Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH 43210, USA.
Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA.
Lab Chip. 2024 Oct 22;24(21):5065-5076. doi: 10.1039/d4lc00565a.
Blood and lymphatic vessels in the body are central to molecular and cellular transport, tissue repair, and pathophysiology. Several approaches have been employed for engineering microfabricated blood and lymphatic vessels , yet traditionally these approaches require specialized equipment, facilities, and research training beyond the capabilities of many biomedical laboratories. Here we present xurography as an inexpensive, accessible, and versatile rapid prototyping technique for engineering cylindrical and lumenized microvessels. Using a benchtop xurographer, or a cutting plotter, we fabricated modular multi-layer poly(dimethylsiloxane) (PDMS)-based microphysiological systems (MPS) that house endothelial-lined microvessels approximately 260 μm in diameter embedded within a user-defined 3-D extracellular matrix (ECM). We validated the vascularized MPS (or vessel-on-a-chip) by quantifying changes in blood vessel permeability due to the pro-angiogenic chemokine CXCL12. Moreover, we demonstrated the reconfigurable versatility of this approach by engineering a total of four distinct vessel-ECM arrangements, which were obtained by only minor adjustments to a few steps of the fabrication process. Several of these arrangements, such as ones that incorporate close-ended vessel structures and spatially distinct ECM compartments along the same microvessel, have not been widely achieved with other microfabrication strategies. Therefore, we anticipate that our low-cost and easy-to-implement fabrication approach will facilitate broader adoption of MPS with customizable vascular architectures and ECM components while reducing the turnaround time required for iterative designs.
体内的血液和淋巴管是分子和细胞运输、组织修复和病理生理学的核心。已经采用了几种方法来工程微制造的血管和淋巴管，但传统上这些方法需要专门的设备、设施和研究培训，超出了许多生物医学实验室的能力。在这里，我们提出 xurography 作为一种廉价、易于获得和通用的快速原型制作技术，用于工程圆柱形和有腔的微血管。使用台式 xurographer 或切割绘图仪，我们制造了模块化多层聚二甲基硅氧烷 (PDMS) 基微生理系统 (MPS)，其中包含约 260 µm 直径的内皮衬里微血管，嵌入用户定义的 3-D 细胞外基质 (ECM) 中。我们通过量化血管生成趋化因子 CXCL12 引起的血管通透性变化来验证血管化 MPS(或芯片上的血管)。此外，我们通过仅对制造过程的几个步骤进行微小调整，就实现了总共四种不同的血管-ECM 排列，从而证明了这种方法的可重构多功能性。其中一些排列，例如包含封闭端血管结构和沿同一微血管具有空间不同的 ECM 隔室的排列，尚未通过其他微制造策略广泛实现。因此，我们预计我们的低成本和易于实施的制造方法将促进具有可定制血管结构和 ECM 成分的 MPS 的更广泛采用，同时减少迭代设计所需的周转时间。
