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Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing.

ABSTRACT: Biomedical research has relied on animal studies and conventional cell cultures for decades. Recently, microphysiological systems (MPS), also known as organs-on-chips, that recapitulate the structure and function of native tissues in vitro, have emerged as a promising alternative. However, current MPS typically lack integrated sensors and their fabrication requires multi-step lithographic processes. Here, we introduce a facile route for fabricating a new class of instrumented cardiac microphysiological devices via multimaterial three-dimensional (3D) printing. Specifically, we designed six functional inks, based on piezo-resistive, high-conductance, and biocompatible soft materials that enable integration of soft strain gauge sensors within micro-architectures that guide the self-assembly of physio-mimetic laminar cardiac tissues. We validated that these embedded sensors provide non-invasive, electronic readouts of tissue contractile stresses inside cell incubator environments. We further applied these devices to study drug responses, as well as the contractile development of human stem cell-derived laminar cardiac tissues over four weeks.

SUBMITTER: Lind JU

PROVIDER: S-EPMC5321777 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing.

Lind Johan U JU Busbee Travis A TA Valentine Alexander D AD Pasqualini Francesco S FS Yuan Hongyan H Yadid Moran M Park Sung-Jin SJ Kotikian Arda A Nesmith Alexander P AP Campbell Patrick H PH Vlassak Joost J JJ Lewis Jennifer A JA Parker Kevin K KK

Nature materials 20161024 3

Biomedical research has relied on animal studies and conventional cell cultures for decades. Recently, microphysiological systems (MPS), also known as organs-on-chips, that recapitulate the structure and function of native tissues in vitro, have emerged as a promising alternative. However, current MPS typically lack integrated sensors and their fabrication requires multi-step lithographic processes. Here, we introduce a facile route for fabricating a new class of instrumented cardiac microphysio ...[more]

PMID: 27775708

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Project description:In this study of three-dimensional (3D) printed composite β-tricalcium phosphate (β-TCP)-/hydroxyapatite/poly(ɛ-caprolactone)-based constructs, the effects of vertical compositional ceramic gradients and architectural porosity gradients on the osteogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells (MSCs) were investigated. Specifically, three different concentrations of β-TCP (0, 10, and 20 wt%) and three different porosities (33% ± 4%, 50% ± 4%, and 65% ± 3%) were examined to elucidate the contributions of chemical and physical gradients on the biochemical behavior of MSCs and the mineralized matrix production within a 3D culture system. By delaminating the constructs at the gradient transition point, the spatial separation of cellular phenotypes could be specifically evaluated for each construct section. Results indicated that increased concentrations of β-TCP resulted in upregulation of osteogenic markers, including alkaline phosphatase activity and mineralized matrix development. Furthermore, MSCs located within regions of higher porosity displayed a more mature osteogenic phenotype compared to MSCs in lower porosity regions. These results demonstrate that 3D printing can be leveraged to create multiphasic gradient constructs to precisely direct the development and function of MSCs, leading to a phenotypic gradient. Impact Statement In this study, three-dimensional (3D) printed ceramic/polymeric constructs containing discrete vertical gradients of both composition and porosity were fabricated to precisely control the osteogenic differentiation of mesenchymal stem cells. By making simple alterations in construct architecture and composition, constructs containing heterogenous populations of cells were generated, where gradients in scaffold design led to corresponding gradients in cellular phenotype. The study demonstrates that 3D printed multiphasic composite constructs can be leveraged to create complex heterogeneous tissues and interfaces.

Dataset Information

Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing.

Publications

Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing.

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