Next Generation Development of Hybrid Continuous Flow Pediatric Total Artificial Heart Technology: Design-Build-Test.

To address the unmet clinical need for pediatric circulatory support, we are developing an operationally versatile, hybrid, continuous-flow, total artificial heart ("Dragon Heart"). This device integrates a magnetically levitated axial and centrifugal blood pump. Here, we utilized a validated axial flow pump, and we focused on the development of the centrifugal pump. A motor was integrated to drive the centrifugal pump, achieving 50% size reduction. The motor design was simulated by finite element analysis, and pump design improvement was attained by computational fluid dynamics. A prototype centrifugal pump was constructed from biocompatible 3D printed parts for the housing and machined metal parts for the drive system. Centrifugal prototype testing was conducted using water and then bovine blood. The fully combined device ( i.e. , axial pump nested inside of the centrifugal pump) was tested to ensure proper operation. We demonstrated the hydraulic performance of the two pumps operating in tandem, and we found that the centrifugal blood pump performance was not adversely impacted by the simultaneous operation of the axial blood pump. The current iteration of this design achieved a range of operation overlapping our target range. Future design iterations will further reduce size and incorporate complete and active magnetic levitation.

Impact of continuous-flow mechanical circulatory support on cerebrospinal fluid motility.

BACKGROUND: Mechanical circulatory support (MCS), including ventricular assist devices (VADs), have emerged as promising therapeutic alternatives for end-stage congestive heart failure (CHF). The latest generation of these devices are continuous flow (CF) blood pumps. While there have been demonstrated benefits to patient outcomes due to CF-MCS, there continue to be significant clinical challenges. Research to-date has concentrated on mitigating thromboembolic risk (stroke), while the downstream impact of CF-MCS on the cerebrospinal fluid (CSF) flow has not been well investigated. Disturbances in the CSF pressure and flow patterns are known to be associated with neurologic impairment and diseased states. Thus, here we seek to develop an understanding of the pathophysiologic consequences of CF-MCS on CSF dynamics. METHODS: We built and validated a computational framework using lumped parameter modeling of cardiovascular, cerebrovascular physics, CSF dynamics, and autoregulation. A sensitivity analysis was performed to confirm robustness of the modeling framework. Then, we characterized the impact of CF-MCS on the CSF and investigated cardiovascular conditions of healthy and end-stage heart failure. RESULTS: Modeling results demonstrated appropriate hemodynamics and indicated that CSF pressure depends on blood flow pulsatility more than CSF flow. An acute equilibrium between CSF production and absorption was observed in the CF-MCS case, characterized by CSF pressure remaining elevated, and CSF flow rates remaining below healthy, but higher than CHF states. CONCLUSION: This research has advanced our understanding of the impact of CF-MCS on CSF dynamics and cerebral hemodynamics.

Channel impeller design for centrifugal blood pump in hybrid pediatric total artificial heart: Modeling, magnet integration, and hydraulic experiments.

BACKGROUND: The purpose of this research is to address ongoing device shortfalls for pediatric patients by developing a novel pediatric hybrid total artificial heart (TAH). The valveless magnetically-levitated MCS device (Dragon Heart) has only two moving parts, integrates an axial and centrifugal blood pump into a single device, and will occupy a compact footprint within the chest for the pediatric patient population. METHODS: Prior work on the Dragon Heart focused on the development of pump designs to achieve hemodynamic requirements. The impeller of these pumps was shaft-driven and thus could not be integrated for testing. The presented research leverages an existing magnetically levitated axial flow pump and focuses on centrifugal pump development. Using the axial pump diameter as a geometric constraint, a shaftless, magnetically supported centrifugal pump was designed for placement circumferentially around the axial pump domain. The new design process included the computational analysis of more than 50 potential centrifugal impeller geometries. The resulting centrifugal pump designs were prototyped and tested for levitation and no-load rotation, followed by in vitro testing using a blood analog. To meet physiologic demands, target performance goals were pressure rises exceeding 90 mm Hg for flow rates of 1-5 L/min with operating speeds of less than 5000 RPM. RESULTS: Three puck-shaped, channel impellers for the centrifugal blood pump were selected based on achieving performance and space requirements for magnetic integration. A quasi-steady flow analysis revealed that the impeller rotational position led to a pulsatile component in the pressure generation. After prototyping, the centrifugal prototypes (3, 4, and 5 channeled designs) demonstrated levitation and no-load rotation. Hydraulic experiments established pressure generation capabilities beyond target requirements. The pressure-flow performance of the prototypes followed expected trends with a dependence on rotational speed. Pulsatile blood flow was observed without pump-speed modulation due to rotating channel passage frequency. CONCLUSION: The results are promising in the advancement of this pediatric TAH. The channeled impeller design creates pressure-flow curves that are decoupled from the flow rate, a benefit that could reduce the required controller inputs and improve treatment of hypertensive patients.

