In recent decades, 3D printing technology to build biological scaffolds has been further developed. Compared to traditional 2D cell culture, 3D cell culture scaffolds have significant advantages in mimicking natural tissue structures. In addition, it has been proved that 3D porous scaffolds can provide higher diffusion efficiency for cell proliferation, proliferation, migration and differentiation through pore structure, thereby promoting cell growth and metabolism. Existing methods for constructing 3D porous structures often use the construction of microsphere sacrificial layers. Although this method successfully reproduces the pore structure, it requires a time-consuming elution step to remove the sacrificial layer. Even when combined with an efficient 3D printing process, the complex post-press elution process reduces manufacturing efficiency and limits the flexible controllability of hole size. In comparison, microfluidic chip "link" can control the pore size efficiently and flexibly, and has great development potential in the preparation of porous scaffolds. Therefore, the construction of 3D porous scaffolds based on microfluidic chips is a work of great research significance.
Studies have attempted to combine microfluidic bubble generators with extrusion 3D printing to obtain a series of 3D porous structures. However, this strategy tends to be less efficient when manufacturing complex structures with higher heights. Digital light processing printing (DLP) technology based on optical crosslinking is very conducive to the construction of high-dimensional complex porous scaffolds due to its advantages of fast optical crosslinking. Therefore, the development of DLP-printed porous structures using bubble generators based on microfluidic chips is a promising research strategy.
Recently, a study by Harvard Medical School in the United States creatively matched a microfluidic bubble generator with a self-developed bottom-up 3D printer (Figure 1), realizing for the first time the one-step manufacturing of a 3D porous scaffold with flexible and controllable porous dimensions and complex geometries. This strategy realizes the free adjustment of the bubble diameter from 747 μm ~ 143 μm by adjusting the flow rate of the printing ink and the air pressure entering the microfluidic bubble generator. Based on this adjustment mechanism, patterns of different complexity are printed, as shown in Figure 2. Even geometries with high build heights (Figure 3) can be easily achieved.
Figure 1 (A) Schematic diagram of microfluidic bubble generator; (B) Schematic diagram of the self-developed DLP top-down 3D printer
Figure 2 (i) Print patterns of different complexity of computer designs; (ii) structures printed using DLP; (iii) Enlarged detail of the printed structure
Figure 3 (i) CAD structure design drawing for DLP printing porous scaffold; (ii) top view and (iii) side view of 3D printed porous holder
Overall, this work realizes the construction of porous biological scaffolds with flexible and controllable bubble size through DLP printing technology combined with microfluidic bubble generator. The success of this strategy is expected to provide new ideas for tissue scaffold construction in tissue engineering and regenerative medicine.
The paper was published in the journal Aggregate under the title "Microfluidic bubble-generator enables digital light processing 3D printing of porous structures." Philipp Weber, a joint master's student at Harvard Medical School, and Cai Ling, a doctoral student at Harvard Medical School, are the co-first authors of this paper. The main corresponding author of this article is Y. Smith, Harvard Medical School. Associate Professor Shrike Zhang, co-corresponding authors are Professor Marco Costantini of the Polish Academy of Sciences and Professor Wojciech Święszkowski of Warsaw University of Technology.
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