Gian Nutal Schädli, Co-founder and CEO of CompagOs, a Swiss biomedical spin-off from ETH, discusses how his company generates and uses 3D-printed bone models to provide oncologists with early warning systems for bone metastasis, as well as their potential applications in drug testing and regenerative medicine.

Supertrends: Welcome to Supertrends interviews. Today, my guest is Gian Nutal Schädli. Gian has a PhD in biomedical engineering and is the Co-founder and CEO of CompagOs, a Swiss spin-off from ETH. Hello, Gian.

Gian Nutal Schädli: Hello. Nice to meet you.

Supertrends: Maybe we could start with you explaining what you do at your company?

GNS: Yes. At my company, I have the role of CEO, and I was responsible for putting the whole team together. I was the initiator of CompagOs, which started in 2021 after I finished my PhD. My first task was to find co-founders because you can’t start a company alone.

Supertrends: What product have you started to develop after setting up the company? What is your focus?

GNS: In a nutshell, our vision is to provide an early warning system for oncologists and their advanced cancer patients. These patients have survived or successfully fought against lung cancer, breast cancer, or prostate cancer, but for some, the cancer will develop and spread into the bones, where it becomes very difficult to treat and is often incurable. The problem is that oncologists rely on symptoms or imaging showing that the cancer has reached the bones. We aim to give them a diagnostic product and early warning system so they can detect bone metastases before they are visible on imaging. We do this using blood samples with the help of our 3D-printed bone models.

Supertrends: Okay, so you develop the bone models. How do you create such an in vitro bone model?

GNS: Yes, that’s probably the most intriguing part of what we do. It starts by creating a bio-ink that includes alginate and gelatin. It has properties suitable for 3D printing. The challenging part is adding mesenchymal stem cells to the bio-ink, so we 3D-print something with living cells. This is done by many labs, and while it sounds complex, it’s feasible in science and academia. What’s unique about us is that we apply mechanical loading to our 3D-printed hydrogels, giving the cells 'exercise.' We call it putting them in 'mini gyms,' which are bioreactors. We load them three times a week for five minutes to mimic in vivo conditions. When you get up and start walking, you load your bones, which is important for bone health. With this process, we create these 3D-printed bone models in the lab.

Supertrends: So the physical pressure you apply helps mimic the physiological conditions, correct?

GNS: Yes, it’s the physical pressure. Organ-like models, or organoids, are already well-established in many labs. Organoids are 3D micro-engineered tissues that are self-assembled from mesenchymal stem cells. These structures are typically spherical in shape, measuring just a few micrometers in size, and are floating in a cell culture medium. We do not precisely fit the established definition of organoids, and our model is actually more advanced. We don’t just let the organoid float in culture media; we provide a mechanical environment with loading to stimulate in vivo conditions. This is crucial for bone because it is mechano-responsive. For example, astronauts lose bone density in space without Earth’s gravity. For an aging population, staying active helps maintain bone health, and we use this knowledge to recreate bone models.

Supertrends: It’s interesting because we often focus on mimicking in vivo conditions through signaling factors, or cell communication, but physical factors are equally important in this context.

GNS: Exactly. Another thing to clarify is that when we say '3D-printed bone models,' people often imagine a “dog bone”. You know, that classic piece of bone that immediately comes to mind for everyone. What we print doesn’t look like that; it’s more of a crisscross pattern, like a waffle.

What I find really cool is that when we print it, it doesn’t contain minerals—it's just the alginate material that the cells grow in. Then, when we culture it over four weeks, we actually see it turn a bit more whitish as the mineral content increases (since minerals are white). Just by looking at it, we can already observe how the color changes. But we can also measure it using a micro-computed tomography (micro-CT), which is a 3D X-ray imaging technique. It’s similar to when you’ve had a bone fracture and get an X-ray—on the X-ray image, the bone shows up as white on the black background. We see something similar with our material: in the beginning, you don’t see much, but over time, the structure we printed starts to show up on the 3D image.

I really like this, especially because I’m an engineer by training. You mentioned cellular signaling, but as an engineer, you can’t directly see or observe cellular signaling. Instead, you measure some value in an assay or an activity. What I find beautiful about the work we do is that we actually get visual data. We can show people images of our models, and how they look.

