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Abstract

Bioengineering

Fibroblast Derived Human Engineered Connective Tissue for Screening Applications

Published: August 20th, 2021

DOI:

10.3791/62700

1Institute of Pharmacology and Toxicology, University Medical Center Goettingen, 2DZHK (German Center for Cardiovascular Research) partner site, Goettingen, 3Cluster of Excellence “Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells” (MBExC), University of Goettingen, 4Center for Neurodegenerative Diseases (DZNE), 5Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP)

Abstract

Fibroblasts are phenotypically highly dynamic cells, which quickly transdifferentiate into myofibroblasts in response to biochemical and biomechanical stimuli. The current understanding of fibrotic processes, including cardiac fibrosis, remains poor, which hampers the development of new anti-fibrotic therapies. Controllable and reliable human model systems are crucial for a better understanding of fibrosis pathology. This is a highly reproducible and scalable protocol to generate engineered connective tissues (ECT) in a 48-well casting plate to facilitate studies of fibroblasts and the pathophysiology of fibrotic tissue in a 3-dimensional (3D) environment. ECT are generated around the poles with tunable stiffness, allowing for studies under a defined biomechanical load. Under the defined loading conditions, phenotypic adaptations controlled by cell-matrix interactions can be studied. Parallel testing is feasible in the 48-well format with the opportunity for the time-course analysis of multiple parameters, such as tissue compaction and contraction against the load. From these parameters, biomechanical properties such as tissue stiffness and elasticity can be studied.

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Keywords Fibroblast

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