The new bioprinting system can print cells from all directions on complex-shaped blood vessel scaffolds.
Using a three-dimensional (3D) printer with bioinks (often containing cells and biomaterials), tissue/organ-mimicking structures can be constructed. 3D bioprinting is one of the most promising technologies to manufacture complex human tissues and organs, which are used in regenerative medicine to treat organ damage or disease.
However, traditional approaches in 3D bioprinting are unable to incorporate blood vessel networks during the bioprinting process, making it challenging to construct functional and long-lived complex organs as the printed cells are deprived of nutrients. Furthermore, to “glue” the printed cells together, current bioprinting technologies require the addition of artificial biomaterials to bioinks, which can prevent functional cell contact and the formation of new blood vessels, thereby interfering with the biological function and long-term survival of bioprinting products.
To address these problems, a joint research team led by Professor Wang Xiujie at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences, Professor Wang C.L. Charlie at the University of Manchester, and Professor Liu Yongjin at Tsinghua University used a multi-axis robotic arm to build a new 3D bioprinting system that can print cells from all directions.
To better preserve the natural functions of the cells after printing, the team designed an oil-based cell printing system that provides a hydrophobic printing environment, promoting the attachment of printed cells to blood vessel scaffolds. The team’s novel system also included a self-designed bioreactor with heating and circulation devices to nurture the cells during and after the bioprinting process. Together, the researchers were able to print cells on a complex-shaped blood vessel scaffold without causing cell damage or affecting cell proliferation and function.
Furthermore, inspired by the natural organ development process, the team employed a print-and-culture strategy, where after printing a certain layer of cells on the blood vessel scaffold, the printed cells would be cultured for a period of time to facilitate the formation of cell-cell contact and new blood vessels before going through another round of bioprinting. This should produce complex tissue/organs with printed cells interlaced and a connected blood vessel network to maintain long-term survival.
To demonstrate how this strategy would work, the researchers carried out bioprinting experiments using endothelial cell bioink and cardiomyocyte bioink on blood vessel scaffolds, and found that the printed endothelial cells formed an intact endothelium and new blood vessels. In addition, the printed cardiomyocytes formed gap junctions and were observed to resumed rhythmic contraction shortly after printing. With this strategy, the constructed piece of vascularised cardiac tissue was able to maintain rhythmic beating and stayed alive for at least six months.
The team’s novel robot bioprinter can also be easily extended by combining multiple robots to complete difficult bioprinting tasks. Here, the researchers established a two-robot cooperation platform and accomplished simultaneous bioprinting of multiple types of cells on complex-shaped blood vessel scaffolds.
Comparing this novel 3D bioprinting system with traditional methods, this study provides a new strategy for us to print cells on complex-shaped vascular scaffolds and facilitate angiogenesis among printed cells, thereby supporting long-term cell survival and demonstrating a feasible way to construct large-scale and functional artificial tissues/organs.
Source: Zhang et al. (2022). A multi-axis robot-based bioprinting system supporting natural cell function preservation and cardiac tissue fabrication. Bioactive Materials.