Supertrends: So, these models are dynamic—they change based on how you interact with them, not just static structures.

GNS: Yes, exactly.

Supertrends: You mentioned that the primary application is in diagnostics for oncology. Are there any other applications for your models?

GNS: Yes, we didn’t originally start with diagnostics for oncology or bone metastasis. The project began with a focus on a rare bone disease called osteogenesis imperfecta, or brittle bone disease. This is a rare genetic condition affecting fewer than 20,000 people in the U.S. and fewer than one in 2,000 in Europe. Developing drugs for these patients is challenging due to limited clinical trial recruitment, so there’s currently no drug targeting this genetic mutation directly; existing drugs are for osteoporosis, which affects older adults. Now, we’re developing a product called Bon3OID™ for researchers, including academic and corporate researchers working on metabolic bone diseases. Bon3OID™is a model to replace animal models and work earlier with human biology because we can add patient cells to our models, making it patient-specific.

Supertrends: So it could be a useful model for drug testing and even replace animal models?

GNS: Yes, we could replace animal models, and in some cases, we are even better. For example, for the rare disease I mentioned, there are many different genetic mutations, for some animal models aren’t viable because they typically result in prenatal death. But we know humans can survive with these mutations. A PhD student at ETH working with the technology created models from patients with these mutations to start testing drugs, allowing us to see if a drug might work for a specific patient, or if it would have no effect. This approach is especially valuable for patients with rare diseases where developing medication is more challenging.

Supertrends: Your models also align with the trend of personalized medicine, right? It’s such a hot topic these days—people prefer personalized solutions over the one-size-fits-all approach.

GNS: Exactly. That’s basically how it started. In the early days of the startup, we pursued this direction. Now, we offer it as a service for those practicing personalized medicine for their patients. The concept is similar to how clothes and shoes are tailored to fit our individual bodies—our shape, height, and size. But with medication, which is far more complex and delves into biology, it often just comes down to measuring weight. That’s where it doesn’t make sense to me. Genetic testing is already available, particularly in cases like cancer, where a lot of testing is done. The therapy you receive is truly tailored to that specific cancer. But when it comes to bone diseases? We’re not there yet.

Supertrends: Speaking of customization, is it challenging to start with a new cell type? Or even from patient to patient, is the procedure complicated, or is it fairly easy for you to adjust the process to specific cells?

GNS: For us in the lab, as soon as we have the cells, it’s the same process. If we want to create a model for an osteogenesis imperfecta patient, we just need a patient sample. Our base model that we print is always the same. We had one project with ETH, where we tried to create a model for osteosarcoma, a highly aggressive primary bone cancer. We took directly patient fragments from a tumor biopsy and implanted them into our bone model, where we observed the tumor growing again and mineralizing. We could also test some drugs on it. In terms of the base model, it’s always the same. Now we’re in the phase of scaling up—planning to produce four to six times as many with a new device, which is more tailored to standardized laboratory testing.

Supertrends: And what’s the most challenging part when scaling up such a process?

GNS: The most challenging part is really an engineering issue. Currently, we have a customized procedure where we train people well on the process, and they produce these bone models. Some people are more talented in the lab, but we’re still in the early stages, often working with students. So, you end up with varying outcomes depending on who’s working with it. It’s like going to a restaurant where the same dish might taste different depending on the chef’s skill level. That’s the challenging part in terms of engineering—you might automate a process, but it doesn’t necessarily mean it’ll be better than when a skilled person does it manually. Some people have a natural talent in the lab and do things intuitively. We’re trying to capture those small details and automate them so every operator can produce the same results.

The other thing is the biological aspect. Even when testing with animals, that are genetically identical, you still find variations. I do not see it really as a challenge but rather as a beauty of working with biological systems—they’re always a bit unique.

Supertrends: Are your products already available in the clinical setting, or are they still in testing?

GNS: Our product is currently only available in unregulated markets, primarily for pharma companies or researchers who want to do preclinical testing. Instead of conducting cell experiments on a 2D plate or some other established method, they use our model.

