Real-time maps of fluid flow fields in porous biomaterials

Mack, Julia J.; Youssef, Khalid; Noel, Onika; Lake, Michael P.; Wu, Ashley; Iruela‐Arispe, M. Luisa; Bouchard, Louis

doi:10.1016/j.biomaterials.2012.11.030

Cited by 12 publications

(7 citation statements)

References 25 publications

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“…2a ), we generated variable flow speeds on a single monolayer of HAECs. Magnetic resonance imaging (MRI) flow mapping 31 was used to obtain a vector field plot of flow velocities in the presence of a flow-conditioned monolayer. From the magnitude of the MRI-derived flow speed (m s −1 ), fluid shear (dynes cm −2 ) values were calculated using an assumption of flow between infinitely wide parallel plates and overlaid on the flow vector field plot as a colormap (Fig.…”

Section: Resultsmentioning

confidence: 99%

NOTCH1 is a mechanosensor in adult arteries

et al. 2017

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Endothelial cells transduce mechanical forces from blood flow into intracellular signals required for vascular homeostasis. Here we show that endothelial NOTCH1 is responsive to shear stress, and is necessary for the maintenance of junctional integrity, cell elongation, and suppression of proliferation, phenotypes induced by laminar shear stress. NOTCH1 receptor localizes downstream of flow and canonical NOTCH signaling scales with the magnitude of fluid shear stress. Reduction of NOTCH1 destabilizes cellular junctions and triggers endothelial proliferation. NOTCH1 suppression results in changes in expression of genes involved in the regulation of intracellular calcium and proliferation, and preventing the increase of calcium signaling rescues the cell–cell junctional defects. Furthermore, loss of Notch1 in adult endothelium increases hypercholesterolemia-induced atherosclerosis in the descending aorta. We propose that NOTCH1 is atheroprotective and acts as a mechanosensor in adult arteries, where it integrates responses to laminar shear stress and regulates junctional integrity through modulation of calcium signaling.

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Section: Resultsmentioning

confidence: 99%

NOTCH1 is a mechanosensor in adult arteries

et al. 2017

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“…The ability to use robust tools and methodologies such as CE‐nanoCT to assess important and potentially critical quality characteristics of TE constructs such as neo‐tissue quantity and homogeneity (across a whole scaffold) and maturation level (i.e., mineralization (Porter et al, ), gives a new perspective to more integrated TE process design strategies whereby neo‐tissue growth kinetics can be also taken into consideration. In order to fully exploit these advantages and link them meaningfully to the biological measurements and characterization, the development of computational tools that will be able to capture neo‐tissue growth and its interplay with the surrounding dynamic culture environment will be essential, given recent developments on real‐time and online measurement modalities (Mack et al, ).…”

Section: Discussionmentioning

confidence: 99%

Spatial optimization in perfusion bioreactors improves bone tissue‐engineered construct quality attributes

Papantoniou

Guyot

Sonnaert

et al. 2014

Biotech & Bioengineering

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Perfusion bioreactors have shown great promise for tissue engineering applications providing a homogeneous and consistent distribution of nutrients and flow-induced shear stresses throughout tissue-engineered constructs. However, non-uniform fluid-flow profiles found in the perfusion chamber entrance region have been shown to affect tissue-engineered construct quality characteristics during culture. In this study a whole perfusion and construct, three dimensional (3D) computational fluid dynamics approach was used in order to optimize a critical design parameter such as the location of the regular pore scaffolds within the perfusion bioreactor chamber. Computational studies were coupled to bioreactor experiments for a case-study flow rate. Two cases were compared in the first instance seeded scaffolds were positioned immediately after the perfusion chamber inlet while a second group was positioned at the computationally determined optimum distance were a steady state flow profile had been reached. Experimental data showed that scaffold location affected significantly cell content and neo-tissue distribution, as determined and quantified by contrast enhanced nanoCT, within the constructs both at 14 and 21 days of culture. However, gene expression level of osteopontin and osteocalcin was not affected by the scaffold location. This study demonstrates that the bioreactor chamber environment, incorporating a scaffold and its location within it, affects the flow patterns within the pores throughout the scaffold requiring therefore dedicated optimization that can lead to bone tissue engineered constructs with improved quality attributes.

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“…23 Furthermore, surface shear stress has previously been applied via fluid movement across the top of 3 mg/mL collagen hydrogels successfully, in addition to interstitial flow, using microfluidic perfusion systems. 25,26 The fluid shear stress generated in our 3D model is calculated as previously described 19 to be 0.065 Pa, based on fluid viscosity (10 À3 Pa s), a maximum 78 flip angle, 1.6-mm fluid depth, 11-mm well length, and 12-second cycle (5 rpm). The significant increase of proliferation rate observed in our see-saw motion-treated group in comparison with the control group confirmed the shear stress influence on cells in our 3D hydrogel samples.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Conjunctival Fibrosis Response Using a 3D Glaucoma Tenon's Capsule + Conjunctival Model

Gater

Ipek

Sadiq

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Surgical techniques such as trabeculectomy aim to treat glaucoma by making an incision into the scleral tissue, to create an alternative drainage pathway for aqueous to flow into the sub-Tenon's/subconjunctival space. However, tissue fibrosis and wound healing occurring after the procedures can reduce the success rate. This study aims to investigate the synergistic effects of aqueous humor in combination with shear stress on the fibrosis response occurring in Tenon's capsule and conjunctival tissue (TCCT) after glaucoma surgery. METHODS. Two-dimensional (2D) and 3D in vitro TCCT models were constructed by seeding porcine Tenon's capsule þ conjunctival fibroblasts in collagen gel. These were used to investigate key growth factors (singular and natural form) with shear stress, which are believed to influence tissue fibrosis after glaucoma surgery. In addition to cell proliferation assessments, a nondestructive assay to quantify neocollagen synthesis in TCCT models, in response to these factors, has been applied up to 14 days. RESULTS. TCCT fibroblast proliferation increased significantly with doses of TGF-b, TNF-a, and VEGF, in comparison with the control. Furthermore, fibroblasts exposed to 50% aqueous humor had significantly increased proliferation and actin expression. Shear stress-induced mechanotransduction was also found to promote metabolic activity across experimental conditions. Neocollagen labeling cross validated the fibrosis process. CONCLUSIONS. Shear stress appeared to enhance the influence of key growth factors and further promoted fibrotic response within the model. These findings offer a useful insight for further study into the wound-healing response triggered by aqueous fluid outflow after glaucoma surgery.

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Real-time maps of fluid flow fields in porous biomaterials

Cited by 12 publications

References 25 publications

NOTCH1 is a mechanosensor in adult arteries

NOTCH1 is a mechanosensor in adult arteries

Spatial optimization in perfusion bioreactors improves bone tissue‐engineered construct quality attributes

Investigation of Conjunctival Fibrosis Response Using a 3D Glaucoma Tenon's Capsule + Conjunctival Model

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