An official website of the United States government
Pediatric heart valve disease affects children worldwide and necessitates valve replacements that remodel and grow with the patient. Current valve manufacturing technologies struggle to create valves that facilitate native tissue remodeling for permanent replacements. Here, we present focused rotary jet spinning (FRJS) for implantable medical devices, such as heart valves, to address this challenge. Combining RJS and a focused air stream, FRJS prints FibraValves, micro- and nanofibrous heart valves, in minutes. The micro- and nanoscale features provide structural cues to orient cells at the biotic-abiotic interface, while the centimeter-scale valve shape regulates cardiac flow. We built valves using poly(L-lactide-co-Ɛ-caprolactone) fiber scaffolds, which supported rapid cellular infiltration and displayed native valve-like mechanical properties. Evaluating clinical translatability, we assessed acute performance in a large animal model using a transcatheter delivery approach. These tests indicate that FRJS is a viable method for manufacturing heart valves and future medical implants.
more »
« less
Early Feasibility Study of a Hybrid Tissue-Engineered Mitral Valve in an Ovine Model
Tissue engineering aims to overcome the current limitations of heart valves by providing a viable alternative using living tissue. Nevertheless, the valves constructed from either decellularized xenogeneic or purely biologic scaffolds are unable to withstand the hemodynamic loads, particularly in the left ventricle. To address this, we have been developing a hybrid tissue-engineered heart valve (H-TEHV) concept consisting of a nondegradable elastomeric scaffold enclosed in a valve-like living tissue constructed from autologous cells. We developed a 21 mm mitral valve scaffold for implantation in an ovine model. Smooth muscle cells/fibroblasts and endothelial cells were extracted, isolated, and expanded from the animal’s jugular vein. Next, the scaffold underwent a sequential coating with the sorted cells mixed with collagen type I. The resulting H-TEHV was then implanted into the mitral position of the same sheep through open-heart surgery. Echocardiography scans following the procedure revealed an acceptable valve performance, with no signs of regurgitation. The valve orifice area, measured by planimetry, was 2.9 cm2, the ejection fraction reached 67%, and the mean transmitral pressure gradient was measured at 8.39 mmHg. The animal successfully recovered from anesthesia and was transferred to the vivarium. Upon autopsy, the examination confirmed the integrity of the H-TEHV, with no evidence of tissue dehiscence. The preliminary results from the animal implantation suggest the feasibility of the H-TEHV.
more »
« less
- Award ID(s):
- 2109959
- PAR ID:
- 10509041
- Publisher / Repository:
- MDPI
- Date Published:
- Journal Name:
- Journal of Cardiovascular Development and Disease
- Volume:
- 11
- Issue:
- 2
- ISSN:
- 2308-3425
- Page Range / eLocation ID:
- 69
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
BackgroundCongenital heart defects affect approximately 1% of births in the United States and Europe, with >1 million children in the United States living with congenital heart defects. Many experience abnormalities in the right ventricular outflow tract, often necessitating surgical intervention early in life. However, the initial repairs typically are temporary solutions as many patients will eventually need pulmonary valve replacement to address pulmonary valve regurgitation and prevent right ventricle failure. Addressing progressive pulmonary valve regurgitation, ideally in patients weighing 8 to 10 kg, is critical to prevent right ventricle dysfunction. Transcatheter pulmonary valve replacement currently treats patients weighing at least 20 kg. Unfortunately, smaller children must wait for valve replacement and risk right ventricular dilation. MethodsTo address this challenge, we have developed the IRIS Valve, a growth‐accommodating transcatheter pulmonary heart valve inspired by origami targeting implantation in at least 8 kg children. The valve stent underwent finite element analysis with validation by fracture testing. Using a 12‐Fr transcatheter system, the IRIS valve was implanted into 8 to 17 kg Yucatan mini pigs for 6 months. ResultsBenchtop fracture testing and finite element analysis confirmed the stent's ability to be crimped to a 3‐mm diameter for loading into a 12‐Fr transcatheter system and expanded to 20 mm without fracture. Animal studies successfully demonstrated excellent integration within the pulmonary valve annulus, intact valve integrity, and favorable tissue response. ConclusionsThe IRIS Valve offers a promising solution for earlier treatment of heart valve disease in pediatric patients with congenital heart defects, potentially improving outcomes in this vulnerable population.more » « less
