Scalable High-Throughput Production of Modular Microgels for In Situ Assembly of Microporous Tissue Scaffolds
Scalable High-Throughput Production of Modular Microgels for In Situ Assembly of Microporous Tissue Scaffolds
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DOI：
10.1002/adfm.201900071
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发表时间：
2019-06-01
影响因子：
19
通讯作者：
Di Carlo, Dino
中科院分区：
文献类型：
--
作者：
de Rutte, Joseph Michael;Koh, Jaekyung;Di Carlo, Dino
水凝胶支架的模板组织结构的再生被广泛探索;然而，通常有一个权衡之间的材料性能，如刚度和互连的孔径，这可能是同样重要的支持组织生长。引入微孔退火颗粒支架以解决这种权衡，同时保持可流动的前体;然而，水凝胶微粒构建块的制造通量、再现性和灵活性是有限的，阻碍了广泛采用。介绍了用于原位形成微孔组织支架的生物活性微凝胶的可扩展的高通量生产。使用并行化的分步乳化装置，实现了单分散微凝胶的可扩展的高通量生成。通过溶解在油相中的质子受体使用pH调节在液滴产生的下游引发交联。这种方法能够连续生产超过12小时的微凝胶，同时确保高度均匀的物理化学性质。使用这个平台，局部基质刚度对细胞生长正交支架孔隙率的影响进行了研究。还证明了可注射的载有细胞的机械异质微孔支架的形成。这种方法特别适合于原位形成模块化的多材料支架，可以应用于3D生物打印或形成更复杂的支架，以增强不规则伤口的再生。
Hydrogel scaffolds that template the regeneration of tissue structures are widely explored; however, there is often a trade-off between material properties, such as stiffness and interconnected pore size, that may be equally important in supporting tissue growth. Microporous annealed particle scaffolds are introduced to address this trade-off while maintaining a flowable precursor; however, manufacturing throughput, reproducibility, and flexibility of hydrogel microparticle building blocks are limited, hindering widespread adoption. The scalable high-throughput production of bioactive microgels for the formation of microporous tissue scaffolds in situ is presented. Using a parallelized step emulsification device, scalable high-throughput generation of monodisperse microgels is achieved. Crosslinking is initiated downstream of droplet generation using pH modulation via proton acceptors dissolved in the oil phase. This approach enables continuous production of microgels for over 12 h while ensuring highly uniform physicochemical properties. Using this platform, the effects of local matrix stiffness on cell growth orthogonal to scaffold porosity are studied. Formation of injectable cell-laden mechanically heterogeneous microporous scaffolds is also demonstrated. This approach is particularly suited for the formation of modular, multimaterial scaffolds in situ, which could be applied to 3D bioprinting or to form more complex scaffolds to enhance regeneration of irregular wounds.