Shenzhen Key Laboratory of Biomimetic Robotics and Intelligent Systems, Department of Mechanical and Energy Engineering, Southern University of Science and Technology, Shenzhen 518055, People's Republic of China.
Guangdong Provincial Key Laboratory of Human-Augmentation and Rehabilitation Robotics in Universities, Southern University of Science and Technology, Shenzhen 518055, China.
Biofabrication. 2022 Apr 5;14(2). doi: 10.1088/1758-5090/ac5e12.
Heterogeneous spheroids that mimic the complex three-dimensional environment of natural tissues are needed in various biomedical applications. Geometric cues from cellular matrix play invaluable roles in governing cell behavior and phenotype. However, the structural complexity of interior morphologies of spheroids is currently limited due to poor spatial resolution of positioning/orientation of cellular constructs. Here, a coaxial capillary microfluidic device is developed to generate gelatin methacrylate (GelMA) microspheres with tunable dimensions and interior morphologies, such as core-shell, or microspheres with interior undulated wavy, or spiral canals, by manipulating the two-phase flow of hydrogel precursor solution and methylcellulose solution. The formation of diverse and exquisite interior morphologies is caused by the interacting viscous instabilities of the two-phase flow in the microfluidic system, followed by water-in-oil emulsion and photo-initiated polymerization. Polyethylene glycol diacrylate (PEGDA) is incorporated into the GelMA solution to tune the mechanical properties of the fabricated microspheres, and an optimized concentration of PEGDA is confirmed by evaluating theproliferation and vascularization of human umbilical vein endothelial cells. Further, a heterogeneous spheroid with spiral blood vessel lumen is constructed to demonstrate the versatility and potential of the proposed droplet-based microfluidic approach for building functional tissue constructs.
需要在各种生物医学应用中使用模拟天然组织复杂三维环境的异质球体。细胞基质的几何线索在控制细胞行为和表型方面发挥着无价的作用。然而，由于细胞构建体的定位/取向的空间分辨率较差，球体的内部形态的结构复杂性目前受到限制。在这里，开发了一种同轴毛细管微流控装置，通过操纵水凝胶前体溶液和甲基纤维素溶液的两相流，可生成具有可调尺寸和内部形态（如核壳，或具有内部起伏的波浪形或螺旋形通道的微球）的明胶甲基丙烯酰胺（GelMA）微球。内部形态的多样性和精致性是由微流控系统中两相流的相互作用粘性不稳定性引起的，随后是水包油乳液和光引发聚合。聚乙二醇二丙烯酸酯（PEGDA）被掺入 GelMA 溶液中以调节所制造的微球的机械性能，并且通过评估人脐静脉内皮细胞的增殖和血管生成来确认 PEGDA 的最佳浓度。此外，构建了具有螺旋血管腔的异质球体，以展示基于液滴的微流控方法在构建功能性组织构建体方面的多功能性和潜力。
