsins. We found that optogenetic inhibition of nociceptive sensory afferents reduced both ongoing pain and evoked cutaneous hypersensitivity in the context of cystitis, but had no effect in uninjured, naïve mice. These results suggest that selective optogenetic silencing of nociceptive bladder afferents may represent a potential future therapeutic strategy for the treatment of bladder pain.

Fully implantable, battery-free wireless optoelectronic devices for spinal optogenetics.

The advent of optogenetic tools has allowed unprecedented insights into the organization of neuronal networks. Although recently developed technologies have enabled implementation of optogenetics for studies of brain function in freely moving, untethered animals, wireless powering and device durability pose challenges in studies of spinal cord circuits where dynamic, multidimensional motions against hard and soft surrounding tissues can lead to device degradation. We demonstrate here a fully implantable optoelectronic device powered by near-field wireless communication technology, with a thin and flexible open architecture that provides excellent mechanical durability, robust sealing against biofluid penetration and fidelity in wireless activation, thereby allowing for long-term optical stimulation of the spinal cord without constraint on the natural behaviors of the animals. The system consists of a double-layer, rectangular-shaped magnetic coil antenna connected to a microscale inorganic light-emitting diode (µ-ILED) on a thin, flexible probe that can be implanted just above the dura of the mouse spinal cord for effective stimulation of light-sensitive proteins expressed in neurons in the dorsal horn. Wireless optogenetic activation of TRPV1-ChR2 afferents with spinal µ-ILEDs causes nocifensive behaviors and robust real-time place aversion with sustained operation in animals over periods of several weeks to months. The relatively low-cost electronics required for control of the systems, together with the biocompatibility and robust operation of these devices will allow broad application of optogenetics in future studies of spinal circuits, as well as various peripheral targets, in awake, freely moving and untethered animals, where existing approaches have limited utility.

Multimodal epidermal devices for hydration monitoring.

Precise, quantitative in vivo monitoring of hydration levels in the near surface regions of the skin can be useful in preventing skin-based pathologies, and regulating external appearance. Here we introduce multimodal sensors with important capabilities in this context, rendered in soft, ultrathin, 'skin-like' formats with numerous advantages over alternative technologies, including the ability to establish intimate, conformal contact without applied pressure, and to provide spatiotemporally resolved data on both electrical and thermal transport properties from sensitive regions of the skin. Systematic in vitro studies and computational models establish the underlying measurement principles and associated approaches for determination of temperature, thermal conductivity, thermal diffusivity, volumetric heat capacity, and electrical impedance using simple analysis algorithms. Clinical studies on 20 patients subjected to a variety of external stimuli validate the device operation and allow quantitative comparisons of measurement capabilities to those of existing state-of-the-art tools.

De Novo Design of a New Class of "Hard-Soft" Amorphous, Microphase-Separated, Polyolefin Block Copolymer Thermoplastic Elastomers.

Sequential cyclic/linear/cyclic living coordination polymerization of 1,6-heptadiene (HPD), propene, and HPD, respectively, employing the well-defined and soluble group 4 transition-metal initiator, {(η5-C5Me5)Hf(Me)[N(Et)C(Me)N(Et)]}[B(C6F5)4], provides the stereoirregular, amorphous poly(1,3-methylenecyclohexane)-b-atactic polypropene-b-poly(1,3-methylenecyclohexane) (PMCH-b-aPP-b-PMCH) polyolefin triblock copolymer (I) in excellent yield. By varying the weight fraction of the end group, minor component "hard" PMCH block domains, fPMCH, relative to that of the midblock "soft" aPP domain, three different compositional grades of these polyolefin block copolymers, Ia-c, were prepared and shown by AFM and TEM to adopt microphase-separated morphologies in the solid state, with spherical and cylindrical morphologies being observed for fPMCH = 0.09 (Ia) and 0.23 (Ic), respectively, and a third more complex morphology being observed for Ib (fPMCH = 0.17). Tensile testing of Ia-c served to establish these materials as a new structural class of polyolefin thermoplastic elastomers, with Ia being associated with superior elastic recovery (94 ± 1%) after each of several stress-strain cycles.

Regio- and Stereospecific Cyclopolymerization of Bis(2-propenyl)diorganosilanes and the Two-State Stereoengineering of 3,5-cis,isotactic Poly(3,5-methylene-1-silacyclohexane)s.

Transition-metal-mediated coordination cyclopolymerization of bis(2-propenyl)dimethylsilane (1a) using the C1-symmetric, group 4 metal preinitiator, (η5-C5Me5)Zr(Me)2[N(Et)C(Me)N(tBu)] (I), in combination with 1 equiv of the borate coinitiator, [PhNHMe2][B(C6F5)4] (II), proceeds in a regio- and stereospecific manner to provide highly stereoregular 3,5-cis,isotactic poly(3,5-methylene-1,1-dimethyl-1-silacyclohexane) (2a). Successful stereoengineering of 2a to eliminate undesirable crystallinity while preserving a high Tg value of >120 °C was subsequently accomplished by employing a "two-state" propagation system that uniquely produces an isotactic stereoblock microstructure of decreasing stereoblock length with decreasing percent level of "activation" of I with II. The controlled character of cyclopolymerization of 1a using the less sterically encumbered preinitiator, (η5-C5Me5)Hf(Me)2[N(Et)C(Me)N(Et)] (III), and 1 equiv of II was used to prepare well-defined poly(1-hexene)-b-poly(3,5-methylene-1-silacyclohexane) block copolymers through sequential monomer additions.

Stereoengineering of poly(1,3-methylenecyclohexane) via two-state living coordination polymerization of 1,6-heptadiene.

External control over the rate of dynamic methyl group exchange between configurationally stable active species and configurationally unstable dormant species with respect to chain-growth propagation within a highly stereoselective and regiospecific living coordination polymerization of 1,6-heptadiene has been used to generate a spectrum of different physical forms of poly(1,3-methylenecyclohexane) (PMCH) in which the stereochemical microstructure has been systematically varied between two limiting forms. The application of this strategy to manipulate the bulk properties of PMCH and the solid-state microphase behavior of well-defined PMCH-b-poly(1-hexene) block copolymers is further demonstrated.