Hemodynamic loads distinctively impact the secretory profile of biomaterial-activated macrophages – implications forin situvascular tissue engineering

• DOI: 10.1039/c9bm01005j
• Publication Date: 2019-11-04T22:26:49Z
• Authors: Tamar B. Wissing; Eline E. van Haaften; Suzanne E. Koch; Bastiaan D. Ippel; Nicholas A. Kurni...; Carlijn V. C. Bouten; Anthal I. P. M. S...
• Keywords: Macrophage polarization; Biomaterial; M2 Macrophage

Biomaterials are increasingly used for in situ vascular tissue engineering, wherein resorbable fibrous scaffolds implanted as temporary carriers to locally initiate regeneration. Upon implantation, macrophages infiltrate and start degrading the scaffold, while simultaneously driving a healing cascade via secretion of paracrine factors that direct behavior tissue-producing cells. This balance between neotissue formation scaffold degradation must be maintained at all times ensure graft functionality. However, grafts continuously exposed hemodynamic loads, which can influence macrophage response hitherto unknown manner thereby tilt this delicate balance. Here we aimed unravel effects physiological levels shear stress cyclic stretch on biomaterial-activated macrophages, terms polarization, signaling cells (i.e. (myo)fibroblasts). Human THP-1-derived were seeded electrospun polycaprolactone bis-urea (∼1 Pa), (∼1.04), or combination thereof 8 days. The results showed polarization distinctly depended specific loading regime applied. In particular, decreased degradative activity, especially conditions stretch. Macrophage activation was enhanced upon exposure stress, evidenced from upregulation both pro- anti-inflammatory cytokines. Exposure supernatant these dynamically cultured found amplify expression formation- remodeling-related genes (myo)fibroblasts statically comparable scaffolds. These emphasize importance mechano-responsiveness biomaterial-driven