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Abstract ObjectiveFluid shear stress is thought to be a regulator of endothelial cell behavior during angiogenesis. The link, however, requires an understanding of stress values at the capillary level in angiogenic microvascular networks. Critical questions remain. What are the stresses? Do capillaries experience similar stress magnitudes? Can variations explain vessel‐specific behavior? The objective of this study was to estimate segment‐specific shear stresses in angiogenic networks. MethodsImages of angiogenic networks characterized by increased vascular density were obtained from rat mesenteric tissues stimulated by compound 48/80‐induced mast cell degranulation. Vessels were identified by perfusion of a 40 kDa fixable dextran prior to harvesting and immunolabeling for PECAM. Using a network flow‐based segment model with physiologically relevant parameters, stresses were computed per vessel for regions across multiple networks. ResultsStresses ranged from 0.003 to 2328.1 dyne/cm2and varied dramatically at the capillary level. For all regions, the maximum segmental shear stresses were for capillary segments. Stresses along proximal capillaries branching from arteriole inlets were increased compared to stresses along capillaries in more distal regions. ConclusionsThe results highlight the variability of shear stresses along angiogenic capillaries and motivate new discussions on how endothelial cells may respond in vivo to segment‐specific microenvironment during angiogenesis.
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Fabrication of endothelialized capillary-like microchannel networks using sacrificial thermoresponsive microfibers
Abstract In the body, capillary beds fulfill the metabolic needs of cells by acting as the sites of diffusive transport for vital gasses and nutrients. In artificial tissues, replicating the scale and complexity of capillaries has proved challenging, especially in a three-dimensional context. In order to better develop thick artificial tissues, it will be necessary to recreate both the form and function of capillaries. Here we demonstrate a top–down method of patterning hydrogels using sacrificial templates formed from thermoresponsive microfibers whose size and architecture approach those of natural capillaries. Within the resulting microchannels, we cultured endothelial monolayers that remain viable for over three weeks and exhibited functional barrier properties. Additionally, we cultured endothelialized microchannels within hydrogels containing fibroblasts and characterized the viability of the co-cultures to demonstrate this approach’s potential when applied to cell-laden hydrogels. This method represents a step forward in the evolution of artificial tissues and a path towards producing viable capillary-scale microvasculature for engineered organs.
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- Award ID(s):
- 2050255
- PAR ID:
- 10555658
- Publisher / Repository:
- IOP Publishing
- Date Published:
- Journal Name:
- Biofabrication
- Volume:
- 17
- Issue:
- 1
- ISSN:
- 1758-5082
- Format(s):
- Medium: X Size: Article No. 015023
- Size(s):
- Article No. 015023
- Sponsoring Org:
- National Science Foundation
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