Background:Tetralogy of Fallot with major aortopulmonary collateral arteries is a heterogeneous form of pulmonary artery (PA) stenosis that requires multiple forms of intervention. We present a patient-specific in vitro platform capable of sustained flow that can be used to train proceduralists and surgical teams in current interventions, as well as in developing novel therapeutic approaches to treat various vascular anomalies. Our objective is to develop an in vitro model of PA stenosis based on patient data that can be used as an in vitro phantom to model cardiovascular disease and explore potential interventions. Methods and Results: From patient-specific scans obtained via computer tomography or 3-dimensional (3D) rotational angiography, we generated digital 3D models of the arteries. Subsequently, in vitro models of tetralogy of Fallot with major aortopulmonary collateral arteries were first 3D printed using biocompatible resins and next bioprinted using gelatin methacrylate hydrogel to simulate neonatal vasculature or second-order branches of an older patient with tetralogy of Fallot with major aortopulmonary collateral arteries. Printed models were used to study creation of extraluminal connection between an atretic PA and a major aortopulmonary collateral artery using a catheter-based interventional method. Following the recanalization, engineered PA constructs were perfused and flow was visualized using contrast agents and x-ray angiography. Further, computational fluid dynamics modeling was used to analyze flow in the recanalized model. Conclusions: New 3D-printed and computational fluid dynamics models for vascular atresia were successfully created. We demonstrated the unique capability of a printed model to develop a novel technique for establishing blood flow in atretic vessels using clinical imaging, together with 3D bioprinting-based tissue engineering techniques. Additive biomanufacturing technologies can enable fabrication of functional vascular phantoms to model PA stenosis conditions that can help develop novel clinical applications.

In infants with ductal-dependent pulmonary blood flow, the impact of palliation strategy on interstage growth and feeding regimen is unknown. Methods and Results: This was a retrospective multicenter study of infants with ductal-dependent pulmonary blood flow palliated with patent ductus arteriosus (PDA) stent or Blalock-Taussig shunt (BTS) from 2008 to 2015. Subjects with a defined interstage, the time between initial palliation and subsequent palliation or repair, were included. Primary outcome was change in weight-for-age Z-score. Secondary outcomes included % of patients on: all oral feeds, feeding-related medications, higher calorie feeds, and feeding-related readmission. Propensity score was used to account for baseline differences. Subgroup analysis was performed in 1- (1V) and 2-ventricle (2V) groups. The cohort included 66 PDA stent (43.9% 1V) and 195 BTS (54.4% 1V) subjects. Prematurity was more common in the PDA stent group (P=0.051). After adjustment, change in weight-for-age Z-score did not differ between groups over the entire interstage. However, change in weight-for-age Z-score favored PDA stent during the inpatient interstage (P=0.005) and BTS during the outpatient interstage (P=0.032). At initial hospital discharge, PDA stent treatment was associated with all oral feeds (P<0.001) and absence of feeding-related medications (P=0.002). Subgroup analysis revealed that 2V but not 1V patients demonstrated significant increase in weight-for-age Z-score. In the 2V cohort, feeding-related readmissions were more common in the BTS group (P=0.008). Conclusions: In infants with ductal-dependent pulmonary blood flow who underwent palliation with PDA stent or BTS, there was no difference in interstage growth. PDA stent was associated with a simpler feeding regimen and fewer feeding-related readmissions.

Purpose of Review: Tissue engineering has expanded into a highly versatile manufacturing landscape that holds great promise for advancing cardiovascular regenerative medicine. In this review, we provide a summary of the current state-of-the-art bioengineering technologies used to create functional cardiac tissues for a variety of applications in vitro and in vivo. Recent Findings: Studies over the past few years have made a strong case that tissue engineering is one of the major driving forces behind the accelerating fields of patient-specific regenerative medicine, precision medicine, compound screening, and disease modeling. To date, a variety of approaches have been used to bioengineer functional cardiac constructs, including biomaterial-based, cell-based, and hybrid (using cells and biomaterials) approaches. While some major progress has been made using cellular approaches, with multiple ongoing clinical trials, cell-free cardiac tissue engineering approaches have also accomplished multiple breakthroughs, although drawbacks remain. Summary: This review summarizes the most promising methods that have been employed to generate cardiovascular tissue constructs for basic science or clinical applications. Further, we outline the strengths and challenges that are inherent to this field as a whole and for each highlighted technology.

