Organ‐On‐A‐Chip Platforms: A Convergence of Advanced Materials, Cells, and Microscale Technologies

Ahadian, Samad; Civitarese, Robert; Bannerman, Dawn; Mohammadi, Mohammad Hossein; Lu, Rick Xing Ze; Wang, Erika; Huyer, Locke Davenport; Lai, Benjamin; Zhang, Boyang; Zhao, Yong; Mandla, Serena; Korolj, Anastasia

doi:10.1002/adhm.201700506

Cited by 239 publications

(167 citation statements)

References 611 publications

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“…Hydrogels have a potential use in the field of tissue engineering. Since the microenvironment of in vivo tissues is mechanically flexible, cells are exposed to mechanical forces of various durations, frequencies, and amplitudes . This work mainly focuses on mechanical flexibility in terms of a stretchable and contractible matrix.…”

Section: Introductionmentioning

confidence: 99%

Characterization of thin gelatin hydrogel membranes with balloon properties for dynamic tissue engineering

Jepsen¹,

Nielsen²,

Almdal³

et al. 2018

Biopolymers

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Cell or tissue stretching and strain are present in any in vivo environment, but is difficult to reproduce in vitro. Here, we describe a simple method for casting a thin (about 500 μm) and soft (about 0.3 kPa) hydrogel of gelatin and a method for characterizing the mechanical properties of the hydrogel simply by changing pressure with a water column. The gelatin is crosslinked with mTransglutaminase and the area of the resulting hydrogel can be increased up 13‐fold by increasing the radial water pressure. This is far beyond physiological stretches observed in vivo. Actuating the hydrogel with a radial force achieves both information about stiffness, stretchability, and contractability, which are relevant properties for tissue engineering purposes. Cells could be stretched and contracted using the gelatin membrane. Gelatin is a commonly used polymer for hydrogels in tissue engineering, and the discovered reversible stretching is particularly interesting for organ modeling applications.

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Section: Introductionmentioning

confidence: 99%

Characterization of thin gelatin hydrogel membranes with balloon properties for dynamic tissue engineering

Jepsen¹,

Nielsen²,

Almdal³

et al. 2018

Biopolymers

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“…Advances in microfluidics combined with cellular engineering have demonstrated the successful applications to serve as a complementary in vitro model of tissue-level human physiology called organ-on-a-chip (30,31). Compared to conventional in vivo and in vitro experimental models, precise control of small-volume samples in organ-on-a-chip systems facilitates highly sensitive analysis to identify and validate critical soluble factors in in vivolike organ-specific microenvironment (30,(32)(33)(34). Recent attempts to integrate organ-on-achip platforms have provided novel approaches to investigate complex cell-cell communications and dynamics between different physiological functional units (33,35).…”

Section: Introductionmentioning

confidence: 99%

Engineered Heterochronic Parabiosis in 3D Microphysiological System for Identification of Muscle Rejuvenating Factors

Lee

Choi

Ahn

et al. 2020

Preprint

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Exposure of aged mice to a young systemic milieu revealed remarkable rejuvenation effects on aged tissues, including skeletal muscle. Although some candidate factors have been identified, the exact identity and the underlying mechanisms of putative rejuvenating factors remain elusive, mainly due to the complexity of in vivo parabiosis. Here, we present an in vitro muscle parabiosis system that integrates young-and old-muscle stem cell vascular niche on a threedimensional microfluidic platform designed to recapitulate key features of native muscle stem cell microenvironment. This innovative system enables mechanistic studies of cellular dynamics and molecular interactions within the muscle stem cell niche, especially in response to conditional extrinsic stimuli of local and systemic factors. We demonstrate that vascular endothelial growth factor (VEGF) signaling from endothelial cells and myotubes synergistically contribute to the rejuvenation of the aged muscle stem cell function. Moreover, with the adjustable on-chip system, we can mimic both blood transfusion and parabiosis and detect the time-varying effects of anti-geronic and pro-geronic factors in a single organ or multi-organ systems. Our unique approach presents a complementary in vitro model to supplement in vivo parabiosis for identifying potential anti-geronic factors responsible for revitalizing aging organs.

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“…By combining modern techniques in microfabrication, biomaterials and tissue engineering, organon-a-chip technology has enabled the construction of promising platforms for mechanistic and pharmaceutical studies, that have great potential for disease modeling as well as the optimization of personalized medical treatments of obesity and diabetes. (27)(28)(29)(30) The integration of tissues with in vivo-like structure and functionality in perfused microenvironments is of particular interest when studying endocrine tissues and multi-factorial diseases, due to the possibility to combine individual chips into multi-organ systems. (31,32) However, although organ-on-a-chip research has burgeoned in recent years, and numerous platforms have been developed for many organs and tissues, WAT appears to have been largely overlooked, and only a few relevant efforts have been undertaken.…”

Section: Introductionmentioning

confidence: 99%

WAT’s up!? – Organ-on-a-chip integrating human mature white adipose tissues for mechanistic research and pharmaceutical applications

Rogal

Binder

Kromidas

et al. 2019

Preprint

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Obesity and its numerous adverse health consequences have taken on global, pandemic proportions. White adipose tissue (WAT) -a key contributor in many metabolic diseasescontributes about one fourth of a healthy human's body mass. Despite its significance, many WAT-related pathophysiogical mechanisms in humans are still not understood, largely due to the reliance on non-human animal models. In recent years, Organ-on-a-chip (OoC) platforms have developed into promising alternatives for animal models; these systems integrate engineered human tissues into physiological microenvironment supplied by a vasculature-like microfluidic perfusion. Here, we report the development of a novel OoC that integrates functional mature human WAT. The WAT-on-a-chip is a multilayer device that features tissue chambers tailored specifically for the maintenance of 3D tissues based on human primary adipocytes, with supporting nourishment provided through perfused media channels. The platform's capability to maintain long-term viability and functionality of WAT was confirmed by real-time monitoring of fatty acid uptake, by quantification of metabolite release into the effluent media as well as by an intact responsiveness to a therapeutic compound. The novel system provides a promising tool for wide-ranging applications in mechanistic research of WAT-related biology, in studying of pathophysiological mechanisms in obesity and diabetes, and in R&D of pharmaceutical industry.WAT's up!? -A human WAT-on-a-chip Rogal, Binder, Kromidas, Probst, Schneider, Schenke-Layland, and Loskill

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Organ‐On‐A‐Chip Platforms: A Convergence of Advanced Materials, Cells, and Microscale Technologies

Cited by 239 publications

References 611 publications

Characterization of thin gelatin hydrogel membranes with balloon properties for dynamic tissue engineering

Characterization of thin gelatin hydrogel membranes with balloon properties for dynamic tissue engineering

Engineered Heterochronic Parabiosis in 3D Microphysiological System for Identification of Muscle Rejuvenating Factors

WAT’s up!? – Organ-on-a-chip integrating human mature white adipose tissues for mechanistic research and pharmaceutical applications

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