We’ve started collaborating and discussing with oncologists in Switzerland. We have contacts with three cantonal hospitals, and over the next few months, our goal is to show that the process we’ve established with blood from blood bank also works for cancer patient samples. We use blood samples from cancer patients to see if we can measure significant differences compared to healthy patients. The theory and science are understood, but we need to demonstrate that we can detect these differences in our tests.

Supertrends: And if you plan to expand into a larger market, what do you think would be the biggest challenge?

GNS: I think the biggest obstacle to any innovation to be successful is always people. It’s about humans being open to new solutions. Oncologists, for instance, are eager to have an early warning system from blood samples. Current imaging techniques can sometimes lead to false positives or uncertainty in diagnosis. If our test works as expected, it could, for example, reclassify a stage 2 lung cancer patient with no visible bone metastasis on a CT scan to a stage 4 patient, potentially changing the course of treatment. But this means that oncologists must accept changes in the standard paradigm they’ve trained in. I think it's something very human that some people adapt quickly, while others prefer more evidence and widespread adoption before they make changes.

Supertrends: Sounds like a common issue for the spread of innovation, as you said.

GNS: Yes.

Supertrends: Could your model eventually support tissue replacement? Moving toward regenerative medicine?

GNS: That’s always been one of my motivations since my Ph.D.—regenerative medicine for bone fractures. We’ve discussed this with orthopedic surgeons, especially for complex cases where healing timelines vary widely. Some patients heal quickly, while others take much longer. We’re exploring whether we can use our bone model to observe mineralization patterns and potentially predict healing rates. This could help determine if a patient is among a group that heals slowly, for example. And then the question arises: 'Why can’t I directly use that bone to fill the gap and heal the fracture?' The patient needs enough biologically active material for proper healing. This is something we've looked into. However, it's a challenging field for a startup. On one hand, it's very attractive because musculoskeletal conditions impose a higher economic burden than oncology due to the sheer number of patients. However, bones have a beautiful ability to heal on their own, and existing solutions from companies in this space are already effective. And, let's say, they're not very complex. So if we come in with a 3D-printed material, we introduce some complexity. It's not that niche market, at least not to get started as a startup, because there are already big players with good products that work.

But if we achieve our current goals—like diagnosing bone metastasis and drug testing—we could potentially expand to offer better treatments for bone fractures and musculoskeletal conditions in the future. For now, though, we’re laser-focused on our current projects: diagnosing bone metastasis and ensuring our product delivers value to early customers.

Regenerative medicine remains an exciting possibility, but I think other tissues or organs might need it more urgently than bone.

Supertrends: It makes sense. Looking at the broader perspective of the bioprinting field, are there any trends or exciting technologies that you're particularly looking forward to?

GNS: From my perspective, what’s really exciting in the 3D bioprinting field is happening in the lab where we’re hosted. We have two professors at the Institute for Biomechanics working on new type of biomaterials that can be 3D printed using light, and they have the latest 3D printers available on the market. They can print very detailed structures with very high resolution.

At the moment, the 3D extrusion process we use is well-established. There’s a lot of talent on the market familiar with extrusion 3D printing, and several companies offer 3D extrusion bio-printers. So, the technology has started maturing. I think we will work with this technology for the next 10 to 15 years. And like in any field, we have cycles of innovations coming in. I’m particularly excited about this new generation of 3D printers that use light for printing with new biomaterials. These innovations will enable higher resolution and faster printing. I look forward to seeing this technology to be established so we can integrate it into our systems.

This is how I see the field evolving at the moment, particularly for the bone field. We are now really at the phase where we can commercialize 3D extrusion printing and bioprinting. But I’m sure, it won’t stay like this. I think this light-based printing will have more commercial applications. Now it's established in research, and I believe it will also transition to commercialization for the type of diagnostic 3D-printed models we create.

Supertrends: Thank you very much for this discussion, Gian. It was super interesting.

GNS: Thanks for the interest. Have a nice day.

The interview, conducted on 4 November 2024, was part of Supertrends' “Interviews with Experts” series. Please note that the transcript may have been lightly edited for editorial reasons.