权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Generating multilayered engineered heart tissue patches to mimic physiological thickness and function using open microfluidics

使用开放微流体生成多层工程心脏组织补片以模拟生理厚度和功能

基本信息

批准号：
10544139
负责人：
Amanda Jean Haack
金额：
$ 4.19万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-16 至 2026-06-15
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10544139
关键词：
3-Dimensional Address Animal Model Animals Architecture Area Blood Vessels Calcium Caliber Cardiac Cardiac Myocytes Cause of Death Cell Culture Techniques Cells Cessation of life Collagen Complex Contracts Coupled Culture Techniques Data Development EFRAC Encapsulated Endothelial Cells Endothelium Engineering Extracellular Matrix Fiber Fibrin Future Gel Generations Goals Heart Heart Diseases Heart failure Human Hydrogels Implant In Situ In Vitro Investigation Isometric Exercise Lead Length Liquid substance Measurement Measures Mechanics Methods Microfluidic Microchips Microfluidics Morphology Natural regeneration Necrosis Needles Patients Pattern Perfusion Pharmaceutical Preparations Physiological Polyethylene Glycols Regenerative Medicine Sarcomeres Shapes Stains Stimulus Structure Surface Surface Tension Techniques Thick Thinness Tissue Engineering Tissues Translating Trees Vascularization Work angiogenesis base bioprinting cardiac implant cardiac tissue engineering confocal imaging crosslink density healthy lifestyle heart damage heart function implantation improved in vivo mimetics novel novel strategies shear stress stem cells success virtual

项目摘要

PROJECT SUMMARY/ABSTRACT Heart disease is the leading cause of death in the U.S., often driven by irreversible cardiac tissue damage leading to heart failure. Cardiac tissue does not naturally regenerate, and thus is an important area of focus for tissue engineering. Previous development into engineered heart tissue (EHT) "patches" with some functional architecture such as pre-patterned vasculature and alignment has shown promising results when implanted into small animal models. Moreover, injected stem cells and implanted cardiac "sheets" have shown some success in restoring some cardiac function when implanted into infarcted hearts of large animals or humans. Despite these successes, scaling EHT that incorporates important functional features such as vascularization and alignment to a physiological thickness (cm-scale) remains a major engineering challenge. The overarching goal of this proposal is to generate in vitro physiologically thick heart tissue patches that can ultimately be implanted into patients to replace damaged tissue. Two key considerations for recapitulating native tissue are (1) cardiac tissue is highly vascularized, and (2) alignment of cells and extracellular matrix within each physiological layer is critical to function. We address these challenges utilizing novel open microfluidic patterning approaches. Our open microfluidic technological advancement offers unique benefits to EHT; for example, it is compatible with virtually any hydrogel, including standard extracellular matrix material such as collagen and fibrin, used extensively for EHT. It is also compatible with specialized stimuli-responsive engineered hydrogels, opening up possibilities for complex engineered tissues with spatial and temporal control. Further, the flow of precursor fluid is driven by passive surface tension forces; thus, sensitive stem-cell- derived cells are not exposed to shear stress from extrusion through a needle or photochemical crosslinking, which are requirements for other tissue fabrication techniques such as 3D bioprinting. Finally, a large area (cm- scale) can be patterned with a single pipetting step, making this fabrication approach ideal for generating large (cm-scale) tissues. In this proposal, I apply these unique attributes of open microfluidic pattering to EHT. Specifically, the ability to pattern enzymatically degradable gels through a background of standard cell culture ECM materials such as collagen or fibrin enables the patterning of complex vasculature in three dimensions. I will also take advantage of previously demonstrated modular stacking of open microfluidic devices and suspended microfluidics to generate aligned EHT patches. In these patches, the tissue is anchored on either end, inducing ECM remodeling and alignment. Each layer is generated and aligned independently. Then, they are stacked together at an angle from the previous layer, creating a multilayered tissue mimicking the heart's helical tissue fiber alignment. As such, I will address in two independent aims, vascularization and tissue alignment of physiologically thick EHT using open microfluidics.

项目总结/文摘