Coordinated Heart Stimulation Testbed: A Platform for Contractile Ventricle Engineering

协调心脏刺激试验台:收缩心室工程平台

基本信息

  • 批准号:
    10712502
  • 负责人:
  • 金额:
    $ 40.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-06-01 至 2028-05-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Heart failure, the main clinical and public health problem, accounts for 13% of deaths in the US. Although transplantation is currently the only therapy for end-stage heart failure, the availability and compatibility of donor hearts cannot meet the clinical demand. Bioengineered whole hearts generated by using either 3D-printed or native scaffolds hold promise to alleviate the donor organ shortage. However, efforts to build a functional bioartificial heart chamber by using human-induced pluripotent stem cells (hiPSCs) are stymied by the immaturity of hiPSC-derived cardiomyocytes. Reliable incubation systems that deliver physiologically mimetic stimulation to train immature heart muscle cells and develop heart tissues are warranted. Without closing this technological gap, cardiovascular tissue engineering will not advance to organ-level engineering, foreclosing the clinical and discovery potential. The long-term goal of this research endeavor is to engineer a transplantable heart by using human cells. In this Katz R01 grant, we propose a new research direction to address the long-standing need for bioreactor cultivation and stimulation technologies completely reimagined for bioartificial organ engineering. Our central hypothesis is that integrating the different maturation approaches in one automated platform will achieve the physiologically relevant levels of function in bioengineered left ventricles. The objective is to engineer a recellularized left ventricle with a physiologically significant ejection fraction through the integration of mechanical, electrical, and metabolic stimuli: enable coordinated mechanical and electrical stimulation in a recellularized left ventricle through a novel multiparametric bioreactor design (Aim 1) and develop a whole organ media composition to support the increased metabolic demands of larger bioartificial left ventricles (Aim 2). Based on our unparalleled experience in regenerative medicine, we will develop the coordinated heart stimulation testbed (CHeST) combined with a novel artificial oxygen carrier and metabolic media supplementation tailor-fitted to the biophysical, biochemical, and metabolic requirements of developing contractile tissue. The expected deliverables of a contractile ventricle construct and multiparametric stimulation bioreactor will vertically advance the field, providing essential novel contributions to the issues impairing cardiac tissue engineering for generating bioengineered ventricles. Mechanistic discovery and bioengineering improvements will abound as other investigators create stimulation training protocols for the heart and other engineered organs. Thus the realization of this project will pave the way for a potential new wave of breakthroughs in cardiac tissue engineering toward building a bioartificial heart.
项目总结

项目成果

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Camila Hochman-Mendez其他文献

Camila Hochman-Mendez的其他文献

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{{ truncateString('Camila Hochman-Mendez', 18)}}的其他基金

Establishing Automated Cryopreservation System for Biospecimen Storage
建立生物标本储存自动化冷冻保存系统
  • 批准号:
    10533660
  • 财政年份:
    2022
  • 资助金额:
    $ 40.42万
  • 项目类别:
Using a Cardiac Microtissue System to Evaluate and Replicate Clinical Therapy Responses using Patient Cell-Derived Exosomes
使用心脏微组织系统评估和复制患者细胞衍生的外泌体的临床治疗反应
  • 批准号:
    9924691
  • 财政年份:
    2019
  • 资助金额:
    $ 40.42万
  • 项目类别:

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