Nouri-Goushki Mahdiyeh, Sharma Abhishek, Sasso Luigi, Zhang Shuang, Van der Eerden Bram C J, Staufer Urs, Fratila-Apachitei Lidy E, Zadpoor Amir A
Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD Delft, The Netherlands.
Department of Precision and Microsystems Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD Delft, The Netherlands.
ACS Biomater Sci Eng. 2019 Nov 11;5(11):6127-6136. doi: 10.1021/acsbiomaterials.9b01155. Epub 2019 Oct 14.
Manufacturing high throughput in vitro models resembling the tissue microenvironment is highly demanded for studying bone regeneration. Tissues such as bone have complex multiscale architectures inside which cells reside. To this end, engineering a microfluidic platform incorporated with three-dimensional (3D) microscaffolds and submicron/nanoscale topographies can provide a promising model for 3D cell cultures. There are, however, certain challenges associated with this goal, such as the need to decorate large surfaces area with high-fidelity 3D submicron structures. Here, we succeeded in fabricating a microfluidic platform embedded with a large area (mm range) of reproducible submicron pillar-based topographies. Using the two-photon polymerization (2PP) as a 3D printing technique based on direct laser writing, uniform submicron patterns were created through optimization of the process parameters and writing strategy. To demonstrate the multiscale fabrication capabilities of this approach, submicron pillars of various heights were integrated onto the surfaces of a 3D microscaffold in a single-step 2PP process. The created submicron topography was also found to improve the hydrophilicity of the surface while being able to withstand flow rates of up to 8 mL/min. The material (IP-Dip resin) used for patterning did not have cytotoxic effects against human mesenchymal stromal cells after 3 days of dynamic culture in the microfluidic device. This proof-of-principle study, therefore, marks a significant step forward in manufacturing submicron structure-on-a-chip models for bone regeneration studies.
为了研究骨再生，制造类似于组织微环境的高通量体外模型的需求十分迫切。诸如骨骼之类的组织具有复杂的多尺度结构，细胞就存在于其中。为此，设计一个结合三维（3D）微支架和亚微米/纳米级拓扑结构的微流控平台，可以为3D细胞培养提供一个有前景的模型。然而，实现这一目标存在一些挑战，比如需要用高保真的3D亚微米结构装饰大面积表面。在此，我们成功制造了一个嵌入大面积（毫米级）可重复的基于亚微米柱的拓扑结构的微流控平台。使用双光子聚合（2PP）作为基于直接激光写入的3D打印技术，通过优化工艺参数和写入策略创建了均匀的亚微米图案。为了证明这种方法的多尺度制造能力，在单步2PP工艺中将各种高度的亚微米柱集成到3D微支架的表面上。还发现所创建的亚微米拓扑结构提高了表面的亲水性，同时能够承受高达8 mL/min的流速。在微流控装置中进行3天动态培养后，用于图案化的材料（IP-Dip树脂）对人间充质基质细胞没有细胞毒性作用。因此，这项原理验证研究标志着在制造用于骨再生研究的亚微米级芯片模型方面向前迈出了重要一步。
