Mechanotherapy: Modulating immune cell function in tissue regeneration and fibrosis.

Mechanotherapy - therapy which uses mechanical forces to produce a remedial or prophylactic effect - has great potential to improve therapeutic outcomes in the fields of regenerative medicine and drug delivery due to its adaptable and tunable nature. In particular, numerous in vivo studies have demonstrated the ability of mechanotherapies to improve functional muscle regeneration and modulate fibrosis. However, the cellular interactions that underlie these tissue level responses are poorly understood.

Pre-Clinical Models of Heart Failure with Preserved Ejection Fraction: Advancing Knowledge for Device Based Therapies.

Heart failure with preserved ejection fraction (HFpEF) is a growing health problem worldwide, accounting for half of all heart failure cases. HFpEF patients present with diverse underlying causes and symptoms, making diagnosis and treatment challenging. Current pharmacological therapies are inadequate, while approved device-based therapies have shown limited success due to patient heterogeneity.

Democratizing cardiac imaging with an automated magnetic resonance exam.

Advanced imaging of the heart, including cardiovascular magnetic resonance imaging (CMR), has revolutionized the diagnosis and prognosis for cardiovascular disease. For the past 40 years, CMR has primarily relied on the acquisition of numerous breath-held 2D images resulting in complex scanner operation, patient discomfort, long scan durations, and cumbersome image interpretation. These limitations constrain CMR use to major academic hospital systems and severely limit patient access to CMR, which makes up < 1% of total cardiovascular imaging despite being represented in two thirds of all AHA/ACC guidelines.

Integrating soft robotics and computational models to study left atrial hemodynamics and device testing in sinus rhythm and atrial fibrillation.

Atrial fibrillation (AF) poses significant clinical challenges due to the complex and variable geometry of the left atrial appendage (LAA), whose structure complicates the development of personalized interventions like LAA occlusion (LAAO) for stroke prevention Current reliance on animal models and cadavers for the assessment of left atrium (LA) and LAA to study AF-related disease and interventions raises reproducibility concerns, necessitating the development of high fidelity, physiologically relevant tools. To address this, we present a multimodal framework combining a soft robotic benchtop simulator, a lumped parameter model (LPM), and finite element analysis (FEA) to replicate LA function in sinus rhythm, atrial flutter, and AF. The system integrates 3D-printed, patient-specific LA geometries with soft robotic actuators to reproduce realistic wall motion and hemodynamics.

Finite Element Modeling of Abdominal Near-Infrared Spectroscopy for Infant Splanchnic Oximetry.

Abdominal near-infrared spectroscopy (NIRS) holds promise for early detection of necrotizing enterocolitis and other infant pathologies prior to irreversible injury, but the optimal NIRS sensor design is not well defined. In this study, we develop and demonstrate a computational method to evaluate NIRS sensor designs for infant splanchnic oximetry. We used a finite element (FE) approach to simulate near-infrared light transport through a 3D model of the infant abdomen constructed from computed tomography (CT) images.

Utilization of Classification Learning Algorithms for Upper-Body Non-Cyclic Motion Prediction.

This study explores two methods of predicting non-cyclic upper-body motions using classification algorithms. Exoskeletons currently face challenges with low fluency, hypothesized to be in part caused by the lag in active control innate in many leader-follower paradigms seen in today's systems, leading to energetic inefficiencies and discomfort. To address this, we employ k-nearest neighbor (KNN) and deep learning models to predict motion characteristics, such as magnitude and category, from surface electromyography (sEMG) signals.

Leveraging Preclinical Modeling for Clinical Advancements in Single Ventricle Physiology: Spotlight on the Fontan Circulation.

Preclinical modeling of human circulation has been instrumental in advancing cardiovascular medicine. Alongside clinical research, the armamentarium of computational (e.g.

Design and Validation of a High-Fidelity Left Atrial Cardiac Simulator for the Study and Advancement of Left Atrial Appendage Occlusion.

Purpose: Atrial fibrillation (AF) is the most common chronic cardiac arrhythmia that increases the risk of stroke, primarily due to thrombus formation in the left atrial appendage (LAA). Left atrial appendage occlusion (LAAO) devices offer an alternative to oral anticoagulation for stroke prevention. However, the complex and variable anatomy of the LAA presents significant challenges to device design and deployment.

Caregiver-child neural synchrony: Magic, mirage, or developmental mechanism?

Young children transition in and out of synchronous states with their caregivers across physiology, behavior, and brain activity, but what do these synchronous periods mean? One body of two-brain studies using functional near-infrared spectroscopy (fNIRS) finds that individual, family, and moment-to-moment behavioral and contextual factors are associated with caregiver-child neural synchrony, while another body of literature finds that neural synchrony is associated with positive child outcomes. Taken together, it is tempting to conclude that caregiver-child neural synchrony may act as a foundational developmental mechanism linking children's experiences to their healthy development, but many questions remain. In this review, we synthesize recent findings and open questions from caregiver-child studies using fNIRS, which is uniquely well suited for use with caregivers and children, but also laden with unique constraints.

Actuation-Mediated Compression of a Mechanoresponsive Hydrogel by Soft Robotics to Control Release of Therapeutic Proteins.

Therapeutic proteins, the fastest growing class of pharmaceuticals, are subject to rapid proteolytic degradation in vivo, rendering them inactive. Sophisticated drug delivery systems that maintain protein stability, prolong therapeutic effects, and reduce administration frequency are urgently required. Herein, a mechanoresponsive hydrogel is developed contained within a soft robotic drug delivery (SRDD) device.

AI-Powered Multimodal Modeling of Personalized Hemodynamics in Aortic Stenosis.

