Engineering of thick human functional myocardium via static stretching and electrical stimulation

• Published in: iScience 2022-03, Vol.25 (3), p.103824-103824, Article 103824
• Main Authors: Pretorius, Danielle, Kahn-Krell, Asher M., LaBarge, Wesley C., Lou, Xi, Zhang, Jianyi
• Format: Article
• Language: English
• Subjects: Biomaterials; Biomedical Engineering; Materials science
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.103824

Human cardiac-muscle patches (hCMPs) constructed from induced pluripotent stem cells derived cardiomyocytes (iCMs) can replicate the genetics of individual patients, and consequently be used for drug testing, disease modeling, and therapeutic applications. However, conventional hCMPs are relatively thin and contain iCMs with fetal cardiomyocyte structure and function. Here, we used our layer-by-layer (lbl) fabrication to construct thicker (>2.1 mm), triple-layered hCMPs, and then evaluated iCM maturity after ten days of standard culture (Control), static stretching (Stretched), or stretching with electrical stimulation at 15 or 22 V (Stretched+15V or Stretched+22V). Assessments of stained hCMPs suggested that expression and alignment of contractile proteins was greater in Stretched+22V, whereas quantification of mRNA abundance and protein expression indicated the Stretched+22V enhanced biomolecular maturation. Transmission electron microscope images indicated that stretching and electrical stimulation were associated with increases in development of Z-lines and gap junctions, and sarcomeres were significantly longer following any of the maturation protocols. [Display omitted] •Thick (>2.1 mm) triple-layered hCMPs were constructed using layer-by-layer fabrication•Combined stretching and electrical stimulation improve hCMP biochemical maturation•Increased ultrastructural components were promoted by all stimulation methods Biomaterials; Biomedical Engineering; Materials science