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

Abstract

Macrophages play a governing role in material-driven tissue regeneration. Here we show that the paracrine signals of macrophages to direct tissue regeneration and scaffold degradation are dependent on hemodynamic loads.

TRPV4—A Missing Link Between Mechanosensation and Immunity

“…This effect is presumably predominantly caused by stretch rather than shear effects. Nevertheless, it is conceivable that shear-dependent activation of macrophages may become relevant in conditions of alveolar fluid accumulation when fluid will cyclically shift in and out of the alveolus resulting in considerable shear forces exerted not only on alveolar epithelial cells but also on alveolar macrophages (88,89).…”

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

“…Based on our previous study, we expected that the contribution of macrophages via direct mechanosensing would lead to increased levels of these cytokines in the presence of hemodynamic loading, especially when both loads are combined. [ 18 ] The discrepancy we find for MCP‐1 and IL‐6 indicate that (myo)fibroblasts and juxtacrine interactions between both cell types must have contributed to these secretion profiles as well. This finding corroborates with previous studies that showed that moderate stretches can promote an anti‐inflammatory environment, both via direct mechanosensing and via indirect paracrine signaling.…”

“…Previously, we showed that macrophages can also stain positive for KI67. [ 18 ] The macrophages, which we obtained from human peripheral blood mononuclear cells (hPBMCs, i.e., the CD45‐positive cells in Figure 2F), were, however, not expected to proliferate in our in vitro setup. This seemingly contrasting result is attributable to the use of a primary cell source rather than a cell line.…”

“…We used this model to study the individual and combined roles of these mechanical cues on biomaterial‐activated macrophages and their downstream effects on human vena saphena derived fibroblasts and myofibroblasts (referred to as (myo)fibroblasts). [ 18 ] The results showed that shear stress enhanced macrophage secretion of both pro‐ and anti‐inflammatory cytokines. Downstream, these effects resulted in the activation of tissue formation‐ and remodeling‐related genes in (myo)fibroblasts.…”

Computationally guided in-vitro vascular growth model reveals causal link between flow oscillations and disorganized neotissue

“…Although this could indicate enhanced oxidative and enzymatic degradative capacity of the macrophages with OSS, a previous study showed that the expression of these genes could not explain the differences in macrophage-driven scaffold mass loss, making it difficult to directly relate gene expression to scaffold degradation [31,32]. In the future, the analysis should therefore be extended with, for example, Raman spectroscopy on cross-sections, allowing the assessment of scaffold degradation across the thickness of the constructs [33].…”