Click and bioprint
The prospect of 3D bioprinting human organs is tantalizing. Around 50,000 people in Europe are currently on organ donation waiting lists, and an average of 19 die each day while waiting, according to the European Directorate for the Quality of Medicines and Healthcare. One route to potentially curb waiting lists is to ‘click and print’ tissues or organs in the clinic using a patient’s own cells. Compared to standard organ transplantation, this personalized approach would dramatically reduce the chances of organ rejection and avoid the reliance on life-long immunosuppressive medication.
What is 3D bioprinting?
While 3D bioprinting of functional organs sounds futuristic, technological advances continue at pace. Bioprinting uses a technology similar to 3D printing to fabricate complex biologically functional structures that closely resemble the characteristics of natural tissue. The biomaterials essential for this process are collectively called bioinks and include living cells, bioactive molecules, and other innovative scaffold components. Their applications range from offering structural support during the printing process to mimicking extracellular matrix necessary for cellular function. Consequently, 3D printed organs or tissue scaffolds can be created by layering or curing bioinks according to digital blueprints dependent on the application required.
Challenges of 3D bioprinting
3D bioprinted organs are promising for numerous applications, but many challenges remain in achieving structurally accurate, functional tissues or organs due to the complexity of their cellular makeup, the biological materials involved, and the printing process itself.
“Cells alone are very difficult to print and manipulate. So, one of the most promising strategies to overcome this limitation is to combine them with materials which are printable,” says Jasper Van Hoorick, CEO and co-founder of BIO INX, a spin-off from Ghent University and Vrije Universiteit Brussel focusing on the commercialization of materials and bioinks for 3D bioprinting. “These materials must serve multiple functions. They should make the cells printable, but also mimic the natural environment of the cells, protect them during printing, keep them alive after printing, and make them feel at home. The materials should also degrade over time and be replaced by natural extracellular matrix.”
While progress is accelerating in academic labs, with successes including multilayered skin, skeletal muscle structures, and blood vessels among other tissues, there are relatively few commercial ‘plug & print’ solutions that take the final steps out of the lab and towards the clinic. BIO INX aims to bridge this gap.
“There is still a big gap between the academic proof of concept of a technology and its clinical relevance,” says Van Hoorick. “The way to the clinic is always standardization and reproducibility, and that’s what we want to achieve with BIO INX.”
For instance, one common component of bioinks is gelatin. While gelatin is an attractive biomaterial as it’s derived from the natural cellular environment and is a side product from the meat industry, it has a reputation of being unreproducible. This is due to several factors related to the types of gelatin used, varying concentrations, and available chemical modifications.
“In order to turn gelatin into an ink, you have to dissolve it and add other components like photo-initiators, flow-modifying additives, or cell culture medium, among other things. You should look at the concentrations, and the other factors you put in there but in practice, everybody does things differently with lots of customization, leading to poor reproducibility,” explains Van Hoorick.
By partnering with Rousselot, an industry leading supplier of medical grade gelatin, BIO INX focuses on developing reproducible ‘plug & print’ bioinks. “By offering ready-to-use kits, we sacrifice a bit of freedom in terms of customization, but we do that on purpose to favor reproducibility. The less areas of customization, the more reproducible your material, and conversely your printed structure becomes.”
Bioinks should also be as compatible as possible to each printing system to streamline their use, and collaborations with bioprinting hardware manufacturers are crucial to realizing its clinical applications. For instance, BIO INX collaborates with Nanoscribe, Upnano, Readily3D, and Regemat 3D, allowing for integration across multiple platforms to maximize reproducibility, standardization and printing performance. Additionally, BIO INX has a strong focus on light-based printing technologies owing to their speed, scalability, and resolution that will be crucial in achieving ‘from light to life’ medical applications.
Bioprint and transplant
In the future, Van Hoorick envisages that hospitals might even have in-house 3D bioprinters directly in operating theatres. “The idea would be that in one treatment, your surgeon could harvest cells, put them in the 3D bioprinter, press print, and then implant the printed tissue or organ. That’s the ideal vision. We’re still far away from there, but that’s where I believe the technology will be in 10 to 15 years, thanks to the incredible increases in bioprinting technology that enables printing of cellularized structures in seconds.”
While printing and transplanting organs is arguably one of the most exciting prospects for this technology, the benefits of 3D bioprinting organs and tissues extend to other areas of healthcare, like drug development, where it could be used as an alternative to animal testing. Combined with organoids, 3D bioprinting will contribute to the necessary 3R’s of animal research – replace, reduce, and refine.
It can also improve efficiency and reduce costs of screening novel drugs, especially if tissues are printed on an organ on a chip technology. “With 3D bioprinted organ on a chip technology you can immediately see how human cells or tissues will react to different compounds. Again, reproducibility is key here because you need your testing platform to be reliable.”
Bioprinting in the stratosphere
BIO INX has recently collaborated on a project called AstroCardia, where they’ve used their technology to 3D bioprint the microvascular structure around a miniature heart-on-a-chip model to study the cardiovascular effects of aging in space. Cardiac aging in astronauts on the International Space Station is about twenty times faster than on Earth due to microgravity and radiation, providing an exciting opportunity to study accelerated aging in action. The VLAIO Icon project, supported by MEDVIA, was made possible with the combined expertise of five Belgian partners: BIO INX, Space Applications Services, the Belgian Nuclear Research Center (SCK CEN), QbD Group, and Antleron. The launch is now scheduled for 2026.
Despite all the hurdles, with future technological advances and multidisciplinary collaborations, we might one day live in a world where organ transplant waiting lists and animal testing are a thing of the past. One day we might even 3D bioprint organs in space…
