In our modern society, people are growing more mindful of ethical and sustainable practices. While collagen has tremendous potential in the field of biomedicine, the current methods for harvesting this bovine or porcine collagen are highly unethical. If there was a way to produce collagen for biomedical applications without harming animals, the problem can be solved. Our proposed implementation seeks to examine how our Collagene solution can be implemented into the real world to benefit patients and the environment. Through the discussion on implementation, our team will focus on the ethical and safety aspects of our project design, as well as how it can be easily and safely integrated into our community.
Proposed End Users & Vision of Usage:
We envision hospitals or clinics as suitable end customers since they will include Collagene products into their daily operations. Patients will be provided with a non-animal derived alternative for specific procedures that is equally effective and has potentially better long-term outcomes. Our team hopes to expand the scope of our product in the future with vascular grafts, bone grafts, organ transplants, and wound closure.
Mr. Daniel Rodger advised us to inform patients of all their treatment options and their components, as well as addressing any concerns patients may have. By existing alongside current biomedical products made without collagen-based materials, patients are given a gamut of treatments to choose from. Autonomy about how our synthetic medical device is created will allow all patients to make an educated decision depending on their beliefs.
Implementation of a biomedical device into the real world is an arduous process that requires approval from the FDA and safety testing. Our team plans to first complete the necessary biocompatibility tests for our biomaterials, specifically for toxicity, irritation, and carcinogenesis. While the testing would unfortunately require the use of animal subjects, which is mandated by the FDA, our team will consult an ethical review board to ensure our procedures are minimally invasive and best for the animals. With the initial animal testing complete, our product would require premarket approval from the FDA to proceed with clinical testing. The extensive review process involves scientific inspections, interviews from advisory panels, and lastly the approval from the FDA.
To do this, we must have a means of mass producing our product for more widespread availability. This is where our yeast bioreactor comes into play. The bioreactor maintains optimal conditions, such as temperature and food, for yeast to reproduce. By using an agitation method of spinning the yeast around using fins and having an aeration system, we spin the yeast so it can more efficiently exchange gas.
Eventually, once Collagene products are approved for clinical use, we hope to bring Collagene to the international market to help patients in need of collagen-based treatments. The plan is to provide the materials directly to hospitals for a reasonably low price, which depends on the price of production and transportation fees. Any licensed hospital or clinic is eligible to receive our Collagene bioproducts. Doctors and surgeons would be able to use these materials similarly to current biomaterials during procedures, giving patients better long-term outcomes.
Our proposed implementation also requires informing the public on the benefits of yeast-derived collagen and the harmlessness of synthetic biology. As with any new technologies, patients will have some hesitancy in using these products, often turning towards traditional techniques. By looking at the human practices survey, most of our sample population rated ‘comfortability with synthetic modification of yeast’ as 4 out of 5, while rating ‘comfortability with bacterial collagen’ lower at a 3 out of 5. These results point towards uncertainty about bacterial collagen and the positive impacts they have in the medical field. Bacteria is a term often perceived with a negative connotation, despite being highly beneficial in our society. In order to receive the trust of patients, we will openly disclose the contents of our Collagene products and emphasize the lack of animal-derived constituents.
Additionally, our team proposes public talks with the community to change peoples’ perspectives on genetically engineered organisms and the impacts in advancing medicine techniques. By furthering education into the field of synthetic biology, our society can more easily accept up-and-rising technologies in the future that utilize genetic engineering.
All products intended for biomedical purposes must undergo extensive clinical testing to ensure they function properly in vivo and are compatible inside the body. Collagen products that work in a lab setting may not always transfer directly into the body. Therefore, our project implementation must address the process of FDA approval.
According to the Medical Device Amendment of 1976, our Collagene products fall under Class III, and thus, require strict premarket approval by the FDA. Most of our products are for internal use as biomaterials, so biocompatibility and non-toxicity must be ensured. The specific tests the FDA recommends for these materials include irritation tests, sensitization assays, hemocompatibility, implantation tests, mutagenicity, and all toxicity tests. By confirming our product is safe in vivo, we can more confidently continue with clinical testing and control trials to test the efficacy of our biodevices.
Our team would also need to individually test the toxicity of genipin, which is used as the crosslinking reagent for our collagen, While it is much less toxic compared to traditional crosslinking reagents such as glutaraldehyde, the long-term effects inside the body are unclear. If no severe side effects occur, it would be considered safe for our team to proceed with this component. During the manufacturing of our Collagene products, we need to prevent any potentially harmful ingredients from remaining in the final product, including the genipin or yeast.
Compared to present-day techniques for harvesting collagen from calves, the process for producing yeast-derived collagen will be significantly more expensive. Even when converted to mass-scale manufacturing, the costs to retrieve these materials is simply much greater. While our goal is to make these materials accessible, the final products may end up more expensive than their animal-derived counterparts. When patients are choosing between two treatment options, cost is often a key factor in their final decision. Our team needs to inform the public of the benefits of Collagene products and how all the components are vegan. People should not have to give up their concerns or beliefs simply because they cannot afford the better option.
All of our Collagene products are intended for biomedical applications, so they cannot be implemented without receiving clinical approval. The FDA must review and approve all our biomaterials for use inside the body to prevent negative side effects. A series of tests must be performed, as well as a scientific analysis to ensure the technology of our products functions properly. If there are any safety problems associated with any products, there will be delays in bringing Collagene to the market.
Long-term Effects of Biodegradability:
Collagen is a material with lots of potential due to its high biocompatibility inside the body and low antigenicity. The catch, however, is that collagen is technically biodegradable. While this may be better when disposing of the biomaterials, we need to ensure that our Collagene products can last inside the body for their designated period of use. If there is any possibility of the product losing function, our team needs to find a solution to provide longevity. Synthetic materials used in current medical practices are less biodegradable and can often last in the human body for extensive periods of time. Our team needs to calculate the rate of biodegradation and whether that will eventually affect our products’ function and efficacy.
Ethical Product Testing:
According to Mr. Daniel Rodger, to abide by FDA guidelines all biomaterials for use internally must undergo animal compatibility testing. It is legally required to follow this step, even if our team does not agree with the testing inside of animals and the potential harm it may cause. Additionally, testing our products inside of animals may technically make it not vegan, even though all the individual components do not come from animals. Our team needs to design the best clinical test to harm the least animals while still properly assessing the compatibility of our collagen. We have considered using lab-grown tissues or other in vitro methods, but currently animal testing is the only approved technique.
Center for Devices and Radiological Health. “PMA Approvals.” U.S. Food and Drug Administration, FDA, https://www.fda.gov/medical-devices/device-approvals-denials-and-clearances/pma-approvals.
Rodger, D., Blackshaw, B.P. Using animal-derived constituents in anaesthesia and surgery: the case for disclosing to patients. BMC Med Ethics 20, 14 (2019). https://doi.org/10.1186/s12910-019-0351-4