Yeast, A "Rising" Approach to Manufacturing Collagen

ProColl, a medical biomaterials company based in South Wales, has created a new method for manufacturing collagens that uses yeast. The company's goal is to empower research exploring collagen-based biotechnologies in a more efficient and cheaper manner than conventional methods.

Technology Networks spoke with Jonathan Widdowson, Director of ProColl and Enterprise Fellow at the Royal Academy of Engineering Enterprise Hub, to learn more about how yeast can be used to manufacture collagens and the applications of this approach.

Molly Campbell (MC): Please can you tell us about the development of ProColl and your aims?

Jonathan Widdowson (JW): ProColl began through my research with Dr Chris Wright at Swansea University. We had experienced first-hand the unaffordability of collagen to researchers through commercial vendors, and the time restraints required to produce the material ourselves, with only a few grams of material produced from a month of solid extraction. We wanted to be able to make collagen affordable and accessible to all within the research community.

Beyond this, we were unhappy that the only sources of collagen available were extracted from animals, usually cattle, the quality and purity of the material being very questionable. The collagen must be pure and reliable to work well in research, as without dependable source material, the results are too variable to work with.

This led us to believe a better solution could be engineered using our combined knowledge in collagen, molecular biology and chemical engineering. Our solution is to brew human chains of collagen using yeast (in a similar fashion to beer production) to produce a pure product, with perfect biocompatibility, that is not generated   via animal slaughter.

This allows us to scale the production to commercial levels while maintaining a high degree of process control and purity; all the while requiring just two technicians to manufacture the product to a global scale. In addition, it means that we can offer researchers across the globe a more affordable solution, outcompeting the animal derived collagens.

MC: What current challenges lie in the manufacturing of collagen?

JW: Collagen is traditionally manufactured using animal tissue that is processed using chemicals to remove other proteins. This process alters the structure of the collagen, reducing its efficacy when used in tissue engineering and repair.

The process itself is very involved requiring large staffing outlay which drives up the cost of the material. Currently collages costs [on average] around £1800 per gram which is problematic considering that ten to hundreds of grams are required to produce the artificially grown organs we are currently working towards as a research community.

Using animals also raises the issue of ethics and the risk of transmission of infectious diseases. These include not only includes Bovine Spongiform Encephalopathies (BSE) but, as we have seen in recent years, other viruses being transmitted from animals, including avian flu, SARS and most recently the Wuhan coronavirus outbreak. Being able to break away from this means we can avoid disease transmission altogether, using organisms that have been employed safely for centuries in the production of food and beverages.

Collagen has more functionality than simply acting as a structural protein. It makes up approximately one third of the proteins in the human body and has many vital roles in signalling for health and wellbeing. The art in collagen extraction is to retain the structure and function of the collagen while making it usable in a research setting. If you go too far you can end up with gelatine and collagen peptides which are used in the cosmetics industry but are not useful for medicine. Too little processing, on the other hand, leaves you with a material that cannot be adapted, modified, printed or molded effectively.

MC: Please can you tell us more about manufacturing collagens using yeast? How does this overcome the current challenges?

JW: Our process uses knowledge gained during the human genome project, chemical engineering, fermentation and molecular biology principles, in order to produce yeast that contain the ability to produce and secrete human collagen. We are then able to collect, purify, examine and store in a highly pure extract. We do not need to use animals or harsh chemicals to modify the structure of the material; instead we can simply collect the collagen and use it in applications from tissue engineering to cancer research models to food and beverage supplements.

The materials we produce are human collagen strands that we can print into fibrils, giving a high order of structure while retaining the manipulation properties necessary for research. As the material is human, it means that models testing new drugs, cancer lines or tissue models will benefit from using the most native collagen possible, allowing for direct integration into hosts with reduced rejection issues associated with animal sources.

The result of this is a process that can produce the first ever vegan compatible collagen products, with no ethical barriers, high purity and biocompatibility with an affordable price tag.

MC: What application may this technology have in the biotherapeutics and biotechnology fields?

JW: Collagen has been used for many years, and its properties and applications are already well known. Collagen is suitable for adaptation into drug delivery, in the treatment of wounds, as well as in the engineering and coating of medical devices where the collagen provides a recognizable material for the patient’s cells.

Most importantly, the technology enables the future of tissue engineering and regenerative medicine to be achieved, using the gold standard in biomaterials for tissues.

The collagen we produce also offers benefits to an enhanced line of cosmetics and nutraceuticals, that can help promote healthier tissues, replacing the material lost due to ageing and damage.

Finally, we are currently working with partners to explore the potential use of collagen as a bioplastic, where it offers a biodegradable and edible replacement for plastic packaging.

MC: What are your next steps?

JW: With the support of the Royal Academy of Engineering Enterprise Hub, AgorIP and EPSRC funding, we have been able to take the technology from an idea through to manufacturing the product at scale. We are now looking to achieve full commercial scale for the manufacture of our human collagen products, enabling ProColl to empower research.

We are currently working with partners having secured manufacturing contracts for the supply of our native, novel collagens in order to bring to market a series of products. We are currently looking for enthusiastic distribution partners around the world, to ensure the materials can have a global reach.

We are about to open our first funding round, that will enable us to accelerate our collagen products and their applications, as well as opening collagen to new markets and sectors globally.

Jonathan Widdowson, Director of ProColl and Enterprise Fellow at the Royal Academy of Engineering Enterprise Hub, was speaking to Molly Campbell, Science Writer, Technology Networks.