As part of our initial brainstorming process we interviewed several sources to better understand which projects would address more pressing issues and be more viable in the long run. We interviewed Professor Gavin Sacks, a professor at Cornell University in the Food Science department with a PhD in Chemistry, who does research on wine and grape chemistry. We discussed one of our project ideas with Professor Sacks, engineering bacteria to detect arsenic in wine, and he gave us valuable feedback that ended up contributing to us deciding to explore a different project. Professor Sacks informed us that in the current wine industry, arsenic is not a widely talked about issue because people do not drink enough wine for the amount of arsenic to have a detrimental effect. Furthermore, he noted that many winemakers in the wine industry are very resistant to GMOs and would never want to use a product that detects arsenic because it would admit that there is a concern for arsenic in wine. The main takeaway of this interview was that the wine industry is slow to adapt to new technology so it is likely many companies would not want our product and because wine is a luxury good there may be better industries to focus on for our project that could potentially be more impactful.
On March 23rd, 2021, our team met with Carol Leggett, a representative from Danimers. Danimers is a biopolymer company that has been producing biodegradable and renewable plastics for over a decade. At this stage of our project, we were unsure of whether to pursue bioplastics or collagen. Ms. Leggett spoke to the immense commercial interest and wide open market for biodegradable polymers. We found that the net profit margin for biopolymers in the industry could be advantageous if we were to pursue the project. The only caveat to making polymers and applying them for biomedical applications, she advised, was that the process of extracting the bacteria and making it medical grade would be highly intensive and government regulated. This knowledge was extremely helpful when considering the business aspect of our project, and from our conversation, we had more aspects to consider when deciding to pursue a collagen based or biopolymer based project.
One of our early project ideas was using an aptamer-based detection system to test air quality. We wanted to discuss the feasibility of this approach, so we decided to contact Dr. Abduallah Ozer, a senior research associate at Cornell University and expert on aptamer biology. From our conversation, we found that although aptamers are better for reusability, in order to stay in line with a synthetic biology project, we needed to introduce bacteria in some way. We then decided to forgo aptamers in favor of antibodies to detect airborne pollutants/pathogens. Another problem we encountered, however, is that it is very difficult for floating, airborne pathogens to bind to immobilized antibodies, so he suggested finding a way to dissolve pathogens into a more feasible medium: water.
During the early stages of our project, we wanted to learn more about producing glycoproteins over bioplastics. We were interested in leaning towards a more biologically relevant medium. Dr. Paszek, an associate professor at Cornell University's School of Chemical and Biomolecular Engineering, emphasized that with just standard polymers (ie. plastics), it would be better to just use synthetic chemistry rather than complicate the system with synthetic biology - which would not be cost-effective. He urged us to use biologically-relevant polymers, such as DNA or biolubricants. Some suggestions he gave us included (1) creating complicated eye drops, (2) immunoengineering, (3) immune-based therapies using glycans, and (4) surgical adhesions. Over time, Dr. Paszek’s suggestions helped us move towards the tissue bioengineering project in Collatrix.
We met with Guillame Lambert to work on better understanding fluidic dynamics of the project. Lambert, a Cornell professor known for his work in single-cell microfluidics, was able to provide great insights on the inner workings of our potential PD systems. We learned that our PD devices would work well if we microsized the project, and that our theorized method of using different light sources to promote specific growth would be difficult to execute. The most essential take-away was that for such a complex system, there are already companies working on alternative plastics so our work would need a unique approach.
Gelita is a company that specializes in collagen peptides but also sells collagen powder as well as beauty and health capsules. They have products both in the pharmaceutical industry and the food industry and we reached out in order to get feedback on whether there would be a market for our project. We interviewed Michelle Montgomery, an employee of Gelita for over nine years. She received her undergraduate degree and PhD from the University of Iowa in Biochemistry and has worked at Gelita ever since. She has worked in research and development, product development, and technological affairs. After discussing our project with her, Michelle gave us some insight into the current market for collagen based products and specifically in regenerative medicine. She noted that if we could work towards a truly vegan collagen, it would likely have success as many people dislike using collagen or gelatin due to the fact it comes from animals. She discussed the current market and how right now it is small but is growing very quickly. She gave us the name of a company to look into that is currently working with bacteria to express collagen. When asked what she thinks our idea could best be applied to in the biomedical industry she agreed that scaffolds and tissue grafts would be a good direction for our project to go in. Her only warning was that endotoxins could be a contaminating factor as less than 1% endotoxins is preferred for the medical field. This was a very good interview for us because it confirmed we were on the right path and there was a market for our project. She gave us some insight into startups we could look at and even let us know that Gelita often works with startups with good ideas as well.
