Microfluidic Cardiac Cell Culture Model (μCCCM)

Guruprasad A. Giridharan, Mai Dung Nguyen, Rosendo Estrada, Vahidreza Parichehreh, Tariq Hamid, Mohamed Ameen Ismahil, Sumanth D. Prabhu, Palaniappan Sethu

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

Physiological heart development and cardiac function rely on the response of cardiac cells to mechanical stress during hemodynamic loading and unloading. These stresses, especially if sustained, can induce changes in cell structure, contractile function, and gene expression. Current cell culture techniques commonly fail to adequately replicate physical loading observed in the native heart. Therefore, there is a need for physiologically relevant in vitro models that recreate mechanical loading conditions seen in both normal and pathological conditions. To fulfill this need, we have developed a microfluidic cardiac cell culture model (μCCCM) that for the first time allows in vitro hemodynamic stimulation of cardiomyocytes by directly coupling cell structure and function with fluid induced loading. Cells are cultured in a small (1 cm diameter) cell culture chamber on a thin flexible silicone membrane. Integrating the cell culture chamber with a pump, collapsible pulsatile valve and an adjustable resistance element (hemostatic valve) in series allow replication of various loading conditions experienced in the heart. This paper details the design, modeling, fabrication and characterization of fluid flow, pressure and stretch generated at various frequencies to mimic hemodynamic conditions associated with the normal and failing heart. Proof-of-concept studies demonstrate successful culture of an embryonic cardiomyoblast line (H9c2 cells) and establishment of an in vivo like phenotype within this system.

Original languageEnglish
Pages (from-to)7581-7587
Number of pages7
JournalAnalytical Chemistry
Volume82
Issue number18
DOIs
StatePublished - Sep 15 2010

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