Luca Rosalia

All Publications

• Soft robotic platform for progressive and reversible aortic constriction in a small-animal model SCIENCE ROBOTICS Rosalia, L., Wang, S. X., Ozturk, C., Huang, W., Bonnemain, J., Beatty, R., Duffy, G. P., Nguyen, C. T., Roche, E. T. 2024; 9 (91): eadj9769

  Abstract

  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. Through catheterization, imaging, and histologic studies, we demonstrate that our platform can recapitulate the hemodynamic and structural changes associated with pressure overload in a controllable manner. We leveraged soft robotics to enable noninvasive aortic debanding, demonstrating that these changes can be partly reversed because of cessation of the biomechanical stimulus. By recapitulating longitudinal disease progression and reversibility, this animal model could elucidate fundamental mechanisms of cardiac remodeling and optimize timing of intervention for pressure overload.

  View details for DOI 10.1126/scirobotics.adj9769

  View details for Web of Science ID 001245468500003

  View details for PubMedID 38865476

• Modulating Cardiac Hemodynamics Using Tunable Soft Robotic Sleeves in a Porcine Model of HFpEF Physiology for Device Testing Applications ADVANCED FUNCTIONAL MATERIALS Rosalia, L., Ozturk, C., Wang, S. X., Quevedo-Moreno, D., Saeed, M. Y., Mauskapf, A., Roche, E. T. 2023

  View details for DOI 10.1002/adfm.202310085

  View details for Web of Science ID 001096975000001

• Soft robotic patient-specific hydrodynamic model of aortic stenosis and ventricular remodeling SCIENCE ROBOTICS Rosalia, L., Ozturk, C., Goswami, D., Bonnemain, J., Wang, S. X., Bonner, B., Weaver, J. C., Puri, R., Kapadia, S., Nguyen, C. T., Roche, E. T. 2023; 8 (75): eade2184

  Abstract

  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.

  View details for DOI 10.1126/scirobotics.ade2184

  View details for Web of Science ID 000962275200002

  View details for PubMedID 36812335

  View details for PubMedCentralID PMC10280738

• A magnetically actuated, optically sensed tensile testing method for mechanical characterization of soft biological tissues SCIENCE ADVANCES Rosalia, L., Hallou, A., Cochrane, L., Savin, T. 2023; 9 (2): eade2522

  Abstract

  Mechanical properties of soft biological tissues play a critical role in physiology and disease, affecting cell behavior and fate decisions and contributing to tissue development, maintenance, and repair. Limitations of existing tools prevent a comprehensive characterization of soft tissue biomechanics, hindering our understanding of these fundamental processes. Here, we develop an instrument for high-fidelity uniaxial tensile testing of soft biological tissues in controlled environmental conditions, which is based on the closed-loop interaction between an electromagnetic actuator and an optical strain sensor. We first validate the instrument using synthetic elastomers characterized via conventional methods; then, we leverage the proposed device to investigate the mechanical properties of murine esophageal tissue and, individually, of each of its constitutive layers, namely, the epithelial, connective, and muscle tissues. The enhanced reliability of this instrument makes it an ideal platform for future wide-ranging studies of the mechanics of soft biological tissues.

  View details for DOI 10.1126/sciadv.ade2522

  View details for Web of Science ID 000911464300034

  View details for PubMedID 36630495

  View details for PubMedCentralID PMC9833656

• A soft robotic sleeve mimicking the haemodynamics and biomechanics of left ventricular pressure overload and aortic stenosis NATURE BIOMEDICAL ENGINEERING Rosalia, L., Ozturk, C., Coll-Font, J., Fan, Y., Nagata, Y., Singh, M., Goswami, D., Mauskapf, A., Chen, S., Eder, R. A., Goffer, E. M., Kim, J. H., Yurista, S., Bonner, B. P., Foster, A. N., Levine, R. A., Edelman, E. R., Panagia, M., Guerrero, J. L., Roche, E. T., Nguyen, C. T. 2022; 6 (10): 1134-+

  Abstract

  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.

  View details for DOI 10.1038/s41551-022-00937-8

  View details for Web of Science ID 000859600200001

  View details for PubMedID 36163494

  View details for PubMedCentralID PMC9588718

• Device-Based Solutions to Improve Cardiac Physiology and Hemodynamics in Heart Failure With Preserved Ejection Fraction JACC-BASIC TO TRANSLATIONAL SCIENCE Rosalia, L., Ozturk, C., Shoar, S., Fan, Y., Malone, G., Cheema, F. H., Conway, C., Byrne, R. A., Duffy, G. P., Malone, A., Roche, E. T., Hameed, A. 2021; 6 (9-10): 772-795

  Abstract

  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.