Aortic stenosis (AS) is the most common valvular heart disease in developed countries. High-fidelity preclinical models can improve AS management by enabling therapeutic innovation, early diagnosis, and tailored treatment planning. However, their use is currently limited by complex workflows necessitating lengthy expert-driven manual operations.

Robotic right ventricle is a biohybrid platform that simulates right ventricular function in (patho)physiological conditions and intervention.

The increasing recognition of the right ventricle (RV) necessitates the development of RV-focused interventions, devices and testbeds. In this study, we developed a soft robotic model of the right heart that accurately mimics RV biomechanics and hemodynamics, including free wall, septal and valve motion. This model uses a biohybrid approach, combining a chemically treated endocardial scaffold with a soft robotic synthetic myocardium.

Robust automated calcification meshing for personalized cardiovascular biomechanics.

Calcification has significant influence over cardiovascular diseases and interventions. Detailed characterization of calcification is thus desired for predictive modeling, but calcium deposits on cardiovascular structures are still often manually reconstructed for physics-driven simulations. This poses a major bottleneck for large-scale adoption of computational simulations for research or clinical use.

Hemodynamic evaluation of biomaterial-based surgery for Tetralogy of Fallot using a biorobotic heart, in silico, and ovine models.

Tetralogy of Fallot is a congenital heart disease affecting newborns and involves stenosis of the right ventricular outflow tract (RVOT). Surgical correction often widens the RVOT with a transannular enlargement patch, but this causes issues including pulmonary valve insufficiency and progressive right ventricle failure. A monocusp valve can prevent pulmonary regurgitation; however, valve failure resulting from factors including leaflet design, morphology, and immune response can occur, ultimately resulting in pulmonary insufficiency.

A bioadhesive pacing lead for atraumatic cardiac monitoring and stimulation in rodent and porcine models.

Current clinically used electronic implants, including cardiac pacing leads for epicardial monitoring and stimulation of the heart, rely on surgical suturing or direct insertion of electrodes to the heart tissue. These approaches can cause tissue trauma during the implantation and retrieval of the pacing leads, with the potential for bleeding, tissue damage, and device failure. Here, we report a bioadhesive pacing lead that can directly interface with cardiac tissue through physical and covalent interactions to support minimally invasive adhesive implantation and gentle on-demand removal of the device with a detachment solution.

Soft robotic platform for progressive and reversible aortic constriction in a small-animal model.

Our understanding of cardiac remodeling processes due to left ventricular pressure overload derives largely from animal models of aortic banding. However, these studies fail to enable control over both disease progression and reversal, hindering their clinical relevance. Here, we describe a method for progressive and reversible aortic banding based on an implantable expandable actuator that can be finely tuned to modulate aortic banding and debanding in a rat model.

Biorobotic hybrid heart as a benchtop cardiac mitral valve simulator.

In this work, we developed a high-fidelity beating heart simulator that provides accurate mitral valve pathophysiology. The benchtop platform is based on a biorobotic hybrid heart that combines preserved intracardiac tissue with soft robotic cardiac muscle providing dynamic left ventricular motion and precise anatomical features designed for testing intracardiac devices, particularly for mitral valve repair. The heart model is integrated into a mock circulatory loop, and the active myocardium drives fluid circulation producing physiological hemodynamics without an external pulsatile pump.

Intermittent actuation attenuates fibrotic behaviour of myofibroblasts.

The foreign body response (FBR) to implanted materials culminates in the deposition of a hypo-permeable, collagen rich fibrotic capsule by myofibroblast cells at the implant site. The fibrotic capsule can be deleterious to the function of some medical implants as it can isolate the implant from the host environment. Modulation of fibrotic capsule formation has been achieved using intermittent actuation of drug delivery implants, however the mechanisms underlying this response are not well understood.

A Tunable Soft Silicone Bioadhesive for Secure Anchoring of Diverse Medical Devices to Wet Biological Tissue.

Silicone is utilized widely in medical devices for its compatibility with tissues and bodily fluids, making it a versatile material for implants and wearables. To effectively bond silicone devices to biological tissues, a reliable adhesive is required to create a long-lasting interface. BioAdheSil, a silicone-based bioadhesive designed to provide robust adhesion on both sides of the interface is introduced here, facilitating bonding between dissimilar substrates, namely silicone devices and tissues.

A Soft Robotic Actuator System for In Vivo Modeling of Normal Pressure Hydrocephalus.

Objective: The intracranial pressure (ICP) affects the dynamics of cerebrospinal fluid (CSF) and its waveform contains information that is of clinical importance in medical conditions such as hydrocephalus. Active manipulation of the ICP waveform could enable the investigation of pathophysiological processes altering CSF dynamics and driving hydrocephalus.

Methods: A soft robotic actuator system for intracranial pulse pressure amplification was developed to model normal pressure hydrocephalus in vivo.

Soft robot-mediated autonomous adaptation to fibrotic capsule formation for improved drug delivery.

The foreign body response impedes the function and longevity of implantable drug delivery devices. As a dense fibrotic capsule forms, integration of the device with the host tissue becomes compromised, ultimately resulting in device seclusion and treatment failure. We present FibroSensing Dynamic Soft Reservoir (FSDSR), an implantable drug delivery device capable of monitoring fibrotic capsule formation and overcoming its effects via soft robotic actuations.

Soft robotics-enabled large animal model of HFpEF hemodynamics for device testing.

Heart failure with preserved ejection fraction (HFpEF) is a major challenge in cardiovascular medicine, accounting for approximately 50% of all cases of heart failure. Due to the lack of effective therapies for this condition, the mortality associated with HFpEF remains higher than that of most cancers. Despite the ongoing efforts, no medical device has yet received FDA approval.