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基于生物打印的海藻酸盐心脏植入物的电学/力学性能:特征描述和体外相衬微断层扫描评估。

Bioprinting Pattern-Dependent Electrical/Mechanical Behavior of Cardiac Alginate Implants: Characterization and Ex Vivo Phase-Contrast Microtomography Assessment.

机构信息

1 Division of Biomedical Engineering, College of Engineering, University of Saskatchewan , Saskatoon, Canada .

2 Department of Surgery, College of Medicine, University of Saskatchewan , Saskatoon, Canada .

出版信息

Tissue Eng Part C Methods. 2017 Sep;23(9):548-564. doi: 10.1089/ten.TEC.2017.0222. Epub 2017 Aug 23.

Abstract

Three-dimensional (3D)-bioprinting techniques may be used to modulate electrical/mechanical properties and porosity of hydrogel constructs for fabrication of suitable cardiac implants. Notably, characterization of these properties after implantation remains a challenge, raising the need for the development of novel quantitative imaging techniques for monitoring hydrogel implant behavior in situ. This study aims at (i) assessing the influence of hydrogel bioprinting patterns on electrical/mechanical behavior of cardiac implants based on a 3D-printing technique and (ii) investigating the potential of synchrotron X-ray phase-contrast imaging computed tomography (PCI-CT) for estimating elastic modulus/impedance/porosity and microstructural features of 3D-printed cardiac implants in situ via an ex vivo study. Alginate laden with human coronary artery endothelial cells was bioprinted layer by layer, forming cardiac constructs with varying architectures. The elastic modulus, impedance, porosity, and other structural features, along with the cell viability and degradation of printed implants were examined in vitro over 25 days. Two selected cardiac constructs were surgically implanted onto the myocardium of rats and 10 days later, the rat hearts with implants were imaged ex vivo by means of PCI-CT at varying X-ray energies and CT-scan times. The elastic modulus/impedance, porosity, and structural features of the implant were inferred from the PCI-CT images by using statistical models and compared with measured values. The printing patterns had significant effects on implant porosity, elastic modulus, and impedance. A particular 3D-printing pattern with an interstrand distance of 900 μm and strand alignment angle of 0/45/90/135° provided relatively higher stiffness and electrical conductivity with a suitable porosity, maintaining high cell viability over 7 days. The X-ray photon energy of 30-33 keV utilizing a CT-scan time of 1-1.2 h resulted in a low-dose PCI-CT, which provided a good visibility of the low-X-ray absorbent alginate implants. After 10 days postimplantation, the PCI-CT provided a reasonably accurate estimation of implant strand thickness and alignment, pore size and interconnectivity, porosity, elastic modulus, and impedance, which were consistent with our measurements. Findings from this study suggest that 3D-printing patterns can be used to modulate electrical/mechanical behavior of alginate implants, and PCI-CT can be potentially used as a 3D quantitative imaging tool for assessing structural and electrical/mechanical behavior of hydrogel cardiac implants in small animal models.

摘要

三维(3D)生物打印技术可用于调节水凝胶结构的电学/力学性能和孔隙率,以制造合适的心脏植入物。值得注意的是,植入后这些特性的表征仍然是一个挑战,这就需要开发新的定量成像技术来原位监测水凝胶植入物的行为。本研究旨在:(i)评估基于 3D 打印技术的水凝胶生物打印图案对心脏植入物电学/力学行为的影响;(ii)通过离体研究,探讨同步加速器 X 射线相衬成像计算机断层扫描(PCI-CT)在原位估计 3D 打印心脏植入物弹性模量/阻抗/孔隙率和微观结构特征的潜力。将载有人冠状动脉内皮细胞的藻酸盐逐层打印,形成具有不同结构的心脏结构。在体外培养 25 天内,检查了弹性模量、阻抗、孔隙率和其他结构特征以及打印植入物的细胞活力和降解情况。将两种选定的心脏结构体通过手术植入大鼠心肌中,10 天后,通过 PCI-CT 在不同的 X 射线能量和 CT 扫描时间下对植入大鼠心脏进行离体成像。通过统计模型从 PCI-CT 图像中推断出植入物的弹性模量/阻抗、孔隙率和结构特征,并与测量值进行比较。打印图案对植入物的孔隙率、弹性模量和阻抗有显著影响。具有 900 μm 相间距离和 0/45/90/135° 链取向角的特定 3D 打印图案提供了相对较高的刚度和导电性,同时保持了 7 天以上的高细胞活力。利用 1-1.2 h 的 CT 扫描时间,X 射线光子能量为 30-33 keV 的低剂量 PCI-CT 提供了低 X 射线吸收率藻酸盐植入物的良好可见度。植入后 10 天,PCI-CT 可以合理准确地估计植入物的链厚度和取向、孔径和连通性、孔隙率、弹性模量和阻抗,与我们的测量结果一致。本研究结果表明,3D 打印图案可用于调节藻酸盐植入物的电学/力学行为,PCI-CT 可能可作为一种用于评估小动物模型中水凝胶心脏植入物结构和电学/力学行为的 3D 定量成像工具。

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