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Severe diaphragm dysfunction can lead to respiratory failure and to the need for permanent mechanical ventilation. Yet permanent tethering to a mechanical ventilator through the mouth or via tracheostomy can hinder a patient’s speech, swallowing ability and mobility. Here we show, in a porcine model of varied respiratory insufficiency, that a contractile soft robotic actuator implanted above the diaphragm augments its motion during inspiration. Synchronized actuation of the diaphragm-assist implant with the native respiratory effort increased tidal volumes and maintained ventilation flow rates within the normal range. Robotic implants that intervene at the diaphragm rather than at the upper airway and that augment physiological metrics of ventilation may restore respiratory performance without sacrificing quality of life.

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 by means of in vivo echocardiography and catheterization studies and via a combination of in vitro and computational analyses. We also quantified, by means of in vivo and in vitro magnetic resonance imaging, the four-dimensional blood-flow velocity profiles associated with the disease and with bicommissural and unicommissural defects recreated by the robotic sleeve. The design of the sleeve, which can be adjusted on the basis of computer-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.

Introduction LigaSure is an electrothermal bipolar vessel-sealing system shown to decrease blood loss and drainage volume compared to electrocautery in axillary node dissection. This prospective randomised controlled trial aimed to assess whether using LigaSure improved perioperative outcomes when compared with monopolar diathermy alone in performing mastectomy without axillary dissection. Methods Mastectomy was performed with the LigaSure device and compared with mastectomy using conventional monopolar diathermy in a prospective randomised trial. Patients were recruited over 39 months and were aged from 33 to 86 years of age. Block randomisation (44 in the Ligasure group and 42 in the diathermy group) was performed. The primary outcome measures include total volume in drain output (ml), time to drain volume less than 30mls in 24 hours and operating time. Results Drain output volume was measured to the day the drain yielded less than 30mls in a 24 hour period in both groups (484 mls in the monopolar group v 494 mls in Ligasure group). This time point was also used to calculate time to drain removal in both groups (Monopolar 7.2 days and Ligasure 7.3 days). Drain output volume and number or days to drain removal did not show any significant difference in both groups (p=0.05). The operative time in both groups was similar (106mins in monopolar group and 112.5 mins in LigaSure group). Conclusion Use of the LigaSure device is feasible in performing mastectomy. It is not associated with reduced drain volume or shorter operative time compared with monopolar diathermy.

Much of the research on bioinspired soft robotics has focused on capturing the interplay of biological form and function. However, existing soft robotic actuators are mostly made with linear or planar fabrication orientations that do not represent the resting geometry of complex biological systems, such as curved musculature. This work introduces the ability to create fiber-reinforced actuators with precurved configurations. By tuning variables such as dimensions and fiber angles, an optimization algorithm can prescribe the mechanical fabrication parameters to create a fiber-reinforced actuator that can generate controlled motion to follow a desired input trajectory. Precurved configurations introduce an additional optimization parameter, the initial bend angle, allowing for a more accurate and robust algorithm and generating a median percent error of1%. With a customized software tool, we can take existing motion data from biological systems-such as medical imaging-and build soft robotic actuators optimized to replicate these trajectories. We can predict the motion of precurved actuators both analytically and numerically and replicate the motion experimentally, with excellent trajectory matching between the three. In constructing actuators that better match the native forms found within biological systems, we find that precurved actuators are more efficient than their initially straight counterparts. This pneumatic efficiency allows for the use of control systems with lower power and precision, lowering the economic cost of the associated control hardware, while more accurately replicating the biological motion. Taking two examples from biology, that of the human diaphragm during respiration and that of a jellyfish bell during locomotion, we design and generate fiber reinforced actuators to mimic these motions.

Best practices in Biomedical Engineering education seek to connect classroom knowledge to practical applications. MIT’s Medical Device Design course is comprised of in-class didactics, individual laboratory assignments, and a semester-long, team- based design and prototyping challenge, based in real unmet biomedical need. Students in the course represent a broad set of undergraduate and graduate students, from diverse educational backgrounds, with different levels of training and expertise. This year, as a precursor to the semester-long project, we designed, piloted, and evaluated a new experiential learning lab based around a syringe pump, selected because of its prevalence in the clinical setting, exemplification of core, multidisciplinary biomedical engineering concepts, and suitability for a team-based learning exercise. Students individually calculated patient dosing requirements and translated desired volume and flow rate into stepper motor commands. Then, during a single in-class session, teams worked from a custom-designed and fabricated kit to assemble a syringe pump, breadboard electronics, implement software controls, and finally close the design loop by evaluating their pumps' dispensing performance. A post-lab survey of the student cohort indicated that this pilot lab provided a sound biomedical learning and teamwork opportunity that improved technical literacy. The survey also identified key opportunities for improvement – students wanted more time and instructor-guided learning to increase their understanding of the mechanical engineering, electrical engineering, and software subtopics. Consequently, next year we will expand the lab into a multi-class exercise, with enhanced lectures and supplementary materials. Overall, we share this problem-based learning exercise, designed to exemplify key concepts, improve teamwork, and foster hands-on tinkering skills, with other biomedical engineering instructors.

