Integrated Human Practices

How do chronic wounds impact patients, clinicians and researchers of the field? Answers to this question and how these have shaped our project can be found here.

In order to ensure that our project is relevant and applicable in the real world, we have been talking to many experts from academia and the clinic as well as people with personal experiences. In addition to that we've been doing background research through literature to understand the extent of the problem and its impact on the world.

We had three main ideas. One was antibody production in yeast and a second was producing energy in bacteria. Our third idea was more vague but it revolved around biofilms. On one hand we were thinking about combating biofilms on medical devices and on the other, the biofilms in wounds.

Below, we have documented the steps we took during our project to evaluate the impact of our solution and how we've adjusted it based on the discussions we've had and the research we've done.

Why should we treat chronic wounds?

Chronic wounds include diabetic foot ulcers, venous leg ulcers and pressure ulcers (Frykberg, 2015). Between 15 % to 25 % of diabetes patients, for instance, develop diabetic foot ulcers (Huang and Kyriakides, 2020). Patients that suffer from diabetic foot ulcers are observed to have a higher morbidity and mortality than both healthy patients and other diabetics with a better-managed condition (Moulik et al., 2003). They have a decreased quality of life and higher amputation rates, as explained to us by local dermatologists, plastic surgeons and wound care nurses at the Helsinki University Central Hospital.

Chronic wounds do not only cause a decrease in the quality of life for the patients themselves, but also for the people around them due to the time and energy spent on caretaking. It has been estimated that in developed countries, 1-3 % of total healthcare costs go towards chronic wound management (Järbrink et al., 2017). Within the EU, up to 50% of the hospital beds are occupied by patients with wounds (Posnett et al., 2009). Though the wounds are a mixture of acute and chronic injuries, the latter take up greater resources due to the many in- and out-patient follow-ups over time consuming both human resources and treatment materials. Those numbers do not describe only the expense to the governments, but also the opportunity cost that could have been used for example in research, treating other patients, development and humanitarian work.

The daily pain of chronic wounds already decreases their sufferers' quality of life, alongside the inconvenience of limiting the movements and resting positions that can be taken. 90 % of chronic wounds have bacteria commonly settling at the wound site and are not easily cleared by the immune system (Attinger and Wolcott, 2012). These bacteria then keep building up into thicker biofilms (a structural community of bacteria), which can cause further issues as they are known to be tolerant to antibiotics and host defences (Høiby et al., 2010).

Since 2020, we have noticed how well-responsive the whole scientific community is when facing an epidemic or pandemic: it comes together in solidarity to work on a solution. But there are other epidemics plaguing the healthcare system - and people's quality of life - that remain silent and that equally deserve such a swift, collaborative reaction. Our team wants, therefore, to bring visibility and a viable solution to one such silent epidemic, chronic wounds (Lindholm and Searle, 2016).

