All Publications

  • Biomechanical analysis of neochordal repair error from diastolic phase inversion of static left ventricular pressurization. JTCVS techniques Park, M. H., Marin-Cuartas, M., Imbrie-Moore, A. M., Wilkerson, R. J., Pandya, P. K., Zhu, Y., Wang, H., Borger, M. A., Woo, Y. J. 2022; 12: 54-64


    Objective: Neochordal implantation is a common form of surgical mitral valve (MV) repair. However, neochord length is assessed using static left ventricular pressurization, leading surgeons to evaluate leaflet coaptation and valve competency when the left ventricle is dilating instead of contracting physiologically, referred to as diastolic phase inversion (DPI). We hypothesize that the difference in papillary muscle (PM) positioning between DPI and physiologic systole results in miscalculated neochord lengths, which might affect repair performance.Methods: Porcine MVs (n=6) were mounted in an exvivo heart simulator and PMs were affixed to robots that accurately simulate PM motion. Baseline hemodynamic and chordal strain data were collected, after which P2 chordae were severed to simulate posterior leaflet prolapse from chordal rupture and subsequent mitral regurgitation. Neochord implantation was performed in the physiologic and DPI static configurations.Results: Although both repairs successfully reduced mitral regurgitation, the DPI repair resulted in longer neochordae (2.19±0.4mm; P<.01). Furthermore, the hemodynamic performance was reduced for the DPI repair resulting in higher leakage volume (P=.01) and regurgitant fraction (P<.01). Peak chordal forces were reduced in the physiologic repair (0.57±0.11N) versus the DPI repair (0.68±0.12N; P<.01).Conclusions: By leveraging advanced exvivo technologies, we were able to quantify the effects of static pressurization on neochordal length determination. Our findings suggest that this post-repair assessment might slightly overestimate the neochordal length and that additional marginal shortening of neochordae might positively affect MV repair performance and durability by reducing load on surrounding native chordae.

    View details for DOI 10.1016/j.xjtc.2022.01.009

    View details for PubMedID 35403058

  • From hardware store to hospital: a COVID-19-inspired, cost-effective, open-source, in vivo-validated ventilator for use in resource-scarce regions. Bio-design and manufacturing Park, M. H., Zhu, Y., Wang, H., Tran, N. A., Jung, J., Paulsen, M. J., Imbrie-Moore, A. M., Baker, S., Wilkerson, R., Marin-Cuartas, M., Mullis, D. M., Woo, Y. J. 2021: 1-8


    Resource-scarce regions with serious COVID-19 outbreaks do not have enough ventilators to support critically ill patients, and these shortages are especially devastating in developing countries. To help alleviate this strain, we have designed and tested the accessible low-barrier in vivo-validated economical ventilator (ALIVE Vent), a COVID-19-inspired, cost-effective, open-source, in vivo-validated solution made from commercially available components. The ALIVE Vent operates using compressed oxygen and air to drive inspiration, while two solenoid valves ensure one-way flow and precise cycle timing. The device was functionally tested and profiled using a variable resistance and compliance artificial lung and validated in anesthetized large animals. Our functional test results revealed its effective operation under a wide variety of ventilation conditions defined by the American Association of Respiratory Care guidelines for ventilator stockpiling. The large animal test showed that our ventilator performed similarly if not better than a standard ventilator in maintaining optimal ventilation status. The FiO2, respiratory rate, inspiratory to expiratory time ratio, positive-end expiratory pressure, and peak inspiratory pressure were successfully maintained within normal, clinically validated ranges, and the animals were recovered without any complications. In regions with limited access to ventilators, the ALIVE Vent can help alleviate shortages, and we have ensured that all used materials are publicly available. While this pandemic has elucidated enormous global inequalities in healthcare, innovative, cost-effective solutions aimed at reducing socio-economic barriers, such as the ALIVE Vent, can help enable access to prompt healthcare and life saving technology on a global scale and beyond COVID-19.Supplementary Information: The online version contains supplementary material available at 10.1007/s42242-021-00164-1.