Asymmetric pumping is a sub-category of valveless pumping in which a flexible tube is rhythmically compressed in the transverse symmetry plane. Due to the resulting asymmetry between the suction and discharge pipes, a net pumping head is achieved. Asymmetric pumping is regarded as one of the main mechanisms responsible for the Liebau effect in addition to impedance pumping. However, there remains a paucity of research surrounding the governing parameters of asymmetric pumping. Here, we conducted an experimental study of the performance of an asymmetric pump, with an aim to assess its potential for extravascular flow augmentation. A custom flexible latex tube and experimental platform were developed for this purpose. We tested various tube thicknesses and pinching frequencies. Our results demonstrate that the performance is within the range of physiological requirements for pediatric circulatory devices (~ 1 L/min and

Frontiers in Cardiovascular Medicine, 9, ISSN:2297-055X

Epicardial delivery of human follistatin-like 1 protein (FSTL1) induces significant cardiac benefit following a myocardial infarction (MI). However, the optimal dosing regimen for maximal therapeutic benefit has not yet been elucidated. To investigate the impact of multiple FSTL1 doses, without the confounding effects of multiple surgical procedures for multidose delivery, alternative delivery strategies are needed. Here, we use an epicardial reservoir that allows non-invasive delivery of additional doses after implantation to investigate the impact of single, double, and triple FSTL1 dose regimens in a rat model of MI. Multidose delivery of FSTL1 improves ejection fraction (3 doses), fractional shortening (1, 2 and 3 doses), and chamber stiffness (2 doses) 28 days after MI. Histologically, multiple FSTL1 doses increase ventricular wall thickness (2 and 3 doses) and reduce infarct size (1, 2, and 3 doses). We also demonstrate a dose-dependent increase in blood vessel number and density in the infarct zone, with three FSTL1 doses leading to the highest improvements. This study shows that multidose delivery of FSTL1 improves cardiac function, healing, and angiogenesis following MI. The epicardial delivery platform used here may be essential in optimizing dosing regimens of various bioagent combinations for a range of clinical indications.

Islamic State propaganda manipulated and combined a culturally embedded sense of Islamic history with a heady, potent mixture of classical and radical apocalyptic, and real and supposed Islamic authority, both sacred and profane. Tapping into a widespread belief in the approach of the Last Hour, the group attempted to change an established “crusader master narrative” by giving “crusaders” and their “crusade” integral roles in Islamic sacred history and an impending Islamic State apocalypse.

Highlights • The prevalence of heart failure with preserved ejection fraction among patients who present with symptoms of heart failure is approximately 50%. • Pharmacologic therapy has not conclusively shown benefits in morbidity and mortality in clinical trials. • Although it represents an active area of research, no device-based therapy has received regulatory approval for the treatment of heart failure with preserved ejection fraction. • Approaches such as atrial shunts, left ventricular expanders, mechanical circulatory support devices, and neurostimulators are at various stages of development., Central Illustration, Summary Characterized by a rapidly increasing prevalence, elevated mortality and rehospitalization rates, and inadequacy of pharmaceutical therapies, heart failure with preserved ejection fraction (HFpEF) has motivated the widespread development of device-based solutions. HFpEF is a multifactorial disease of various etiologies and phenotypes, distinguished by diminished ventricular compliance, diastolic dysfunction, and symptoms of heart failure despite a normal ejection performance; these symptoms include pulmonary hypertension, limited cardiac reserve, autonomic imbalance, and exercise intolerance. Several types of atrial shunts, left ventricular expanders, stimulation-based therapies, and mechanical circulatory support devices are currently under development aiming to target one or more of these symptoms by addressing the associated mechanical or hemodynamic hallmarks. Although the majority of these solutions have shown promising results in clinical or preclinical studies, no device-based therapy has yet been approved for the treatment of patients with HFpEF. The purpose of this review is to discuss the rationale behind each of these devices and the findings from the initial testing phases, as well as the limitations and challenges associated with their clinical translation.

Aortic stenosis (AS) affects approximately 1.5 million people in the US 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 of high-fidelity testing platforms for these devices. We propose a soft robotic model of AS capable of recapitulating patient-specific hemodynamics of AS and secondary ventricular remodeling, 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, while a left ventricular sleeve recapitulates loss of ventricular compliance, and impaired filling 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 to methods based on image-guided aortic root reconstruction, and parameters of cardiac function which rigid systems fail to mimic physiologically. Finally, we demonstrate the use of this model for the evaluation 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 secondary remodeling, this work pioneers the use of patient-specific soft robotic platforms of cardiovascular disease, with potential application in device development, procedural planning, and outcome prediction in industrial and clinical settings.One Sentence SummaryA high-fidelity, soft robotics-driven model recreates patient-specific biomechanics and hemodynamics of cardiovascular disease.

