Mussel-inspired 3D fiber scaffolds for heart-on-a-chip toxicity studies of engineered nanomaterials

Seungkuk Ahn, Herdeline Ann M. Ardoña, Johan U. Lind, Feyisayo Eweje, Sean L. Kim, Grant M. Gonzalez, Qihan Liu, John F. Zimmerman, Georgios Pyrgiotakis, Zhenyuan Zhang, Juan Beltran-Huarac, Paul Carpinone, Brij M. Moudgil, Philip Demokritou, Kevin Kit Parker

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Due to the unique physicochemical properties exhibited by materials with nanoscale dimensions, there is currently a continuous increase in the number of engineered nanomaterials (ENMs) used in consumer goods. However, several reports associate ENM exposure to negative health outcomes such as cardiovascular diseases. Therefore, understanding the pathological consequences of ENM exposure represents an important challenge, requiring model systems that can provide mechanistic insights across different levels of ENM-based toxicity. To achieve this, we developed a mussel-inspired 3D microphysiological system (MPS) to measure cardiac contractility in the presence of ENMs. While multiple cardiac MPS have been reported as alternatives to in vivo testing, most systems only partially recapitulate the native extracellular matrix (ECM) structure. Here, we show how adhesive and aligned polydopamine (PDA)/polycaprolactone (PCL) nanofiber can be used to emulate the 3D native ECM environment of the myocardium. Such nanofiber scaffolds can support the formation of anisotropic and contractile muscular tissues. By integrating these fibers in a cardiac MPS, we assessed the effects of TiO2 and Ag nanoparticles on the contractile function of cardiac tissues. We found that these ENMs decrease the contractile function of cardiac tissues through structural damage to tissue architecture. Furthermore, the MPS with embedded sensors herein presents a way to non-invasively monitor the effects of ENM on cardiac tissue contractility at different time points. These results demonstrate the utility of our MPS as an analytical platform for understanding the functional impacts of ENMs while providing a biomimetic microenvironment to in vitro cardiac tissue samples. [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)6141-6154
Number of pages14
JournalAnalytical and Bioanalytical Chemistry
Volume410
Issue number24
DOIs
StatePublished - Sep 1 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry

Keywords

  • Cardiotoxicity
  • Microphysiological systems
  • Nanofiber
  • Nanotoxicology
  • Polydopamine

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