Soft robotic patient-specific hydrodynamic model of aortic stenosis and ventricular remodeling.

Aortic stenosis (AS) affects about 1.5 million people in the United States and is associated with a 5-year survival rate of 20% if untreated. In these patients, aortic valve replacement is performed to restore adequate hemodynamics and alleviate symptoms. The development of next-generation prosthetic aortic valves seeks to provide enhanced hemodynamic performance, durability, and long-term safety, emphasizing the need for high-fidelity testing platforms for these devices. We propose a soft robotic model that recapitulates patient-specific hemodynamics of AS and secondary ventricular remodeling which we validated against clinical data. The model leverages 3D-printed replicas of each patient's cardiac anatomy and patient-specific soft robotic sleeves to recreate the patients' hemodynamics. An aortic sleeve allows mimicry of AS lesions due to degenerative or congenital disease, whereas a left ventricular sleeve recapitulates loss of ventricular compliance and diastolic dysfunction (DD) associated with AS. Through a combination of echocardiographic and catheterization techniques, this system is shown to recreate clinical metrics of AS with greater controllability compared with methods based on image-guided aortic root reconstruction and parameters of cardiac function that rigid systems fail to mimic physiologically. Last, we leverage this model to evaluate the hemodynamic benefit of transcatheter aortic valves in a subset of patients with diverse anatomies, etiologies, and disease states. Through the development of a high-fidelity model of AS and DD, this work demonstrates the use of soft robotics to recreate cardiovascular disease, with potential applications in device development, procedural planning, and outcome prediction in industrial and clinical settings.

A soft robotic sleeve mimicking the haemodynamics and biomechanics of left ventricular pressure overload and aortic stenosis.

Preclinical models of aortic stenosis can induce left ventricular pressure overload and coarsely control the severity of aortic constriction. However, they do not recapitulate the haemodynamics and flow patterns associated with the disease. Here we report the development of a customizable soft robotic aortic sleeve that can mimic the haemodynamics and biomechanics of aortic stenosis. By allowing for the adjustment of actuation patterns and blood-flow dynamics, the robotic sleeve recapitulates clinically relevant haemodynamics in a porcine model of aortic stenosis, as we show via in vivo echocardiography and catheterization studies, and a combination of in vitro and computational analyses. Using in vivo and in vitro magnetic resonance imaging, we also quantified the four-dimensional blood-flow velocity profiles associated with the disease and with bicommissural and unicommissural defects re-created by the robotic sleeve. The design of the sleeve, which can be adjusted on the basis of computed tomography data, allows for the design of patient-specific devices that may guide clinical decisions and improve the management and treatment of patients with aortic stenosis.

Dynamic actuation enhances transport and extends therapeutic lifespan in an implantable drug delivery platform.

Fibrous capsule (FC) formation, secondary to the foreign body response (FBR), impedes molecular transport and is detrimental to the long-term efficacy of implantable drug delivery devices, especially when tunable, temporal control is necessary. We report the development of an implantable mechanotherapeutic drug delivery platform to mitigate and overcome this host immune response using two distinct, yet synergistic soft robotic strategies. Firstly, daily intermittent actuation (cycling at 1 Hz for 5 minutes every 12 hours) preserves long-term, rapid delivery of a model drug (insulin) over 8 weeks of implantation, by mediating local immunomodulation of the cellular FBR and inducing multiphasic temporal FC changes. Secondly, actuation-mediated rapid release of therapy can enhance mass transport and therapeutic effect with tunable, temporal control. In a step towards clinical translation, we utilise a minimally invasive percutaneous approach to implant a scaled-up device in a human cadaveric model. Our soft actuatable platform has potential clinical utility for a variety of indications where transport is affected by fibrosis, such as the management of type 1 diabetes.

Design Considerations for Macroencapsulation Devices for Stem Cell Derived Islets for the Treatment of Type 1 Diabetes.

Stem cell derived insulin producing cells or islets have shown promise in reversing Type 1 Diabetes (T1D), yet successful transplantation currently necessitates long-term modulation with immunosuppressant drugs. An alternative approach to avoiding this immune response is to utilize an islet macroencapsulation device, where islets are incorporated into a selectively permeable membrane that can protect the transplanted cells from acute host response, whilst enabling delivery of insulin. These macroencapsulation systems have to meet a number of stringent and challenging design criteria in order to achieve the ultimate goal of reversing T1D. In this progress report, the design considerations and functional requirements of macroencapsulation systems are reviewed, specifically for stem-cell derived islets (SC-islets), highlighting distinct design parameters. Additionally, a perspective on the future for macroencapsulation systems is given, and how incorporating continuous sensing and closed-loop feedback can be transformative in advancing toward an autonomous biohybrid artificial pancreas.

Exploiting Mechanical Instabilities in Soft Robotics: Control, Sensing, and Actuation.

