Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels

Wang, Xiaolin; Phan, Duc T. T.; Sobrino, Agua; George, Steven C.; Hughes, Christopher C.W.; Lee, Abraham P.

doi:10.1039/c5lc01050k

Cited by 210 publications

(209 citation statements)

References 31 publications

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“…For certain applications, it is necessary to confine the gel at a specific location with a well-controlled gel interface curvature. For example, a relatively flat gel interface is required for an endothelial cell monolayer to mimic a vessel wall [15, 20]. With the addition of the pressure regulator module, it is possible to control the specific gel interface curvature positioned at the perfusion microvalve by designing a corresponding safety microvalve with a certain width.…”

Section: Methodsmentioning

confidence: 99%

An on-chip microfluidic pressure regulator that facilitates reproducible loading of cells and hydrogels into microphysiological system platforms

Wang

Phan

et al. 2016

Lab Chip

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Coculturing multiple cell types together in 3-dimensional (3D) cultures better mimics the in vivo microphysiological environment, and has become widely adopted in recent years with the development of organ-on-chip systems. However, a bottleneck in set-up of these devices arises as a result of the delivery of the gel into the microfluidic chip being sensitive to pressure fluctuations, making gel confinement at a specific region challenging, especially when manual operation is performed. In this paper, we present a novel design of an on-chip regulator module with pressure-releasing safety microvalves that can facilitate stable gel delivery into designated microchannel regions while maintaining well-controlled, non-bursting gel interfaces. This pressure regulator design can be integrated into different microfluidic chip designs and is compatible with a wide variety of gel injection apparatuses operated automatically or manually at different flow rates. The sensitivity and working range of this pressure regulator can be adjusted by changing the width of its pressure releasing safety microvalve design. The effectiveness of the design is validated by its incorporation into a microfluidic platform we have developed for generating 3D vascularized micro-organs (VMOs). Reproducible gel loading is demonstrated for both an automatic syringe pump and a manually-operated micropipettor. This design allows for rapid and reproducible loading of hydrogels into microfluidic devices without the risk of bursting gel-air interfaces.

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Section: Methodsmentioning

confidence: 99%

An on-chip microfluidic pressure regulator that facilitates reproducible loading of cells and hydrogels into microphysiological system platforms

Wang

Phan

et al. 2016

Lab Chip

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“…Reproduced from Wang et al [21] with permission from RSC 3. Block medium inlet and outlet of one side microfluidic channel with plugs.…”

Section: Fig 4 Progression Of Vasculogenesis Over Time (A) After Esmentioning

confidence: 99%

“…Scale bars, 100 μm. Reproduced from Wang et al [21] with permission from RSC 9. Remove blocking solution from all plastic vials, leaving a small amount at the bottom to avoid air bubbles.…”

Section: Figmentioning

confidence: 99%

“…Building on our previous publications [18][19][20][21][22], this protocol seeks to provide detailed practical procedures to develop a complete and contiguous 3D perfused microvascular network without nonphysiological leakage. The enabling technologies detailed here include microfluidic device design and microfabrication, cell-seeded hydrogel preparation and loading, maintenance of cell culture in the microfluidic chip, flow control for different stages of vascular development, and immunostaining of the vascular network.…”

Section: Introductionmentioning

confidence: 99%

“…(b) DAPI nuclear staining. Reproduced from Wang et al [21] with permission from RSC 8. Placing the container with the developer and wafer into an ultrasonic instrument will highly accelerate the development speed.…”

mentioning

confidence: 99%

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3D Anastomosed Microvascular Network Model with Living Capillary Networks and Endothelial Cell-Lined Microfluidic Channels

Wang

Phan

George

et al. 2017

Methods in Molecular Biology

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This protocol describes detailed practical procedures for generating 3D intact and perfusable microvascular network that connects to microfluidic channels without appreciable leakage. This advanced 3D microvascular network model incorporates different stages of vascular development including vasculogenesis, endothelial cell (EC) lining, sprouting angiogenesis, and anastomosis in sequential order. The capillary network is first induced via vasculogenesis in a middle tissue chamber and then EC linings along the microfluidic channel on either side serve as artery and vein. The anastomosis is then induced by sprouting angiogenesis to facilitate tight interconnection between the artery/vein and the capillary network. This versatile device design and its robust construction methodology establish a physiological microcirculation transport model of interconnected perfused vessels from artery to vascularized tissue to vein.

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Senescent Cells with Augmented Cytokine Production for Microvascular Bioengineering and Tissue Repairs

et al. 2019

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Controlled delivery of cytokines and growth factors has been an area of intense research interest for molecular and cellular bioengineering, immunotherapy, and regenerative medicine. This study shows that primary human lung fibroblasts chemically induced to senescence (cell cycle arrest) can act as a living source to transiently produce factors essential for promoting vasculogenesis or angiogenesis, such as vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and interleukin 8 (IL‐8). Coculture of senescent fibroblasts with human umbilical vein endothelial cells in a fibrin gel demonstrate accelerated formation and maturation of microvessel networks in as early as three days. Unlike the usage of nonsenescent fibroblasts as the angiogenesis‐promoting cells, this approach eliminates drawbacks related to the overproliferation of fibroblasts and the subsequent disruption of tissue architecture, integrity, or function. Coculture of mouse pancreatic islets with senescent fibroblasts and endothelial cells in a gel matrix maintains the viability and function of islets ex vivo for up to five days. Applying senescent fibroblasts to wound repair in vivo leads to increased blood flow in a diabetic mouse model. Together, this work points to a new direction for modeling the delivery of cytokines and growth factors that promote microvascular tissue engineering and tissue repairs.

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Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels

Cited by 210 publications

References 31 publications

An on-chip microfluidic pressure regulator that facilitates reproducible loading of cells and hydrogels into microphysiological system platforms

An on-chip microfluidic pressure regulator that facilitates reproducible loading of cells and hydrogels into microphysiological system platforms

3D Anastomosed Microvascular Network Model with Living Capillary Networks and Endothelial Cell-Lined Microfluidic Channels

Senescent Cells with Augmented Cytokine Production for Microvascular Bioengineering and Tissue Repairs

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