Development of Tissue Engineered Heart Valves for Percutaneous Transcatheter Delivery in a Fetal Ovine Model

Zakko, Jason; Blum, Kevin M.; Drews, Joseph D.; Wu, Yen‐Lin; Hatoum, Hoda; Russell, Madeleine; Gooden, Shelley; Heitkemper, Megan; Conroy, Olivia; Kelly, John; Carey, Stacey; Sacks, Michael S.; Texter, Karen; Ragsdale, Ellie; Strainic, James; Bocks, Martin L.; Wang, Yadong; Dasi, Lakshmi Prasad; Armstrong, Aimee K.; Breuer, Christopher K.

doi:10.1016/j.jacbts.2020.06.009

Cited by 19 publications

(6 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There have been recent advances in developing fetal TAVR, Zakko et al demonstrated the transcatheter delivery of a tissue-engineered heart valve in a fetal ovine model, which survived to birth. 37 …”

Section: Discussionmentioning

confidence: 99%

Fluid Mechanical Effects of Fetal Aortic Valvuloplasty for Cases of Critical Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome

Wong

Tulzer

et al. 2023

Ann Biomed Eng

View full text Add to dashboard Cite

Fetuses with critical aortic stenosis (FAS) are at high risk of progression to HLHS by the time of birth (and are thus termed “evolving HLHS”). An in-utero catheter-based intervention, fetal aortic valvuloplasty (FAV), has shown promise as an intervention strategy to circumvent the progression, but its impact on the heart’s biomechanics is not well understood. We performed patient-specific computational fluid dynamic (CFD) simulations based on 4D fetal echocardiography to assess the changes in the fluid mechanical environment in the FAS left ventricle (LV) directly before and 2 days after FAV. Echocardiograms of five FAS cases with technically successful FAV were retrospectively analysed. FAS compromised LV stroke volume and ejection fraction, but FAV rescued it significantly. Calculations to match simulations to clinical measurements showed that FAV approximately doubled aortic valve orifice area, but it remained much smaller than in healthy hearts. Diseased LVs had mildly stenotic mitral valves, which generated fast and narrow diastolic mitral inflow jet and vortex rings that remained unresolved directly after FAV. FAV further caused aortic valve damage and high-velocity regurgitation. The high-velocity aortic regurgitation jet and vortex ring caused a chaotic flow field upon impinging the apex, which drastically exacerbated the already high energy losses and poor flow energy efficiency of FAS LVs. Two days after the procedure, FAV did not alter wall shear stress (WSS) spatial patterns of diseased LV but elevated WSS magnitudes, and the poor blood turnover in pre-FAV LVs did not significantly improve directly after FAV. FAV improved FAS LV’s flow function, but it also led to highly chaotic flow patterns and excessively high energy losses due to the introduction of aortic regurgitation directly after the intervention. Further studies analysing the effects several weeks after FAV are needed to understand the effects of such biomechanics on morphological development.

show abstract

Section: Discussionmentioning

confidence: 99%

Fluid Mechanical Effects of Fetal Aortic Valvuloplasty for Cases of Critical Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome

Wong

Tulzer

et al. 2023

Ann Biomed Eng

View full text Add to dashboard Cite

show abstract

“…The risk of damage to the valve in the event of a stent complication or to the stent in the case of a valvular intervention has yet to be fully described. Still in its beginning stages, a zinc–aluminum alloy degradable metal stent housing a synthetic, electrospun polycaprolactone valve is being used in a fetal transcatheter ovine model and may provide an alternative solution to the issue of long-term stent placement [ 42 ]. Despite zinc being an essential metal for many cellular processes, there are still only limited in vitro and in vivo data demonstrating its impact within the cardiovascular system and tissue regeneration pathway [ 50 , 51 ].…”

