The combination of two-photon polymerization (2PP) 3D printers with innovative hydrogel-based bio-inks can directly 3D print structures containing meso-scale and micro-scale living cells. NanoUp Bio, developed by UpNano GmbH, is a 3D printer based on the NanoOne series of laser-driven two-photon polymerization. The printer can construct 12 orders of magnitude structure.

This new type of hydrogel was developed by Xpect INX (headquartered in Ghent, Belgium), and it is the only resin that can embed living cells directly from the culture plate into a highly accurate 3D printed structure.

For decades, two-dimensional cell culture has been the standard for preclinical drug development and biomedical research. More and more evidences show that these models cannot well represent the 3D-level cell interactions in living systems. Therefore, drug development based on 2D systems is often misguided, leading to billions of dollars in ineffective R&D costs.

Due to the lack of suitable materials and printing systems, the use of embedded living cells to construct complex and highly accurate 3D structures has been hampered. As Xpect INX and UpNano jointly developed a new type of Bioink based on hydrogel, combined with UpNano's new printing model, this work has now become a reality.

UpNano's comprehensive capabilities in developing 3D printing equipment are well integrated with Xpect INX's comprehensive capabilities in designing innovative materials for 3D printing, said Peter Gruber, Head of Technology and Co-founder of UpNano. We jointly developed a highly biocompatible hydrogel X Hydrobio INX©U200, and at the same time, we provided a two-photon polymerization 3D printing device, which can provide the largest range of print sizes on the market.

X Hydrobio INX U200 is a water-soluble hydrogel that can transfer cell cultures from 2D culture plates to complex 3D structures. The gelatin-based X Hydrobio INX U200 is specially developed for the packaging of multiple cell types, so complex 3D microstructures can be generated. The hydrogel mimics the natural cell environment and is biodegradable, allowing cells to gradually replace this material with newly formed tissues.

The gel solves the problems encountered with standard growth media on which cell cultures are incubated in 2D. The hydrogel containing living cells can be directly fed into NanoOne Bio (a high-precision 2-photon 3D printer developed by UpNano). Extensive research has shown that NanoOne Bio's 780 nm red laser will not cause damage to living cells even if it uses very high power for NanoOne printers. In fact, the unique high laser power of UpNano's 2-Photon 3D printing system allows the use of optical devices, which enables the rapid production of large-scale structures at the centimeter level with extremely high precision, even reaching the nanometer level.

The combination of X Hydrobio INX U200 and NanoOne Bio provides new possibilities for biomedical research and development in industry and academia. Professor James J. Yoo of the Wake Forest Institute of Regenerative Medicine in the United States realized the huge potential and decided to advise UpNano on the future development. Well-known tissue engineering and biomanufacturing experts will join the company’s advisory board in April 2021 and will guide the continued further development of novel applications for biomedical research and development. Now it is not only possible to produce lab-on-a-chip with unprecedented precision, but also to directly use embedded living cells to produce chips, which saves time and increases the importance of results.

It is now possible to create a surface structure similar to natural tissues (biomimetic structure), allowing a near-natural interaction between living cells and their growth environment. It has been observed in living tissues that cells grown in a two-dimensional manner on a standard growth medium are far from the natural environment encountered, and they lack all-round interaction with surrounding cells, marketing and business development Director Denise Mandt explained with the co-founder of UpNano. It has been recognized in biomedical research and development that this lack of 3D cell-to-cell contact has a negative impact on the interpretation of the results obtained by using cell models in humans.

The combination of NanoOne Bio and the newly developed X Hydrobio INX U200 kit will greatly change this approach. Pharmaceutical companies and research institutions will be able to design cell models that mimic the natural growth conditions of the human body. In fact, NanoOne Bio allows the production of surface structures or complex 3D scaffolds with embedded cells within the centimeter range with the highest precision.

With a specific light path, optimized scanning algorithm and proprietary adaptive resolution technology, the NanoOne system also provides significantly faster production time than other systems, and its advantages have been recognized by customers in the industry and academia. The expansion of the range of clients in biomedical research has aroused great interest.

Link to this article： 3D printing of living cell structures with meso and microstructures

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