A multifunctional micropore-forming bioink with enhanced anti-bacterial and anti-inflammatory properties.

Three-dimensional (3D) bioprinting has emerged as an enabling tool for various biomedical applications, such as tissue regeneration and tissue model engineering. To this end, the development of bioinks with multiple functions plays a crucial role in the applications of 3D bioprinting technologies. In this study, we propose a new bioink based on two immiscible aqueous phases of gelatin methacryloyl (GelMA) and dextran, further endowed with anti-bacterial and anti-inflammatory properties. This micropore-forming GelMA-dextran (PGelDex) bioink exhibited excellent printability with vat-polymerization, extrusion, and handheld bioprinting methods. The porous structure was confirmed after bioprinting, which promoted the spreading of the encapsulated cells, exhibiting the exceptional cytocompatibility of this bioink formulation. To extend the applications of such a micropore-forming bioink, interleukin-4 (IL-4)-loaded silver-coated gold nanorods (AgGNRs) and human mesenchymal stem cells (MSCs) were simultaneously incorporated, to display synergistic anti-infection behavior and immunomodulatory function. The results revealed the anti-bacterial properties of the AgGNR-loaded PGelDex bioink for both Gram-negative and Gram-positive bacteria. The data also indicated that the presence of IL-4 and MSCs facilitated macrophage M2-phenotype differentiation, suggesting the potential anti-inflammatory feature of the bioink. Overall, this unique anti-bacterial and immunomodulatory micropore-forming bioink offers an effective strategy for the inhibition of bacterial-induced infections as well as the ability of immune-regulation, which is a promising candidate for broadened tissue bioprinting applications.

Uniaxial and Coaxial Vertical Embedded Extrusion Bioprinting.

The 3D bioprinting technologies have attracted increasing attention due to their flexibility in producing architecturally relevant tissue constructs. Here, a vertical embedded extrusion bioprinting strategy using uniaxial or coaxial nozzles is presented, which allows formation of vertical structures of homogeneous or heterogeneous properties. By adjusting the bioprinting parameters, the characteristics of the bioprinted vertical patterns can be precisely controlled. Using this strategy, two proof-of-concept applications in tissue biofabrication are demonstrated. Specifically, intestinal villi and hair follicles, two liner-shaped tissues in the human body, are successfully generated with the vertical embedded bioprinting method, reconstructing some of their key structures as well as restoring partial functions in vitro. Caco-2 cells in the bioprinted intestinal villus constructs proliferated and aggregated properly, also showing functional biomarker expressions such as ZO-1 and villin. Moreover, preliminary hair follicle structures featuring keratinized human keratinocytes and spheroid-shaped human dermal papilla cells are formed after vertical bioprinting and culturing. In summary, this vertical embedded extrusion bioprinting technique harnessing a uniaxial or coaxial format will likely bring further improvements in the reconstruction of certain human tissues and organs, especially those with a linear structure, potentially leading to wide utilities in tissue engineering, tissue model engineering, and drug discovery.