Construction of 3D printed constructs based on microfluidic microgel for bone regeneration
Construction of 3D printed constructs based on microfluidic microgel for bone regeneration
复制标题
基于微流控微凝胶的 3D 打印结构的构建用于骨再生
DOI：
10.1016/j.compositesb.2021.109100
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发表时间：
2021-06-29
影响因子：
13.1
通讯作者：
He, Chuanglong
中科院分区：
文献类型：
--
作者：
Chai, Ningwen;Zhang, Jingtian;He, Chuanglong
在利用三维生物打印技术构建组织工程化结构的过程中，挤出过程中的剪切力和交联光的照射对细胞活性有很大的影响。具有独立控制隔间的微凝胶被证明为细胞包埋提供保护。在这里，我们建议制备核壳结构的微凝胶用于细胞的封装，以防止挤出3D打印过程中剪切应力对细胞的破坏。采用一步创新的微流控技术，通过多通道微流控装置制备了以I型胶原为核心层、海藻酸盐为壳层的核壳结构微凝胶。在微流体参数中，醋酸浓度和水相与油相的流量比对微凝胶的形态和微囊化细胞的活力有明显的影响。合成了甲基丙烯酸化丝素蛋白(SILMA)和甲基丙烯酸明胶(GelMA)，并将其与细胞微凝胶共混作为生物墨水，制备了3D打印载体。随着Silma含量的增加，Silma/GelMA水凝胶的孔径减小，压缩性能提高。重要的是，与Silma/GelMA相比，含有微凝胶的Silma/GelMA结构确保了细胞增殖的改善。体内实验表明，与15%Silma/GelMA构建相比，微凝胶-15%Silma/GelMA构建具有良好的生物相容性和更好的成骨性能。因此，基于微流控技术制备细胞微凝胶以提高细胞在生物打印过程中的存活率的策略在组织工程构建中是可行和有效的。
For the fabrication of engineered tissue constructs by three-dimensional (3D) bioprinting technology, the cell viability will be significantly affected by the shear stress during extrusion process and the exposure of light for cross-linking. Microgels with independently controlled compartments were demonstrated to provide protection for cells encapsulation. Here, we proposed to prepare the core-shell structured microgels for cells encapsulation to prevent the cell damage from the shear stress in extrusion-based 3D printing processes. The core-shell structured microgels with core layer of type I collagen and shell layer of alginate were prepared using a onestep innovational microfluidics technology through a multichannel microfluidic device. In the microfluidic parameters, acetic acid concentration and flow rate ratios of water phase to oil phase were found to evidently affect the morphology of microgels and viability of encapsulated cells. Methacrylated silk fibroin (SilMA) and methacrylated gelatin (GelMA) were synthesized and blended with cell-laden microgels as bioinks to fabricate the 3Dprinted constructs. The increasing content of SilMA would decrease the pore size and increase the compression property of SilMA/GelMA hydrogels. Importantly, the microgels-containing SilMA/GelMA construct ensure the improved cell proliferation as compared to the SilMA/GelMA counterpart. Furthermore, the in vivo experiments demonstrated that Microgels-15%SilMA/GelMA construct exhibited good biocompatibility and better bone formation performance compared with 15%SilMA/GelMA construct. Therefore, the strategy of preparing cellladen microgels based on microfluidic technology to improve the survival rate of cells in the bioprinting process can be available and effective in development of tissue engineered constructs.