Novel hybrid total artificial heart with integrated oxygenator.

There continues to be an unmet therapeutic need for an alternative treatment strategy for respiratory distress and lung disease. We are developing a portable cardiopulmonary support system that integrates an implantable oxygenator with a hybrid, dual-support, continuous-flow total artificial heart (TAH). The TAH has a centrifugal flow pump that is rotating about an axial flow pump. By attaching the hollow fiber bundle of the oxygenator to the base of the TAH, we establish a new cardiopulmonary support technology that permits a patient to be ambulatory during usage. In this study, we investigated the design and improvement of the blood flow pathway from the inflow-to-outflow of four oxygenators using a mathematical model and computational fluid dynamics (CFD). Pressure loss and gas transport through diffusion were examined to assess oxygenator design. The oxygenator designs led to a resistance-driven pressure loss range of less than 35 mmHg for flow rates of 1-7 L/min. All of the designs met requirements. The configuration having an outside-to-inside blood flow direction was found to have higher oxygen transport. Based on this advantageous flow direction, two designs (Model 1 and 3) were then integrated with the axial-flow impeller of the TAH for simulation. Flow rates of 1-7 L/min and speeds of 10,000-16,000 RPM were analyzed. Blood damage studies were performed, and Model 1 demonstrated the lowest potential for hemolysis. Future work will focus on developing and testing a physical prototype for integration into the new cardiopulmonary assist system.

Development of the Centrifugal Blood Pump for a Hybrid Continuous Flow Pediatric Total Artificial Heart: Model, Make, Measure.

Clinically-available blood pumps and total artificial hearts for pediatric patients continue to lag well behind those developed for adults. We are developing a hybrid, continuous-flow, magnetically levitated, pediatric total artificial heart (TAH). The hybrid TAH design integrates both an axial and centrifugal blood pump within a single, compact housing. The centrifugal pump rotates around the separate axial pump domain, and both impellers rotate around a common central axis. Here, we concentrate our development effort on the centrifugal blood pump by performing computational fluid dynamics (CFD) analysis of the blood flow through the pump. We also conducted transient CFD analyses (quasi-steady and transient rotational sliding interfaces) to assess the pump's dynamic performance conditions. Through modeling, we estimated the pressure generation, scalar stress levels, and fluid forces exerted on the magnetically levitated impellers. To further the development of the centrifugal pump, we also built magnetically-supported prototypes and tested these in an in vitro hydraulic flow loop and via 4-h blood bag hemolytic studies (n = 6) using bovine blood. The magnetically levitated centrifugal prototype delivered 0-6.75 L/min at 0-182 mmHg for 2,750-4,250 RPM. Computations predicted lower pressure-flow performance results than measured by testing; axial and radial fluid forces were found to be <3 N, and mechanical power usage was predicted to be <5 Watts. Blood damage indices (power law weighted exposure time and scalar stress) were <2%. All data trends followed expectations for the centrifugal pump design. Six peaks in the pressure rise were observed in the quasi-steady and transient simulations, correlating to the blade passage frequency of the 6-bladed impeller. The average N.I.H value (n = 6) was determined to be 0.09 ± 0.02 g/100 L, which is higher than desired and must be addressed through design improvement. These data serve as a strong foundation to build upon in the next development phase, whereby we will integrate the axial flow pump component.

Invited commentary: Total anomalous pulmonary venous connection remains a challenging pediatric disease.

Cervantes-Salazar and colleagues report the long-term surgical outcomes of 414 patients with total anomalous pulmonary venous connection (TAPVC) from January 2003 to June 2019. With an overall survival rate of 87.2% from 2003 to 2019, the authors found that an increased mortality risk was associated with infracardiac TAPVC, pulmonary venous obstruction, and postoperative mechanical ventilation. Their comprehensive study with a large sample size of varying age groups, and patients with late referrals for surgery, provide valuable insight into TAPVC surgical outcomes. Improved survival for these patients continues to be a major goal of clinical teams striving to transform treatment paradigms. The promising result of the study reported by Cervantes-Salazar and colleagues gives our field hope for a better future for these patients.

Mechanical and interventional support for heart failure with preserved ejection fraction: A review.

