Ren Xueqing, Wang Xin, Cai Xiaolu, Zou Yi, Chen Peng, Liu Bi-Feng, Li Yiwei
Key Laboratory of Molecular Biophysics of MOE and Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology - The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.
Lab Chip. 2025 Sep 9;25(18):4756-4764. doi: 10.1039/d5lc00467e.
Hydrogel microspheres, derived from natural or synthetic materials, serve as crucial platforms for three-dimensional (3D) cell culture and tissue engineering. While traditional production methods like emulsification and microfluidics are widely used, they often involve complex processes and oil phases that can compromise biocompatibility. Here, we present a novel centrifugal microfluidic device with an air gap for producing hydrogel microspheres. Centrifugal force provides a driving force for uniform parallel channels, enabling high-throughput microsphere generation while ensuring size uniformity. The system enables precise size control through centrifugal speed modulation, producing microspheres with diameters ranging from 140.6 ± 17.3 μm to 417.1 ± 34.4 μm with a coefficient of variation below 4.8%. The air gap within the microchannel establishes a step-structure that enables oil-free microsphere generation while ensuring biocompatibility. Moreover, by blending a collagen solution into sodium alginate as the matrix, oil-free microspheres with an interpenetrating polymer network (IPN) can be fabricated, which exhibit excellent biocompatibility to support the culture and adipogenic differentiation of mesenchymal stem cells (MSCs). When cells are cultured with a microsphere-formed scaffold, they exhibit aggregation behavior for enhanced cell-cell communication, which further elevated their adipogenic differentiation potential. Overall, this simplified, high-throughput approach offers a unique platform for applications in cell delivery, drug screening, and tissue engineering.
由天然或合成材料制成的水凝胶微球，是三维（3D）细胞培养和组织工程的关键平台。虽然乳化和微流控等传统生产方法被广泛使用，但它们通常涉及复杂的过程和油相，这可能会影响生物相容性。在此，我们展示了一种带有气隙的新型离心微流控装置，用于生产水凝胶微球。离心力为均匀的平行通道提供驱动力，实现高通量微球生成，同时确保尺寸均匀性。该系统通过调节离心速度实现精确的尺寸控制，生产出直径范围为140.6±17.3μm至417.1±34.4μm的微球，变异系数低于4.8%。微通道内的气隙形成了一种阶梯结构，能够实现无油微球生成，同时确保生物相容性。此外，通过将胶原蛋白溶液混入海藻酸钠作为基质，可以制备具有互穿聚合物网络（IPN）的无油微球，这些微球表现出优异的生物相容性，以支持间充质干细胞（MSC）的培养和脂肪生成分化。当细胞与微球形成的支架一起培养时，它们表现出聚集行为，以增强细胞间通讯，这进一步提高了它们的脂肪生成分化潜力。总体而言，这种简化的高通量方法为细胞递送、药物筛选和组织工程应用提供了一个独特的平台。
