Researchers from the Swiss École Polytechnique Fédérale de Lausanne (EPFL) and the University Medical Center Utrecht in the Netherlands have developed a bioprinting process that allows simultaneous production of the entire volume of complex shapes, providing much greater flexibility and faster production than layer-by-layer 3D printing. Details on the process, called volumetric printing, and printer were published in Advanced Materials.
Three of the researchers have formed a new company, Readily3D SAS, to take the process to market.
Using visible light projection, the approach creates cell-laden tissues from gelatin-based photoresponsive hydrogels. The 3D accumulation of light inside the volumetric 3D printer causes solidification of the shape in seconds.
"Unlike conventional bioprinting – a slow, layer-by-layer process – our technique is fast and offers greater design freedom without jeopardizing the cells' viability," said co-author Damien Loterie, a researcher at the laboratory of applied photonics devices at EPFL. The speed of the process reduces the stress on the embedded cells, resulting in viability rates greater than 85%.
Real change coming to 3D printing
So far, the researchers have created a meniscus, a working valve similar to a heart valve, and a challenging part of a femur. The process permits production of interlocking structures and free-form shapes as well.
"The characteristics of human tissue depend to a large extent on a highly sophisticated extracellular structure, and the ability to replicate this complexity could lead to a number of real clinical applications," said co-author Paul Delrot, a researcher at the laboratory of applied photonics devices at EPFL.
"We have currently printed one cm3 to two cm3 structures with cells," co-author Riccardo Levato, assistant professor at the regenerative medicine center and department of orthopedics, University Medical Center Utrecht told BioWorld MedTech. "The volume could, in theory, scale up to approximately one liter, and the resolution is below 100 um at the moment and improving continuously."
After printing, the researchers vascularized the constructs with endothelial cells. "The endothelial cells were seeded together with supporting pericyte-like cells into the pores of the trabecular bone model, which was laden with bioprinted osteogenic mesenchymal stromal cells (MSC). We used a standard endothelial culture media, and observed spontaneous capillary formation. The presence of the bioprinted MSC provided signals that lead to better neo-vascularization, compared to controls in which printed MSCs were not present."
Fast production of constructs of clinically useful size could dramatically simplify testing of drugs in vitro, eliminating the need for animal testing, according to the team.
The technique produces a usable, customized hearing aid in 20 seconds.
"This is just the beginning. We believe that our method is inherently scalable towards mass fabrication and could be used to produce a wide range of cellular tissue models, not to mention medical devices and personalized implants," said Christophe Moser, head of the laboratory of applied photonics devices at EPFL.
From research to market
The team aims to bring their technique to market quickly. Readily3D should be up and running in a few months, Levato said. Patents are pending for the technology and the company has already received initial funding.
The company's current leadership includes three researchers involved in the recently published study -Loterie, who will be CEO; Delrot, chief technology officer; and Moser, business advisor. The basis of the company combined research Loterie did as a PhD student on the use of light shaping in complex media and Delrot's graduate research in additive manufacturing.
In addition to overseeing the work in the lab where the new printing process was developed, Moser has strong credentials in startups. He co-founded Composyt Light labs, which Intel acquired in 2014. He also co-founded and served as CEO of Ondax, which was acquired by Coherent Inc. last year.
"The bioprinting process will be commercialized soon for use in research labs," said Levato. "When it comes to biomedical applications, especially regenerative medicine, there is still work to do particularly regarding further biological and regulatory challenges, typical of engineered tissues, that still need to be considered. These include maturation of the printed constructs and their assessment of safety and functionality according to the guidelines provided by regulatory agency for advanced medical product."