Brabant is at the heart of various developments in the field of biomaterials and regenerative medicine. Artificial heart valves that are naturally absorbed by the body, arteries that repair themselves without invasive surgery, jawbone that can grow with a gel and all kinds of other self-healing materials: the world of biomaterials and regenerative medicine is full of promise. And Brabant is at the heart of various developments in this area. Companies such as Xeltis, Vivolta, Stentit, Osteo Pharma and FujiFilm are now making their mark on this new sector of medical technology. Two developments are currently giving an extra boost to this trend. In Brabant itself, Smart BioMaterials Consortium (SBMC) is being formed with the Brabant Development Company (BOM), Eindhoven University of Technology, the Province of Noord-Brabant, Pivot Park Oss, Brainport Industries Campus and dozens of companies as participants. In addition, there is a collaboration at national level between Leiden, Utrecht, Eindhoven and Maastricht for the realization of various development and production lines in regenerative medicine. This national network is part of ‘RegMed XB’: regenerative medicine crossing borders, an international initiative in regenerative medicine (RG) that connects top clusters in the Netherlands and Flanders. Within RegMed XB, researchers, companies and governments in the Netherlands and Flanders are joining forces to create a new industry here, including new innovative companies based on knowledge-intensive labour. RegMed XB is ambitious: it wants to create a nationwide RG pilot factory, as the basis for a new manufacturing industry that makes RG therapies, production technology and production equipment for the whole world. A subsidy of €56 million from the Growth Fund (on a total investment of more than 200 million until 2027) should give RegMed XB an acceleration. This brings the combined pilot factory with thematic focus on stem cells (Leiden), microtissue (Utrecht), biomaterials (Eindhoven) and complete organs (Maastricht) a lot closer. Benefit too The development of the Brabant biomaterials consortium is gaining momentum by carrying out part of the Growth Fund project for the RG pilot plant, but quartermaster Jan Rietsema emphasizes that SBMC would have started anyway. “Our consortium focuses on hydrogels and biodegradable implants. Biomaterials play a major role in the production and deployment of regenerative therapies. Hydrogels are used to accelerate cell culture and to deliver drugs or cells and tissues into the body. The latter also applies to biodegradable implants. These are biomaterials specifically constructed to support the growth of new functional tissue in the body. They dissolve in the body so they don’t have to be surgically removed.” SBMC wants to make the move towards industrialization, partly thanks to the impulse of the Growth Fund. Rietsema: “A lot is already possible at a scientific level, but success on a petri dish is not yet a successful company.” And that’s what it should lead to. Unlike in Leiden, Utrecht and Maastricht, the role of the business community in the Brabant leg of the collaboration is therefore relatively strong. “About forty Brabant companies are already involved in the consortium. We have only just been established and are still in a very dynamic phase. Although we are very industry-driven, the role of TU Eindhoven is also essential. And with the input of the province, the triple helix is complete.” Apart from setting up a foundation and putting together a board, the focus is mainly on the content. The first ideas have already been collected for this: there were workshops with the forty companies and now it comes down to further detailing of the plans – because now they only exist in outline. “The goal is a joint development facility where companies can develop applications together. There are already many existing collaborations. For example, there are close ties between Vivolta with Stentit and Xeltis. We want this to take place as much as possible in open innovation, whereby we will have to pay attention to protection of IP and patents. We do have experience with that, so that will probably be fine, but it does require attention. Also from the companies themselves.” High demands High demands are made on both the materials and the method of production – such as the electrospinning of fibers and 3D bioprinting. Rietsema: “Everything must be clinically validated and produced under strictly controlled conditions of Good Manufacturing Practice.” The SBMC will realize two facilities: the development facility, whose central location will preferably be located in the vicinity of Eindhoven University of Technology, and the pilot production facility elsewhere. In the development facility, parties work together in projects on the optimized production and assembly of biomaterials, (including hydrogels), on functional testing, assessment and prediction of implant function, scaling-up problems and the restrictions for clinical production. In the pilot production location, parties are working together on