    View details for DOI 10.1007/s42242-021-00164-1

    View details for PubMedID 34567825

  • Heart Valve Biomechanics: The Frontiers of Modeling Modalities and the Expansive Capabilities of Ex Vivo Heart Simulation. Frontiers in cardiovascular medicine Park, M. H., Zhu, Y., Imbrie-Moore, A. M., Wang, H., Marin-Cuartas, M., Paulsen, M. J., Woo, Y. J. 2021; 8: 673689


    The field of heart valve biomechanics is a rapidly expanding, highly clinically relevant area of research. While most valvular pathologies are rooted in biomechanical changes, the technologies for studying these pathologies and identifying treatments have largely been limited. Nonetheless, significant advancements are underway to better understand the biomechanics of heart valves, pathologies, and interventional therapeutics, and these advancements have largely been driven by crucial in silico, ex vivo, and in vivo modeling technologies. These modalities represent cutting-edge abilities for generating novel insights regarding native, disease, and repair physiologies, and each has unique advantages and limitations for advancing study in this field. In particular, novel ex vivo modeling technologies represent an especially promising class of translatable research that leverages the advantages from both in silico and in vivo modeling to provide deep quantitative and qualitative insights on valvular biomechanics. The frontiers of this work are being discovered by innovative research groups that have used creative, interdisciplinary approaches toward recapitulating in vivo physiology, changing the landscape of clinical understanding and practice for cardiovascular surgery and medicine.

    View details for DOI 10.3389/fcvm.2021.673689

    View details for PubMedID 34307492

  • Artificial papillary muscle device for off-pump transapical mitral valve repair. The Journal of thoracic and cardiovascular surgery Imbrie-Moore, A. M., Zhu, Y. n., Park, M. H., Paulsen, M. J., Wang, H. n., Woo, Y. J. 2020


    New transapical minimally invasive artificial chordae implantation devices are a promising alternative to traditional open-heart repair, with the potential for decreased postoperative morbidity and reduced recovery time. However, these devices can place increased stress on the artificial chordae. We designed an artificial papillary muscle to alleviate artificial chordae stresses and thus increase repair durability.The artificial papillary muscle device is a narrow elastic column with an inner core that can be implanted during the minimally invasive transapical procedure via the same ventricular incision site. The device was 3-dimensionally printed in biocompatible silicone for this study. To test efficacy, porcine mitral valves (n = 6) were mounted in a heart simulator, and isolated regurgitation was induced. Each valve was repaired with a polytetrafluoroethylene suture with apical anchoring followed by artificial papillary muscle anchoring. In each case, a high-resolution Fiber Bragg Grating sensor recorded forces on the suture.Hemodynamic data confirmed that both repairs-with and without the artificial papillary muscle device-were successful in eliminating mitral regurgitation. Both the peak artificial chordae force and the rate of change of force at the onset of systole were significantly lower with the device compared with apical anchoring without the device (P < .001 and P < .001, respectively).Our novel artificial papillary muscle could integrate with minimally invasive repairs to shorten the artificial chordae and behave as an elastic damper, thus reducing sharp increases in force. With our device, we have the potential to improve the durability of off-pump transapical mitral valve repair procedures.

    View details for DOI 10.1016/j.jtcvs.2020.11.105

    View details for PubMedID 33451843

  • Quadrupling the N95 Supply during the COVID-19 Crisis with an Innovative 3D-Printed Mask Adaptor. Healthcare (Basel, Switzerland) Imbrie-Moore, A. M., Park, M. H., Zhu, Y. n., Paulsen, M. J., Wang, H. n., Woo, Y. J. 2020; 8 (3)


    The need for personal protective equipment during the COVID-19 pandemic is far outstripping our ability to manufacture and distribute these supplies to hospitals. In particular, the medical N95 mask shortage is resulting in healthcare providers reusing masks or utilizing masks with filtration properties that do not meet medical N95 standards. We developed a solution for immediate use: a mask adaptor, outfitted with a quarter section of an N95 respirator that maintains the N95 seal standard, thereby quadrupling the N95 supply. A variety of designs were 3D-printed and optimized based on the following criteria: seal efficacy, filter surface area and N95 respirator multiplicity. The final design is reusable and features a 3D-printed soft silicone base as well as a rigid 3D-printed cartridge to seal one-quarter of a 3M 1860 N95 mask. Our mask passed the computerized N95 fit test for six individuals. All files are publicly available with this publication. Our design can provide immediate support for healthcare professionals in dire need of medical N95 masks by extending the current supply by a factor of four.

