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

• DOI: 10.1002/adbi.201900249
• Publication Date: 2020-05-11T06:41:57Z
• Authors: Eline E. van Haaften; Tamar B. Wissing; Nicholas A. Kurni...; Anthal I. P. M. S...; Carlijn V. C. Bouten
• Keywords: Proinflammatory cytokine

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