Bioprinted Tissues Could Transform Regenerative Medicine

We first developed volumetric bioprinting in 2019. A research group at EPFL Switzerland was working on a technique for volumetrically printing plastic materials for very different, non-biomedical applications. We had the idea that, with some tuning, we could make it work with our cells and materials, which are biocompatible.

We just thought the speed and the nature of how the printing works made it an amazing candidate to really increase the scale and the architectural complexity of the bioprinted structures we were making in our lab. So, we tried it, and it actually worked. The cells seemed to be quite happy with the process.

If we have a 3D model or a file that we want to print, we first create tomographic images. These are converted into projections of light, and we end up with a little movie of light projections that is directed through an optical setup toward a rotating reservoir. We place our light-sensitive biomaterials in this reservoir and start shining this little movie projection straight into the vat. When light accumulates in the specific region of interest, the object appears in a single step.

We're not building things adding one little block after the other anymore; in a single-step approach, we're creating these large-scale objects.

Our Swiss collaborators then created a spin-off company that now works almost entirely in the biomedical field. We still work with them to further develop the technology, but we primarily focus on advancing the biological applications.

I think the sweet spot is in the “layerless” nature of the technique. Normal 3D printing that you see in a variety of industries is generally layer-by-layer or even point-by-point. If you make something large and complex, the process then becomes very slow as the cells don't like being in these harsh environments for long.

For some techniques, when we're mechanically pushing cells through a small needle, syringe or nozzle, we are introducing shear stresses that the cells might not be used to and might not enjoy.

As we have a contactless, light-based approach, whatever is inside the printing vat is not manipulated or mechanically stressed at all. Using light as a stimulus to create these 3D objects – borrowing the working principles from computer tomography imaging – makes the process largely stress-free for even extremely sensitive cell types.

Being able to print different types of stem cells or patient-derived cellular units without damaging them, and in such a short time is, I think, the biggest selling point of technology.

We’ve seen the effect that printing large, complex structures loaded with organoids or other cell aggregates, which by themselves are already quite powerful from a functional standpoint, can have for boosting the functional readouts of our bioprinted tissues. The fact that this can happen in tens of seconds can be a game changer for biomedical applications. 

In many ways. From an in vitro modeling perspective, you have the freedom to incorporate any cell type, even from patient-derived samples, and then create these tissues in the lab.

In our lab we are exploring the possibility of applying this technology to different tissues and organs, as well as different disease models. We also work a lot in developing smart, printable materials that not only act as passive carriers for cells but can directly enhance cellular processes like migration and vascularization.

The 3D bioprinting process allows us to explore whether shape gives rise to function, like it does so often in the body. The freedom of design that we get with volumetric printing, for example, enables us to tweak the architectural properties of our prints to better mimic the functions of the tissue or organ we are trying to replicate. Take the liver as an example, in one of our first publications we aimed to create a functional “mini-liver” that could metabolize waste products. We knew that for this process and this particular organ, we needed to have a lot of surface area to increase the exchange of molecules, so we designed something according to that requirement in the tissue, even if it didn’t look like a real human liver at all. Turns out that the design with the higher surface area enabled our printed liver organoids to metabolize much more efficiently. If you have something that contracts, you need a material and a shape that has the properties to enable and resist the required tensile strength. We can tweak all those things quite nicely with these printers and the materials that we develop.

Bioprinting is quite a young field, and we are still taking the first steps towards making the leap to medical applications. The first big hurdle is demonstrating that the tissue analogues that we print in the lab can 100% match native function and establishing reproducible ways to validate this functionality across different labs/facilities.

Next, we have to ensure that the processes and materials that we use are in line with GMP regulations and have the adequate quality control to meet regulatory standards. After all this, we need to see if this whole process of tissue biofabrication is economically viable to enter the medical or pharmaceutical sectors. I think all these steps are going to be a challenge for the next few years and am curious to see how things develop in the field. 

I think in 10 years we're going to start seeing the first attempts at clinical translation. There have been quite a few in vivo studies of the materials and of some printed structures that we fabricate in the lab. We're getting funding to take these promising projects and try to put them through a clean room and a standardized protocol. I think, hopefully, we will get somewhere close by then.

As far as a whole functional tissue, maybe 10 years is still a bit soon – but I think it also depends on the tissue.

There are a lot of labs that are working on the mass expansion of organoids and cells. But, for this application, if you think of a fully functional tissue or organ, you need hundreds of millions, possibly billions of cells, which is already a big effort. Plus, all the other issues of regulatory approval of the materials and devices that we use.  

I think we’re seeing big steps already. There are a lot of people working in the field and quite a lot of funding for these technologies to hopefully take the translational step. I think it’s promising.

I finished my PhD last year. I worked on developing applications for the volumetric bioprinting technology, especially in the area of preclinical in vitro models. Right now, I'm in the same lab, continuing to explore the possibilities of these exciting technologies.

I think volumetric bioprinting is still such a young technique. There are so many things that we are working on. We’re in the fun and exciting stage of exploring various tissues, biological tools and biomaterials to see what yields promising functional results to try to take things to the next level of the translational pipeline.