Perfusion systems that minimize vascular volume fraction in engineered tissues

Truslow, James G.; Tien, Joe

doi:10.1063/1.3576926

Cited by 16 publications

(10 citation statements)

References 31 publications

(25 reference statements)

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“…At first glance, these expressions appear to imply that one should make the drainage channel as wide as possible to maximize the efficacy of drainage. A trade-off exists, however, between ease of drainage and the fraction of the scaffold that is occupied by the channel 27 ; a wide drainage channel will drain the scaffold quickly but will occupy a large volume, decreasing the fraction of the scaffold that is not devoted to drainage. Lining the channel with lymphatic endothelium (or, in principle, any other cell type that displays flow-dependent hydraulic conductivity) has the potential advantage of maintaining high solute drainage rates without increasing the channel volume fraction, and this capability may provide some flexibility in scaffold design to achieve a desired drainage rate.…”

Section: Discussionmentioning

confidence: 99%

Design principles for lymphatic drainage of fluid and solutes from collagen scaffolds

Thompson

Margolis

Ryan

et al. 2017

J Biomedical Materials Res

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In vivo, tissues are drained of excess fluid and macromolecules by the lymphatic vascular system. How to engineer artificial lymphatics that can provide equivalent drainage in biomaterials remains an open question. This study elucidates design principles for engineered lymphatics, by comparing the rates of removal of fluid and solute through type I collagen gels that contain lymphatic vessels or unseeded channels, or through gels without channels. Surprisingly, no difference was found between the fluid drainage rates for gels that contained vessels or bare channels. Moreover, solute drainage rates were greater in collagen gels that contained lymphatic vessels than in those that had bare channels. The enhancement of solute drainage by lymphatic endothelium was more pronounced in longer scaffolds and with smaller solutes. Whole-scaffold imaging revealed that endothelialization aided in solute drainage by impeding solute reflux into the gel without hindering solute entry into the vessel lumen. These results were reproduced by computational models of drainage with a flow-dependent endothelial hydraulic conductivity. This study shows that endothelialization of bare channels does not impede the drainage of fluid from collagen gels and can increase the drainage of macromolecules by preventing solute transport back into the scaffold.

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Section: Discussionmentioning

confidence: 99%

Design principles for lymphatic drainage of fluid and solutes from collagen scaffolds

Thompson

Margolis

Ryan

et al. 2017

J Biomedical Materials Res

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“…Engineering thick tissues will require perfusion via vascular networks or arrays that maximize transport efficiency. 27 Addition of perfusion vessels in a tissue construct will increase the demand for drainage, 21 and therefore it is important to also increase drainage capacity.…”

Section: Drainage Of Vascular Arrays In Large-area Fibrin Patchesmentioning

confidence: 99%

Artificial lymphatic drainage systems for vascularized microfluidic scaffolds

Wong¹,

Truslow²,

Khankhel³

et al. 2012

J Biomedical Materials Res

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The formation of a stably perfused microvasculature continues to be a major challenge in tissue engineering. Previous work has suggested the importance of a sufficiently large transmural pressure in maintaining vascular stability and perfusion. Here we show that a system of empty channels that provides a drainage function analogous to that of lymphatic microvasculature in vivo can stabilize vascular adhesion and maintain perfusion rate in dense, hydraulically resistive fibrin scaffolds in vitro. In the absence of drainage, endothelial delamination increased as scaffold density increased from 6 mg/mL to 30 mg/mL and scaffold hydraulic conductivity decreased by a factor of twenty. Single drainage channels exerted only localized vascular stabilization, the extent of which depended on the distance between vessel and drainage as well as scaffold density. Computational modeling of these experiments yielded an estimate of 0.40–1.36 cm H2O for the minimum transmural pressure required for vascular stability. We further designed and constructed fibrin patches (0.8 by 0.9 cm2) that were perfused by a parallel array of vessels and drained by an orthogonal array of drainage channels; only with the drainage did the vessels display long-term stability and perfusion. This work underscores the importance of drainage in vascularization, especially when a dense, hydraulically resistive scaffold is used.

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“…5 Although more complex devices were envisioned in a mathematical modeling study focusing on designing networks that minimize vascular volume fraction, no designs were experimentally implemented and seeded with cells. 10 Although biologists may not be willing to fabricate the platform on their own, the platform contains all the components required for its operation. Thus, it could be easily packaged along with the microfluidic chips in a way that does not require assembly and delivered directly to the end user as an off-the-shelf product, thus facilitating technology adoption.…”

Section: Drug Induced Nitric Oxide Secretion and Monocyte Adhesionmentioning

confidence: 99%

“…Current microfluidic approaches either culture endothelial cells simply on the bottom of a micro-channel [5][6][7] or coat endothelial cells around a rectangular channel with sharp corners. [6][7][8][9][10] These approaches can establish a vasculature quickly in defined conditions but ignore the artifacts generated by the sharp corners on the endothelialized lumen. Although remodeling of collagen gels allows for formation of circular lumens, fragility of these gels limits the complexity of branching structures and levels of branching, enabling creation of structures that branch only to the first order, 6 in contrast to the native vasculature that follows fractal rules in branching.…”

Section: Introductionmentioning

confidence: 99%

A standalone perfusion platform for drug testing and target validation in micro-vessel networks

et al. 2013

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Studying the effects of pharmacological agents on human endothelium includes the routine use of cell monolayers cultivated in multi-well plates. This configuration fails to recapitulate the complex architecture of vascular networks in vivo and does not capture the relationship between shear stress (i.e. flow) experienced by the cells and dose of the applied pharmacological agents. Microfluidic platforms have been applied extensively to create vascular systems in vitro; however, they rely on bulky external hardware to operate, which hinders the wide application of microfluidic chips by non-microfluidic experts. Here, we have developed a standalone perfusion platform where multiple devices were perfused at a time with a single miniaturized peristaltic pump. Using the platform, multiple micro-vessel networks, that contained three levels of branching structures, were created by culturing endothelial cells within circular micro-channel networks mimicking the geometrical configuration of natural blood vessels. To demonstrate the feasibility of our platform for drug testing and validation assays, a drug induced nitric oxide assay was performed on the engineered micro-vessel network using a panel of vasoactive drugs (acetylcholine, phenylephrine, atorvastatin, and sildenafil), showing both flow and drug dose dependent responses. The interactive effects between flow and drug dose for sildenafil could not be captured by a simple straight rectangular channel coated with endothelial cells, but it was captured in a more physiological branching circular network. A monocyte adhesion assay was also demonstrated with and without stimulation by an inflammatory cytokine, tumor necrosis factor-a. V C 2013 AIP Publishing LLC. [http://dx

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Perfusion systems that minimize vascular volume fraction in engineered tissues

Cited by 16 publications

References 31 publications

Design principles for lymphatic drainage of fluid and solutes from collagen scaffolds

Design principles for lymphatic drainage of fluid and solutes from collagen scaffolds

Artificial lymphatic drainage systems for vascularized microfluidic scaffolds

A standalone perfusion platform for drug testing and target validation in micro-vessel networks

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