Mar.
Project Ideation with Our PIs
Project Ideation with Our PIs
Our first point of contact was, and still is, our PIs and advisors. Our PIs Heli Viskari and Markus Linder and advisors Sesilja Aranko and Ville Paavilainen have been a tremendous help especially when narrowing down our ideas. They gave us valuable feedback, while we were trying to decide between the three final ideas. They gave us the idea of combining our two ideas, to produce antibodies that would then attack the biofilm. They also then recommended us to contact professor Alexander Frey to learn more about his research.
Alexander Frey
Apr.
Alexander Frey
We got excited about the idea of degrading a biofilm with antibodies. At this point we contacted professor Alexander Frey, who studies antibodies and their production in yeast. We were originally searching for advice in working in the same area as him, but while talking with him, he suggested we could look into different types of molecules that work similarly to antibodies. Two examples that stuck with us were lectins and DARPins, and the latter suggestion ended up becoming a core component of our project.
(Figure created with BioRender)
May
Christopher Jonkergouw
Christopher Jonkergouw
To measure the impact of the DARPins we were to design, we needed also to plan parts for a bioreporter. We met with Dr. Christopher Jonkergouw, who had worked on a bioreporter for researching bacterial communication between gram-negative bacteria. He had got pointers on what proteins we should aim to target with our DARPin. After the meeting, based on the feedback we got, we decided to focus on the signalling molecules AIPs instead of the receptor proteins to prevent fast-track evolution.
Jouni Lounasmaa
May
Jouni Lounasmaa
During the spring we were put in contact with Jouni Lounasmaa, the previous CEO of the Startup Foundation. He was curious to hear more about iGEM and our project. During our meeting he gave us valuable feedback on how to manage our project. He asked many questions about our group's dynamics and the division of the workload and consequently made us consider those aspects more deeply. Our leaders especially felt that the discussion with him helped them lead the project more consistently, taking on lessons from the start-up sector regarding goal- and agenda-setting throughout the project.
May
Wound Professor Dr. Esko Kankuri
Wound Professor Esko
We needed to get the perspective of specialist researchers in the regenerative medicine and wound healing field to confirm that we were heading in the right direction with our solution's relevance, ideation and expected research methods. The input we needed was given by Dr. Esko Kankuri, a Professor in the Department of Pharmacology, Faculty of Medicine, University of Helsinki. Several of Esko's own research projects involve the optimisation of wound healing, and he encouraged us that we were heading in the right direction because blocking the formation of biofilms could make bacteria vulnerable to antimicrobials. At the same time he asked some pointed, necessary questions about aspects we hadn't yet considered. Especially, Esko suggested to think of the unintended negative effects of blocking quorum sensing, such as causing the biofilm bacteria to hyper-proliferate in a new way. He also suggested looking at potential biomaterials like gels and wound dressings that could help introduce the DARPins to the wound site, as this could enhance the effectiveness of combining them with antimicrobials introduced in similar ways. Lastly, he gave us the contact details of clinicians to further delve into the use of a solution like ours in a hospital, patient-centred setting. To learn more about our proposed administration method, please refer to Dresden collab and implementation.
Clinicians (Heli Lagus, Milla Kallio)
June
Clinicians (Heli Lagus, Milla Kallio)
To get an insight of what doctors and nurses face every day in the clinic, we spoke with De. Heli Lagus (plastic surgeon), Dr. Milla Kallio (vascular surgeon) and two wound and burn unit nurses Maria Honkala and Minna Hellgren via Zoom. The clinicians recounted and expanded on some of the main issues caused by biofilm, including difficulties in identifying the original cause of the wound (as many patients have comorbidities) and the need to use multiple treatments at once. It was eye-opening to realise just how little standardisation there is in chronic wound care, as the wide range of individual factors affecting treatment response (underlying disease, tissue condition, patient age and lifestyle) means that the only way for doctors to go is usually trial-and-error. This confirmed to us that our preventive treatment should look for a common denominator to target, namely a biofilm component present in all chronic wounds.

The clinicians shed a much better light on the patient side, too, especially the treatment adherence difficulties experienced. For example, patients do not tend to continue regularly applying treatment to their wounds as prescribed once they become outpatients, highlighting the need for a very simple, straightforward and effective solution to prevent biofilm formation. The clinicians agreed for us to interview patients, and advised us to get official approval for this from the Ethics Committee. Even though we weren't able to interview patients in the end, we got good advice on the consent form and patient interview questions from them.

