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Native extracellular matrix-derived semipermeable, optically transparent, and inexpensive membrane inserts for microfluidic cell culture.

ABSTRACT: Semipermeable cell culture membranes are commonly used in multilayered microfluidic devices to mimic the basement membrane in vivo and to create compartmentalized microenvironments for physiological cell growth and differentiation. However, existing membranes are predominantly made up of synthetic polymers, providing limited capacity to replicate cellular interactions with native extracellular matrices that play a crucial role in the induction of physiological phenotypes. Here we describe a new type of cell culture membranes engineered from native extracellular matrix (ECM) materials that are thin, semipermeable, optically transparent, and amenable to integration into microfluidic cell culture devices. Facile and cost-effective fabrication of these membranes was achieved by controlled sequential steps of vitrification that transformed three-dimensional (3D) ECM hydrogels into structurally stable thin films. By modulating the composition of the ECM, our technique provided a means to tune key membrane properties such as optical transparency, stiffness, and porosity. For microfluidic cell culture, we constructed a multilayered microdevice consisting of two parallel chambers separated by a thin membrane insert derived from different types of ECM. This study showed that our ECM membranes supported attachment and growth of various types of cells (epithelial, endothelial, and mesenchymal cells) under perfusion culture conditions. Our data also revealed the promotive effects of the membranes on adhesion-associated intracellular signaling that mediates cell-ECM interactions. Moreover, we demonstrated the use of these membranes for constructing compartmentalized microfluidic cell culture systems to induce physiological tissue differentiation or to replicate interfaces between different tissue types. Our approach provides a robust platform to produce and engineer biologically active cell culture substrates that serve as promising alternatives to conventional synthetic membrane inserts. This strategy may contribute to the development of physiologically relevant in vitro cell culture models for a wide range of applications.

SUBMITTER: Mondrinos MJ

PROVIDER: S-EPMC5782796 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Native extracellular matrix-derived semipermeable, optically transparent, and inexpensive membrane inserts for microfluidic cell culture.

Mondrinos Mark J MJ Yi Yoon-Suk YS Wu Nan-Kun NK Ding Xueting X Huh Dongeun D

Lab on a chip 20170901 18

Semipermeable cell culture membranes are commonly used in multilayered microfluidic devices to mimic the basement membrane in vivo and to create compartmentalized microenvironments for physiological cell growth and differentiation. However, existing membranes are predominantly made up of synthetic polymers, providing limited capacity to replicate cellular interactions with native extracellular matrices that play a crucial role in the induction of physiological phenotypes. Here we describe a new ...[more]

PMID: 28809418

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Project description:RATIONALE:More than 25 million individuals have heart failure worldwide, with ?4000 patients currently awaiting heart transplantation in the United States. Donor organ shortage and allograft rejection remain major limitations with only ?2500 hearts transplanted each year. As a theoretical alternative to allotransplantation, patient-derived bioartificial myocardium could provide functional support and ultimately impact the treatment of heart failure. OBJECTIVE:The objective of this study is to translate previous work to human scale and clinically relevant cells for the bioengineering of functional myocardial tissue based on the combination of human cardiac matrix and human induced pluripotent stem cell-derived cardiomyocytes. METHODS AND RESULTS:To provide a clinically relevant tissue scaffold, we translated perfusion-decellularization to human scale and obtained biocompatible human acellular cardiac scaffolds with preserved extracellular matrix composition, architecture, and perfusable coronary vasculature. We then repopulated this native human cardiac matrix with cardiomyocytes derived from nontransgenic human induced pluripotent stem cells and generated tissues of increasing 3-dimensional complexity. We maintained such cardiac tissue constructs in culture for 120 days to demonstrate definitive sarcomeric structure, cell and matrix deformation, contractile force, and electrical conduction. To show that functional myocardial tissue of human scale can be built on this platform, we then partially recellularized human whole-heart scaffolds with human induced pluripotent stem cell-derived cardiomyocytes. Under biomimetic culture, the seeded constructs developed force-generating human myocardial tissue and showed electrical conductivity, left ventricular pressure development, and metabolic function. CONCLUSIONS:Native cardiac extracellular matrix scaffolds maintain matrix components and structure to support the seeding and engraftment of human induced pluripotent stem cell-derived cardiomyocytes and enable the bioengineering of functional human myocardial-like tissue of multiple complexities.

Dataset Information

Native extracellular matrix-derived semipermeable, optically transparent, and inexpensive membrane inserts for microfluidic cell culture.

Publications

Native extracellular matrix-derived semipermeable, optically transparent, and inexpensive membrane inserts for microfluidic cell culture.

Similar Datasets

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