Updated: Apr 7
Achieving high viability and intrinsic function of the cells mixed in the hydrogel are goals to be pursued during a bioprinting process. Several printing techniques are being studied and improved to fabricate 3D living constructs, such as inkjet-based bioprinting, laser-assisted bioprinting, and pressure-assisted bioprinting. Each method has its advantages and limitations [1,2].
A new method known as coaxial bioprinting, which has been considered highly effective, makes use of a coaxial nozzle composed of an outer and an inner needle. This technique allows printing fibers from various solution pairs, such as core-sheath, hollow, and functional fibers .
Coaxial bioprinting enables the fabrication of complex tissue constructs by the controlled deposition of biomaterials, from simple tubular vasculatures, developed to integrate complex cell composition, to multi-material with gradient profiles. The solutions flow in the inner and outer channels of the nozzle converge at the end and the flow rate in each channel can be independently controlled to produce 3D constructs with optimal features .
A regular bioprinter that works with coaxial nozzles is exclusively equipped with a nozzle with concentric layers. By extruding different types of materials in each layer, which are carried in the sheath and core fluids, it is possible to modulate hydrogels, sacrificial and crosslinking materials within each fluid layer of the nozzle. This enables the generation of a wide range of structures that allow to accomplish co-cultures, perfusable tubular constructs, and high-resolution scaffolds .
Figure 1: A typical setup of extrusion coaxial bioprinter .
Several studies have demonstrated the interconnection between the use of bioprinting with hydrogels, like a gelatin-based hydrogel, and the excellent performance of vascularization in engineered constructs, in addition to other attributes such as high biocompatibility and biodegradability . Liu et al. (2018) used alginate to develop hollow microfibers to serve as templates for generating cell-laden gelatin methacryloyl (GelMA) constructs, using a coaxial nozzle setup. They were able to assess the diffusibility and perfusability of the bioprinted hollow structures. The GelMA pre-hydrogel, which contained calcium chloride as a crosslinking agent for the alginate, was used as a bioink for the core phase during bioprinting. At extremely low concentrations - under 1,5% - the GelMA could be extruded to support proliferation and spreading for the cell effectively. This strategy is likely to enable a high degree of control over the 3D microenvironments for the encapsulated cells of various types, which other conventional bioprinting strategies have been struggling to achieve .
Figure 2: Strategy of bioprinting GelMA/alginate core/sheath microfibers into 3D constructs with tunable microenvironments .
Through another approach, Shao et al. (2020) reported a novel 3D bioprinting method to directly print cell-laden structures with effectively vascularized nutrient delivery channels. On the outer coaxial nozzle, bioinks with desired tissue cells and endothelial cells (ECs) were separately and simultaneously printed mixed with GelMA. In contrast, on the inner coaxial nozzle, they were printed mixed with gelatin, resulting in a printed large-scale tissue consisting of sheath-core fibers. Simultaneously, the ECs deposit and adhere to the channels automatically due to the dissolved core fibers which generated the channels. This technique reported firsthand 3D cell-laden vascularized tissue constructs with a long-term culture. This advanced bioprinting strategy was able to generate vascularized cancer tissue constructs, evidencing its potential for building large-scale vascularized tissue constructs for applications in tissue engineering and organ repair.
1- Dai, X.; Liu, L.; Ouyang, J.; Li, X.; Zhang, X.; Lan, Q.; Xu, T. (2017). Coaxial 3D bioprinting of self-assembled multicellular heterogeneous tumor fibers. Scientific Reports 7:1457.
2- Gao, Q.; He, Y.; Fu, J.-Z.; Liu, A. Ma, L. (2015). Coaxial nozzle-assisted 3D bioprinting with built-in microchannels for nutrients delivery. Biomaterials 6, 203-215.
3- Liu, Y.; Li, K.; Mohideen, M.M.; Ramakrishna, S. (2019). Three-dimensional (3D) printing based on controlled melt electrospinning in polymeric biomedical materials. Melt Electrospinning, Ch.8, 159-172.
4- Kjar, A.; McFarland, B.; Mecham, K.; Harward, N.; Huang, Y. (2021). Engineering of tissue constructs using coaxial bioprinting. Bioactive Materials 6, 460-471.
5- Hong, S.; Kim, J.S.; Jung, B.; Won, C.; Hwang, C. (2019). Coaxial bioprinting of cell-laden vascular constructs using a gelatin-tyramine bioink. Biomaterials Science 7, 4578-4587.
6- Liu, W.; Zhong, Z.; Hu, N. et al. (2018). Coaxial extrusion bioprinting of 3D microfibrous constructs with cell-favorable gelatin methacryloyl microenvironments. Biofabrication 10(2):024102.
7- Shao, L.; Gao, Q.; Xie, C.; Fu, J.; Xiang, M.; He, Y. (2020). Directly coaxial 3D bioprinting of large-scale vascularized tissue constructs. Biofabrication 12(3):035014.