A VERSATILE HELPER

To date, this beneficial protein has been almost exclusively derived from starting materials of animal origin— traditionally cattle and pigs, and more recently marine animals such as fish and jellyfish. Around 95 percent of the collagen used in the pharmaceutical and medical technology industry comes from these sources. A small percentage is extracted from human placentas and cells from umbilical cords and used for research (see Collagen: Facts and figures )

However, collagens derived from animal materials can sometimes be problematic. They can transmit illnesses such as bovine spongiform encephalopathy (BSE), which is more commonly known as mad cow disease. For many consumers and patients, that’s enough reason alone to reject the use of collagen. Moreover, between two and four percent of people are allergic to collagen from cattle or pigs. A similar percentage of people are allergic to fish and marine animals. Studies have shown that contact with animal collagen can cause an immune reaction in three to ten percent of people.

The extraction of animal collagen is being increasingly criticized because it is linked to high emissions of climate-damaging gases and extensive land use. For vegetarians, vegans, and members of a diverse array of religions such as Hinduism, Buddhism, Islam, and Judaism, products from cattle or pigs are taboo in any case.

Evonik is meeting these challenges by means of an innovative production process. “Our process completely dispenses with animal starting material and makes it possible to produce an easily soluble and ultra-pure form of collagen that is safe and sustainable,” says Andreas Karau, who heads the Biomaterials product line. The special feature of this technology is that it can produce different types of collagen with little effort. In other words, it serves as a technology platform. “Thanks to this collagen platform, we are satisfying numerous market requirements that were previously unmet,” says Karau.

Evonik is using microbial fermentation processes to produce collagen. In these processes, the genetic information of a specific collagen structure is implanted into microorganisms. The collagen is then produced by the microorganisms in a few days. During this period, the collagen is transferred to ever larger fermentation vessels until the desired volume has been reached. Today this Evonik platform can already produce four different types of collagen. “The process is always the same, but depending on the customer’s needs we use different microorganisms that have specific genetic information and we adapt certain process parameters,” Karau explains. “Thus, we can generate exactly the right collagen required for a specific area of application.”

Fermentation is one of the Nutrition & Care division’s core competencies, and one of its growth drivers. Many biotech innovations of the past few years have been based on microbial conversion, and have initiated disruptive developments in their respective market segments. Evonik is a market leader in the area of fermentatively produced biosurfactants, and it is now collaborating with the consumer goods producer Unilever to develop the next generation of completely biodegradable cleaning agents.

Another product of fermentation is the algae oil rich in omega-3 fatty acids that was developed by Evonik together with its Dutch partner DSM in the joint venture Veramaris. This oil makes it possible, for the first time, to raise salmon in aquaculture without feeding them with fish oil. This is making fish farming more sustainable and protecting the biodiversity of the oceans.

“Biotechnology enables us to develop new products very quickly and produce them on a commercial scale,” says Riermeier. “At the moment, we’re seeing a very dynamic development in the market for fermentatively produced products, and we expect that in the future proteins made via fermentation in particular will make up a significant part of our biotechnology portfolio.

“The new process for collagen production is also enabling a quantum leap in terms of quality. “Because the fermentation takes place under precisely defined conditions, the product’s high quality always remains the same. For medical applications especially, it’s important to make sure that every batch has the same characteristics.”

The demand for such ultra-pure collagens in the pharmaceutical and medical technology sector is growing by about six percent annually. In 2023, this business is expected to amount to US$1.5 billion. Tissue engineering is one important driver of this development. “For the regeneration of tissue such as skin, bones or organs that have been damaged or even destroyed, collagen is often used as the matrix material within which the new cells form,” says Andreas Karau. Living cells are cultivated on the matrix, using it as a scaffold that contains not only nutrients but also other additives that promote growth. The collagen ensures that the cells grow in the right shape and develop their biological function. That’s especially important for the imitation of organs in the laboratory.

Evonik is currently conducting more than ten in vitro studies in order to investigate the biofunctionality of the new fermentative collagen. These studies are expected to highlight under which conditions the biomaterial can initiate collagen synthesis inside the human body—for example, in order to promote the healing process after operations. In addition, the studies are testing processes for developing hydrogels containing collagen for aesthetic and regenerative medicine—in other words, for treatments such as wrinkle injection and tissue repair.

Maria Montero Mirabet, a biotechnologist at the Health Care business line, heads these studies. She helped to develop the new collagen and coordinated the collaboration between the project teams at the various Evonik locations and with research partners such as the University Hospital and the Translational Center for Regenerative Therapies of the Fraunhofer Institute in Würzburg. “The production processes were mainly developed by teams in Hanau and at other biotechnology centers in Europe. The application tests were conducted at Innovation Management in Darmstadt, the Medical Device Competence Center in Birmingham (USA), and the Tissue Engineering Project House in Singapore,” says Montero Mirabet.

Initial customers are already testing the recombinant collagen from Evonik—as a coating for implants, as a dermal filler for smoothing the skin, and in several blood vessel applications. They can rely on Evonik’s know-how regarding the formulation, application, and production of biomaterials and drugs, as well as the company’s proficiency in tissue engineering. As a result, in the future collagen will not only make people fit and wrinkle-free but also healthy.

Photos: Ollanski, Stefan Wildhirt/Evonik (3), Evonik, Karsten Bootmann/Evonik

Illustrations: Maximilian Nertinger (5), Oriana Fenwick/Kombinatrotweiss with photo templates by Stefan Wildhirt/Evonik