Tis 17 maj / År 40 / Nr 1 2022

West Sweden – Epicenter for Medical Technology and Biomaterials

The West Sweden region has traditionally been a hotbed for people looking for a better life for themselves and their families. For centuries, people have travelled here and begun to build their future.

My own great-grandfather came to Gothenburg with his brother from the border area Denmark and Germany sometime in the middle of the 19th century. They were entrepreneurs and started factories and businesses here. Herring was harvested and there was a need for conservation and a factory in Gårda was established.
Per-Ingvar Brånemark, a more well-known immigrant from Skåne, came to Gothenburg about a century later and then helped in building the University of Gothenburg’s Medical Faculty’s reputation in medicine on the international stage. Through his creativity and entrepreneurship, people around him have continued to create ideas, research groups, companies and treatments for various illnesses.

What were the results of Professor Brånemark’s research and development efforts?
From a corporate perspective, Nobel Biocare and Entific were formed, both pioneers in the development of treatments for toothlessness as well as bone-anchored hearing aids. Nobel Biocare is still active, now headquartered in Switzerland and a world leader in its field. Entific was acquired by Cochlear, an Australian company, with its research unit still operating from Mölnlycke, Gothenburg. Just like Nobel Biocare, Cochlear is a world leader in its field.

Relationship between technology and medicine
There has always been a close connection between technical research and education and medical practice. Chalmers University of Technology and the Sahlgrenska Academy (the very heart of medical research at the University of Gothenburg) and the Sahlgrenska University Hospital are all located in the vicinity of each other.
For a decade, collaborations have generally been conducted at individual or research group level. An important breakthrough for longer-term collaborations has been joint strategic applications for major research programs from Chalmers and the University of Gothenburg. These have been relatively successful. Examples are the joint research programs within Transport and Materials, respectively, which were granted within the framework of the Swedish Governmental research strategic initiatives. Within Chalmers and the University of Gothenburg’s Area of ??Advanced Materials Science, Materials for Medicine is an important profile. In this program, basic studies are focused on, among other things, future sensors, new materials designed at the nano-level and advanced experiments with a focus on new, bacteria-repellent materials.

A large number of graduate engineers will be attractive employees in the region’s medical technology companies. Today, research and development projects are run in teamwork where different fields of science interact. However, the need for specialist functions is and will always be important. The discussion can also be reversed: do doctors not have a need to gain a certain deeper insight into the technical solutions that are continuously introduced in healthcare? The frightening absence of such insight has been demonstrated in cases known from television. A physician usually has limited knowledge of concepts such as tissue friendliness, prosthetic material and stem cells, especially when materials, cells and drugs are combined as part of advanced treatment. On the educational side, there is a lack of a comprehensive so-called Biomedical Engineering education in Gothenburg.
By introducing a training program in Medical Technology in Civil Engineering for the first time this year, Chalmers has taken an important step in stimulating students in technology to increase understanding of medical issues, methodology and clinical areas.
Another example is the initiative taken by Sahlgrenska University Hospital in which up to ten specialised doctors are offered a joint contact area for technology and engineering (Läkartidningen. 2019; 116: FMZU; Läkartidningen. 2019; 116: FXUL). The program runs for two years and accounts for 20 percent of working hours. The training program includes, among other things, making your own innovation project, from needs analysis to finished concept. Participants will also get to try out innovation environments outside the hospital.

How is West Sweden Medical Technology doing and what does the future hold?
The short answer is; Excellent! And the reasons are as follows:

