(C.J.W); frank.pigula@ulp.org (F.A.P.) Overline: Cardiovascular diseaseOne Sentence Summary: A soft robotic sleeve modeled on the structure of the human heart assists cardiovascular function in an ex vivo and in vivo porcine model of heart failure. Abstract:There is much interest in form-fitting, low modulus, implantable devices or soft robots that can mimic or assist in complex biological functions such as the contraction of heart muscle. Here we present a soft robotic sleeve that is implanted around the heart and actively compresses and twists to act as a cardiac ventricular assist device. The sleeve does not contact blood, obviating the need for anticoagulation therapy or blood thinners, and reduces complications with current ventricular assist devices such as clotting and infection. Our approach used a biologically inspired design to orient individual contracting elements or actuators in a layered helical and circumferential fashion, mimicking the orientation of the outer two muscle layers of the mammalian heart. The resulting implantable soft robot mimicked the form and function of the native heart, with a stiffness value of the same order of magnitude as native heart tissue. We demonstrated feasibility of this soft sleeve device for supporting heart function in a porcine model of acute heart failure. The soft robotic sleeve can be customized to patient-specific needs and may have the potential to act as a bridge to transplant for patients with heart failure.

Previous soft robotic ventricular assist devices have generally targeted biventricular heart failure and have not engaged the interventricular septum that plays a critical role in blood ejection from the ventricle. We propose implantable soft robotic devices to augment cardiac function in isolated left or right heart failure by applying rhythmic loading to either ventricle. Our devices anchor to the interventricular septum and apply forces to the free wall of the ventricle to cause approximation of the septum and free wall in systole and assist with recoil in diastole. Physiological sensing of the native hemodynamics enables organ-in-the-loop control of these robotic implants for fully autonomous augmentation of heart function. The devices are implanted on the beating heart under echocardiography guidance. We demonstrate the concept on both the right and the left ventricles through in vivo studies in a porcine model. Different heart failure models were used to demonstrate device function across a spectrum of hemodynamic conditions associated with right and left heart failure. These acute in vivo studies demonstrate recovery of blood flow and pressure from the baseline heart failure conditions. Significant reductions in diastolic ventricle pressure were also observed, demonstrating improved filling of the ventricles during diastole, which enables sustainable cardiac output.

Soft robotic devices have significant potential for medical device applications that warrant safe synergistic interaction with humans. This article describes the optimization of an implantable soft robotic system for heart failure whereby soft actuators wrapped around the ventricles are programmed to contract and relax in synchrony with the beating heart. Elastic elements integrated into the soft actuators provide recoiling function so as to aid refilling during the diastolic phase of the cardiac cycle. Improved synchronization with the biological system is achieved by incorporating the native ventricular pressure into the control system to trigger assistance and synchronize the device with the heart. A three-state electro-pneumatic valve configuration allows the actuators to contract at different rates to vary contraction patterns. An in vivo study was performed to test three hypotheses relating to mechanical coupling and temporal synchronization of the actuators and heart. First, that adhesion of the actuators to the ventricles improves cardiac output. Second, that there is a contraction-relaxation ratio of the actuators which generates optimal cardiac output. Third, that the rate of actuator contraction is a factor in cardiac output.

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.

Efficient coupling of soft robotic cardiac assist devices to the external surface of the heart is crucial to augment cardiac function and represents a hurdle to translation of this technology. In this work, we compare various fixation strategies for local and global coupling of a direct cardiac compression sleeve to the heart. For basal fixation, we find that a sutured Velcro band adheres the strongest to the epicardium. Next, we demonstrate that a mesh-based sleeve coupled to the myocardium improves function in an acute porcine heart failure model. Then, we analyze the biological integration of global interface material candidates (medical mesh and silicone) in a healthy and infarcted murine model and show that a mesh interface yields superior mechanical coupling via pull-off force, histology, and microcomputed tomography. These results can inform the design of a therapeutic approach where a mesh-based soft robotic DCC is implanted, allowed to biologically integrate with the epicardium, and actuated for active assistance at a later timepoint. This strategy may result in more efficient coupling of extracardiac sleeves to heart tissue, and lead to increased augmentation of heart function in end-stage heart failure patients.