INTRODUCTION: Restrictive cardiomyopathy (RCM) and hypertrophic cardiomyopathy (HCM) are two disease processes that are known to progress to heart failure with preserved ejection fraction (HFpEF). Pharmacologic therapies for HFpEF have not improved patient outcomes or reduced mortality in this patient cohort; thus, there continues to be substantial interest in other treatment strategies, including surgical interventions and devices. In this article, we explore and report the current utility of percutaneous therapies and surgically implanted mechanical support in the treatment of patients with HFpEF. RESULTS: Treatment strategies include percutaneous interventions with interatrial shunts, left atrial assist devices (LAADs), and ventricular assist devices (VADs) in various configurations. Although VADs have been employed to treat patients with heart failure with reduced ejection fraction, their efficacy is limited in those with RCM and HCM. A left atrial-to-aortic VAD has been proposed to directly unload the left atrium, but data is limited. Alternatively, a LAAD could be placed in the mitral position and simultaneously unload the left atrium, while filling the left ventricle. CONCLUSION: A left atrial assist device in the mitral position is a promising solution to address the hemodynamic abnormalities in RCM and HCM; these pumps, however, are still under development.

Invited commentary for: Essential role of cardiac computed tomography for surgical decision making in children with total anomalous pulmonary venous connection and single ventricle.

Thousands of neonates are born each year with complex congenital heart defects, such as total anomalous pulmonary venous connection combined with single ventricle physiology. This dual diagnosis with significant vessel and ventricular complexity requires alternative additional imaging to fully visualize the anatomical challenge and devise the appropriate treatment strategy for the patient.

Technology landscape of pediatric mechanical circulatory support devices: A systematic review 2010-2021.

BACKGROUND: Mechanical circulatory support (MCS) devices, such as ventricular assist devices (VADs) and total artificial hearts (TAHs), have become a vital therapeutic option in the treatment of end-stage heart failure for adult patients. Such therapeutic options continue to be limited for pediatric patients. Clinicians initially adapted or scaled existing adult devices for pediatric patients; however, these adult devices are not designed to support the anatomical structure and varying flow capacities required for this population and are generally operated "off-design," which risks complications such as hemolysis and thrombosis. Devices designed specifically for the pediatric population which seek to address these shortcomings are now emerging and gaining FDA approval. METHODS: To analyze the competitive landscape of pediatric MCS devices, we conducted a systematic literature review. Approximately 27 devices were studied in detail: 8 were established or previously approved designs, and 19 were under development (11 VADs, 5 Fontan assist devices, and 3 TAHs). RESULTS: Despite significant progress, there is still no pediatric pump technology that satisfies the unique and distinct design constraints and requirements to support pediatric patients, including the wide range of patient sizes, increased cardiovascular demand with growth, and anatomic and physiologic heterogeneity of congenital heart disease. CONCLUSIONS: Forward-thinking design solutions are required to overcome these challenges and to ensure the translation of new therapeutic MCS devices for pediatric patients.

Microscale impeller pump for recirculating flow in organs-on-chip and microreactors.

Fluid flow is an integral part of microfluidic and organ-on-chip technology, ideally providing biomimetic fluid, cell, and nutrient exchange as well as physiological or pathological shear stress. Currently, many of the pumps that actively perfuse fluid at biomimetic flow rates are incompatible with use inside cell culture incubators, require many tubing connections, or are too large to run many devices in a confined space. To address these issues, we developed a user-friendly impeller pump that uses a 3D-printed device and impeller to recirculate fluid and cells on-chip. Impeller rotation was driven by a rotating magnetic field generated by magnets mounted on a computer fan; this pump platform required no tubing connections and could accommodate up to 36 devices at once in a standard cell culture incubator. A computational model was used to predict shear stress, velocity, and changes in pressure throughout the device. The impeller pump generated biomimetic fluid velocities (50-6400 µm s-1) controllable by tuning channel and inlet dimensions and the rotational speed of the impeller, which were comparable to the order of magnitude of the velocities predicted by the computational model. Predicted shear stress was in the physiological range throughout the microchannel and over the majority of the impeller. The impeller pump successfully recirculated primary murine splenocytes for 1 h and Jurkat T cells for 24 h with no impact on cell viability, showing the impeller pump's feasibility for white blood cell recirculation on-chip. In the future, we envision that this pump will be integrated into single- or multi-tissue platforms to study communication between organs.

Retrograde flow in aortic isthmus in normal and fetal heart disease by principal component analysis and computational fluid dynamics.

OBJECTIVES: Reverse flow Retrograde flow (RF) of blood in the aortic isthmus can be observed in different types of fetal heart disease (FHD), including abnormalities in heart structure and function. This study sought to investigate the relationship between RF and blood flow parameters, and develop a computational fluid dynamics (CFD) model to understand the mechanisms underlying this observation. MATERIAL AND METHODS: A total of 281 fetuses (gestational age [GA] 26.6±.3 weeks) with FHD and 2803 normal fetuses (GA: 26.1±.1 weeks) by fetal echocardiography collected from May 2016 to December 2018. Principal component analysis (PCA) was performed to find the relationship and the CFD model reconstructed from 3D/4D spatio-temporal image correlation (STIC) images to simulate hemodynamics. RESULTS: There was a significant difference in the percentages of RF between the study (80/201 (39%)) and control (29/2803 (1%)) groups (p < 0.05). The RF occur when the aorta flow rate (left heart) is reduced to 60% by CFD stimulation. Pearson correlation analysis showed significant correlations between flow rate and wall shear stress(WSS) (r = .883, p = 0.047) variables at the AI. CONCLUSION: Volumetric flow rate of AO or left heart was the main component of the cause of RF. The hemodynamics of the cardiovascular system have highly complex behavior hinge on the turbulent nature of circulating blood flow.

