Construction of 3D printed constructs based on microfluidic microgel for bone regeneration

Abstract 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 one-step 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 3D-printed 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 cell-laden 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.