Section: Tissue-engineered Pulmonary Valvementioning

confidence: 99%

“…The image in the top left is from an editorial on a PTFE RV-PA conduit [ 40 ]. The images in the bottom left box are of different views of the Xeltis biodegradable pulmonary valve conduit [ 41 ] from a bioabsorbable metal stent PVR from Zakko et al, 2020 [ 42 ]. PVR: Pulmonary valve replacement; PV: pulmonary valve; RV: Right ventricle; the green and red squares are to emphasize.…”

Section: Figurementioning

confidence: 99%

The Real Need for Regenerative Medicine in the Future of Congenital Heart Disease Treatment

et al. 2021

View full text Add to dashboard Cite

Bioabsorbable materials made from polymeric compounds have been used in many fields of regenerative medicine to promote tissue regeneration. These materials replace autologous tissue and, due to their growth potential, make excellent substitutes for cardiovascular applications in the treatment of congenital heart disease. However, there remains a sizable gap between their theoretical advantages and actual clinical application within pediatric cardiovascular surgery. This review will focus on four areas of regenerative medicine in which bioabsorbable materials have the potential to alleviate the burden where current treatment options have been unable to within the field of pediatric cardiovascular surgery. These four areas include tissue-engineered pulmonary valves, tissue-engineered patches, regenerative medicine options for treatment of pulmonary vein stenosis and tissue-engineered vascular grafts. We will discuss the research and development of biocompatible materials reported to date, the evaluation of materials in vitro, and the results of studies that have progressed to clinical trials.

show abstract

“…Consequentially, electrospun microfibrous substrates have been used in numerous applications for tissue engineering (Xue et al, 2019). Polycaprolactone (PCL) is commonly used for substrate fabrication in tissue engineering for its biocompatibility, flexibility, electrospinnability, and slow biodegradation rate, and it has been FDA‐approved for use in many medical applications (Zakko et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Polycaprolactone (PCL) is commonly used for substrate fabrication in tissue engineering for its biocompatibility, flexibility, electrospinnability, and slow biodegradation rate, and it has been FDA-approved for use in many medical applications (Zakko et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Fibrin gel enhanced trilayer structure in cell‐cultured constructs

Snyder

Jana

2023

Biotech & Bioengineering

View full text Add to dashboard Cite

Efficient cell seeding and subsequent support from a substrate ensure optimal cell growth and neotissue development during tissue engineering, including heart valve tissue engineering. Fibrin gel as a cell carrier may provide high cell seeding efficiency and adhesion property, improved cellular interaction, and structural support to enhance cellular growth in trilayer polycaprolactone (PCL) substrates that mimic the structure of native heart valve leaflets. This cell carrier gel coupled with a trilayer PCL substrate may enable the production of native-like cell-cultured leaflet constructs suitable for heart valve tissue engineering. In this study, we seeded valvular interstitial cells onto trilayer PCL substrates with fibrin gel as a cell carrier and cultured them for 1 month in vitro to determine if this gel can improve cell proliferation and production of extracellular matrix within the trilayer cell-cultured constructs. We observed that the fibrin gel enhanced cellular proliferation, their vimentin expression, and collagen and glycosaminoglycan production, leading to improved structure and mechanical properties of the developing PCL cell-cultured constructs. Fibrin gel as a cell carrier significantly improved the orientations of the cells and their produced tissue materials within trilayer PCL substrates that mimic the structure of native heart valve leaflets and, thus, may be highly beneficial for developing functional tissue-engineered leaflet constructs.

show abstract

Development of Tissue Engineered Heart Valves for Percutaneous Transcatheter Delivery in a Fetal Ovine Model

Abstract: Visual Abstract

Cited by 19 publications

References 45 publications

Fluid Mechanical Effects of Fetal Aortic Valvuloplasty for Cases of Critical Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome

Fluid Mechanical Effects of Fetal Aortic Valvuloplasty for Cases of Critical Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome

The Real Need for Regenerative Medicine in the Future of Congenital Heart Disease Treatment

Fibrin gel enhanced trilayer structure in cell‐cultured constructs

Contact Info

Product

Resources

About