School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ 85287, USA.
Department of Physics, Arizona State University, Tempe, AZ 85287, USA; Center for Biological Physics, Arizona State University, Tempe, AZ 85287, USA.
Acta Biomater. 2016 Sep 1;41:133-46. doi: 10.1016/j.actbio.2016.05.027. Epub 2016 May 20.
The development of advanced biomaterials is a crucial step to enhance the efficacy of tissue engineering strategies for treatment of myocardial infarction. Specific characteristics of biomaterials including electrical conductivity, mechanical robustness and structural integrity need to be further enhanced to promote the functionalities of cardiac cells. In this work, we fabricated UV-crosslinkable gold nanorod (GNR)-incorporated gelatin methacrylate (GelMA) hybrid hydrogels with enhanced material and biological properties for cardiac tissue engineering. Embedded GNRs promoted electrical conductivity and mechanical stiffness of the hydrogel matrix. Cardiomyocytes seeded on GelMA-GNR hybrid hydrogels exhibited excellent cell retention, viability, and metabolic activity. The increased cell adhesion resulted in abundance of locally organized F-actin fibers, leading to the formation of an integrated tissue layer on the GNR-embedded hydrogels. Immunostained images of integrin β-1 confirmed improved cell-matrix interaction on the hybrid hydrogels. Notably, homogeneous distribution of cardiac specific markers (sarcomeric α-actinin and connexin 43), were observed on GelMA-GNR hydrogels as a function of GNRs concentration. Furthermore, the GelMA-GNR hybrids supported synchronous tissue-level beating of cardiomyocytes. Similar observations were also noted by, calcium transient assay that demonstrated the rhythmic contraction of the cardiomyocytes on GelMA-GNR hydrogels as compared to pure GelMA. Thus, the findings of this study clearly demonstrated that functional cardiac patches with superior electrical and mechanical properties can be developed using nanoengineered GelMA-GNR hybrid hydrogels.
In this work, we developed gold nanorod (GNR) incorporated gelatin-based hydrogels with suitable electrical conductivity and mechanical stiffness for engineering functional cardiac tissue constructs (e.g. cardiac patches). The synthesized conductive hybrid hydrogels properly accommodated cardiac cells and subsequently resulted in excellent cell retention, spreading, homogeneous distribution of cardiac specific markers, cell-cell coupling as well as robust synchronized (tissue-level) beating behavior.
开发先进的生物材料是增强组织工程策略治疗心肌梗死疗效的关键步骤。生物材料的特定特性，包括导电性、机械强度和结构完整性，需要进一步增强，以促进心脏细胞的功能。在这项工作中，我们制备了具有增强的材料和生物学特性的可紫外光交联的金纳米棒（GNR）掺入的明胶甲基丙烯酯（GelMA）杂化水凝胶，用于心脏组织工程。嵌入的 GNR 提高了水凝胶基质的导电性和机械刚度。在 GelMA-GNR 杂化水凝胶上接种的心肌细胞表现出优异的细胞保留、活力和代谢活性。增加的细胞黏附导致局部组织的 F-肌动蛋白纤维丰富，导致在嵌入 GNR 的水凝胶上形成整合的组织层。整合素 β-1 的免疫染色图像证实了在杂化水凝胶上改善了细胞-基质相互作用。值得注意的是，作为 GNR 浓度的函数，在 GelMA-GNR 水凝胶上观察到心脏特异性标志物（肌节α-肌动蛋白和连接蛋白 43）的均匀分布。此外，GelMA-GNR 杂化还支持心肌细胞的同步组织水平跳动。通过钙瞬变测定也观察到类似的观察结果，表明与纯 GelMA 相比，GelMA-GNR 水凝胶上的心肌细胞具有节律性收缩。因此，这项研究的结果清楚地表明，可以使用纳米工程化的 GelMA-GNR 杂化水凝胶来开发具有优异的电和机械性能的功能性心脏贴片。
在这项工作中，我们开发了具有适当导电性和机械刚度的金纳米棒（GNR）掺入的基于明胶的水凝胶，用于工程功能性心脏组织构建体（例如心脏贴片）。合成的导电杂化水凝胶适当容纳心脏细胞，随后导致优异的细胞保留、扩展、心脏特异性标志物的均匀分布、细胞-细胞偶联以及稳健的同步（组织水平）跳动行为。