Invited commentary: A prospective randomized trial on parents' disease knowledge and quality of life. Shall WeChat about telehealth?

WeChat and access to wireless communication may offer a continuum of care following medical and surgical intervention. This cardiac surgery research study evaluates the process of parental education and social support following pediatric cardiac surgery utilizing standard of care compared to telehealth.

The newly emerging field of pediatric engineering: Innovation for our next generation.

Neonates, infants, and children have unique physiology and body surface areas that dramatically change during growth and development, and the substantial diversity of complicated pediatric illnesses and rare childhood diseases are distinct from the adult sphere. Unfortunately, medical innovation is generally constrained to retrofitting adult treatment strategies for this heterogeneous population. This conventional, but limited, approach ignores the dynamic biopsychosocial, growth, and developmental complexities that abound, as one progresses through this life cycle from newborn onward toward early adulthood. Forward-thinking solutions are essential to advance the state-of-the-art to address the challenges and unmet clinical needs that are uniquely presented by the pediatric population, and it has become obvious that newly trained engineers are essential for success. These unmet clinical needs and the necessity of new technical skills and expertise give rise to the emergence of an entirely new field of engineering and applied science: Pediatric Engineering. The field of Pediatric Engineering flips conventional wisdom that adult therapies can simply be scaled or successfully modified for children. It commandeers design to suit the specific needs of the child, while anticipating the dynamic growth and development into adulthood. We are growing a new pipeline of educated scientists and engineers who will have developed a unique toolbox of skills that they can use to tackle unmet clinical needs in global pediatric healthcare for years to come.

A Cross University-Led COVID-19 Rapid-Response Effort: Design, Build, and Distribute Drexel AJFlex Face Shields.

The purpose of this article is to demonstrate how a new cross-community leadership team came together, collaborated, coordinated across academic units with external community partners, and executed a joint mission to address the unmet clinical need for medical face shields during these unprecedented times. Key aspects of this success include the ability to forge and leverage new opportunities, overcome challenges, adapt to changing constraints, and serve the significant need across the Philadelphia region and healthcare systems. We teamed to design-build durable face shields (AJFlex Shields). This was accomplished by high-volume manufacturing via injection molding and by 3-D printing the key headband component that supports the protective shield. Partnering with industry collaborators and civic-minded community allies proved to be essential to bolster production and deliver approximately 33,000 face shields to more than 100 organizations in the region. Our interdisciplinary team of engineers, clinicians, product designers, manufacturers, distributors, and dedicated volunteers is committed to continuing the design-build effort and providing Drexel AJFlex Shields to our communities.

Tunable Blood Shunt for Neonates With Complex Congenital Heart Defects.

Despite advancements in procedures and patient care, mortality rates for neonatal recipients of the Norwood procedure, a palliation for single ventricle congenital malformations, remain high due to the use of a fixed-diameter blood shunt. In this study, a new geometrically tunable blood shunt was investigated to address limitations of the current treatment paradigm (e.g., Modified Blalock-Taussig Shunt) by allowing for controlled modulation of blood flow through the shunt to accommodate physiological changes due to the patient's growth. First, mathematical and computational cardiovascular models were established to investigate the hemodynamic requirements of growing neonatal patients with shunts and to inform design criteria for shunt diameter changes. Then, two stages of prototyping were performed to design, build and test responsive hydrogel systems that facilitate tuning of the shunt diameter by adjusting the hydrogel's degree of crosslinking. We examined two mechanisms to drive crosslinking: infusion of chemical crosslinking agents and near-UV photoinitiation. The growth model showed that 15-18% increases in shunt diameter were required to accommodate growing patients' increasing blood flow; similarly, the computational models demonstrated that blood flow magnitudes were in agreement with previous reports. These target levels of diameter increases were achieved experimentally with model hydrogel systems. We also verified that the photocrosslinkable hydrogel, composed of methacrylated dextran, was contact-nonhemolytic. These results demonstrate proof-of-concept feasibility and reflect the first steps in the development of this novel blood shunt. A tunable shunt design offers a new methodology to rebalance blood flow in this vulnerable patient population during growth and development.