Human Practices Groningen

Introduction

The issue of biofilm formation on prosthetic joint implants has been extensively discussed in both the Home and Project Description sections. Dealing with infections related to implants is a complex challenge, requiring a deep dive into all its intricacies and implications. This was our primary goal in our Human Practices efforts - to comprehensively grasp the problem. We aimed to develop a customized solution, starting from the context of joint replacement surgeries, delving into complications like revision procedures and infection treatments, and considering the long-term impact of implants on patients' lives. We meticulously examined all potential stakeholders associated with this issue and focused on understanding how our design could address their respective needs and preferences.

Human practices play a pivotal role in our product development process. By incorporating elements of human practices, we gained a deeper understanding of the challenges we faced and were able to devise a tailored solution. However, when engaging in synthetic biology, it is essential to consider human practices in a broader context. Progress in the field of genetic engineering must always be conducted with a strong foundation in ethics and responsible practices.

As the array of tools available for scientists continues to expand, pushing the boundaries of what is possible, it becomes increasingly crucial to contemplate the broader implications of scientific work. To give substance to our research, we must extend our focus beyond what occurs within the confines of the laboratory. Translating our project into the real world and anchoring it there requires meticulous examination of the surrounding context. Active engagement with stakeholders and the integration of their feedback is key to grounding our project.

At all times our project should adhere to relevant regulations and guidelines. Even more importantly, our project should engage the (un)informed public through educational efforts in biotechnology and synthetic biology. This involves initiating an open dialogue and having an interdisciplinary approach to ensure a well-rounded project that is based on societal debate, and consensus, and is in touch with the wants and needs of all stakeholders involved.

The section on (Integrated) Human Practices illustrates the measures we've undertaken to ensure that Bye-O-Film is as practical, safe, and ethically sound as it can be. We offer a detailed overview of our interactions with various stakeholders to acquire and apply their knowledge and experiences, as well as the actions we've taken to enhance the iGEM community for future teams. Our Human Practices approach was based on and adapted from the frameworks developed by the iGEM Groningen 2021 team and futher expanded by the iGEM Groningen 2022 team ^[3-6]. Their work allowed us to reach a large number of stakeholders and gave us a clear and well developed framework to work within. We also applied the AREA framework, as described by the 2019 iGEM team from Exeter ^[7].

Problem definition

Joint replacement surgery has become increasingly common worldwide, affecting a broader range of people. This growing trend is also noticeable in the Netherlands, where 2% of prosthetic joint surgeries are complicated by infections. Healthcare professionals face the daunting task of identifying biofilm infections, managing associated complications, and administering appropriate treatments. Biofilms pose a significant threat to both the patient’s health and, due to costly treatment, the healthcare systems.

Accurately pinpointing biofilm infections is challenging due to the inadequacy of infection symptoms and test results in determining the location of infection. Often, treatments involve invasive procedures that can elevate the risk of infection. The current methods are insufficient in preventing biofilm formation on implants. Researchers are actively exploring ways to detect and treat these infections, while companies are developing smart materials to prevent their occurrence. However, there is >no comprehensive solution available—one that can both identify biofilms and provide the necessary treatments. With the utmost concern for patient health and well-being, we have developed Bye-O-Film as a user-friendly and whole answer to this problem.

Approach

To thoroughly understand the problem we set out to solve, we took a systematic approach by breaking it down into its detailed components and conducting an in-depth analysis to grasp and improve each part. Our quest for essential information began with a comprehensive review of existing scientific literature and a careful examination of the stakeholders involved.

While studying the literature gave us a strong theoretical foundation for our project, our engagement with stakeholders was an even more critical step to tune our design into a practical, real-world solution. We focused on two main aspects: ensuring the satisfaction of patients and selecting the most suitable technologies. To do this, we arranged meetings and conducted interviews with a variety of experts, medical professionals, and researchers. This collaborative effort played a crucial role in refining Bye-O-Film. We meticulously documented our journey and are now sharing our findings for future reference.

Conducting surveys with patients and performing engineering analyses provided valuable insights into the specific requirements that Bye-O-Film must meet. All our efforts related to Human Practices have been seamlessly integrated into the product's design. Importantly, we conducted these activities in strict adherence to ethical principles, how we adhere to these principles is further elaborated at the bottom of this page. Our ultimate goal is to deliver a solution that effectively addresses all the challenges posed by biofilm infections linked to prosthetic joints in an efficient user-friendly manner.

