Synchronized stimulation and continuous insulin sensing in a microfluidic human Islet on a Chip designed for scalable manufacturing

Glieberman, Aaron L.; Pope, Benjamin D.; Zimmerman, John F.; Liu, Qihan; Ferrier, John P.; Kenty, Jennifer Hyoje-Ryu; Schrell, Adrian M.; Mukhitov, Nikita; Shores, Kevin L.; Tepole, Adrián Buganza; Melton, Douglas A.; Roper, Michael G.; Parker, Kevin Kit

doi:10.1039/c9lc00253g

Cited by 76 publications

(87 citation statements)

References 73 publications

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“…Coupled with the use of intelligently engineered materials and a host of biofabrication techniques, these systems can recapitulate niche‐level or microenvironmental physiologies with a high degree of physiological accuracy. Although not discussed in this review, investigation of other microvascular physiological niches including pancreatic islets, [ 351,518–522 ] musculoskeletal niche, [ 523–526 ] and the placental barrier, [ 318 ] among others, are also gaining prominence. Recent efforts to integrate individual organ‐niches into multiorgan microphysiological systems have provided insight into metabolic and biochemical crosstalk between separate compartments, toxicological assessment of candidate drug compounds, and their biodistribution in preclinical studies.…”

Section: Resultsmentioning

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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Section: Resultsmentioning

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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“…Replacing the commonly used PDMS with PMMA as the base fabrication material avoided many of the critical challenges faced in using PDMS-MPS for drug screening or long-term organoid culture, such as problems with accurate large-scale manufacturing and biofouling ( 29 , 30 ). While others have also made this transition using polycarbonate ( 31 ), long-term microfluidic culture using plastic-based MPS is challenged by the poor oxygen permeability of these materials ( 32 ). We address this issue by integrating a PFA membrane, an oxygen-permeable and low biofouling perfluorinated polymer, into the acrylic MPS platform ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Organoid microphysiological system preserves pancreatic islet function within 3D matrix

et al. 2021

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Three-dimensional (3D) multicellular organoids recapitulate the native complexities of human tissue better than traditional cellular monolayers. As organoids are insufficiently supported using standard static culture, microphysiological systems (MPSs) provide a key enabling technology to maintain organoid physiology in vitro. Here, a polydimethylsiloxane-free MPS that enables continuous dynamic culture and serial in situ multiparametric assessments was leveraged to culture organoids, specifically human and rodent pancreatic islets, within a 3D alginate hydrogel. Computational modeling predicted reduced hypoxic stress and improved insulin secretion compared to static culture. Experimental validation via serial, high-content, and noninvasive assessments quantitatively confirmed that the MPS platform retained organoid viability and functionality for at least 10 days, in stark contrast to the acute decline observed overnight under static conditions. Our findings demonstrate the importance of a dynamic in vitro microenvironment for the preservation of primary organoid function and the utility of this MPS for in situ multiparametric assessment.

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“…Such an integrated platform has the potential to effectively boost stem cell differentiation toward cardiomyocytes [177] and could be promising also in driving the differentiation of pancreatic progenitors towards mature β-cells [178].…”

Section: Discussionmentioning

confidence: 99%

Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction

Galli

Marku

Marciani

et al. 2020

Cells

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Embryonic and pluripotent stem cells hold great promise in generating β-cells for both replacing medicine and novel therapeutic discoveries in diabetes mellitus. However, their differentiation in vitro is still inefficient, and functional studies reveal that most of these β-like cells still fail to fully mirror the adult β-cell physiology. For their proper growth and functioning, β-cells require a very specific environment, the islet niche, which provides a myriad of chemical and physical signals. While the nature and effects of chemical stimuli have been widely characterized, less is known about the mechanical signals. We here review the current status of knowledge of biophysical cues provided by the niche where β-cells normally live and differentiate, and we underline the possible machinery designated for mechanotransduction in β-cells. Although the regulatory mechanisms remain poorly understood, the analysis reveals that β-cells are equipped with all mechanosensors and signaling proteins actively involved in mechanotransduction in other cell types, and they respond to mechanical cues by changing their behavior. By engineering microenvironments mirroring the biophysical niche properties it is possible to elucidate the β-cell mechanotransductive-regulatory mechanisms and to harness them for the promotion of β-cell differentiation capacity in vitro.

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Synchronized stimulation and continuous insulin sensing in a microfluidic human Islet on a Chip designed for scalable manufacturing

Abstract: A device engineered from scalable materials for automated islet loading, synchronized stimulus delivery, and continuous on-chip insulin detection.

Cited by 76 publications

References 73 publications

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Organoid microphysiological system preserves pancreatic islet function within 3D matrix

Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction

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