    View details for DOI 10.3390/healthcare8030225

    View details for PubMedID 32717841

  • Biomimetic six-axis robots replicate human cardiac papillary muscle motion: pioneering the next generation of biomechanical heart simulator technology. Journal of the Royal Society, Interface Imbrie-Moore, A. M., Park, M. H., Paulsen, M. J., Sellke, M. n., Kulkami, R. n., Wang, H. n., Zhu, Y. n., Farry, J. M., Bourdillon, A. T., Callinan, C. n., Lucian, H. J., Hironaka, C. E., Deschamps, D. n., Joseph Woo, Y. n. 2020; 17 (173): 20200614


    Papillary muscles serve as attachment points for chordae tendineae which anchor and position mitral valve leaflets for proper coaptation. As the ventricle contracts, the papillary muscles translate and rotate, impacting chordae and leaflet kinematics; this motion can be significantly affected in a diseased heart. In ex vivo heart simulation, an explanted valve is subjected to physiologic conditions and can be adapted to mimic a disease state, thus providing a valuable tool to quantitatively analyse biomechanics and optimize surgical valve repair. However, without the inclusion of papillary muscle motion, current simulators are limited in their ability to accurately replicate cardiac biomechanics. We developed and implemented image-guided papillary muscle (IPM) robots to mimic the precise motion of papillary muscles. The IPM robotic system was designed with six degrees of freedom to fully capture the native motion. Mathematical analysis was used to avoid singularity conditions, and a supercomputing cluster enabled the calculation of the system's reachable workspace. The IPM robots were implemented in our heart simulator with motion prescribed by high-resolution human computed tomography images, revealing that papillary muscle motion significantly impacts the chordae force profile. Our IPM robotic system represents a significant advancement for ex vivo simulation, enabling more reliable cardiac simulations and repair optimizations.

    View details for DOI 10.1098/rsif.2020.0614

    View details for PubMedID 33259750

  • FDA Emergency Use Authorization-Approved Novel Coronavirus Disease 2019, Pressure-Regulated, Mechanical Ventilator Splitter That Enables Differential Compliance Multiplexing. ASAIO journal (American Society for Artificial Internal Organs : 1992) Paulsen, M. J., Zhu, Y., Park, M. H., Imbrie-Moore, A. M., Baker, S., Walter Edmonston, D., Dawson, T., Ly, E., Martin Bell, S., Tran, N. A., Jung, J., Cedarleaf-Pavy, J., Sridhar, K. R., Venkataraman, V., Woo, Y. J. 2022


    Infection with the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may cause viral pneumonia and acute respiratory distress syndrome (ARDS). Treatment of ARDS often requires mechanical ventilation and may take weeks for resolution. In areas with a large outbreaks, there may be shortages of ventilators available. While rudimentary methods for ventilator splitting have been described, given the range of independent ventilatory settings required for each patient, this solution is suboptimal. Here, we describe a device that can split a ventilator among up to four patients while allowing for individualized settings. The device has been validated in vitro and in vivo.

    View details for DOI 10.1097/MAT.0000000000001756

    View details for PubMedID 35667305

  • Ex vivo biomechanical analysis of flexible versus rigid annuloplasty rings in mitral valves using a novel annular dilation system. BMC cardiovascular disorders Zhu, Y., Imbrie-Moore, A. M., Wilkerson, R. J., Paulsen, M. J., Park, M. H., Woo, Y. J. 2022; 22 (1): 73


