Direct cell writing of 3D microorgan for in vitro pharmacokinetic model
Direct cell writing of 3D microorgan for in vitro pharmacokinetic model
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DOI：
10.1089/ten.tec.2007.0392
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发表时间：
2008-06-01
影响因子：
3
通讯作者：
Sun, Wei
中科院分区：
文献类型：
--
作者：
Chang, Robert;Nam, Yae;Sun, Wei
组织工程的一个新的有针对性的应用是开发用于药物筛选和毒理学的体外药代动力学模型。需要体外药代动力学模型来真实可靠地预测人体对药物给药和潜在毒性暴露的体内反应。本文详细介绍了微流体装置的制造工艺开发和适应，以创建这种生理相关的药代动力学模型。首先，基于自动化注射器的分层直接细胞写入 (DCW) 生物打印工艺创建了一个 3D 微器官，该微器官仿生细胞的自然微环境并具有增强的功能。接下来，使用软光刻微图案技术来制造微型体外装置来容纳 3D 微生物。本文展示了 DCW 工艺的可行性，用于自由形式生物制造具有定义的可重复模式的 3D 细胞封装的水凝胶基组织结构、将 3D 结构直接集成到微流体装置上以实现连续灌注药物流、以及具有可预测的细胞活力/增殖结果和比传统培养方法增强的功能的 3D 组织结构的表征。
A novel targeted application of tissue engineering is the development of an in vitro pharmacokinetic model for drug screening and toxicology. An in vitro pharmacokinetic model is needed to realistically and reliably predict in vivo human response to drug administrations and potential toxic exposures. This paper details the fabrication process development and adaptation of microfluidic devices for the creation of such a physiologically relevant pharmacokinetic model. First, an automated syringe-based, layered direct cell writing (DCW) bioprinting process creates a 3D microorgan that biomimics the cell's naturalmicroenvironment with enhanced functionality. Next, soft lithographic micropatterning techniques are used to fabricate a microscale in vitro device to house the 3D microorgan. This paper demonstrates the feasibility of the DCW process for freeform biofabrication of 3D cell-encapsulated hydrogel-based tissue constructs with defined reproducible patterns, direct integration of 3D constructs onto a microfluidic device for continuous perfusion drug flow, and characterization of 3D tissue constructs with predictable cell viability/proliferation outcomes and enhanced functionality over traditional culture methods.