Characterizing the Process Physics of Ultrasound-Assisted Bioprinting
Characterizing the Process Physics of Ultrasound-Assisted Bioprinting
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DOI：
10.1038/s41598-019-50449-w
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发表时间：
2019-09-25
影响因子：
4.6
通讯作者：
Shirwaiker, Rohan
中科院分区：
文献类型：
--
作者：
Chansoria, Parth;Shirwaiker, Rohan
3D生物打印已经发展成为临床、诊断和研究应用的工程组织制造的重要策略。生物打印的一个主要优点是能够利用细胞生物墨水再现患者特异性组织的宏观结构。生物打印的有效性可以通过在3D结构中优先组织细胞成分的能力来显著增强，以模仿天然组织的内在微结构特征。因此，这项工作的重点是一种新的非接触和无标签的方法，称为超声辅助生物打印（UAB），它利用声阻抗原理来排列生物打印结构中的细胞。我们描述了潜在的过程物理，并开发和验证了计算模型，以确定超声过程参数（激励模式，激励时间，频率，电压幅值）对相关温度，压力分布和对准时间特性的影响。利用计算模型的知识，我们实验研究了选择的工艺参数（频率、电压振幅）对海藻酸盐中MG63细胞的关键质量属性（细胞链宽度、链间间距和活力）的影响，作为模型生物链接系统。最后，我们展示了具有平行（0度-0度）和正交（0度-90度）细胞跨层排列的双层结构的UAB。这项工作的结果突出了UAB工艺设计与排列细胞结构特征之间的关键相互作用，并代表了我们创建仿生工程组织的重要下一步。
3D bioprinting has been evolving as an important strategy for the fabrication of engineered tissues for clinical, diagnostic, and research applications. A major advantage of bioprinting is the ability to recapitulate the patient-specific tissue macro-architecture using cellular bioinks. The effectiveness of bioprinting can be significantly enhanced by incorporating the ability to preferentially organize cellular constituents within 3D constructs to mimic the intrinsic micro-architectural characteristics of native tissues. Accordingly, this work focuses on a new non-contact and label-free approach called ultrasound-assisted bioprinting (UAB) that utilizes acoustophoresis principle to align cells within bioprinted constructs. We describe the underlying process physics and develop and validate computational models to determine the effects of ultrasound process parameters (excitation mode, excitation time, frequency, voltage amplitude) on the relevant temperature, pressure distribution, and alignment time characteristics. Using knowledge from the computational models, we experimentally investigate the effect of selected process parameters (frequency, voltage amplitude) on the critical quality attributes (cellular strand width, inter-strand spacing, and viability) of MG63 cells in alginate as a model bioink system. Finally, we demonstrate the UAB of bilayered constructs with parallel (0 degrees-0 degrees) and orthogonal (0 degrees-90 degrees) cellular alignment across layers. Results of this work highlight the key interplay between the UAB process design and characteristics of aligned cellular constructs, and represent an important next step in our ability to create biomimetic engineered tissues.