After the meeting and to guide our collaboration with Dresden, we continued to look into the different administration methods of our treatment, like creams and bandages that release therapeutic molecules into wounds, to make it as easy and convenient as possible for ambulatory patients to use. We also found a lot more information on public health costs associated with chronic wounds, as suggested to us by surgeon Heli Lagus.
July
Ribosomal Display \w Anja Paatero
Ribosomal Display \w Anja Paatero
During the spring months we did a lot of research on how to research the binding of the DARPin to the AIP. Ribosome display was something that came up in a meeting with our PIs, so we decided to look more into that. We researched different protocols, and met also with post doc Anja Paatero, who had been working with in vitro translation and transcription before. We compared our protocols and decided that instead of doing the needed reagents ourselves like Anja does, we should invest in kits to be time efficient. We also talked about the DARPin fragment construct, and Anja was able to give good contacts for further questions regarding this. She suggested we should have our DARPin sequences as a fragment not put in a vector. This decision saved both resources and time.
Sequencing \w Lars Paulin
July
Sequencing \w Lars Paulin
For the DARPins we decided that we require sequencing in order to differentiate between them after the ribosome display. In order to do this we had a meeting with Lab. engineer Lars Paulin from the Institute of Biotechnology. We received advice on different sequencing techniques and alternatives and were recommended the Amplicon method for our DARPin differentiation as it seemed to be the most successful method to sequence for our project. In the end our fragment was too long for Amplicon, so our sequences were processed with PacBio.
July
Ribosome Display \w Ville and Kah Ng
Ribosome Display \w Ville and Kah Ng
We had struggled a bit as a team to decide if we needed to do the DARPin construct in a plasmid or order as a ready fragment. After the meeting with Anja Paatero and deciding that we would add the needed promoter, tags and spacer, and order them as a fragment, we wanted to confirm our plan with our advisor Ville Paavilainen and researcher Doctoral researcher Kah Ying Ng who has experience with in vitro protein synthesis. We got help with finding another spacer sequence as we had a few issues with repeats in the first one we had chosen. We also got good advice on what type of in vitro transcription and translation kit to order from Kah Ying, and she promised to help us with the first round of experiments, so we could get more comfortable with the process.
Rita Turpin and Noemi Gutierrez-Valdes
(The Science Basement)
Sep
Rita Turpin and Noemi Gutierrez-Valdes
(The Science Basement)
Two weeks prior to the presentation that we jointly held with Turku on 24th September, we had the chance to do a practice run of the talk with two staff members from The Science Basement. This served as a coaching session, where we received feedback on the content and style of our presentation that guided how we position our science communication both with the public and with the Grand Jamboree judges. Two of the crucial points that changed how our project presentation were the need to build a clearer narrative around the significance of chronic wounds, and to be more specific and step-wise with how our solution's eventual implementation would actually change the lives of patients and the work of clinicians. This was valuable, as it also informed how we explain implementation on our Wiki.
Sep
Kenia Fita and Suvi Sundqvist
(The Science Basement)
Kenia Fita and Suvi Sundqvist
(The Science Basement)
In addition to our 24th September presentation at The Science Basement, we also wrote an article raising awareness about chronic wounds to be published on their website. Initially, the article was a bit disorganised as we struggled to fix a clear direction for it: we were introducing iGEM, our team dynamics, how biofilm works, and the chronic wound problem. The guidance provided by Kenia and Suvi, particularly in editing and refining the article text, gave us great direction in picking one main thread - raising awareness about what chronic wounds are, their usual treatment and their societal impact. The feedback has helped us to write with more focus, which we applied to how we write our Wiki pages, too. We have also been using components of this article to build our narrative for the final judging presentation.

Personal Experience

Our initial plan was to interview patients from the wound clinic, but unfortunately because of limitations we weren't able to contact any patients in the timeframe we had. Instead we decided to look for patient experiences from people we know.

We collected three stories from our team members, that have or had a relative suffering from a chronic wound. The stories are described below:

  1. "My grandmother's struggles began with a minor wound in a toe that was caused by a nail technician cutting a bit of the skin next to a toenail. When you recall the story after years have passed, it seems ironic that trying to take care of yourself as a diabetic patient led to the reason she lost her leg and eventually her life.

    As is being said, everything started with a minor wound, however for diabetic patient's even minor wounds are important to be properly taken care of. How the wound was treated was just like from the text books; regularly cleaned and covered with wound dressings. Unfortunately, the wound just got more infected and no antibiotics helped. My grandmother was taken to a hospital when we noticed her toe had started turning black, meaning that her toe was undergoing gangrene, a tissue death caused by the lack of blood supply. Diabetes patients' are well known to have poor circulation in limbs.

    Doctors decided that the only option is amputation at the middle of lower limbs, hoping that the circulation would be better and the amputation wound would heal properly. This was a major setback in my grandmother's life, however there was still hope that she could live on her own with little additional help. After the surgery, the healing process prolonged until she once again had a chronic wound that would not close or be uninfected. The blood circulation was not just enough. At this point, our family really started to feel the pain of our grandmother's fate. She was a lively person who enjoyed cultural events and visiting family members. That person seemed to fade away slowly.

    The only option was to amputate the leg even higher, this time over the knee. It was clear that she would never be able to return home and would spend the rest of her life in elderly house or hospital. After the second amputation, it felt like the person in the hospital bed was not anymore my grandmother, the crippling depression had taken over her completely. Even after the second amputation the new wound would not heal. At this point, my grandmother's wish was to leave without pain. All the medications were stopped and she passed away the next day.

    The process took almost two years. I can only imagine how my grandmother had felt during that time, but it was hard for the relatives as well. You never want to see them suffer. It truly showed me how small things can really turn into a worst nightmare, and how limited the options are for chronic wound patients.”

  2. “My great-aunt has been in and out of hospitals for quite some time now with different health problems. Among these, she has diabetes. Few months back, her toe had to be amputated because of a chronic wound that decreased her quality of life.”
  3. “My maternal grandmother's side of the family is prone to diabetes, and quite a few of her relatives have been at least pre-diabetic with elevated blood sugar, causing them to severely restrict their diet. The worst case was her older brother, my great-uncle. He had been living with type diabetes for over a decade, perhaps even close to two decades, injecting insulin into his abdomen around every meal time. His disease and his sedentary lifestyle in old age also cause bad circulation problems in his lower limbs, eventually leading to tissue necrosis in several toes. These toes had to be amputated, and he died shortly after, a few years back. It was very difficult for his wife to care for him all those years, and for my grandmother to see her brother deteriorating and get increasingly weak.”

These stories emphasised the importance of our project and proves that our solution is needed and provides a positive impact on the world. We hope to improve the quality of life for patients who suffer from chronic wounds. As the issue is so complex, our solution would likely be one part of the entire treatment process. These personal experiences and stories we heard were a big reason why the work we were doing felt so important to us. To better the quality of life or even to save a life is a huge reason to try to find an effective treatment. To realise so many encounters with these wounds in their lifetime motivated us to find a solution.

We have measured the impact of our project with our Integrated Human Practices through thorough literacy research, the feedback of professionals and the stories from patients themselves. We have concluded that our project does have a positive impact on the world. Additionally, the discussions we' ve had have impacted and steered our project development through the whole process. We have listened to the feedback we have gotten and tried to change our project for the better.

Conclusions

We have measured the impact of our project through thorough literacy research, the feedback of professionals and the stories from patients themselves. We have concluded that our project does have a positive impact on the world. Additionally, the discussions we've had have impacted and steered our project development through the whole process. We have listened to the feedback we have gotten and tried to change our project for the better.

References

  1. Attinger, C. and Wolcott, R., (2012)
    Clinically addressing biofilm in chronic wounds
    Advances in wound care, 1(3), pp.127-132
  2. Frykberg, R.G. and Banks, J. (2015).
    Challenges in the Treatment of Chronic Wounds
    Advances in Wound Care, [online] 4(9), pp.560-582
  3. Høiby, N., Bjarnsholt, T., Givskov, M., Molin, S. and Ciofu, O. (2010)
    Antibiotic resistance of bacterial biofilms
    International Journal of Antimicrobial Agents, 35(4), pp.322-332
  4. Huang, Y. and Kyriakides, T.R. (2020)
    The role of extracellular matrix in the pathophysiology of diabetic wounds
    Matrix Biology Plus, p.100037
  5. Järbrink, K., Ni, G., Sönnergren, H., Schmidtchen, A., Pang, C., Bajpai, R., & Car, J. (2017)
    The humanistic and economic burden of chronic wounds: a protocol for a systematic review
    Systematic reviews, 6(1), 15
  6. Lindholm, C. and Searle, R., (2016)
    Wound management for the 21st century: combining effectiveness and efficiency
    International wound journal, 13, pp.5-15
  7. Milla Kallio, Heli Lagus, Kirsi Isoherranen & Niina Matikainen (2020)
    Yhteistyö haavanhoidossa: mahdollisuus parantaa laatua ja vähentää kustannuksia
    Duodecim 2020;136:1702-4
  8. Moulik, P.K., Mtonga, R. and Gill, G.V. (2003)
    Amputation and Mortality in New-Onset Diabetic Foot Ulcers Stratified by Etiology
    Diabetes Care, 26(2), pp.491-494
  9. Posnett, J. et al. (April 2009)
    The Resource Impact of Wounds on Health-care Providers in Europe
    J. Wound Care, vol.18 (4)
  10. Rémy, Benjamin, et al. (2018)
    Interference in bacterial quorum sensing: a biopharmaceutical perspective
    Frontiers in pharmacology 9: 203