the industrial production of biomaterials and degradable implants. According to Rietsema, the revenue model of this part of the RG pilot factory is a combination of sales (of mainly hydrogels) and contract manufacturing (of biodegradable implants), supplemented with advice and support in the development of products and production technology. “The customers are companies that want to purchase biomaterials, organizations that develop new production technology and the other players in the RG pilot plant, who use the biomaterials in their pilot line. In this way, a manufacturing industry around biomaterials can develop with the Brabant production cluster for hydrogels and biodegradable implants as the focal point.” The province of Noord-Brabant and Eindhoven University of Technology have taken the lead in realizing the infrastructure with the SBMC as the basis for a production ecosystem with a leading position in Europe. Pioneers Rietsema calls Eindhoven University of Technology one of the Dutch pioneers in the field of regenerative medicine and an internationally progressive in the field of biomaterials for RG applications. There is also a good financial basis, he says. “The BOM has a lot of experience with large funds in the field of biotechnology and works closely with TU/e and other (early phase) investors such as Braventure and the Brabant Startup Fund.” In addition to TU Eindhoven, Pivot Park in Oss and Brainport Industries Campus (BIC) in Eindhoven also play a role in building a high-tech manufacturing industry around biomaterials. Pivot Park in Oss is an initiative of MSD in collaboration with the province, municipality of Oss, the ministries of EZK and VWS and the BOM. BIC is a campus where companies are located that share their knowledge of product development and technology and work closely together in the field of research and development. BOM also played a major role in the creation of the innovation program at the Brainport Industries Campus. Examples Whether it concerns materials, technology, research or concrete applications, Brabant has a series of initiatives that turn the province into a hotbed of biomaterials. Of the approximately forty companies that are already associated with SBMC, these are some notable examples: Xeltis
Xeltis builds on the technology of Eindhoven University of Technology. From the TU/e Campus, it focuses on the development of implantable, growing heart valves. It starts with an implant, but step by step the body absorbs the artificial valve and builds a new, natural valve around it. In this way, the patient forms his own tissue inside the Xeltis heart valve, creating a new, natural and fully functional heart valve. The first successes of this formula have also led to the fact that the bioabsorbable polymers that make Xeltis’ heart valves are now also used for the formation of blood vessels. The valves are in clinical trials in the EU, Asia and the US and the first patients have now reached their 5-year follow-up. The company has raised nearly $100 million in funding in several rounds. Of the 50 employees, 45 work on the TU/e campus, where the research is conducted. Everyone knows someone who has had an angioplasty or a bypass of the clogged blood vessels around the heart, says co-founder and Chief Technology Officer Martijn Cox. “Such operations are done millions of times a year worldwide. The procedure is then that one or two blood vessels from the patient’s own leg are used. That leg has to open for that, which causes scars and discomfort. Those kegs often close up again after a while. We have now devised an alternative for this based on our technology. New patient-own tissue then grows in that artificial blood vessel, which slowly takes over its tasks again. And where normally the problem is that material starts to deposit against the walls of those super small vessels, causing the vessel to silt up again, you see much better results with our biocompatible materials.” Stentit
Stentit is also a spin-off of Eindhoven University of Technology and focuses on regenerating the arteries without invasive surgery. “The idea of our regenerative stent was born in the TU/e laboratories,” says CEO Bart Sanders. “Thanks to the growing regenerative medicine ecosystem that is developing in the region, there are resources and facilities to start up new businesses. We took advantage of that.” Sanders has also become acquainted with the obstacles that exist before you can put a medical product on the market. “There are very strict controls for this. We must demonstrate that the stent is working properly and that the potential for negative consequences for the patient is minimal. The studies we have to do to prove this are very expensive. It’s hard to get that money together. Investors are hesitant because they see it as a high risk. The further the product has been developed and tested, the smaller the risk for investors becomes. But to achieve that, we need investments.” Fortunately, there is enough help, from different sides. As part of RegMedXB for example. Nevertheless, it is still difficult to raise sufficient funding at this stage, says Sanders. “It just takes a lot of money to really bring the product to market. We receive support from the Dutch government. The university also supports us. For example, we are allowed to use the laboratory with microscopes and the like. Of course, as a start-up, we couldn’t immediately purchase all of that ourselves.” Stentit is well on its way to the clinical trials phase and the ultimate goal is clear: “We really want to change patients’ lives. We started this company as two scientists with the question of how we as researchers can bring our idea to the patient.” Fujifilm
