Figure: Timeline of our Integrated Human Practice Activities for iGEM 2021
Our initial project idea was that of an antibacterial surface coating that minimizes the risk of transfer of infection due to pathogens being able to live on surfaces for hours, or even days after being contaminated. The original design was to use a hydrogel substance to coat walls and other hard surfaces, with genetically modified bacteria being incorporated into the design. These bacteria would secrete enzymes that prevented biofilm formation and would also secrete other anti-viral properties.
The Human Practices team carried out research into global stakeholders that could benefit from our project idea and what materials could make it possible to minimise the manufacturing necessary. The aim was to be able to manufacture the product locally to each stakeholder area both in low and high economically developed countries. From this research, the team made the decision to focus on using chitosan as a hydrogel material, as we saw the opportunity to manufacture our product responsibly using seafood waste.
Chitosan is derived from shellfish waste, thus the team researched NGOs and contacted local fisheries to see whether the production of chitosan for the product would be a viable option. We found that chitosan also has some properties that made it unsuitable for purpose, such as the fact it was antibacterial in our target service environment, so any bacteria that we modified would be killed by the hydrogel itself. We attempted to move forward using Chitin (also another derivative from shellfish waste), but decided to first focus on determining our final application before looking into other materials.
Figure: Underlying Principles for Team:Manchester's Human Practices Activities for iGEM 2021
As the design progressed, the team wanted to work on a specific application. Members of the HP team interviewed obstetrics professor Prof. Nick Macklon and urologist Dr Maciej Szwedowski, who gave feedback on two on the teams' two most significant application ideas: wound healing and catheter coating. From all the initial interviews and surveys carried out, it was concluded that catheter coatings received a lot of enthusiastic feedback, as did wound healing coatings-- specifically for groinal injuries. The HP team then looked into catheter usage in hospitals, and noted the link between extended catheter usage and Catheter Acquired Urinary Tract Infections (CAUTIs). We then broadened this approach and interviewed a cardiologist to inquire about other indwelling catheters that could cause infections in other parts of the body, and found that some specialists were enthusiastic about such a product being used in their surgeries.
The take-away from these initial findings was that a catheter coating that prevented CAUTIs would be most useful for medical professionals, and the technology could be applied to different products in the future.
One of our team members arranged an interview with Dr. Christopher Blanford (Senior Lecturer in Biomaterials at the University of Manchester) to discuss the specificities of the hydrogel. It was suggested in this interview to perhaps use cellulose rather than chitin or chitosan. The necessity for the porosity of the hydrogel to suit bacterial functions was discussed, as well as the feasibility of our hydrogel material selection. Chitin or chitosan requires harsh, corrosive chemicals to process and quality control is challenging. Due to these concerns, we moved to an alternative biopolymer as the matrix of our engineered bacteria.
This decision was then backed following a meeting with Professor Phil Shapira from SYNBIOCHEM, where the team discussed issues the product could potentially face if we were to produce it using “waste-derived” products such as chitin or chitosan. It was also debated whether or not we could label the product as “waste-derived” due to inappropriate data collection in shellfish producing companies, and labelling a material that is being reused as waste. This discussion also further raised concerns regarding allergic reactions to potential allergens that could contaminate the chitin or chitosan extracted from shellfish waste.
The HP team then researched whether it would be feasible to use chitin due to the number of people globally with shellfish allergies (0.5-2.5% of the global population), and the team found that shellfish allergies in particular can range in severity. “Hypoallergenic” chitin-based polymers were also researched, but the methods to synthesise these polymers were high-cost and multistep to ensure a maximal chitin purity, however, this then would limit our product to high-income providers. With all the direction we had been given in the interviews, we decided to use cellulose derivatives (NaCMC and HPMC) and began our modelling work.
As the team now had a more in-depth idea of what materials we were going to use for the catheter-coating, specific stakeholder feedback was required in order to help to influence the design and purpose of the product further. Three further interviews were carried out: first with a chronic UTI patient, second with a urologist, and finally with a GP senior partner in order to gain further insight as to how Urigel could potentially benefit both doctors and UTI patients. From the interviews, we found that inflammation associated with CAUTIs is often the aspect of the infection that patients suffer the most from-- and so it was suggested that instead of just preventing UTIs, the team include an anti-inflammatory aspect within the design. The HP team also evaluated the consequences of inflammation on a patient, and found that inflammation often leads to infections, and requires increased use of anti-inflammatory drugs and painkillers. There is also increased risk of chronic infections, stricture formations and chronic pain.
The team prepared a literature review study to investigate the difference in adopting new medical technologies in low and high income countries, how are resources managed for medical device technologies, would medical staff use new medical devices when given accessibility to the appropriate equipment, how do the behaviours of patients differ between state-sponsored or self-purchased novel medical devices. We decided to keep this for our collaboration and to narrow our research questions to focus more on our design for UriGel.
After the KCL-organised UK virtual meetup, we began our collaboration with the King’s College London team. We started forming a mentorship and had bi-weekly meetings to discuss our projects and troubleshoot specific research, modelling and other problems.
We started to write a literature review on the costs, treatment and care quality outcomes for CAUTI patients in low and high income countries. This was done to better understand the institutional environment our project would be used in. In particular, it was important to understand the different factors influencing care quality and how it could be incorporated into UriGel design.
In planning to make an accessible and inclusive Wiki, we contacted the Disabled Society and Rosalind Bell to get recommendations and feedback. The outcome of the interview was that websites should be designed with accessibility in mind upfront. However, to make sure all the governmental guidelines are addressed, we planned to make our wiki customisable so that the user can change the font size, font style and background colour.
We expanded our collaboration into the human practices realm. We each collaborated through our team presenting a lecture on synthetic biology and the environment for KCL's Biologix competition. We used this as an opportunity for improving our interactive presentation techniques and to advertise our podcast, The Living Revolution, which we invited KCL on.
Alongside KCL, we were interested in whether or not there was a gap in communication between researchers and practicing healthcare professionals regarding novel therapies, and so we investigated this. We designed a questionnaire collaboratively, and interviewed a doctor who works at a hospital with a Research and Innovation department to gather opinions on whether this was indeed an issue that limited the use of novel therapies. From this interaction we learned about how the researcher-healthcare practitioner communication could be streamlined to provide a more integrated person-centered healthcare, something which we will take into consideration in our future entrepreneurship strategies.
From our literature review, we were able to demonstrate the key differences in care quality both between and within high and low income countries. These disparities originated from policy, procedures, lack of resources as well as factors in how digital health data was used to aid treatment of CAUTIs. This raised future considerations for the team in how we might incorporate digital healthcare and recording keeping into the design. Additionally, it presented a significant need for a point-of-care approach to our design.
You can find a PDF copy of the review here.