Alan Taylor, Jiazhu Xu, Nicholas Rogozinski, Huikang Fu, Lia Molina Cortez, Sara McMahan, Karla Perez, Yan Chang, Zui Pan, Huaxiao Yang, Jun Liao and Yi Hong*,
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引用次数: 0
摘要
导电生物材料为提高培养心肌细胞的成熟度提供了前景广阔的解决方案。传统的在非导电材料上培养心肌细胞会导致更多不成熟特征,而导电微环境则有可能支持体外心肌细胞的肌节发育、间隙连接形成和搏动。在这项研究中,我们系统地研究了心肌细胞在由掺有不同浓度还原氧化石墨烯(rGO)的弹性和可生物降解聚氨酯(PU)组成的排列整齐的电纺纤维膜上的行为。与 PU 膜和 PU-4%rGO 膜相比,PU-10%rGO 膜的电导率最高,接近原生心脏组织的电导率水平。PU-rGO 膜保持了与猪左心室相似的各向异性粘弹性行为和卓越的拉伸强度。PU-rGO膜上的新生大鼠心肌细胞(NRCMs)和人类诱导多能干细胞衍生的心肌细胞(hiPSC-CMs)显示出更高的成熟度,细胞排列整齐,肌节结构和间隙连接形成增强,其中PU-10%rGO的肌节结构和CX-43的存在得到最大改善。总体而言,PU-10%rGO 在心肌细胞成熟方面表现最佳。导电 PU-rGO 膜为体外心肌细胞培养提供了一种前景广阔的基质,促进了细胞的成熟/功能,并具有治疗心脏疾病的潜力。
Reduced Graphene-Oxide-Doped Elastic Biodegradable Polyurethane Fibers for Cardiomyocyte Maturation
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.
期刊介绍:
ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics:
Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology
Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions
Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis
Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering
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Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials
Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture