Fiocruz invests in 3D bioprinters for the production of biological tissues

A technology for the manufacturing of low-cost, open-source 3D bioprinters, developed by the Oswaldo Cruz Institute (IOC/Fiocruz) in collaboration with Veiga de Almeida University (UVA), may soon reach the market. 3D bioprinting allows for creating artificial biological tissues with potential applications in biomedical research, human and animal health, and even in the food industry.

A bio-printer can produce three-dimensional structures similar to biological tissues in the desired shape (photo: Josué Damacena)

The equipment works similarly to a conventional 3D printer. However, while the 3D printer uses materials such as plastics and other polymers to print objects, the bioprinter uses bioink to print structures similar to biological tissues in the laboratory.

One of the project leaders, Luiz Anastacio Alves, a researcher at the IOC's Cellular Communication Laboratory, explains that the bioink is made up of living cells immersed in a biopolymer hydrogel. This protein-rich material, such as collagen, promotes cell adhesion in a similar way to what happens in the body. "Bioprinting builds a three-dimensional structure, with better interaction between the cells, producing a microenvironment similar to the one we have in the body. This gives more reliable results than 2D cell cultures. Additionally, it allows for building complex structures, similar to biological tissues and organs, which can be used for clinical research and transplantation," says the researcher.

The development of the technology was funded by the Health Research Networks Program of the State of Rio de Janeiro, of the Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro (Faperj).

Based on the results achieved, the researchers will begin a new stage of technological development. Anael Viana, a biomedical graduate from IOC/Fiocruz, was selected for Faperj's Doctor Entrepreneur Program: Transforming Knowledge into Innovation.

The winning proposal, submitted with the support of the IOC's Cellular Communication Laboratory and the company QuipoTech, aims to set up a company to develop and produce 3D bioprinters and bioinks.

The project is expected to give rise to the Institute's first spin-off. A relevant figure in the contemporary innovation scene, spin-offs are companies created to commercially exploit knowledge, technology, or research results developed at a science and technology institution.

Potential for research and transplantations

One of the successful examples based on the use of 3D bioprinters is the production of artificial skin. The strategy has been used to treat patients with extensive burn injuries and to test new medicines and cosmetics.

The experts highlight the potential of the technology for developing therapies and transplantations. "Bioprinting has great potential to produce study models for investigating complex biological mechanisms and conducting toxicological tests of new drugs, reducing the use of animals in research," says Anael, who holds a PhD from the Graduate Program in Cellular and Molecular Biology at IOC/Fiocruz.

"Simpler tissues, such as skin, cornea and cartilage, have already been produced and tested as proof of concept. The expectation is that, in the future, it will be possible to print complex organs such as the heart, lungs and kidneys," says Luiz Anastacio, who supervised Anael in graduate school and endorsed the proposal for the Doctor Entrepreneur program.

Expanding market

The price of a conventional bioprinter ranges from 13,000 to 300,000 dollars. The cost of bioink is between 3.85 and 100 thousand dollars per gram. The high cost of the equipment and the expected expansion of the area reinforce the importance of the project.

"The production of this equipment is key for Brazil, which has a trade deficit of billions of reais in health supplies. With innovation and domestic production, the country gains independence and can pass on this technology to poorer, low-income countries," Luiz points out.

"Bioprinting technology is booming. Currently, the value of this market is estimated at 1.5 billion dollars, expected to reach 6 billion in the next five years. This means that we have room to develop our products and grow along with the market," says Anael.

Open-source technology

At the core of the project is the technology for producing low-cost bioprinters using recycled materials, which was presented in an article published in the scientific journal Frontiers in Bioengineering and Biotechnology last year.

The equipment was built using scrap metal and electronic components easily found on the market, at a cost of around one thousand reais. The development was led by Luiz Anastácio in partnership with physicist José Aguiar Coelho Neto, professor at UVA and researcher at the National Institute of Industrial Property (Inpi).

Following the trend of open-source medical and experimental hardware, the researchers used open-source methodologies and published a step-by-step guide for building the bioprinter in an open-source repository. "We demonstrated that the cells in the bioink remained viable for over seven days after printing with the scrap bioprinter, which is a sufficient timeframe for many experiments and even medical procedures. This allows research groups with few resources to have access to the technology," says Luiz.

Two bioprinters were produced using the methodology. The latest model is being used in a research project aimed at producing mini-livers for transplants.

Project milestones

The Doctor Entrepreneur program is scheduled to last two years. In ten months, the new company should be officially incorporated and, at the end of the period, the developed products will be presented. The commercial equipment will be produced using the knowledge acquired in building the open-source bioprinter. The aim is to develop a model with three extrusion nozzles to produce skin and other more complex tissues.

"Compared to an ordinary printer, it would be like having a device with three ink cartridges. With a three-nozzle bioprinter, we can use three different bioinks and produce a complex tissue with three cell types, such as a mini-pancreas," explains Anael.

The other stages of the project include improving the software for operating the device and developing bioinks. "We already have a software, developed with free code, and we are going to add modifications to make it easier for the customer to use. Additionally, we want to develop two bioinks, one compatible with human tissues and the other compatible with animal tissues, to meet the needs of both human and veterinary healthcare," says Anael.