Anisotropic microfibrous scaffolds enhance the organization and function of cardiomyocytes derived from induced pluripotent stem cells

Abstract

Engineering of myocardial tissue constructs is a promising approach for treatment of coronary heart disease. To engineer myocardial tissues that better mimic the highly ordered physiological arrangement and function of native cardiomyocytes, we generated electrospun microfibrous polycaprolactone scaffolds with either randomly oriented (14-µm fiber diameter) or parallel-aligned (7-µm fiber diameter) microfiber arrangement and co-seeded the scaffolds with human induced pluripotent stem cell-derived cardiomyocytes (iCMs) and endothelial cells (iECs) for up to 12 days after iCM seeding. Here we demonstrated that aligned microfibrous scaffolds induced iCM alignment along the direction of the aligned microfibers after 2 days of iCM seeding, as well as promoted greater iCM maturation by increasing the sarcomeric length and gene expression of myosin heavy chain adult isoform (MYH7), in comparison to randomly oriented scaffolds. Furthermore, the benefit of scaffold anisotropy was evident in the significantly higher maximum contraction velocity of iCMs on the aligned scaffolds, compared to randomly oriented scaffolds, at 12 days of culture. Co-seeding of iCMs with iECs led to reduced contractility, compared to when iCMs were seeded alone. These findings demonstrate an dominant role of scaffold anisotropy in engineering cardiovascular tissues that maintain iCM organization and contractile function.

Tendon Biomimetic Electrospun PLGA Fleeces Induce an Early Epithelial-Mesenchymal Transition and Tenogenic Differentiation on Amniotic Epithelial Stem Cells

“…Indeed, after only 48 h culture, oAECs were influenced by the topology of the fleece and acquired a spindle tenocyte-like shape, whereas in randomly oriented fiber rd-PLGA fleeces, used as control, the cells retained their native morphology. As supported by prior studies, the findings herein presented confirm that the aligned direction of fibers leads to a cell alignment and organization along the fiber arrangement [14,47,51,[68][69][70].…”

Combining Stem Cells and Biomaterial Scaffolds for Constructing Tissues and Cell Delivery

“…Poly caprolactone (PCL), a popular low-cost polymer with an extended degradation rate, can be used to form a wide range of scaffolds with different properties, including novel topographies and controlled release, for applications in tissue engineering as reviewed recently [230]. These scaffolds are often fabricated using both solution and melt electrospinning, and then seeded with stem cells to engineer tissues, including cartilage, nerve, muscle, and bone [231][232][233][234][235]. Figure 5 shows an example of how such scaffolds can be combined with adipose-derived stem cells to produce fat tissue as well as how topographical cues can influence stem cell behavior [236].…”

Aligned electrospun cellulose scaffolds coated with rhBMP-2 for both in vitro and in vivo bone tissue engineering

“…The change in cell adhesion and elongated cellular morphology on nanofibrous scaffolds can be explained by the classical theory of contact guidance (Jamaiyar et al, 2017). Aligned nanofibers have recently been explored to employ spatial instruction for different stem cells types, such as endothelial cells (Chou et al, 2017), neuronal cells (Hyysalo, Ristola, Joki, Honkanen, Vippola & Narkilahti, 2017), cardiomyocytes (Wanjare, Hou, Nakayama, Kim, Mezak & Abilez, 2017), and BMSCs (Perikamana et al, 2015). When BMSCs were cultured on aligned poly(L-lactic acid) (PLLA) nanofibers, the same morphological changes were observed as we reported (Perikamana et al, 2015).…”