A multichamber fluidic device for 3D cultures under interstitial flow with live imaging: Development, characterization, and applications

Abstract

Interstitial flow is an important biophysical cue that can affect capillary morphogenesis, tumor cell migration, and fibroblast remodeling of the extracellular matrix, among others. Current models that incorporate interstitial flow and that are suitable for live imaging lack the ability to perform multiple simultaneous experiments, for example, to compare effects of growth factors, extracellular matrix composition, etc. We present a nine-chamber radial flow device that allows simultaneous 3D fluidic experiments for relatively long-term culture with live imaging capabilities. Flow velocity profiles were characterized by fluorescence recovery after photobleaching (FRAP) for flow uniformity and estimating the hydraulic conductivity. We demonstrate lymphatic and blood capillary morphogenesis in fibrin gels over 10 days, comparing flow with static conditions as well as the effects of an engineered variant of VEGF that binds fibrin via Factor XIII. We also demonstrate the culture of contractile fibroblasts and co-cultures with tumor cells for modeling the tumor microenvironment. Therefore, this device is useful for studies of capillary morphogenesis, cell migration, contractile cells like fibroblasts, and multicellular cultures, all under interstitial flow. Biotechnol. Bioeng. 2010;105: 982-991.

Influence of flow rate and scaffold pore size on cell behavior during mechanical stimulation in a flow perfusion bioreactor

“…Differences in geometrical configurations of perfusion bioreactor systems and the complex internal architecture of scaffolds (Bancroft et al, 2002;Bonvin et al, 2010;Wendt et al, 2003;Zhao and Ma, 2005) makes correlating observed biological outcomes on the basis of inlet fluid flow-rate very difficult. Calculation of the  within systems allows comparisons to be made on a single representative scale.…”

Influence of Shear Stress in Perfusion Bioreactor Cultures for the Development of Three-Dimensional Bone Tissue Constructs: A Review

“…Numerous bioreactor types have been designed for 3D tissue engineering applications and their roles have been reviewed by Martin et al, 47 spinner flasks, rotating wall bioreactors, hollow fiber membrane systems, and perfusion rigs being the most common. Several perfusion bioreactor styles have been devised to date 43,[48][49][50][51] ( Fig. 1).…”

Transport and shear in a microfluidic membrane bilayer device for cell culture

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