    BACKGROUND: Mitral annuloplasty rings restore annular dimensions to increase leaflet coaptation, serving a fundamental component in mitral valve repair. However, biomechanical evaluations of annuloplasty rings are lacking. We aim to biomechanically analyze flexible and rigid annuloplasty rings using an ex vivo mitral annular dilation model.METHODS: Juvenile porcine mitral valves (n=4) with intercommissural distance of 28mm were dilated to intercommissural distances of 40mm using a 3D-printed dilator and were sewn to an elastic mount. Fiber bragg grating sensors were anchored to native chordae to measure chordal forces. The valves were repaired using size 28 rigid and flexible annuloplasty rings in a random order. Hemodynamic data, echocardiography, and chordal force measurements were collected.RESULTS: Mitral annular dilation resulted in decreased leaflet coaptation height and increased mitral regurgitation fraction. Both the flexible and rigid annuloplasty rings effectively increased leaflet coaptation height compared to that post dilation. Rigid ring annuloplasty repair significantly decreased the mitral regurgitation fraction. Flexible annuloplasty ring repair reduced the chordal rate of change of force (7.1±4.4N/s versus 8.6±5.9N/s, p=0.02) and peak force (0.6±0.5N versus 0.7±0.6N, p=0.01) compared to that from post dilation. Rigid annuloplasty ring repair was associated with higher chordal rate of change of force (9.8±5.8N/s, p=0.0001) and peak force (0.7±0.5N, p=0.01) compared to that after flexible ring annuloplasty repair.CONCLUSIONS: Both rigid and flexible annuloplasty rings are effective in increasing mitral leaflet coaptation height. Although the rigid annuloplasty ring was associated with slightly higher chordal stress compared to that of the flexible annuloplasty ring, it was more effective in mitral regurgitation reduction. This study may help direct the design of an optimal annuloplasty ring to further improve patient outcomes.

    View details for DOI 10.1186/s12872-022-02515-x

    View details for PubMedID 35219298

  • A Novel Device for Intraoperative Direct Visualization of a Pressurized Root in Aortic Valve Repair. The Annals of thoracic surgery Zhu, Y., Imbrie-Moore, A. M., Paulsen, M. J., Park, M. H., Tran, N. A., Woo, Y. J. 2022


    PURPOSE: One major challenge in generating reproducible aortic valve (AV) repair results is the inability to assess AV morphology under physiologic pressure. A transparent intraoperative aortic valve visualization device was designed and manufactured.DESCRIPTION: This device is comprised of an open proximal end, a cantilevered edge to allow attachment of the device to the aorta or graft, a distal viewing surface, and two side ports for fluid delivery and air removal.EVALUATION: The performance of the device was evaluated ex vivo using normal porcine AV in situ (n=3), AV after valve-sparing aortic root replacement (VSARR, n=3), and porcine pulmonary valve in Ross procedure (n=3), and in 3 patients who underwent VSARR. AV morphology was clearly visualized using the device in all experiments. In human, the use of this device successfully illustrated cusp prolapse after the initial VSARR and effectively guided additional cusp repair.CONCLUSIONS: This device successfully allows for direct visual assessment of the AV apparatus under physiologic pressure. The use of this device can potentially increase the adoptability of AV repair in clinical practice.

    View details for DOI 10.1016/j.athoracsur.2022.02.013

    View details for PubMedID 35216987

  • Biomechanical engineering analysis of an acute papillary muscle rupture disease model using an innovative 3D-printed left heart simulator. Interactive cardiovascular and thoracic surgery Marin-Cuartas, M., Zhu, Y., Imbrie-Moore, A. M., Park, M. H., Wilkerson, R. J., Leipzig, M., Pandya, P. K., Paulsen, M. J., Borger, M. A., Woo, Y. J. 1800


    OBJECTIVES: The severity of acute papillary muscle (PM) rupture varies according to the extent and site of the rupture. However, the haemodynamic effects of different rupture variations are still poorly understood. Using a novel ex vivo model, we sought to study acute PM rupture to improve clinical management.METHODS: Using porcine mitral valves (n=32) mounted within an ex vivo left heart simulator, PM rupture was simulated. The mitral valve was divided into quadrants for analysis according to the PM heads. Acute PM rupture was simulated by incrementally cutting from 1/3 to the total number of chordae arising from 1 PM head of interest. Haemodynamic parameters were measured.RESULTS: Rupture >2/3 of the chordae from 1 given PM head or regurgitation fraction >60% led to markedly deteriorated haemodynamics. Rupture at the anterolateral PM had a stronger negative effect on haemodynamics than rupture at the posteromedial PM. Rupture occurring at the anterior head of the anterolateral PM led to more marked haemodynamic instability than rupture occurring at the other PM heads.CONCLUSIONS: The haemodynamic effects of acute PM rupture vary considerably according to the site and extent of the rupture. Rupture of ≤2/3 of chordae from 1 PM head or rupture at the posteromedial PM lead to less marked haemodynamics effects, suggesting a higher likelihood of tolerating surgery. Rupture at the anterolateral PM, specifically the anterior head, rupture of >2/3 of chordae from 1 PM head or regurgitation fraction >60% led to marked haemodynamic instability, suggesting the potential benefit from bridging strategies prior to surgery.

