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Bioengineering Cardiac Tissue Constructs With Adult Rat Cardiomyocytes

Tao, Ze-Wei*,†; Mohamed, Mohamed; Jacot, Jeffrey G.*; Birla, Ravi K.†,‡

doi: 10.1097/MAT.0000000000000765
Tissue Engineering/ Biomaterials

Bioengineering cardiac tissue constructs with adult cardiomyocytes may help treat adult heart defects and injury. In this study, we fabricated cardiac tissue constructs by seeding adult rat cardiomyocytes on a fibrin gel matrix and analyzed the electromechanical properties of the formed cardiac tissue constructs. Adult rat cardiomyocytes were isolated with a collagenase type II buffer using an optimized Langendorff perfusion system. Cardiac tissue constructs were fabricated using either indirect plating with cardiomyocytes that were cultured for 1 week and dedifferentiated or with freshly isolated cardiomyocytes. The current protocol generated (3.1 ± 0.5) × 106 (n = 5 hearts) fresh cardiomyocytes from a single heart. Tissue constructs obtained by both types of plating contracted up to 30 days, and electrogram (ECG) signals and contractile twitch forces were detected. The constructs bioengineered by indirect plating of dedifferentiated cardiomyocytes produced an ECG R wave amplitude of 15.1 ± 5.2 µV (n = 7 constructs), a twitch force of 70–110 µN, and a spontaneous contraction rate of about 390 bpm. The constructs bioengineered by direct plating of fresh cardiomyocytes generated an ECG R wave amplitude of 6.3 ± 2.5 µV (n = 8 constructs), a twitch force of 40–60 µN, and a spontaneous contraction rate of about 230 bpm. This study successfully bioengineered three-dimensional cardiac tissue constructs using primary adult cardiomyocytes.

From the *Department of Bioengineering, University of Colorado Denver/Anschutz Medical Campus, Aurora, Colorado

Department of Biomedical Engineering, University of Houston, Houston, Texas

Texas Heart Institute, Stem Cell Engineering Lab, Houston, Texas.

Submitted for consideration June 2017; accepted for publication in revised form January 2018.

Disclosure: The authors have no conflicts of interest to report.

This work was supported by NIH R01-EB011516.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML and PDF versions of this article on the journal’s Web site (www.asaiojournal.com).

Correspondence: Ravi K. Birla, Stem Cell Engineering Lab, Texas Heart Institute, 6770 Bertner Avenue, Houston, TX 77030. Email: rbirla@texasheart.org.

Copyright © 2018 by the American Society for Artificial Internal Organs