1. Creativity en masse

Creativity a crucial factor
Creativity is a crucial factor in research, and of course also in development projects in the medical technology industry. Problem solving requires people who dare to challenge current ideas. A consideration of research and industrial development in the field, with a focus on creativity and problem solving where real needs (patient needs) exist, provide many examples, some of which are mentioned here.
When Brånemark and co-workers challenged common beliefs by showing that anchoring of teeth could take place via implants, the dental profession was challenged. After a long time, and with a lot of setbacks, the breakthrough came with this treatment. The concept of titanium osseointegration revolutionised dentistry globally.
When Dahlin, Linde and Nyman and others challenged their colleagues in the dental profession a number of decades later, the idea was to facilitate a new formation or even regeneration of bone by shielding damage and holes in bone from competing cells from soft tissue. Membranes made of millimetre-thin plastic materials, with varying degrees of porosity and permeability, to gases and proteins but not soft-tissue cells, such as fibroblasts, were used. From the beginning, the treatment was only two-step-based with insertion of membranes, waiting for new bone formation and in a second session removal of membranes.
Today, twenty years later, there are also degradable and malleable materials and the recent years’ continued research in Gothenburg has mapped some of the biological mechanisms for this so-called controlled tissue healing. This has created good conditions for new treatment concepts with membranes, largely run industrially through the international company Neoss.
Does the membrane treatment have anything to do with dental implants?
Interestingly, it has been shown that controlled tissue treatment with membranes is used in connection with no less than about 40 per cent of the treatments with dental implants. From a Swedish odontologic perspective, both of these creative efforts play a major role: the treatments benefit patients and create growth and jobs. From an academic point of view, it is obvious that Swedish odontological biomaterial research has had the ability to regenerate even after the Brånemark era.
Another valuable example is the Chalmers chemist Tomas Fabo’s invention of what became Safetac, a soft silicone-based wound treatment dressing, with great patient benefit and which has since become a big seller for the Gothenburg company Mölnlycke Health Care. In 2011, Fabo received the Stora Teknikpriset, established by Ny Teknik and Vinnova, for his efforts.

2. Major unresolved global challenges in focus

Medical device-related infections
Prevention and treatment of infections is one of the most important global health goals. It is also one of the strategic global goals that the University of Gothenburg addresses. The creation of the Center for Antibiotic Resistance Research (CARe) is an excellent initiative and a good example of how the academy can act with the times.
Is it particularly important to prevent the onset of infection and improve the treatment of patients with implants or prosthetic treatment? Figures show that infected implants and prostheses are extremely difficult to treat. The basic hypothesis is that a so-called biofilm of bacteria can develop on surfaces. This biofilm develops into its own ecosystem where even super-high doses of antibiotics are barely enough to kill the bacteria.
A very important research and development work is to optimise not only properties of materials (for example to prevent or minimise bacteria settling on the prosthesis surface) but also medical preparations (patient, surgical technique, early detection and diagnosis of implant-associated infection, biofilm eradicating antibiotic dose and so on). The area has an obvious significance and many Swedish and West Sweden-based organisations and companies have this field on their agenda.
For several years, the West Sweden wound care companies have developed in-depth knowledge. Essity, Abigo and Mölnlycke Health Care all have a track record of products for the treatment of advanced wounds. Gothenburg University and Chalmers, the research institute RISE and relevant clinical specialties (dermatology, orthopedics, et cetera) are also linked in this. It is likely that the central or regional funding organisations will find a need for larger, long-term investments in the area. West Sweden has a competitive advantage through the good collaborative climate between academia, clinic and medical technology companies.

Durability, simplification, fidelity to nature
Synthesis of new materials with sought-after properties, processing and post-processing, cleaning, sterilisation and packaging are important parts in the development cycle of medical devices. For many products, traditional subtractive processing is a key step, but for many researchers and engineers, the dream is to be able to build a prosthesis or organ from scratch, without taking away any parts, with durability or elasticity, with living cells and stimulating factors and a frame that enables adequate cell function for a specific period of time.
The ingredients may seem obvious but not entirely obvious. The production can be called 3D printing or additive manufacturing. In the mid-1990s, American researchers promised to develop “a beating heart” within a five-year period through so-called “tissue engineering”. The initial initiative, through the Whitaker Foundation, has been followed by US Government initiatives to varying degrees and the laboratory part of tissue engineering is now spread around the world. Despite the great potential, however, the clinical use of all or part of organs created in test tubes is still in its infancy. Swedish organisations have initiated scattered, half-hearted direct tissue engineering investments during the past 25-year period, and the academic and industrial scope and development in this area in Sweden can currently be considered relatively small. The time span from idea to realisation is probably large and long-term (risk) capital may have been lacking. A Swedish exception is the international company CELLINK’s success with, among other things, the development of a so-called bio-ink for a broad use in tissue engineering. This entrepreneurially led company is located in Gothenburg and has established prestigious collaborations with international research groups and at the same time attracted long-term investors.
A second Gothenburg / Mölndal example of research, development and industrial development in additive manufacturing is the success story Arcam.

