Physiologic flow-conditioning limits vascular dysfunction in engineered human capillaries

Haase, Kristina; Piatti, Filippo; Marcano, Minerva; Shin, Yoojin; Visone, Roberta; Redaelli, Alberto; Rasponi, Marco; Kamm, Roger D.

doi:10.1016/j.biomaterials.2021.121248

Cited by 38 publications

(46 citation statements)

References 59 publications

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“…Ensuring perfusability may explain that many published reports show perfusable MVNs with both capillary-like vessels and much larger vessels (Figure S1, Supporting Information). [3,5,8,9,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] To reliably form perfusable MVNs with the desired capillary-like geometry, we investigated the effect of seeding parameters on MVN geometry and, in doing so, established a robust two-step seeding strategy that allows us to provide favorable conditions for open vessels between microposts and capillary-like MVNs throughout the central region.…”

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confidence: 99%

A Robust Method for Perfusable Microvascular Network Formation In Vitro

et al. 2022

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Micropost‐based microfluidic devices are widely used for microvascular network (MVN) formation in diverse research fields. However, consistently generating perfusable MVNs of physiological morphology and dimension has proven to be challenging. Here, how initial seeding parameters determine key characteristics of MVN formation is investigated and a robust two‐step seeding strategy to generate perfusable physiological MVNs in microfluidic devices is established.

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confidence: 99%

A Robust Method for Perfusable Microvascular Network Formation In Vitro

et al. 2022

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“…Hence, these flow niches act as a mechanical stimulus and generate a shear ‘map’ that regulates fibroblast differentiation. ECM stiffness in cell differentiation is well established 20 , but evidence shows that FSS is also essential for the differentiation of embryonic stem cells 21 , endothelial cells 23 and fibroblasts 35 . Future efforts will assess how shear and chemical (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we propose two types of laminar flow regimes: (1) flow landscapes with fixed laminar shear referred as ‘homogeneous flow’ and (2) flow landscapes with mixed laminar shear referred as ‘heterogeneous flow’. In vivo fluid shear varies from 0 – 70 dynes/cm 2 and is responsible for triggering intracellular signaling, transduction 17 and cell migration 18 and are important in maintaining the homeostasis of tissue niches 19 , initiating tissue repair 20 , bone development 21 , cancer metastasis 16, 22 , angiogenesis 23 , regulating cardiac fibrosis and impacts on thrombosis 24 .…”

Section: Introductionmentioning

confidence: 99%

“…Despite this, the majority of tissue-on-chip 25 or organ-on-chip 26 systems are generally designed with homogeneous fluid shear stress (FSS) in soft lithographic hollow channels lined by a single layer of cultured cells or tissue. We argue that the oversimplification of flow is primarily because of the limited direct 3D flow channel fabrication methods that fail to adequately reflect in vivo fluid motion 12, 13, 23 .…”

Section: Introductionmentioning

confidence: 99%

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Patterning High to Low Heterogenous Fluid Shear Stress Landscapes with Multiphoton Inner Laser Lithography (MILL) for Live Cell Adhesion and Translocation

Lim

Zhang

Lin

et al. 2022

Preprint

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Current 3D microfluidic fabrication methods require hours and specialized equipment to fabricate microstructures in a single channel so as to recapitulate mixed (homogenous and heterogeneous) in vivo fluid flow. Inspired by the ancient art form of inside painting, we developed a technique for 3D fabrication of micro-patterned flow channels and mixed in vivo fluid flow in a matter of minutes. We termed this technique Multiphoton Inner Laser Lithography (MILL). We further showed that MILL is compatible with both flat and curved channel shapes. MILL recapitulated in vivo tissue topology and 3D fluid flow of the tissue microenvironment, all of which are vital for understanding of how extracellular fluid flow regulates cell function. Cells in MILL capillary tubes response to a variety of in vivo-like laminar flow patterns (homogenous and heterogeneous). Live cells were observed to organize, translocate and adhere along different fluid shear landscapes (0 - 81 dynes/cm2) in real time. Parallel strips of MILL channels were assembled for platelet function tests (~2000 microthrombi per test). The MILL technique heralds a new paradigm where dynamics of in vivo fluid flow can be readily reproduced in minutes on a standard multiphoton imaging microscope and benefit preclinical screening of drug pharmacokinetics.

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“…First, it enhances transport of nutrients and gas exchange for maintenance of long-term cultures. Second, flow-mediated shear stress improves microvascular formation and reduces vascular permeability [ 101 , 125 ]. Specifically, flow stimuli have been demonstrated to promote the differentiation of vascular ECs into a more physiological phenotype, with the highest expression of tight junction proteins and membrane transporters, producing further reductions in permeability [ 126 ].…”

Section: Remaining Challenges In Modeling Response To Cell Therapiesmentioning

confidence: 99%

Engineered Microphysiological Systems for Testing Effectiveness of Cell-Based Cancer Immunotherapies

Shelton

Chen

Kamm

et al. 2022

Cancers

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Cell therapies, including adoptive immune cell therapies and genetically engineered chimeric antigen receptor (CAR) T or NK cells, have shown promise in treating hematologic malignancies. Yet, immune cell infiltration and expansion has proven challenging in solid tumors due to immune cell exclusion and exhaustion and the presence of vascular barriers. Testing next-generation immune therapies remains challenging in animals, motivating sophisticated ex vivo models of human tumor biology and prognostic assays to predict treatment response in real-time while comprehensively recapitulating the human tumor immune microenvironment (TIME). This review examines current strategies for testing cell-based cancer immunotherapies using ex vivo microphysiological systems and microfluidic technologies. Insights into the multicellular interactions of the TIME will identify novel therapeutic strategies to help patients whose tumors are refractory or resistant to current immunotherapies. Altogether, these microphysiological systems (MPS) have the capability to predict therapeutic vulnerabilities and biological barriers while studying immune cell infiltration and killing in a more physiologically relevant context, thereby providing important insights into fundamental biologic mechanisms to expand our understanding of and treatments for currently incurable malignancies.

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Physiologic flow-conditioning limits vascular dysfunction in engineered human capillaries

Cited by 38 publications

References 59 publications

A Robust Method for Perfusable Microvascular Network Formation In Vitro

A Robust Method for Perfusable Microvascular Network Formation In Vitro

Patterning High to Low Heterogenous Fluid Shear Stress Landscapes with Multiphoton Inner Laser Lithography (MILL) for Live Cell Adhesion and Translocation

Engineered Microphysiological Systems for Testing Effectiveness of Cell-Based Cancer Immunotherapies

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