Integrated Manufacturing of Suspended and Aligned Nanofibrous Scaffold for Structural Maturation and Synchronous Contraction of HiPSC-Derived Cardiomyocytes

Liu, Lingling; Xu, Feng; Qiu, Bin; Yang, Jianhui; Zhang, Wangzihan; Gao, Qiang; Bai, Lin; Chen, Songyue; Sun, Dao Heng

doi:10.3390/bioengineering10060702

Cited by 10 publications

(4 citation statements)

References 57 publications

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“…The maturation of cardiomyocytes is influenced by the substrate’s topography, mechanics, and electroconductivity. ,, Aligned fibers facilitated the alignment and interactions of cardiomyocytes and were more elongated. , NRCM and hiPSC-CMs revealed the high degree of uniformity that arises from the aligned fibrous morphology (Figures C and ). Cardiomyocytes cultured on the conductive membranes (PU-rGO) exhibited signs of maturation and improved functionality compared to nonconductive membranes (PU).…”

Section: Discussionmentioning

confidence: 99%

Reduced Graphene-Oxide-Doped Elastic Biodegradable Polyurethane Fibers for Cardiomyocyte Maturation

Taylor,

Xu,

Rogozinski

et al. 2024

ACS Biomater. Sci. Eng.

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Conductive biomaterials offer promising solutions to enhance the maturity of cultured cardiomyocytes. While the conventional culture of cardiomyocytes on nonconductive materials leads to more immature characteristics, conductive microenvironments have the potential to support sarcomere development, gap junction formation, and beating of cardiomyocytes in vitro. In this study, we systematically investigated the behaviors of cardiomyocytes on aligned electrospun fibrous membranes composed of elastic and biodegradable polyurethane (PU) doped with varying concentrations of reduced graphene oxide (rGO). Compared to PU and PU-4%rGO membranes, the PU-10%rGO membrane exhibited the highest conductivity, approaching levels close to those of native heart tissue. The PU-rGO membranes retained anisotropic viscoelastic behavior similar to that of the porcine left ventricle and a superior tensile strength. Neonatal rat cardiomyocytes (NRCMs) and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on the PU-rGO membranes displayed enhanced maturation with cell alignment and enhanced sarcomere structure and gap junction formation with PU-10%rGO having the most improved sarcomere structure and CX-43 presence. hiPSC-CMs on the PU-rGO membranes exhibited a uniform and synchronous beating pattern compared with that on PU membranes. Overall, PU-10%rGO exhibited the best performance for cardiomyocyte maturation. The conductive PU-rGO membranes provide a promising matrix for in vitro cardiomyocyte culture with promoted cell maturation/functionality and the potential for cardiac disease treatment.

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Section: Discussionmentioning

confidence: 99%

Reduced Graphene-Oxide-Doped Elastic Biodegradable Polyurethane Fibers for Cardiomyocyte Maturation

Taylor,

Xu,

Rogozinski

et al. 2024

ACS Biomater. Sci. Eng.

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“…Cells were cultured at 37 °C with 5% CO 2 and the culture medium was changed every day. Cell proliferation was analyzed by CCK-8 according to our previous work . hiPSC-derived cardiomyocytes were cultured and purified according to our previous publication .…”

Section: Methodsmentioning

confidence: 99%

3D Aligned Nanofiber Scaffold Fabrication with Trench-Guided Electrospinning for Cardiac Tissue Engineering

Qiu,

Wu,

Xue

et al. 2024

Langmuir

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Constructing three-dimensional (3D) aligned nanofiber scaffolds is significant for the development of cardiac tissue engineering, which is promising in the field of drug discovery and disease mechanism study. However, the current nanofiber scaffold preparation strategy, which mainly includes manual assembly and hybrid 3D printing, faces the challenge of integrated fabrication of morphology-controllable nanofibers due to its cross-scale structural feature. In this research, a trench-guided electrospinning (ES) strategy was proposed to directly fabricate 3D aligned nanofiber scaffolds with alternative ES and a direct ink writing (DIW) process. The electric field effect of DIW poly(dimethylsiloxane) (PDMS) side walls on guiding whipping ES nanofibers was investigated to construct trench design rules. It was found that the width/height ratio of trenches greatly affected the nanofiber alignment, and the trench width/height ratio of 1.5 provided the nanofiber alignment degree over 60%. As a proof of principle, 3D nanofiber scaffolds with controllable porosity (60−80%) and alignment (30−60%) were fabricated. The effect of the scaffolds was verified by culturing human-induced pluripotent stem cellderived cardiomyocytes (hiPSC-CMs), which resulted in the uniform 3D distribution of aligned hiPSC-CMs with ∼1000 μm thickness. Therefore, this printing strategy shows great potential for the efficient engineered tissue construction.

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“…The hiPSCs were labeled with green fluorescent by introducing an EGFP expressional element in an AAVS1 locus. HiPSC-CMs were cultured according to previous publications 38 , 39 .…”

Section: Methodsmentioning

confidence: 99%

Digital light processing printed hydrogel scaffolds with adjustable modulus

Xu,

Jin,

et al. 2024

Sci Rep

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Hydrogels are extensively explored as biomaterials for tissue scaffolds, and their controlled fabrication has been the subject of wide investigation. However, the tedious mechanical property adjusting process through formula control hindered their application for diverse tissue scaffolds. To overcome this limitation, we proposed a two-step process to realize simple adjustment of mechanical modulus over a broad range, by combining digital light processing (DLP) and post-processing steps. UV-curable hydrogels (polyacrylamide-alginate) are 3D printed via DLP, with the ability to create complex 3D patterns. Subsequent post-processing with Fe3+ ions bath induces secondary crosslinking of hydrogel scaffolds, tuning the modulus as required through soaking in solutions with different Fe3+ concentrations. This innovative two-step process offers high-precision (10 μm) and broad modulus adjusting capability (15.8–345 kPa), covering a broad range of tissues in the human body. As a practical demonstration, hydrogel scaffolds with tissue-mimicking patterns were printed for cultivating cardiac tissue and vascular scaffolds, which can effectively support tissue growth and induce tissue morphologies.

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Integrated Manufacturing of Suspended and Aligned Nanofibrous Scaffold for Structural Maturation and Synchronous Contraction of HiPSC-Derived Cardiomyocytes

Cited by 10 publications

References 57 publications

Reduced Graphene-Oxide-Doped Elastic Biodegradable Polyurethane Fibers for Cardiomyocyte Maturation

Reduced Graphene-Oxide-Doped Elastic Biodegradable Polyurethane Fibers for Cardiomyocyte Maturation

3D Aligned Nanofiber Scaffold Fabrication with Trench-Guided Electrospinning for Cardiac Tissue Engineering

Digital light processing printed hydrogel scaffolds with adjustable modulus

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