Advanced biomanufacturing of scalable, perfusable, pre-vascularized adipose tissues

可扩展、可灌注、预血管化脂肪组织的先进生物制造

基本信息

  • 批准号:
    2128176
  • 负责人:
  • 金额:
    $ 43.58万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-01 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

Adipose/fat tissue is a dynamic endocrine organ that acts as a major site of energy storage, shock absorption, and a crucial regulator of metabolism, glucose, temperature, and hormonal processes. Accordingly, engineering adipose tissues is of critical importance for understanding physiology and pathology (such as obesity and diabetes), and for repairing body surface defects that can result from traumatic injury and invasive surgical procedures. While tissue engineering has been explored for these purposes, approaches have met limited success due to diffusion constraints, and insufficient adipose cell density and stability compared to the native tissue. This project aims to address these engineering challenges by delivering an innovative technology for manufacturing high-density, large human adipose tissues with integrated, perfusable vascular systems. The educational impact of this project will be achieved through integrating research-related demonstrations with existing biomedical engineering courses and facilitating opportunities to enhance the representation of underrepresented minorities in research. The goal of this project is to integrate adipose and vascular tissue engineering using a decellularized lung matrix (DLM) and offer a transformative solution for engineering perfusable, vascularized, high-density adipose tissue models. The lung is one of the most highly vascularized organs with high flow, low resistance, and a large blood-alveolar interface separated by a very thin basement membrane (1 µm). The DLM offers the following unique advantages for adipose tissue engineering: (1) its large volume alveolar compartment can accommodate high-density adipose cell filling; (2) it offers a preserved, acellular vascular bed allowing efficient tissue perfusion and vascular cell seeding; (3) the alveolar compartment shields buoyant and fragile adipocytes from harmful high shear stresses by confining high flow rates to the vascular bed where they are required for proper endothelial functionality; and (4) it is scalable and can be adapted for critically sized defects using scaffold materials derived from large donor sources (example: pigs). Specific project tasks will: (1) engineer scalable, pre-vascularized adipose tissues; and (2) model adipose-vascular-extracellular matrix interactions during hyperglycemia. This model will facilitate the acquisition of basic knowledge on adipose physiology as well as provide a tissue-engineering platform for repairing critically sized (200 mL) subcutaneous tissue defects.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
脂肪/脂肪组织是一种动态的内分泌器官,它是能量储存、冲击吸收的主要场所,也是新陈代谢、葡萄糖、温度和激素过程的重要调节器。因此,工程脂肪组织对于了解生理和病理(如肥胖和糖尿病),以及修复创伤和侵入性外科手术可能导致的体表缺陷至关重要。虽然组织工程学已经被探索用于这些目的,但由于扩散限制,以及与天然组织相比脂肪细胞密度和稳定性不足,这些方法取得的成功有限。该项目旨在通过提供一种制造高密度、大型人体脂肪组织的创新技术来应对这些工程挑战,该组织具有集成的、可灌流的血管系统。这一项目的教育影响将通过将与研究有关的演示与现有的生物医学工程课程结合起来,并促进提高少数群体在研究中的代表性的机会来实现。该项目的目标是使用脱细胞肺基质(DLM)整合脂肪和血管组织工程,并为设计可灌流的、血管化的高密度脂肪组织模型提供一种变革性的解决方案。肺是高度血运丰富的器官之一,具有高流量、低阻力和由非常薄的基底膜(1微米)隔开的大的血液-肺泡界面。DLM为脂肪组织工程提供了以下独特的优势:(1)其大容量的肺泡腔可以容纳高密度脂肪细胞的填充;(2)它提供了一个保存的、无细胞的血管床,允许有效的组织灌流和血管细胞播种;(3)通过将高流速限制在血管床上,使浮力和脆弱的脂肪细胞免受有害的高剪应力的影响;(4)它是可扩展的,可以使用来自大捐赠者来源(例如:猪)的支架材料来修复严重尺寸的缺陷。具体的项目任务将:(1)设计可伸缩的、血管前脂肪组织;(2)模拟高血糖期间脂肪-血管-细胞外基质的相互作用。该模型将有助于获得脂肪生理学的基本知识,并为修复严重尺寸(200毫升)的皮下组织缺损提供组织工程平台。该奖项反映了NSF的法定使命,并通过使用基金会的智力优势和更广泛的影响审查标准进行评估,被认为值得支持。

项目成果

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Rosalyn Abbott-Beauregard其他文献

Rosalyn Abbott-Beauregard的其他文献

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{{ truncateString('Rosalyn Abbott-Beauregard', 18)}}的其他基金

CAREER: 3D Printing High Lipid Content Cultivated Meat to Minimize Livestock Environmental Impacts
事业:3D 打印高脂质含量的栽培肉以最大限度地减少牲畜环境影响
  • 批准号:
    2236998
  • 财政年份:
    2023
  • 资助金额:
    $ 43.58万
  • 项目类别:
    Continuing Grant

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