Vessel‐on‐a‐chip with Hydrogel‐based Microfluidics

Nie, Jing; Gao, Qing; Wang, Yidong; Zeng, Jiahui; Zhao, Huijie; Sun, Yuan; Shen, Jian; Ramezani, Hamed; Fu, Zhenliang; Liu, Zhenjie; Xiang, Meixiang; Fu, Jianzhong; Zhao, Peng; Chen, Wei; He, Yong

doi:10.1002/smll.201802368

Cited by 139 publications

(114 citation statements)

References 51 publications

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“…The photo‐crosslikable GelMA hydrogel is made by attaching methacrylate groups to gelatin, holding an abundance of cell binding motifs (e.g., RGD). It has been widely used to manufacture vascular‐like structure due to its tunable properties with variable concentration and density . Khademhosseini and co‐workers reported a sacrificial bioprinting technique to establish microchannel networks integrated in OOC systems with GelMA as chips and printed agarose as templates .…”

Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

“…Hydrogel‐based microvascular networks are desirable for engineering functional 3D vascularized tissues in OOC . Zhang et al developed an AngioChip scaffold with a built‐in perfusable vascular network fabricated using a synthetic polymer POMaC by 3D stamping technique, in which a complex microchannel network can be embedded within a 3D scaffold .…”

Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

“…Several defined hydrogels have been proven to facilitate organoids formation as substitutes to undefined animal‐derived matrix for improving the reproducibility and maturity of organoids by precise control of their componential, architectural, and/or mechanical conditions . With respect to OOC platforms, hydrogels have been applied to improve the physiological relevance of tissue models on chips by replicating 3D matrix, tissue interfaces, vascularized network, cell–cell and cell–ECM interactions in a biomimetic microenvironment …”

Section: Introductionmentioning

confidence: 99%

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Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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The major motivation is to better mimic human physiology and functions at multiscales from the molecular to the cellular, tissue, organ or even whole organism level. Current model systems primarily rely on the monolayer cell cultures and animal models. Simplistic monolayer cultures have their advantages, but they are often significantly different in gene expression, epigenetics, and cell function compared to native 3D tissues. [1,2] Also, they often lack cell-cell and cell-matrix interactions, [2,3] leading to the absence of tissue specific properties. Although animal models are widely used in biomedical research, they fail to faithfully predict human responses in a physiologically relevant manner due to the significant species divergences. [4] The limitations of these systems have provided an impetus for the development of alternative cell-based 3D models in vitro that better resemble the complex functionalities of living organs. Over the last several years, organoids and organ-on-a-chip (OOC), representing the major technological breakthrough, have emerged as two distinct model systems to achieve the same goal of building 3D organotypic models in vitro by bridging the gap between animal models and monolayer cultures. These engineered models are different in terms of cell source, tissue composition, architectural variability, functional features, scales, cellular fidelity, etc. Organoids, primarily evolving from developmental principles, refer to 3D multicellular tissues by self-organization of stem cells or organ-specific progenitors, which can recapitulate the intricate architectures and functionalities of in vivo organs. [5][6][7] Recent breakthroughs in organoid technology have enabled the successful generation of a variety of human organoids, such as the brain, [8,9] intestine, [10,11] liver, [12] kidney, [13,14] lung, [15] etc. These near physiological 3D organoids have garnered momentum for their potential applications in human organ development and disease modeling, drug screening and regenerative medicine. The explosion of organoids research has been catalyzed by the significant progress of stem cell biology and availability of human stem cells. In contrast, the OOC, relying on the bioengineering design principle, is a miniaturized in vitro model that can recreate the functional units of living organs on a microfluidic cell culture device using predifferentiated cells, often cell lines. [1,16] The OOC is primarily evolved from the convergence of tissue engineering and microfabricated technologies, which is characterized by the capability to simulate cellular microenvironment by precise control over fluid flow, mechanical forces and biochemical factors. [4,17] Remarkable progress has been made Significant advances in materials, microscale technology, and stem cell biology have enabled the construction of 3D tissues and organs, which will ultimately lead to more effective diagnostics and therapy. Organoids and organs-on-a-chip (OOC), evolved from developmental biology and bioengineering principles, have e...