Dr. Donohue is an orthopedic surgeon for Cayuga Health. He provided the team with essential insight on medical applications of a collagen product, in addition to recounting similar devices that are already present in the field. Dr. Donohue suggested that the most useful uses for a bacterial collagen product, specifically a hydro gel, would be to help heal ACL tears and rotator cuff issues. It was also suggested that to make any potential product successful in the medical field we would need good marketing. Our concern of people resisting our collagen treatment due to its bacterial nature was relieved, as Dr. Donohue said people are unconcerned with what treatments are made from. As for technical suggestions, the hydro gel or patch would need to be at most 2 cm x 3 cm to be functional. Another important point was to test for how well a patch would take wear and tear, as doctors are more likely to use a product that has longevity in the body and won’t cause inflammation. Dr. Donohue’s final concern was to be aware of regulatory issues if this project were to actually be produced one day. Overall, our meeting with Dr. Donohue gave us direction as to what our final goal for the project could be and how to resolve important technical issues.
Our Policy and Practices team, along with Product Development, met virtually with Jos Olijve, a member of the Scientific Development Team at Rousselot. Rousselot is a biomedical and pharmaceutical company specializing in animal-based collagen and gelatin products, which are aptly applied to our project. Olijve has been working on new applications and developments of gelatin products for over 25 years. Due to his familiarity with the market, he advised us that we should consider aspects including cost, the speed of healing/bone regeneration, and being able to use materials secreted by cells without the cells themselves. These key focuses would allow our end product to look more promising in the collagen market. Additionally, Olijve gave us valuable insight on our methods of crosslinking our gelatin. We were in the process of choosing to use either UV light or glutaraldehyde to crosslinking, when Olijve shared from his experience that with UV, people may be afraid of the effects of such light exposure and that we may want to use blue light instead. As for glutaraldehyde, the toxicity component should be considered if we want to crosslink them that way. Our interview with Mr. Olijve helped us in deciding what would be best for our next steps and reassured us that there is a great need for recombinant based collagen, as long as we can remove toxins produced by E.coli.
We met with plastic surgeon and researcher Dr. Jason Spector to discuss his experience with collagen scaffolds in the medical field. Dr. Spector has done extensive research on tissue engineering with collagen and is an associate professor of plastic surgery at Weill Cornell Medicine. When talking about the use of bacteria based collagen, Dr. Spector mentioned that the downside of animal-based products could lead to immune reactions from the loss of cell antigens. We would have to consider this when making our collagen hydrogels, and to aim for a high grade type of collagen (type 1) when considering our product for wound applications or tissue healing. He emphasized that we should make sure to do post translational modifications to ensure that there are no immune system reactions when planning to use for human tissue. Dr. Spector gave us insight into what hospital professionals and patients look for in soft and bone tissue, heavily emphasizing the cleanliness of our collagen.
Avathamsa Athirasa, a graduate student in the Bertassoni lab at OHSU talked with us to elaborate on the intricacies of current collagen research and help refine our lab process. The Bertassoni lab works with 3D bioprinting, biomanufacturing, and biomaterial engineering. Athirasa suggested a potential application of our project would be to introduce scaffolding technology into the tissue engineering world as a method to further current research. She also warned that to produce collagen at the scale we aimed for would be a challenge, and it would require extensive testing to perfect. As for PD work, Athirasa offered many protocol and testing suggestions to improve our procedure for manufacturing hydrogels.
The essential takeaway for this interview was that while our general process is efficient, we need to set realistic expectations on what our collagen products will be able to accomplish in the limited time before competition.