May 12, 2020

Human In Vitro Model Mimicking Material-Driven Vascular Regeneration Reveals How Cyclic Stretch and Shear Stress Differentially Modulate Inflammation and Matrix Deposition

Advanced Biosystems
Eline E van HaaftenCarlijn V C Bouten

Abstract

Resorbable synthetic scaffolds designed to regenerate living tissues and organs inside the body have emerged as a clinically attractive technology to replace diseased blood vessels. However, mismatches between scaffold design and in vivo hemodynamic loading (i.e., cyclic stretch and shear stress) can result in aberrant inflammation and adverse tissue remodeling, leading to premature graft failure. Yet, the underlying mechanisms remain elusive. Here, a human in vitro model is presented that mimics the transient local inflammatory and biomechanical environments that drive scaffold-guided tissue regeneration. The model is based on the coculture of human (myo)fibroblasts and macrophages in a bioreactor platform that decouples cyclic stretch and shear stress. Using a resorbable supramolecular elastomer as the scaffold material, it is revealed that cyclic stretch initially reduces proinflammatory cytokine secretion and, especially when combined with shear stress, stimulates IL-10 secretion. Moreover, cyclic stretch stimulates downstream (myo)fibroblast proliferation and matrix deposition. In turn, shear stress attenuates cyclic-stretch-induced matrix growth by enhancing MMP-1/TIMP-1-mediated collagen remodeling, and synergistically a...Continue Reading

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Mentioned in this Paper

Body Structure
Coculture Techniques
In Vivo
Tissue-Inhibitor of Metalloproteinase-1
Interleukin-10
Hemodynamics
Fibroblasts
Cell Secretion
Stress
Vascular Graft (Body Structure)

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