We introduce an implantable intracardiac soft robotic right ventricular ejection device (RVED) for dynamic approximation of the right ventricular (RV) free wall and the interventricular septum (IVS) in synchrony with the cardiac cycle to augment blood ejection in right heart failure (RHF). The RVED is designed for safe and effective intracardiac operation and consists of an anchoring system deployed across the IVS, an RV free wall anchor, and a pneumatic artificial muscle linear actuator that spans the RV chamber between the two anchors. Using a ventricular simulator and a custom controller, we characterized ventricular volume ejection, linear approximation against different loads and the effect of varying device actuation periods on volume ejection. The RVED was then tested in vivo in adult pigs (n = 5). First, we successfully deployed the device into the beating heart under 3D echocardiography guidance (n = 4). Next, we performed a feasibility study to evaluate the device’s ability to augment RV ejection in an experimental model of RHF (n = 1). RVED actuation augmented RV ejection during RHF; while further chronic animal studies will provide details about the efficacy of this support device. These results demonstrate successful design and implementation of the RVED and its deployment into the beating heart. This soft robotic ejection device has potential to serve as a rapidly deployable system for mechanical circulatory assistance in RHF.

In this work, we describe a benchtop model that recreates the motion and function of the diaphragm using a combination of advanced robotic and organic tissue. First, we build a high-fidelity anthropomorphic model of the diaphragm using thermoplastic and elastomeric material based on clinical imaging data. We then attach pneumatic artificial muscles to this elastomeric diaphragm, pre-programmed to move in a clinically relevant manner when pressurized. By inserting this diaphragm as the divider between two chambers in a benchtop model—one representing the thorax and the other the abdomen—and subsequently activating the diaphragm, we can recreate the pressure changes that cause lungs to inflate and deflate during regular breathing. Insertion of organic lungs in the thoracic cavity demonstrates this inflation and deflation in response to the pressures generated by our robotic diaphragm. By tailoring the input pressures and timing, we can represent different breathing motions and disease states. We instrument the model with multiple sensors to measure pressures, volumes, and flows and display these data in real-time, allowing the user to vary inputs such as the breathing rate and compliance of various components, and so they can observe and measure the downstream effect of changing these parameters. In this way, the model elucidates fundamental physiological concepts and can demonstrate pathology and the interplay of components of the respiratory system. This model will serve as an innovative and effective pedagogical tool for educating students on respiratory physiology and pathology in a user-controlled, interactive manner. It will also serve as an anatomically and physiologically accurate testbed for devices or pleural sealants that reside in the thoracic cavity, representing a vast improvement over existing models and ultimately reducing the requirement for testing these technologies in animal models. Finally, it will act as an impactful visualization tool for educating and engaging the broader community.

In this work, a lumped‐parameter Windkessel model of the cardiovascular system that simulates biomechanical parameters of the human physiology is presented. The object‐oriented platform provided by the MATLAB‐based modeling environment SIMSCAPE is employed to compute blood pressures and flows in each heart chamber and at various sites of the vascular tree. The hydraulic domain allows the determination of cardiovascular hemodynamics intuitively from geometrical and mechanical properties of the system, while custom elements model the pumping action of the heart and the effects of respiration on blood flow. The model is validated by comparing predicted hemodynamics with normal physiology during both systole and diastole, demonstrating that changes in arterial pressures with breathing are consistent with reported physiological effects of cardiorespiratory coupling. The capabilities of this platform are explored through two exemplary case studies: i) pressure‐overload heart failure due to aortic constriction, validated in vitro and via finite element analysis, and ii) single‐ventricle Fontan physiology, validated in vitro and compared with the clinical literature. This platform provides a practical tool for the calculation of cardiovascular hemodynamics from hydraulic parameters, enabling the intuitive creation of in silico representations of complex circulatory loops, the planning and optimization of medical interventions, and the prediction of clinically relevant patient‐specific hemodynamics.