Characterization of<i>In Vitro</i>Endothelial Linings Grown Within Microfluidic Channels

Esch, Mandy B.; Post, D.; Shuler, Michael L.; Stokol, Tracy

doi:10.1089/ten.tea.2010.0371

Cited by 62 publications

(60 citation statements)

References 44 publications

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“…This work demonstrated that the 3D scaffold architecture in the organ-on-a-chip platform allows for cellular interactions that promote 3D capillary morphogenesis through vascular cells. The presence of shear stress was also shown to be responsible for the formation of endothelial vessel linings [38]. Such mechanical stimuli associated with physiological organ motion provide physical cues enabling specific function beyond static tissue culture [27].…”

Section: Fundamental Strategies To Maximize the Efficiency And Predicmentioning

confidence: 99%

Organ-On-A-Chip: Development and Clinical Prospects Toward Toxicity Assessment with an Emphasis on Bone Marrow

et al. 2015

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Conventional approaches for toxicity evaluation of drugs and chemicals, such as animal tests, can be impractical due to the large experimental scale and the immunological differences between species. Organ-on-a-chip models have recently been recognized as a prominent alternative to conventional toxicity tests aiming to simulate the human in vivo physiology. This review focuses on the organ-on-a-chip applications for high-throughput screening of candidate drugs against toxicity, with a particular emphasis on bone-marrow-on-a-chip. Studies in which organ-on-a-chip models have been developed and utilized to maximize the efficiency and predictability in toxicity assessment are introduced. The potential of these devices to replace tests of acute systemic toxicity in animals, and the challenges that are inherent in simulating the human immune system are also discussed. As a promising approach to overcome the limitations, we further focus on an in-depth analysis of the development of bone-marrow-on-a-chip that is capable of simulating human immune responses against external stimuli due to the key roles of marrow in immune systems with hematopoietic activities. Owing to the complex interactions between hematopoietic stem cells and marrow microenvironments, precise control of both biochemical and physical niches that are critical in maintenance of hematopoiesis remains a key challenge. Thus, recently developed bone-marrow-on-a-chip models support immunogenicity and immunotoxicity testing in long-term cultivation with repeated antigen stimulation. In this review, we provide an overview of clinical studies that have been carried out on bone marrow transplants in patients with immune-related diseases and future aspects of clinical and pharmaceutical application of bone-marrow-on-a-chip.

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Section: Fundamental Strategies To Maximize the Efficiency And Predicmentioning

confidence: 99%

Organ-On-A-Chip: Development and Clinical Prospects Toward Toxicity Assessment with an Emphasis on Bone Marrow

et al. 2015

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“…Specifically, they are designed to actively influence protein adsorption (the first step of the FBR) and tissue interactions by controlling parameters such as material structure (on a micro/nano level), porosity, drug loading, and surface chemistry (Brodbeck et al, 2002; Bryers et al, 2012; Healy et al, 1996; Lan et al, 2005; Puleo and Nanci, 1999; Ratner, 2002, 2001; Roach et al, 2007; Shin et al, 2003). Commonly, biomimetic materials modify functional groups on the surface of a material or coat the material with ECM molecules (Brodbeck et al, 2002; Chen et al, 2013; Esch et al, 2011; Healy et al, 1996; Lan et al, 2005; Puleo and Nanci, 1999; Roach et al, 2007; Shin et al, 2003). Another thrust of engineering biomimetic materials is to create topographies that either elicit specific biological responses (such as microchannels) or mimic the structure of the ECM (Boudriot et al, 2006; Esch et al, 2011; Roach et al, 2007; Stevens and George, 2005).…”

Section: Biomaterialsmentioning

confidence: 99%

“…Commonly, biomimetic materials modify functional groups on the surface of a material or coat the material with ECM molecules (Brodbeck et al, 2002; Chen et al, 2013; Esch et al, 2011; Healy et al, 1996; Lan et al, 2005; Puleo and Nanci, 1999; Roach et al, 2007; Shin et al, 2003). Another thrust of engineering biomimetic materials is to create topographies that either elicit specific biological responses (such as microchannels) or mimic the structure of the ECM (Boudriot et al, 2006; Esch et al, 2011; Roach et al, 2007; Stevens and George, 2005). …”

Section: Biomaterialsmentioning

confidence: 99%

Matricellular proteins and biomaterials

Morris

Kyriakides

2014

Matrix Biology

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Biomaterials are essential to modern medicine as components of reconstructive implants, implantable sensors, and vehicles for localized drug delivery. Advances in biomaterials have led to progression from simply making implants that are nontoxic to making implants that are specifically designed to elicit particular functions within the host. The interaction of implants and the extracellular matrix during the foreign body response is a growing area of concern for the field of biomaterials, because it can lead to implant failure. Expression of matricellular proteins is modulated during the foreign body response and these proteins interact with biomaterials. The design of biomaterials to specifically alter the levels of matricellular proteins surrounding implants provides a new avenue for the design and fabrication of biomimetic biomaterials.

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“…188 Using microuidic channels, it has also been determined that endothelial cells require a minimum initial shear stress in vitro to enable their growth and development to conuent layers that express VE-cadherin, a standard marker for adherence junctions. 189 While polydimethylsiloxane (PDMS) is the most popular material for microuidic systems and carries many advantages, the material properties of the PDMS surface are not ideal. 190 There are concerns that the adsorption of compounds from the medium may interfere with an accurate experimental outcome.…”

Section: Microuidicsmentioning

confidence: 99%

‘Body-on-a-Chip’ Technology and Supporting Microfluidics

Smith¹,

Long²,

McAleer³

et al. 2014

Human-Based Systems for Translational Research

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In order to effectively streamline current drug development protocols, there is a need to generate high information content preclinical screens capable of generating data with a predictive power in relation to the activity of novel therapeutics in humans. Given the poor predictive power of animal models, and the lack of complexity and interconnectivity of standard in vitro culture methodologies, many investigators are now moving toward the development of physiologically and functionally accurate culture platforms composed of human cells to investigate cellular responses to drug compounds in high-throughput preclinical studies. The generation of complex, multi-organ in vitro platforms, built to recapitulate physiological dimensions, flow rates and shear stresses, is being investigated as the logical extension of this drive. Production and application of a biologically accurate multi-organ platform, or ‘body-on-a-chip’, would facilitate the correct modelling of the dynamic and interconnected state of living systems for high-throughput drug studies as well as basic and applied biomolecular research. This chapter will discuss current technologies aimed at producing ‘body-on-a-chip’ models, as well as highlighting recent advances and important challenges still to be met in the development of biomimetic single-organ systems for drug development purposes.

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Characterization ofIn VitroEndothelial Linings Grown Within Microfluidic Channels

Cited by 62 publications

References 44 publications

Organ-On-A-Chip: Development and Clinical Prospects Toward Toxicity Assessment with an Emphasis on Bone Marrow

Organ-On-A-Chip: Development and Clinical Prospects Toward Toxicity Assessment with an Emphasis on Bone Marrow

Matricellular proteins and biomaterials

‘Body-on-a-Chip’ Technology and Supporting Microfluidics

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