Fujifilm, based in Tilburg, is one of the leading international companies in biomedical materials for regenerative medicine. At the end of 2021, the company will open a new Life Science Manufacturing factory. Fujifilm will soon be producing cell culture media in this factory: an essential raw material for bioproduction and cell and gene therapy. Cell culture media are used in the biopharmaceutical industry and serve as a nutrient for cells in the manufacture of drugs or vaccines. This biopharmaceutical market is growing rapidly. For this reason, Fujifilm is continuously expanding its activities in the field of preventive health care and treatment. The new Life Science Manufacturing factory has been built on the site of the former film factory in Tilburg. The installations and equipment are currently being validated, so that the factory can open before the end of the year. Fujifilm’s cell culture media is free of animal or human ingredients and is used by Fujifilm’s customers Irvine Scientific for growing cells on petri dishes or in bioreactors. The new factory will soon produce, among other things, cell culture media, powder mixtures and Water For Injection (WFI). Erik Vaessen, Executive Director Life Sciences at Fujifilm Irvine Scientific says the expansion makes sense for his company: “When a European producer of bioproducts or cell therapies needs products from Fujifilm Irvine Scientific, they currently receive them from our headquarters in California or from our second factory in Japan. With our third production facility in Tilburg, we are strengthening the supply chain and bringing our products and services, including the capacity to produce liquids in large volumes, to a local level. By reducing overseas transport, we help our customers save costs and we also ensure that our logistics are greener.” Vivolta
Vivolta (until recently known as IME Medical Electrospinning) offers medical solutions to help the human body regenerate itself. Implants based on nanofibres ensure that tissues and organ structures in the human body repair themselves. Xeltis is one of the companies using Vivolta’s technology and equipment; Stentit is also a customer. CEO Judith Heikoop calls her company’s mission “extremely decisive” in all her choices. “The only reason I’m doing this is because I believe you can help so many patients with a solution that will allow them to regenerate their bodies. And that applies not just to me, but to the entire company.” In recent years, Vivolta has evolved from a high-tech device builder to a MedTech company developing products in the fields of medical devices, tissue engineering and drug delivery solutions. “We want to help our customers bring premium electrospun nanofiber-based medical devices, tissue engineering products and drug delivery solutions to patients, helping the body heal itself.” Many mission-driven companies sometimes encounter the fact that the market is not yet ‘ready’ for the solution offered. Judith Heikoop also notices this. “Our medical devices are recognized by the body as their own. There are no scars, there is no rejection. So you would say: this is a no-brainer for the medical industry; everyone wants this, so let’s get it done. But that is different. The reality is that we are way ahead. We have, completely wrongly, suffered a lot from the consequences of The Implant-Files, which brought up the implant tampering. As much as I would like the world to see what we can do, apparently it doesn’t work that way. We need early adopters to create a market step by step and generate traction. That takes a lot of attention.” Osteo Pharma
Osteo-Pharma BV develops new products from Pivot Park Oss for orthopedic and dental applications for the local treatment of bone fractures and bone defects. In the OsteoActivator technology, additional amounts of low molecular weight bone healing compounds are encapsulated in a biodegradable carrier, resulting in a local sustained release of these compounds over a period of four to six weeks. During this period, bone formation is promoted and bone breakdown is inhibited at the same time, resulting in a net effect of increased bone growth. The OsteoActivator-P is ready for clinical trial in dentistry. In addition, preclinical studies are underway into improved fracture healing and the treatment of reduced bone formation in osteoarthritis. Preclinical studies with OsteoActivator coated implants that prevent implant loosening have now been successfully completed.