Coronary artery fistulas (CAFs) are exceedingly rare.1 They are defined as an abnormal communication between a coronary artery and another cardiac structure or major thoracic vessel. While largely presumed to be asymptomatic, a recent study showed that a majority of neonates/infants presented with heart failure–type symptoms, albeit many of them had a larger fistula size.2 Indications for intervention on CAFs have been controversial because many patients are asymptomatic; however, delaying intervention is associated with a significantly greater risk of death preoperatively and an increased risk of morbidity and mortality postoperatively.3 Therefore, the majority of CAFs are addressed when they are identified. Transcatheter and surgical approaches have been both been used with good success rates; however, the number of neonates undergoing repair by either method remains low.2,4 Here, we present a case of surgical repair of a large CAF in a neonate after an attempted transcatheter closure resulted in iatrogenic tricuspid regurgitation (TR). The institutional review board of Children's Healthcare of Atlanta approved the study protocol and publication of data (approval number: STUDY00001462, date approved: July 18, 2022). Patient written consent for the publication of the study data was waived by the institutional review board, as it was determined to be research not involving human subjects.

The heart is the first organ to develop in the human embryo through a series of complex chronological processes, many of which critically rely on the interplay between cells and the dynamic microenvironment. Tight spatiotemporal regulation of these interactions is key in heart development and diseases. Due to suboptimal experimental models, however, little is known about the role of microenvironmental cues in the heart development. This study investigates the use of 3D bioprinting and perfusion bioreactor technologies to create bioartificial constructs that can serve as high-fidelity models of the developing human heart. Bioprinted hydrogel-based, anatomically accurate models of the human embryonic heart tube (e-HT, day 22) and fetal left ventricle (f-LV, week 33) are perfused and analyzed both computationally and experimentally using ultrasound and magnetic resonance imaging. Results demonstrate comparable flow hemodynamic patterns within the 3D space. We demonstrate endothelial cell growth and function within the bioprinted e-HT and f-LV constructs, which varied significantly in varying cardiac geometries and flow. This study introduces the first generation of anatomically accurate, 3D functional models of developing human heart. This platform enables precise tuning of microenvironmental factors, such as flow and geometry, thus allowing the study of normal developmental processes and underlying diseases.

Transcatheter electrosurgery is a wire-based technique used to traverse or cut tissue within blood-filled spaces using alternating current delivered by guidewires or catheters. The use of transcatheter electrosurgical techniques in the pediatric population has been limited. We are reporting the first case of retrograde pulmonary vein recanalization using transcatheter electrosurgery. (Level of Difficulty: Advanced.)

3D bioprinting techniques have shown great promise in various fields of tissue engineering and regenerative medicine. Yet, creating a tissue construct that faithfully represents the tightly regulated composition, microenvironment, and function of native tissues is still challenging. Among various factors, biomechanics of bioprinting processes play fundamental roles in determining the ultimate outcome of manufactured constructs. This review provides a comprehensive and detailed overview on various biomechanical factors involved in tissue bioprinting, including those involved in pre, during, and post printing procedures. In preprinting processes, factors including viscosity, osmotic pressure, and injectability are reviewed and their influence on cell behavior during the bioink preparation is discussed, providing a basic guidance for the selection and optimization of bioinks. In during bioprinting processes, we review the key characteristics that determine the success of tissue manufacturing, including the rheological properties and surface tension of the bioink, printing flow rate control, process-induced mechanical forces, and the in situ cross-linking mechanisms. Advanced bioprinting techniques, including embedded and multi-material printing, are explored. For post printing steps, general techniques and equipment that are used for characterizing the biomechanical properties of printed tissue constructs are reviewed. Furthermore, the biomechanical interactions between printed constructs and various tissue/cell types are elaborated for both in vitro and in vivo applications. The review is concluded with an outlook regarding the significance of biomechanical processes in tissue bioprinting, presenting future directions to address some of the key challenges faced by the bioprinting community.