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Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

Section: Hydrogels In Organs‐on‐a‐chip Engineeringmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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“…Systems that allow the measurement of fundamental aspects of drug safety, pharmacokinetics and efficacy, therefore, hold great potential value for patients. In particular, 3D models of the human microvasculature (endothelium‐on‐chip, made by bioprinting, casting, or combination approaches, among others) can be used to quantify the distribution of circulating therapeutic molecules across the capillary wall into the interstitial space where they access cellular targets and elicit pharmacological response …”

Section: Introductionmentioning

confidence: 99%

Application of Transmural Flow Across In Vitro Microvasculature Enables Direct Sampling of Interstitial Therapeutic Molecule Distribution

Offeddu

Possenti

Loessberg-Zahl

et al. 2019

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In vitro prediction of physiologically relevant transport of therapeutic molecules across the microcirculation represents an intriguing opportunity to predict efficacy in human populations. On‐chip microvascular networks (MVNs) show physiologically relevant values of molecular permeability, yet like most systems, they lack an important contribution to transport: the ever‐present fluid convection through the endothelium. Quantification of transport through the MVNs by current methods also requires confocal imaging and advanced analytical techniques, which can be a bottleneck in industry and academic laboratories. Here, it is shown that by recapitulating physiological transmural flow across the MVNs, the concentration of small and large molecule therapeutics can be directly sampled in the interstitial fluid and analyzed using standard analytical techniques. The magnitudes of transport measured in MVNs reveal trends with molecular size and type (protein versus nonprotein) that are expected in vivo, supporting the use of the MVNs platform as an in vitro tool to predict distribution of therapeutics in vivo.

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“…Aside from vascular tissue engineering, we explored whether the VF‐3DP approach could be used to print a hydrogel‐based microfluidic device ( Figure A). Using hydrogels as base materials for microfluidics has recently attracted attention, since they can better support cell migration and tissue remodeling compared to the more common elastomer‐based systems. For example, angiogenesis and perivascular interactions have been studied with microvessels formed in degradable hyaluronic acid and collagen .…”

Section: Resultsmentioning

confidence: 99%

Void‐Free 3D Bioprinting for In Situ Endothelialization and Microfluidic Perfusion

Ouyang

Armstrong

et al. 2019

Adv Funct Materials

126

101

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Two major challenges of 3D bioprinting are the retention of structural fidelity and efficient endothelialization for tissue vascularization. Both of these issues are addressed by introducing a versatile 3D bioprinting strategy, in which a templating bioink is deposited layer-by-layer alongside a matrix bioink to establish void-free multimaterial structures. After crosslinking the matrix phase, the templating phase is sacrificed to create a well-defined 3D network of interconnected tubular channels. This void-free 3D printing (VF-3DP) approach circumvents the traditional concerns of structural collapse, deformation, and oxygen inhibition, moreover, it can be readily used to print materials that are widely considered "unprintable." By preloading endothelial cells into the templating bioink, the inner surface of the channels can be efficiently cellularized with a confluent endothelial layer. This in situ endothelialization method can be used to produce endothelium with a far greater cell seeding uniformity than can be achieved using the conventional postseeding approach. This VF-3DP approach can also be extended beyond tissue fabrication and toward customized hydrogel-based microfluidics and self-supported perfusable hydrogel constructs.

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Vessel‐on‐a‐chip with Hydrogel‐based Microfluidics

Cited by 139 publications

References 51 publications

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Application of Transmural Flow Across In Vitro Microvasculature Enables Direct Sampling of Interstitial Therapeutic Molecule Distribution

Void‐Free 3D Bioprinting for In Situ Endothelialization and Microfluidic Perfusion

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