  View details for DOI 10.1016/j.jacbts.2021.06.002

  View details for Web of Science ID 000711000100009

  View details for PubMedID 34754993

  View details for PubMedCentralID PMC8559325

• Geometry-Based Customization of Bending Modalities for 3D-Printed Soft Pneumatic Actuators IEEE ROBOTICS AND AUTOMATION LETTERS Rosalia, L., Ang, B., Yeow, R. 2018; 3 (4): 3489-3496

  View details for DOI 10.1109/LRA.2018.2853640

  View details for Web of Science ID 000440851800014

• AI-Powered Multimodal Modeling of Personalized Hemodynamics in Aortic Stenosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Ozturk, C., Pak, D. H., Rosalia, L., Goswami, D., Robakowski, M. E., McKay, R., Nguyen, C. T., Duncan, J. S., Roche, E. T. 2024: e2404755

  Abstract

  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. Here, we propose an AI-powered computational framework for accelerated and democratized patient-specific modeling of AS hemodynamics from computed tomography (CT). First, we demonstrate that the automated meshing algorithms can generate task-ready geometries for both computational and benchtop simulations with higher accuracy and 100 times faster than existing approaches. Then, we show that the approach can be integrated with fluid-structure interaction and soft robotics models to accurately recapitulate a broad spectrum of clinical hemodynamic measurements of diverse AS patients. The efficiency and reliability of these algorithms make them an ideal complementary tool for personalized high-fidelity modeling of AS biomechanics, hemodynamics, and treatment planning.

  View details for DOI 10.1002/advs.202404755

  View details for PubMedID 39665137

• A Soft Robotic Actuator System for In Vivo Modeling of Normal Pressure Hydrocephalus. IEEE transactions on bio-medical engineering Flurenbrock, F., Rosalia, L., Podgorsak, A., Sapozhnikov, K., Trimmel, N. E., Weisskopf, M., Oertel, M. F., Roche, E., Zeilinger, M. N., Korn, L., Daners, M. S. 2024; 71 (3): 998-1009

  Abstract

  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. Different end actuators were designed for intraventricular implantation and manufactured by applying cyclic tensile loading on soft rubber tubing. Their mechanical properties were investigated, and the type that achieved the greatest pulse pressure amplification in an in vitro simulator of CSF dynamics was selected for application in vivo. A hydraulic actuation device based on a linear voice coil motor was developed to enable automated and fast operation of the end actuators. The combined system was validated in an acute ovine pilot in vivo study.RESULTS: in vitro results show that variations in the used materials and manufacturing settings altered the end actuator's dynamic properties, such as the pressure-volume characteristics. In the in vivo model, a cardiac-gated actuation volume of 0.125 mL at a heart rate of 62 bpm caused an increase of 205% in mean peak-to-peak amplitude but only an increase of 1.3% in mean ICP.CONCLUSION: The introduced soft robotic actuator system is capable of ICP waveform manipulation.SIGNIFICANCE: Continuous amplification of the intracranial pulse pressure could enable in vivo modeling of normal pressure hydrocephalus and shunt system testing under pathophysiological conditions to improve therapy for hydrocephalus.

  View details for DOI 10.1109/TBME.2023.3325058

  View details for PubMedID 37847623

• A Multi-Domain Simulation Study of a Pulsatile-Flow Pump Device for Heart Failure With Preserved Ejection Fraction FRONTIERS IN PHYSIOLOGY Ozturk, C., Rosalia, L., Roche, E. T. 2022; 13: 815787

  Abstract

  Mechanical circulatory support (MCS) devices are currently under development to improve the physiology and hemodynamics of patients with heart failure with preserved ejection fraction (HFpEF). Most of these devices, however, are designed to provide continuous-flow support. While it has been shown that pulsatile support may overcome some of the complications hindering the clinical translation of these devices for other heart failure phenotypes, the effects that it may have on the HFpEF physiology are still unknown. Here, we present a multi-domain simulation study of a pulsatile pump device with left atrial cannulation for HFpEF that aims to alleviate left atrial pressure, commonly elevated in HFpEF. We leverage lumped-parameter modeling to optimize the design of the pulsatile pump, computational fluid dynamic simulations to characterize hydraulic and hemolytic performance, and finite element modeling on the Living Heart Model to evaluate effects on arterial, left atrial, and left ventricular hemodynamics and biomechanics. The findings reported in this study suggest that pulsatile-flow support can successfully reduce pressures and associated wall stresses in the left heart, while yielding more physiologic arterial hemodynamics compared to continuous-flow support. This work therefore supports further development and evaluation of pulsatile support MCS devices for HFpEF.

  View details for DOI 10.3389/fphys.2022.815787

  View details for Web of Science ID 000752846800001

  View details for PubMedID 35145432

  View details for PubMedCentralID PMC8822361

• Computational Modeling of a Low-Cost Fluidic Oscillator for Use in an Educational Respiratory Simulator ADVANCED NANOBIOMED RESEARCH Dillon, T., Ozturk, C., Mendez, K., Rosalia, L., Gollob, S., Kempf, K., Roche, E. 2021; 1 (12): 2000112

  Abstract

  Herein, the computational modeling of a fluidic oscillator for use in an educational respiratory simulator apparatus is presented. The design provides realistic visualization and tuning of respiratory biomechanics using a part that is (i) inexpensive, (ii) easily manufactured without the need for specialized equipment, (iii) simple to assemble and maintain, (iv) does not require any electronics, and (v) has no moving components that could be prone to failure. A computational fluid dynamics (CFD) model is used to assess flow characteristics of the system, and a prototype is developed and tested with a commercial benchtop respiratory simulator. The simulations show clinically relevant periodic oscillation with outlet pressures in the range of 8-20 cmH2O and end-user-tunable frequencies in the range of 3-6 s (respiratory rate [RR] of 10-20 breaths per minute). The fluidic oscillator presented here functions at physiologically relevant pressures and frequencies, demonstrating potential as a low cost, hands-on, and pedagogical tool. The model will serve as a realistic model for educating Science, Technology, Engineering, and Mathematics (STEM) students on the relationship between flow, pressure, compliance, and volume in respiratory biomechanics while simultaneously exposing them to basic manufacturing techniques.