Few evidence-based programs exist to help women with a history of gestational diabetes reduce their risk of developing type 2 diabetes. In secondary analyses from a randomized clinical trial of a web-based lifestyle intervention program for postpartum women with recent gestational diabetes, we studied changes in self-efficacy for diet and physical activity and readiness to change health behaviors. Women were randomized at ∼6 weeks postpartum and completed questionnaires at 6 weeks and 6, 12, 18, and 24 months. Our study included 181 women (mean age 32.4 ± 5.2 years; 48% White, 19% Asian, 14% Black or African American, 17% other/mixed race; 34% Hispanic). In a linear mixed effects model, women in the intervention had significantly greater improvement in overall self-efficacy scores for physical activity compared with the control group at 24 months (difference in change scores between groups .35, 95% CI: .03 to .67, P = .03). The intervention group also demonstrated significantly greater improvement in self-efficacy scores for both physical activity subdomains, specifically “sticking to it” at 24 months and “making time” at 12 months. Participants in the intervention did not experience a significant difference in change in self-efficacy for diet or readiness to change compared with those in the control arm.

Benchtop testing of endovascular medical devices under accurately simulated physiological conditions is a critical part of device evaluation prior to clinical assessment. Currently, glass, acrylic and silicone vascular models are predominantly used as anatomical simulator test beds for in vitro testing. However, most current models lack the ability to mimic the non-linear radial compliance of native vessels and are typically limited to being compliance-matched at a single mean pressure comparison point or not at all. Hence, a degree of caution needs to be shown when analysing results from such models under simulated physiological or pathophysiological conditions. Similarly, the clinical translation of proposed biomimetic compliance-matched vascular grafts has undoubtedly been curtailed due to performance and material limitations. Here, we propose a new design for synthetic vessels where compliance can be precisely modulated across a wide physiological pressure range by customising design parameters. Building on previously demonstrated methods of 3D printing composite compliant cylindrical structures, we demonstrate proof of principle in creating composite vascular constructs designed via a finite element model. Our constructs are 3D printable and consist of a soft silicone matrix with embedded polyurethane fibres. The fibre layer consists of circumferential sinusoidal waves with an amplitude that can be altered to result in tuneable internal radial compliances of 5.2-15.9%/mmHg × 10-2 at a mean pressure of 100 mmHg. Importantly, the design presented here allows preservation of the non-linear exponentially decaying compliance curve of native arteries and veins with an increasing mean pressure. This model offers a design toolbox for 3D printable vascular models that offer biomimetic compliance. The robust nature of this model will lead to rapidly accelerating the design process for biomimetic vascular anatomical simulators, lumped parameter model flow loops, endovascular device benchtop testbeds, and compliance-matched synthetic grafts. Science Foundation Ireland Fulbright Ireland Student Award 12 month embargo - AC

The treatment of end-stage heart failure has evolved substantially with advances in medical treatment, cardiac transplantation, and mechanical circulatory support (MCS) devices such as left ventricular assist devices and total artificial hearts. However, current MCS devices are inherently blood contacting and can lead to potential complications including pump thrombosis, hemorrhage, stroke, and hemolysis. Attempts to address these issues and avoid blood contact led to the concept of compressing the failing heart from the epicardial surface and the design of direct cardiac compression (DCC) devices. We review the fundamental concepts related to DCC, present the foundational devices and recent devices in the research and commercialization stages, and discuss the milestones required for clinical translation and adoption of this technology.

Vesicovaginal fistulas (VVFs), abnormal openings between the vagina and bladder, disrupt the lives of over 3 million people worldwide due to resulting incontinence and infections. VVFs are commonly treated with surgery after the fistula has had time to heal over several months. In low-resource areas, immediate incontinence often leads to ostracization from the community and can be devastating for the patient. To address this problem, we have designed a three-tiered silicone plug consisting of a bladder-dwelling disk, a midfistula disk, and a vagina-dwelling cross-shaped tapered plug, all supported on a central stem. The system is designed to occlude the fistula and enable full continence until the patient is able to access surgery. This proof-of-concept device withstands typical expulsion forces from the bladder and does not leak under typical bladder filling or urination pressures. The maximum device expulsion force is 3.69 N and it is watertight up to 9.8 kPa. It is designed to be easily deployed by trained community members.

Mechanical or biological aortic valves are incorporated in physical cardiac simulators for surgical training, educational purposes, and device testing. They suffer from limitations including either a lack of anatomical and biomechanical accuracy or a short lifespan, hence limiting the authentic hands-on learning experience. Medical schools utilize hearts from human cadavers for teaching and research, but these formaldehyde-fixed aortic valves contort and stiffen relative to native valves. Here, we compare a panel of different chemical treatment methods on explanted porcine aortic valves and evaluate the microscopic and macroscopic features of each treatment with a primary focus on mechanical function. A surfactant-based decellularization method after formaldehyde fixation is shown to have mechanical properties close to those of the native aortic valve. Valves treated in this method were integrated into a custom-built left heart cardiac simulator to test their hemodynamic performance. This decellularization, post-fixation technique produced aortic valves which have ultimate stress and elastic modulus in the range of the native leaflets. Decellularization of fixed valves reduced the valvular regurgitation by 60% compared to formaldehyde-fixed valves. This fixation method has implications for scenarios where the dynamic function of preserved valves is required, such as in surgical trainers or device test rigs.