Vascularized microfluidic organ-chips for drug screening, disease models and tissue engineering

Osaki, Tatsuya; Sivathanu, Vivek; Kamm, Roger D.

doi:10.1016/j.copbio.2018.03.011

Cited by 103 publications

(87 citation statements)

References 63 publications

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“…While traditional tissue engineering aims to recapitulate whole organs in vitro, organ-on-chip systems "combines the key features of specific tissue microenvironments and architecture within a microfabricated device, facilitating the creation of 3D models that exhibit functional hallmarks of native tissues" (Zhang et al, 2018). They provide minimal units mimicking specific features of living organs and human physiology, as the tissue barrier properties of the human gut and lung, the parenchymal function of cardiac and hepatic tissue, the multiorgan interactions between the lymph node and the skin ( Huh et al, 2011;Osaki et al, 2018;Ronaldson-Bouchard and Vunjak-Novakovic, 2018;Zhang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Primary Human Osteoblasts Cultured in a 3D Microenvironment Create a Unique Representative Model of Their Differentiation Into Osteocytes

Nasello

Alamán‐Díez

Schiavi

et al. 2020

Front. Bioeng. Biotechnol.

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Microengineered systems provide an in vitro strategy to explore the variability of individual patient response to tissue engineering products, since they prefer the use of primary cell sources representing the phenotype variability. Traditional in vitro systems already showed that primary human osteoblasts embedded in a 3D fibrous collagen matrix differentiate into osteocytes under specific conditions. Here, we hypothesized that translating this environment to the organ-on-a-chip scale creates a minimal functional unit to recapitulate osteoblast maturation toward osteocytes and matrix mineralization. Primary human osteoblasts were seeded in a type I collagen hydrogel, to establish the role of lower (2.5 × 10 5 cells/ml) and higher (1 × 10 6 cells/ml) cell density on their differentiation into osteocytes. A custom semi-automatic image analysis software was used to extract quantitative data on cellular morphology from brightfield images. The results are showing that cells cultured at a high density increase dendrite length over time, stop proliferating, exhibit dendritic morphology, upregulate alkaline phosphatase (ALP) activity, and express the osteocyte marker dental matrix protein 1 (DMP1). On the contrary, cells cultured at lower density proliferate over time, do not upregulate ALP and express the osteoblast marker bone sialoprotein 2 (BSP2) at all timepoints. Our work reveals that microengineered systems create unique conditions to capture the major aspects of osteoblast differentiation into osteocytes with a limited number of cells. We propose that the microengineered approach is a functional strategy to create a patient-specific bone tissue model and investigate the individual osteogenic potential of the patient bone cells.

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Section: Introductionmentioning

confidence: 99%

Primary Human Osteoblasts Cultured in a 3D Microenvironment Create a Unique Representative Model of Their Differentiation Into Osteocytes

Nasello

Alamán‐Díez

Schiavi

et al. 2020

Front. Bioeng. Biotechnol.

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“…and can be switched on or off or be modified. This enables one to unravel the roles of these factors, individual or combined [2,16,[30][31][32][33][34][35]. However, it is important to ensure that the chosen method is best suited for the given research question while keeping the biological relevance in mind.…”

Section: Current Models For Recapitulating Vasculature-on-chipmentioning

confidence: 99%

Recapitulating the Vasculature Using Organ-On-Chip Technology

Pollet

Toonder

2020

Bioengineering

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The development of Vasculature-on-Chip has progressed rapidly over the last decade and recently, a wealth of fabrication possibilities has emerged that can be used for engineering vessels on a chip. All these fabrication methods have their own advantages and disadvantages but, more importantly, the capability of recapitulating the in vivo vasculature differs greatly between them. The first part of this review discusses the biological background of the in vivo vasculature and all the associated processes. We then evaluate the biological relevance of different fabrication methods proposed for Vasculature-on-Chip, we indicate their possibilities and limitations, and we assess which fabrication methods are capable of recapitulating the intrinsic complexity of the vasculature. This review illustrates the complexity involved in developing in vitro vasculature and provides an overview of fabrication methods for Vasculature-on-Chip in relation to the biological relevance of such methods.

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“…The implementation of various organ‐on‐a‐chip, human‐on‐a‐chip, and disease‐on‐a‐chip platforms to create microphysiological systems have revolutionized the mimicry of human pathophysiology in miniaturized in vitro devices. [ 12,22,24,179 ] Microphysiological systems have enabled mechanistic investigations of multiple biological variables on vascular‐parenchymal microenvironments as well as testing efficacies and toxicity profiles of therapeutic agents and potential drug candidates. The ability to integrate these systems with other techniques (self‐assembly, bioprinting, photolithography, laser‐based techniques), compatibility with a wide range of biomaterials, parallelization of fluidic operations in multiplexed culture systems, and high‐content imaging have accelerated the commercial translation of these systems for drug discovery applications.…”

Section: Modeling Vascular Mechanopathology In Vascularized Microphysmentioning

confidence: 99%

“…[ 18–21 ] Several microphysiological systems have been developed for disease modeling and drug development. [ 12,22–25 ] The demand for employing these platforms is primarily driven by the added benefits of: 1) recapitulation of complex 3D, tissue‐specific microphysiology via use of multicellular co‐cultures and ECM‐mimetic biomaterials, 2) use of microliter‐ to picoliter‐scale reagents and media, 3) user‐defined, programmable, and continuous control of 3D vessel structure and flow, 4) spatiotemporal control over the distribution of biochemical gradients, and 5) the ability to monitor associated cellular and tissue events with high spatial and temporal resolution over extended time periods.…”

Section: Introductionmentioning

confidence: 99%

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Pradhan

Banda

Farino

et al. 2020

Adv Healthcare Materials

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The vascular system is integral for maintaining organ‐specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue‐engineered constructs and microphysiological on‐chip platforms. These in vitro systems permit studies of biochemical regulation of vascular networks and parenchymal tissue and provide mechanistic insights into the biophysical and hemodynamic forces acting in organ‐specific niches. Detailed understanding of these forces and the mechanotransductory pathways involved is necessary to develop preventative and therapeutic strategies targeting the vascular system. This review describes vascular structure and function, the role of hemodynamic forces in maintaining vascular homeostasis, and measurement approaches for cell and tissue level mechanical properties influencing vascular phenomena. State‐of‐the‐art techniques for fabricating in vitro microvascular systems, with varying degrees of biological and engineering complexity, are summarized. Finally, the role of vascular mechanobiology in organ‐specific niches and pathophysiological states, and efforts to recapitulate these events using in vitro microphysiological systems, are explored. It is hoped that this review will help readers appreciate the important, but understudied, role of vascular‐parenchymal mechanotransduction in health and disease toward developing mechanotherapeutics for treatment strategies.

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Vascularized microfluidic organ-chips for drug screening, disease models and tissue engineering

Cited by 103 publications

References 63 publications

Primary Human Osteoblasts Cultured in a 3D Microenvironment Create a Unique Representative Model of Their Differentiation Into Osteocytes

Primary Human Osteoblasts Cultured in a 3D Microenvironment Create a Unique Representative Model of Their Differentiation Into Osteocytes

Recapitulating the Vasculature Using Organ-On-Chip Technology

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

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