The rapidly expanding field of soft robotics has provided multiple examples of how entirely soft machines and actuators can outperform conventional rigid robots in terms of adaptability, maneuverability, and safety. Unfortunately, the soft and flexible materials used in their construction impose intrinsic limitations on soft robots, such as low actuation speeds and low output forces. Nature offers multiple examples where highly flexible organisms exploit mechanical instabilities to store and rapidly release energy. Guided by these examples, researchers have recently developed a variety of strategies to overcome speed and power limitations in soft robotics using mechanical instabilities. These mechanical instabilities provide, through rapid transitions from structurally stable states, a new route to achieve high output power amplification and attain impressive actuation speeds. Here, an overview of the literature related to the development of soft robots and actuators that exploit mechanical instabilities to expand their actuation speed, output power, and functionality is presented. Additionally, strategies using structural phase transitions to address current challenges in the area of soft robotic control, sensing, and actuation are discussed. Approaches using instabilities to create entirely soft logic modules to imbue soft robots with material intelligence and distributed computational capabilities are also reviewed.

The Influence of Airway Closure Technique for Right Pneumonectomy on Wall Tension During Positive Pressure Ventilation: An Experimental Study.

Bronchopleural fistula (BPF) remains a significant source of morbidity and mortality after right pneumonectomy (RPN). Postoperative mechanical ventilation represents a primary risk factor for BPF. We undertook an experiment to determine the influence of airway diameter on suture line tension during mechanical ventilation after RPN. RPN was performed in 6 fresh human adult cadavers. After initial standard bronchial stump closure (BSC), the airway suture lines were subjected to 5 cm H2O incremental increases in airway pressures beginning at 5-40 cm H2O. To minimize airway diameter, a carinal resection was then performed with trachea to left main bronchial anastomosis and the airway suture lines subjected to similar incremental airway pressures. Wall tension (N/m) at the suture lines was measured using piezoresistive sensors at each pressure point. As delivered airway pressure increased, there was a concomitant increase in wall tension after BSC and carinal resection. At every point of incremental positive pressure, wall tension was however significantly lower after carinal resection when compared to BSC (P < 0.05). Additionally the differences in airway tension became even more significant with higher delivered airway pressure (P < 0.001). Airway diverticulum after BSC leads to significantly increased tension on the bronchial closure with positive airway pressure as compared to a closure which minimize airway diameter after RPN. This supports the role of Laplacian Law where small increases in airway diameter result in significant increases on closure site tension. Techniques which reduce airway diameter at the airway closure will more reliably reduce the incidence of BPF following RPN.

Conformal, waterproof electronic decals for wireless monitoring of sweat and vaginal pH at the point-of-care.

While the monitoring of pH has demonstrated to be an effective technique to monitor an individual's health state, the design of wearable biosensors is subject to critical challenges, such as high fabrication costs, thermal drift, sensitivity to moisture, and the limited applicability for users with metal allergies. This work describes the low-cost fabrication of waterproof electronic decals (WPEDs): highly conformable disposable biosensors capable of monitoring sweat and vaginal pH. WPEDs contain a polyaniline/silver microflakes sensing layer optimized for accurate impedance-based pH quantification across the clinically relevant range of variation of most biofluids. WPEDs also contain a heating layer that serves to both stimulate sweating and prevent saturation of the sensing area, reducing the variability of the measurements. The conformability of WPEDs enables their simple and allergy-free attachment to skin, where they can monitor sweat pH, or to the surface of paper-based sample containers, for the pH-based diagnosis of bacterial vaginosis. WPEDs are mostly transparent, self-adhesive, breathable, flexible, moisture-insensitive, and able to maintain their accuracy under significant mechanical and thermal stresses. A cost-effective wearable and portable impedance analyzer wirelessly transmits pH data in real-time to the smartphone of the user, where a custom-developed App enables long term monitoring and telemedicine applications. Our results demonstrate the feasibility of using inexpensive single-use WPEDs and a reusable, wireless impedance analyzer to provide a wearable solution for the real-time monitoring of sweat pH and the accurate at-home diagnosis of bacterial vaginosis, improving the capabilities of current low-cost, point-of-care diagnostic tests.

Enhanced Photodetection with Crystalline Si Nanoclusters.

SiOx nanodots were fabricated on a TiO2 thin film using glancing angle deposition technique. The fabricated samples were annealed at 950 °C in open air configuration to obtain Si nanoclusters resulting from phase separation of SiOx nanodots. Field Emission Gun Scanning electron microscopy and atomic force microscopy were used to examine the topography of the samples. The elemental composition of the samples was analyzed using energy dispersive X-ray mapping and their crystallinity was confirmed by analyzing the bandgap determined from the Tauc plots. The annealed samples show a broadband absorption which is about two folds in magnitude as compared to the as deposited (unannealed) samples. The photoluminescence spectra confirms the quantum confinement effect in the annealed samples. A photodetector was fabricated from an annealed sample by depositing gold contacts on top of it. This photodetector showed a two-fold increase in dark current and a 1.5-fold increase in light current compared to a photodetector made from the as-deposited SiOx samples-which is due to the increased crystallinity in Si nanoclusters. Finally, the rise and fall times of the device were measured through a switching experiment.