  View details for DOI 10.1002/anbr.202000112

  View details for Web of Science ID 000782100900001

  View details for PubMedID 33786536

  View details for PubMedCentralID PMC7995041

• Object-Oriented Lumped-Parameter Modeling of the Cardiovascular System for Physiological and Pathophysiological Conditions ADVANCED THEORY AND SIMULATIONS Rosalia, L., Ozturk, C., Van Story, D., Horvath, M. A., Roche, E. T. 2021; 4 (3)

  View details for DOI 10.1002/adts.202000216

  View details for Web of Science ID 000617117500001

• Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction JOVE-JOURNAL OF VISUALIZED EXPERIMENTS Rosalia, L., Ozturk, C., Roche, E. T. 2021

  Abstract

  Scientific efforts in the field of computational modeling of cardiovascular diseases have largely focused on heart failure with reduced ejection fraction (HFrEF), broadly overlooking heart failure with preserved ejection fraction (HFpEF), which has more recently become a dominant form of heart failure worldwide. Motivated by the paucity of HFpEF in silico representations, two distinct computational models are presented in this paper to simulate the hemodynamics of HFpEF resulting from left ventricular pressure overload. First, an object-oriented lumped-parameter model was developed using a numerical solver. This model is based on a zero-dimensional (0D) Windkessel-like network, which depends on the geometrical and mechanical properties of the constitutive elements and offers the advantage of low computational costs. Second, a finite element analysis (FEA) software package was utilized for the implementation of a multidimensional simulation. The FEA model combines three-dimensional (3D) multiphysics models of the electro-mechanical cardiac response, structural deformations, and fluid cavity-based hemodynamics and utilizes a simplified lumped-parameter model to define the flow exchange profiles among different fluid cavities. Through each approach, both the acute and chronic hemodynamic changes in the left ventricle and proximal vasculature resulting from pressure overload were successfully simulated. Specifically, pressure overload was modeled by reducing the orifice area of the aortic valve, while chronic remodeling was simulated by reducing the compliance of the left ventricular wall. Consistent with the scientific and clinical literature of HFpEF, results from both models show (i) an acute elevation of transaortic pressure gradient between the left ventricle and the aorta and a reduction in the stroke volume and (ii) a chronic decrease in the end-diastolic left ventricular volume, indicative of diastolic dysfunction. Finally, the FEA model demonstrates that stress in the HFpEF myocardium is remarkably higher than in the healthy heart tissue throughout the cardiac cycle.

  View details for DOI 10.3791/62167

  View details for Web of Science ID 000646178300084

  View details for PubMedID 33645575

• A SOFT ROBOTIC SLEEVE FOR COMPRESSION THERAPY OF THE LOWER LIMB Rosalia, L., Lamberti, K. K., Landry, M. K., Leclerc, C. M., Shuler, F. D., Hanumara, N. C., Roche, E. T., IEEE IEEE. 2021: 1280-1283

  Abstract

  'We present the development of a soft robotic-inspired device for lower limb compression therapy with application in the treatment of lymphedema. This device integrates the control capabilities of pneumatic devices with the wearability and low cost of compression garments. The design consists of a three-layered soft robotic sleeve that ensures safe skin contact, controls compression, and secures the device to the patient limb. The expandable component is made of interconnected pockets of various heights, which passively create a graduated compression profile along the lower limb. The system is inflated by a pump and a microcontroller-actuated valve, with force sensors embedded in the sleeve that monitor the pressure applied to the limb. Testing on healthy individualsq demonstrated the ability to reach clinically relevant target pressures (30, 40, 50 mmHg) and establish a distal-to-proximal descending pressure gradient of approximately 40 mmHg. Device function was shown to be robust against variations in subject anatomy.Clinical Relevance- This system provides controllable, graduated, compression therapy to lymphedema patients in an economical, portable, and customizable package.

  View details for DOI 10.1109/EMBC46164.2021.9630924

  View details for Web of Science ID 000760910501070

  View details for PubMedID 34891519

• An organosynthetic soft robotic respiratory simulator APL BIOENGINEERING Horvath, M. A., Hu, L., Mueller, T., Hochstein, J., Rosalia, L., Hibbert, K. A., Hardin, C. C., Roche, E. T. 2020; 4 (2): 026108

  Abstract

  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.

  View details for DOI 10.1063/1.5140760

  View details for Web of Science ID 000540971700001

  View details for PubMedID 32566890

  View details for PubMedCentralID PMC7286700