-
Given the complexity of human left heart anatomy and valvular structures, the fluid–structure interaction (FSI) simulation of native and prosthetic valves poses a significant challenge for numerical methods. In this review, recent numerical advancements for both fluid and structural solvers for heart valves in patient-specific left hearts are systematically considered, emphasizing the numerical treatments of blood flow and valve surfaces, which are the most critical aspects for accurate simulations. Numerical methods for hemodynamics are considered under both the continuum and discrete (particle) approaches. The numerical treatments for the structural dynamics of aortic/mitral valves and FSI coupling methods between the solid Ωs and fluid domain Ωf are also reviewed. Future work toward more advanced patient-specific simulations is also discussed, including the fusion of high-fidelity simulation within vivo measurements and physics-based digital twining based on data analytics and machine learning techniques.more » « less
-
Clinically serious congenital heart valve defects arise from improper growth and remodeling of endocardial cushions into leaflets. Genetic mutations have been extensively studied but explain less than 20% of cases. Mechanical forces generated by beating hearts drive valve development, but how these forces collectively determine valve growth and remodeling remains incompletely understood. Here, we decouple the influence of those forces on valve size and shape, and study the role of YAP pathway in determining the size and shape. The low oscillatory shear stress promotes YAP nuclear translocation in valvular endothelial cells (VEC), while the high unidirectional shear stress restricts YAP in cytoplasm. The hydrostatic compressive stress activated YAP in valvular interstitial cells (VIC), whereas the tensile stress deactivated YAP. YAP activation by small molecules promoted VIC proliferation and increased valve size. Whereas YAP inhibition enhanced the expression of cell-cell adhesions in VEC and affected valve shape. Finally, left atrial ligation was performed in chick embryonic hearts to manipulate the shear and hydrostatic stress in vivo. The restricted flow in the left ventricle induced a globular and hypoplastic left atrioventricular (AV) valves with an inhibited YAP expression. By contrast, the right AV valves with sustained YAP expression grew and elongated normally. This study establishes a simple yet elegant mechanobiological system by which transduction of local stresses regulates valve growth and remodeling. This system guides leaflets to grow into proper sizes and shapes with the ventricular development, without the need of a genetically prescribed timing mechanism.more » « less
-
Ghorbel, Mohamed; May-Newman, Karen (Ed.)Heart disease is a leading cause of mortality, with calcific aortic valve disease (CAVD) being the most prevalent subset. Being able to predict this disease in its early stages is important for monitoring patients before they need aortic valve replacement surgery. Thus, this study explored hydrodynamic, mechanical, and hemodynamic differences in healthy and very mildly calcified porcine small intestinal submucosa (PSIS) bioscaffold valves to determine any notable parameters between groups that could, possibly, be used for disease tracking purposes. Three valve groups were tested: raw PSIS as a control and two calcified groups that were seeded with human valvular interstitial and endothelial cells (VICs/VECs) and cultivated in calcifying media. These two calcified groups were cultured in either static or bioreactor-induced oscillatory flow conditions. Hydrodynamic assessments showed metrics were below thresholds associated for even mild calcification. Young’s modulus, however, was significantly higher in calcified valves when compared to raw PSIS, indicating the morphological changes to the tissue structure. Fluid–structure interaction (FSI) simulations agreed well with hydrodynamic results and, most notably, showed a significant increase in time-averaged wall shear stress (TAWSS) between raw and calcified groups. We conclude that tracking hemodynamics may be a viable biomarker for early-stage CAVD tracking.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/jcdd11020069
