Samal Pinak, Kumar Samal Jay Rabindra, Rho Hoon Suk, van Beurden Denis, van Blitterswijk Clemens, Truckenmüller Roman, Giselbrecht Stefan
MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Universiteitssingel 40, 6229 ER, Maastricht, the Netherlands.
Mepsgen Co., Ltd., 7F, Hanyang Tower, 12, Beobwon-ro-11-gil, Songpa-gu, Seoul, Republic of Korea.
Mater Today Bio. 2023 Aug 29;22:100779. doi: 10.1016/j.mtbio.2023.100779. eCollection 2023 Oct.
Microengineering is increasingly being used for controlling the microenvironment of stem cells. Here, a novel method for fabricating structures with subcellular dimensions in commonly available thermoplastic poly(methyl methacrylate) (PMMA) is shown. Microstructures are produced in PMMA substrates using Deep Ultraviolet lithography, and the effect of different developers is described. Microgrooves fabricated in PMMA are used for the neuronal differentiation of mouse embryonic stem cells (mESCs) directly on the polymer. The fabrication of 3D, curvilinear patterned surfaces is also highlighted. A 3D multilayered microfluidic chip is fabricated using this method, which includes a porous polycarbonate (PC) membrane as cell culture substrate. Besides directly manufacturing PMMA-based microfluidic devices, an application of the novel approach is shown where a reusable PMMA master is created for replicating microstructures with polydimethylsiloxane (PDMS). As an application example, microchannels fabricated in PDMS are used to selectively expose mESCs to soluble factors in a localized manner. The described microfabrication process offers a remarkably simple method to fabricate for example multifunctional topographical or microfluidic culture substrates outside cleanrooms, thereby using inexpensive and widely accessible equipment. The versatility of the underlying process could find various applications also in optical systems and surface modification of biomedical implants.
微工程技术越来越多地用于控制干细胞的微环境。本文展示了一种在常用热塑性聚甲基丙烯酸甲酯（PMMA）中制造具有亚细胞尺寸结构的新方法。利用深紫外光刻技术在PMMA基板上制备微结构，并描述了不同显影剂的效果。在PMMA中制造的微槽用于直接在聚合物上诱导小鼠胚胎干细胞（mESC）的神经元分化。本文还重点介绍了三维曲线图案化表面的制造。使用该方法制造了一种三维多层微流控芯片，其中包括一个多孔聚碳酸酯（PC）膜作为细胞培养基板。除了直接制造基于PMMA的微流控装置外，本文还展示了该新方法的一个应用，即创建一个可重复使用的PMMA母版，用于用聚二甲基硅氧烷（PDMS）复制微结构。作为一个应用实例，在PDMS中制造的微通道用于以局部方式将mESC选择性地暴露于可溶性因子。所描述的微制造工艺提供了一种非常简单的方法，例如可以在洁净室之外制造多功能地形或微流控培养基板，从而使用廉价且易于获得的设备。该基础工艺的多功能性在光学系统和生物医学植入物的表面改性中也可能有各种应用。