    View details for DOI 10.1093/icvts/ivab373

    View details for PubMedID 35022737

  • Ex Vivo Model of Ischemic Mitral Regurgitation and Analysis of Adjunctive Papillary Muscle Repair. Annals of biomedical engineering Imbrie-Moore, A. M., Zhu, Y., Bandy-Vizcaino, T., Park, M. H., Wilkerson, R. J., Woo, Y. J. 2021


    Ischemic mitral regurgitation (IMR) is particularly challenging to repair with lasting durability due to the complex valvular and subvalvular pathologies resulting from left ventricular dysfunction. Ex vivo simulation is uniquely suited to quantitatively analyze the repair biomechanics, but advancements are needed to model the nuanced IMR disease state. Here we present a novel IMR model featuring a dilation device with precise dilatation control that preserves annular elasticity to enable accurate ex vivo analysis of surgical repair. Coupled with augmented papillary muscle head positioning, the enhanced heart simulator system successfully modeled IMR pre- and post-surgical intervention and enabled the analysis of adjunctive subvalvular papillary muscle repair to alleviate regurgitation recurrence. The model resulted in an increase in regurgitant fraction: 11.6 ± 1.7% to 36.1 ± 4.4% (p<0.001). Adjunctive papillary muscle head fusion was analyzed relative to a simple restrictive ring annuloplasty repair and, while both repairs successfully eliminated regurgitation initially, the addition of the adjunctive subvalvular repair reduced regurgitation recurrence: 30.4 ± 5.7% vs. 12.5 ± 2.6% (p=0.002). Ultimately, this system demonstrates the success of adjunctive papillary muscle head fusion in repairing IMR as well as provides a platform to optimize surgical techniques for increased repair durability.

    View details for DOI 10.1007/s10439-021-02879-9

    View details for PubMedID 34734363

  • Exvivo biomechanical analysis of the Ross procedure using the modified inclusion technique in a 3-dimensionally printed left heart simulator. The Journal of thoracic and cardiovascular surgery Zhu, Y., Marin-Cuartas, M., Park, M. H., Imbrie-Moore, A. M., Wilkerson, R. J., Madira, S., Mullis, D. M., Woo, Y. J. 2021


    OBJECTIVE: The inclusion technique was developed to reinforce the pulmonary autograft to prevent dilation after the Ross procedure. Anticommissural plication (ACP), a modification technique, can reduce graft size and create neosinuses. The objective was to evaluate pulmonary valve biomechanics using the inclusion technique in the Ross procedure with and without ACP.METHODS: Seven porcine and 5 human pulmonary autografts were harvested from hearts obtained from a meat abattoir and from heart transplant recipients and donors, respectively. Five additional porcine autografts without reinforcement were used as controls. The Ross procedure was performed using the inclusion technique with a straight polyethylene terephthalate graft. The same specimens were tested both with and without ACP. Hemodynamic parameter data, echocardiography, and high-speed videography were collected via the exvivo heart simulator.RESULTS: Porcine autograft regurgitation was significantly lower after the use of inclusion technique compared with controls (P<.01). ACP compared with non-ACP in both porcine and human pulmonary autografts was associated with lower leaflet rapid opening velocity (3.9±2.4cm/sec vs 5.9±2.4cm/sec; P=.03; 3.5±0.9cm/sec vs 4.4±1.0cm/sec; P=.01), rapid closing velocity (1.9±1.6cm/sec vs 3.1±2.0cm/sec; P=.01; 1.8±0.7cm/sec vs 2.2±0.3cm/sec; P=.13), relative rapid opening force (4.6±3.0 vs 7.7±5.2; P=.03; 3.0±0.6 vs 4.0±2.1; P=.30), and relative rapid closing force (2.5±3.4 vs 5.9±2.3; P=.17; 1.4±1.3 vs 2.3±0.6; P=.25).CONCLUSIONS: The Ross procedure using the inclusion technique demonstrated excellent hemodynamic parameter results. The ACP technique was associated with more favorable leaflet biomechanics. Invivo validation should be performed to allow direct translation to clinical practice.