Arcam, partly based on Chalmers research, early developed a technology that enables the manufacture of complex parts, such as aircraft turbines and joint prostheses by, with the help of a three-dimensional electronic drawing, directing an electron beam at metal powder in a machine with a vacuum. The technology is called Electron Beam Melting (EBM) for additive manufacturing or freeform manufacturing. By building layer by layer, a product is created which requires cleaning and, as a rule, some surface treatment.
Early on, Arcam targeted implant manufacturers in orthopaedics, as well as aircraft manufacturers and their subcontractors. In comparison with other competing technologies, EBM-manufactured prostheses showed very good material properties, minimal material waste and short lead times. In collaboration with the Sahlgrenska Academy, it has been shown that both titanium and cobalt-chromium implants (common materials for prostheses) can be manufactured and integrated into living tissue.
Common to 3D printing / additive manufacturing is that there is a great element of freedom to construct both form and details. The white canvas can be filled with personal dimensions. Through medical imaging and three-dimensional electronic drawings, e.g. a patient- and injury-specific local tissue defect can obtain an individualised prosthesis with virtually perfect fit. The industrial story of Arcam’s talented staff and management is not over. The company was sold to General Electric in 2017, remains in West Sweden and is from an economic point of view one of the long-term owner Industrifonden’s three best investments ever.

3. Critical mass

West Sweden is an important node
The West Sweden region has historically been based on outside influences, trade and innovative individuals. West Sweden is an important node for future pharmaceutical and medical technology development in Sweden. Over decades, research groups and companies have developed, often in close collaboration with each other. Entrepreneurs have, for various reasons, changed workplaces, moved from one company to another, or been involved in creating a new one. There are at least two examples of how West Swedish medical technology companies have emerged in this way and grown to be among the top on the world market. In both of these cases, foreign principal owners have eventually taken over, but the research departments remain in West Sweden.
In industry, employees form a major resource, probably the most important resource in each company. Through their competence and experience, product ideas are driven, contact routes and networks are developed. Leadership in the industry has been significant, many of the companies’ management teams own or co-own the companies. Ideally you stay and develop the companies here in West Sweden, not to primarily sell here, you do that internationally. The medical technology companies in the region are generally of a good size, they are successful but perhaps not yet so large that there is a need for external development nodes.
Another major advantage for the region is the emergence of smaller, creative start-ups and spin-outs that have taken place during the last 10-year period. In business hubs with a focus on Life Science, there are the meeting places that were previously missing. In these contexts, it is important to point out that a number of specialist functions are required. Going from idea to market is a diligent, systematic work where skilled experts in, for example, clinical studies and regulatory processes are indispensable. In academic contexts and in the general public, it is sometimes difficult to understand the time it takes to safely and effectively introduce a new diagnostic method or treatment. This group of experts, such as CROs and specialised subcontractors, will most likely have a lot more to do in the future.

How will the collaboration take place in the future?
The goals should be high. Within academia, there is complete freedom to formulate one’s hypotheses and to choose approaches. Limiting factors are usually brains and resources. The academy with its research and education is a necessary prerequisite for the companies’ supply of skills. It is therefore a pity that it has been difficult to create an international medical technology top education between the two higher education institutions and Sahlgrenska University Hospital, where all medical technology companies are an important ingredient. The conditions are there.
Interdisciplinarity and cross-border cooperation are part of the key words, another is language comprehension. A researcher in technology or an engineer does not need to become a doctor but needs an understanding of the complex biology in which technology is applied. A biomedical researcher or doctor needs a fundamental dose of physics, chemistry and materials science to not be afraid when the formulas spray over the whiteboard.

Peter Thomsen
Professor, MD, PhD
Sahlgrenska Academy
Fellow of the Royal Swedish Academy of Engineering Sciences