Rapid Fabrication of Epidermal Paper-Based Electronic Devices Using Razor Printing.

This work describes the use of a benchtop razor printer to fabricate epidermal paper-based electronic devices (EPEDs). This fabrication technique is simple, low-cost, and compatible with scalable manufacturing processes. EPEDs are fabricated using paper substrates rendered omniphobic by their cost-effective silanization with fluoroalkyl trichlorosilanes, making them inexpensive, water-resistant, and mechanically compliant with human skin. The highly conductive inks or thin films attached to one of the sides of the omniphobic paper makes EPEDs compatible with wearable applications involving wireless power transfer. The omniphobic cellulose fibers of the EPED provide a moisture-independent mechanical reinforcement to the conductive layer. EPEDs accurately monitor physiological signals such as ECG (electrocardiogram), EMG (electromyogram), and EOG (electro-oculogram) even in high moisture environments. Additionally, EPEDs can be used for the fast mapping of temperature over the skin and to apply localized thermotherapy. Our results demonstrate the merits of EPEDs as a low-cost platform for personalized medicine applications.

Wearable and Implantable Epidermal Paper-Based Electronics.

Traditional manufacturing methods and materials used to fabricate epidermal electronics for physiological monitoring, transdermal stimulation, and therapeutics are complex and expensive, preventing their adoption as single-use medical devices. This work describes the fabrication of epidermal, paper-based electronic devices (EPEDs) for wearable and implantable applications by combining the spray-based deposition of silanizing agents, highly conductive nanoparticles, and encapsulating polymers with laser micromachining. EPEDs are inexpensive, stretchable, easy to apply, and disposable by burning. The omniphobic character and fibrous structure of EPEDs make them breathable, mechanically stable upon stretching, and facilitate their use as electrophysiological sensors to record electrocardiograms, electromyograms, and electrooculograms, even under water. EPEDs can also be used to provide thermotherapeutic treatments to joints, map temperature spatially, and as wirelessly powered implantable devices for stimulation and therapeutics. This work makes epidermal electronic devices accessible to high-throughput manufacturing technologies and will enable the fabrication of a variety of wearable medical devices at a low cost.

Early detection and monitoring of chronic wounds using low-cost, omniphobic paper-based smart bandages.

The growing socio-economic burden of chronic skin wounds requires the development of new automated and non-invasive analytical systems capable of wirelessly monitoring wound status. This work describes the low-cost fabrication of single-use, omniphobic paper-based smart bandages (OPSBs) designed to monitor the status of open chronic wounds and to detect the formation of pressure ulcers. OPSBs are lightweight, flexible, breathable, easy to apply, and disposable by burning. A reusable wearable potentiostat was fabricated to interface with the OPSB simply by attaching it to the back of the bandage. The wearable potentiostat and the OPSB can be used to simultaneously quantify pH and uric acid levels at the wound site, and wirelessly report wound status to the user or medical personnel. Additionally, the wearable potentiostat and the OPSBs can be used to detect, in an in-vivo mouse model, the formation of pressure ulcers even before the pressure-induced tissue damage becomes visible, using impedance spectroscopy. Our results demonstrate the feasibility of using inexpensive single-use OPSBs and a reusable, wearable potentiostat that can be easily sterilized and attached to a new OPSB during the dressing change, to provide long term wound progression data to guide treatment decisions.

Roll-to-Roll Nanoforming of Metals Using Laser-Induced Superplasticity.

This Letter describes a low-cost, scalable nanomanufacturing process that enables the continuous forming of thin metallic layers with nanoscale accuracy using roll-to-roll, laser-induced superplasticity (R2RLIS). R2RLIS uses a laser shock to induce the ultrahigh-strain-rate deformation of metallic films at room temperature into low-cost polymeric nanomolds, independently of the original grain size of the metal. This simple and inexpensive nanoforming method does not require access to cleanrooms and associated facilities, and can be easily implemented on conventional CO2 lasers, enabling laser systems commonly used for rapid prototyping or industrial cutting and engraving to fabricate uniform and three-dimensional crystalline metallic nanostructures over large areas. Tuning the laser power during the R2RLIS process enables the control of the aspect ratio and the mechanical and optical properties of the fabricated nanostructures. This roll-to-roll technique successfully fabricates mechanically strengthened gold plasmonic nanostructures with aspect ratios as high as 5 that exhibit high oxidation resistance and strong optical field enhancements. The CO2 laser used in R2RLIS can also integrate the fabricated nanostructures on transparent flexible substrates with robust interfacial contact. The ability to fabricate ultrasmooth metallic nanostructures using roll-to-roll manufacturing enables the large scale production, at a relatively low-cost, of flexible plasmonic devices toward emerging applications.