    View details for DOI 10.1016/j.jtcvs.2021.06.070

    View details for PubMedID 34625236

  • Collagen-Supplemented Incubation Rapidly Augments Mechanical Property of Fibroblast Cell Sheets. Tissue engineering. Part A Zhu, Y., Thakore, A. D., Farry, J. M., Jung, J., Anilkumar, S., Wang, H., Imbrie-Moore, A. M., Park, M. H., Tran, N. A., Woo, Y. J. 2020


    Cell sheet technology using UpCell plates is a modern tool that enables the rapid creation of a single-layered cells without using extracellular matrix enzymatic digestion. Although this technique has the advantage of maintaining a sheet of cells without needing artificial scaffolds, these cell sheets remain extremely fragile. Collagen, the most abundant extracellular matrix component, is an attractive candidate for modulating tissue mechanical properties given its tunable property. In this study, we demonstrated rapid mechanical property augmentation of human dermal fibroblast cell sheets after incubation with bovine type I collagen for 24 hours on UpCell plates. We showed that treatment with collagen resulted in increased collagen I incorporation within the cell sheet without affecting cell morphology, cell type, or cell sheet quality. Atomic force microscopy measurements for controls, and cell sheets that received 50g/mL and 100g/mL collagen I treatments revealed an average Young's modulus of their respective intercellular regions: 6.6±1.0, 14.4±6.6, and 19.8±3.8 kPa during the loading condition, and 10.3±4.7, 11.7±2.2, and 18.1±3.4 kPa during the unloading condition. This methodology of rapid mechanical property augmentation of a cell sheet has a potential impact on cell sheet technology by improving the ease of construct manipulation, enabling new translational tissue engineering applications.

    View details for DOI 10.1089/ten.TEA.2020.0128

    View details for PubMedID 32703108

  • Ex Vivo Analysis of a Porcine Bicuspid Aortic Valve and Aneurysm Disease Model. The Annals of thoracic surgery Zhu, Y., Imbrie-Moore, A. M., Park, M. H., Paulsen, M. J., Wang, H., MacArthur, J. W., Woo, Y. J. 2020


    We identified an extremely rare congenital porcine type 0 lateral bicuspid aortic valve (BAV) from a fresh porcine heart. Using a 3D-printed ex vivo left heart simulator, we analyzed valvular hemodynamics at baseline, in an aortic aneurysm disease model, and after valve-sparing root replacement (VSRR). We showed that BAV regurgitation due to aortic aneurysm can be successfully repaired without significant hemodynamic impairment with the VSRR technique in an individualized approach. Our results provide direct hemodynamic evidence supporting the use of VSRR for patients with BAV regurgitation.

    View details for DOI 10.1016/j.athoracsur.2020.05.086

    View details for PubMedID 32663472

  • A Novel Aortic Regurgitation Model from Cusp Prolapse with Hemodynamic Validation Using an Ex Vivo Left Heart Simulator. Journal of cardiovascular translational research Zhu, Y. n., Imbrie-Moore, A. M., Paulsen, M. J., Priromprintr, B. n., Park, M. H., Wang, H. n., Lucian, H. J., Farry, J. M., Woo, Y. J. 2020


    Although ex vivo simulation is a valuable tool for surgical optimization, a disease model that mimics human aortic regurgitation (AR) from cusp prolapse is needed to accurately examine valve biomechanics. To simulate AR, four porcine aortic valves were explanted, and the commissure between the two largest leaflets was detached and re-implanted 5 mm lower to induce cusp prolapse. Four additional valves were tested in their native state as controls. All valves were tested in a heart simulator while hemodynamics, high-speed videography, and echocardiography data were collected. Our AR model successfully reproduced cusp prolapse with significant increase in regurgitant volume compared with that of the controls (23.2 ± 8.9 versus 2.8 ± 1.6 ml, p = 0.017). Hemodynamics data confirmed the simulation of physiologic disease conditions. Echocardiography and color flow mapping demonstrated the presence of mild to moderate eccentric regurgitation in our AR model. This novel AR model has enormous potential in the evaluation of valve biomechanics and surgical repair techniques. Graphical Abstract.

    View details for DOI 10.1007/s12265-020-10038-z

    View details for PubMedID 32495264