Biomaterial-associated microbial contaminations in biologically conducive three-dimensional (3D) tissue-engineered constructs have significantly limited the clinical applications of scaffold systems. To prevent such infections, antimicrobial biomaterials are rapidly evolving. Yet, the use of such materials in bioprinting-based approaches of scaffold fabrication has not been examined. This study introduces a new generation of bacteriostatic gelatin methacryloyl (GelMA)-based bioinks, incorporated with varying doses of antibacterial superparamagnetic iron oxide nanoparticles (SPIONs). The SPION-laden GelMA scaffolds showed significant resistance against the Staphylococcus aureus growth, while providing a contrast in magnetic resonance imaging. We simulated the bacterial contamination of cellular 3D GelMA scaffolds in vitro and demonstrated the significant effect of functionalized scaffolds in inhibiting bacterial growth, while maintaining cell viability and growth. Together, these results present a new promising class of functionalized bioinks to 3D bioprint tissue-engineered scaffold with markedly enhanced properties for the use in a variety of in vitro and clinical applications.

Guidelines for management of Melody transcatheter pulmonary valve (TPV) infective endocarditis (IE) are lacking. We aimed to identify factors associated with surgical valve removal versus antimicrobial therapy in Melody TPV IE. Multicenter retrospective analysis of all patients receiving Melody TPV from 10/2010 to 3/2019 was performed to identify cases of IE. Surgical explants versus non-surgical cases were compared. Of the 663 Melody TPV implants, there were 66 cases of IE in 59 patients (59/663, 8.8%). 39/66 (59%) were treated with IV antimicrobials and 27/66(41%) underwent valve explantation. 26/59 patients (44%) were treated medically without explantation or recurrence with average follow-up time of 3.5 years (range:1–9). 32% of Streptococcus cases, 53% of MSSA, and all MRSA cases were explanted. 2 of the 4 deaths had MSSA. CART analysis demonstrated two important parameters associated with explantation: a peak echo gradient ≥ 47 mmHg at IE diagnosis(OR 10.6, p < 0.001) and a peak echo gradient increase of > 24 mmHg compared to baseline (OR 6.7, p = 0.01). Rates of explantation varied by institution (27 to 64%). In our multicenter experience, 44% of patients with Melody IE were successfully medically treated without valve explantation or recurrence. The degree of valve stenosis at time of IE diagnosis was strongly associated with explantation. Rates of explantation varied significantly among the institutions.

The adult myocardium has a limited regenerative capacity following heart injury, and the lost cells are primarily replaced by fibrotic scar tissue. Suboptimal efficiency of current clinical therapies to resurrect the infarcted heart results in injured heart enlargement and remodeling to maintain its physiological functions. These remodeling processes ultimately leads to ischemic cardiomyopathy and heart failure (HF). Recent therapeutic approaches (e.g., regenerative and nanomedicine) have shown promise to prevent HF postmyocardial infarction in animal models. However, these preclinical, clinical, and technological advancements have yet to yield substantial enhancements in the survival rate and quality of life of patients with severe ischemic injuries. This could be attributed largely to the considerable gap in knowledge between clinicians and nanobioengineers. Development of highly effective cardiac regenerative therapies requires connecting and coordinating multiple fields, including cardiology, cellular and molecular biology, biochemistry and chemistry, and mechanical and materials sciences, among others. This review is particularly intended to bridge the knowledge gap between cardiologists and regenerative nanomedicine experts. Establishing this multidisciplinary knowledge base may help pave the way for developing novel, safer, and more effective approaches that will enable the medical community to reduce morbidity and mortality in HF patients.