A visual summary of our comprehensive approach to Integrated Human Practices is depicted in Figure 1. This figure shows how human practices work and forms the basis to get to the finished product, at the top. It is worth mentioning that, although the representation is a bottom-up approach, human practice is an iterative process. Sometimes new insights are gained that require rethinking the approaches we apply to interact with the stakeholders and processes described at the bottom of the pyramid.

Later on this page, we will come back to the AREA framework, a tool we use to clearly structure our human practice efforts to clearly and concisely state the benefits and new insights we gained when interacting with a professional or other stakeholder ^[7]. We will continue to describe how the gained knowledge influenced our key values which ultimately shaped our final product, the Bye-o-Film.

Figure 1: A visual summary of our comprehensive approach to Integrated Human Practices. This figure is adapted from figure 2 of iGEM Groningen 2021 ^[4]. This figure was made using BioRender.com.

Values and Impact

When designing our project, we held a multitude of values in mind, each contributing to the overall mission and purpose of our endeavor. On the social front, our primary goal was to provide crucial support to patients grappling with the uncertainty and challenges of implant infections. We wanted to put the wants and needs of the patient central to our design problem. To achieve this, we actively engaged with patients through surveys to ensure their perspectives were integral to our process. Moreover, our project bore social and economic dimensions, benefiting not only patients but also taking into account the perspectives of health professionals, patients' families, and insurance companies by potentially reducing the financial burden associated with treating implant infections.

From a scientific perspective, our project embraced innovation by incorporating cutting-edge techniques such as biosensors and phage therapy. These choices aimed to explore alternative methods for diagnostics and therapeutics, positioning us on the frontier of medical advancements. Morally and socially, our project was driven by the desire to raise awareness about implant infections, improving the quality of life for affected individuals while adhering to ethical research practices.

In pursuit of these values, we diligently consulted a diverse array of resources and communities. This included engaging directly with patients and the general public, seeking insights from medical professionals who deal with implant-related issues, and collaborating with experts in phage therapy and phage utilization. We also extended our outreach to the general public, fostering broader awareness and understanding of the critical issues surrounding implant infections. To demonstrate the responsibility and positive impact of our project on the world, we prioritize user-friendliness in our device design. We actively seek feedback and input from patients and medical professionals, ensuring that our solution is both effective and user-centric. By considering the practical needs and preferences of those who will use our product, we aim to create a responsible and valuable contribution to the healthcare landscape.

The impact we envision for our project is multifaceted and far-reaching. Foremost, we aspire to enhance the quality of life for patients with medical implants, mitigating the physical and emotional toll of implant infections. Simultaneously, our efforts could lead to a reduction in healthcare costs and complications, alleviating the burden on healthcare systems. Improved mental health outcomes among patients, stemming from reduced anxiety associated with implant infections, are another dimension of our anticipated impact, as patients undergoing revision surgeries due to prosthetic joint infections have a four times higher prevalence of preoperative depressive symptoms than patients undergoing aseptic revision ^[1]. Additionally, by advancing diagnostics and therapeutics, our project has implications for the broader field of medical research. Currently, late detection results in more invasive treatment. Our commitment to raising awareness about implant infections could translate into better-informed decision-making and a proactive approach to healthcare. Lastly, by reducing the need for antibiotics, we contribute to the global effort to combat antibiotic resistance, safeguarding the future of healthcare.

In terms of our proposed end users, our project is designed with the well-being of patients with medical implants at its core. These individuals, facing the challenges of implant infections, are the primary beneficiaries of our efforts. Our aim is to provide them with a solution that enhances their quality of life and reduces the physical, emotional, and financial burdens associated with implant-related infections. For a deeper understanding of the biofilm infection issue’s context see our [Project Description page.]

Progress Timeline

Figure 2: This progress timeline includes key points of our design process that shaped the final product. The arrows represent our workflow and the connections between different stages. We highlighted three meetings in particular that significantly helped us define the project. This image was created using BioRender.com

In our project, "Bye-O-film," we've put great emphasis on a dynamic design process, constantly incorporating feedback as we progress. Over the past few months, we've gone through various design phases, and we've sought external expertise to guide our decision-making. This approach ensures that our project aligns with our initial values and considers the practical needs of end-users and the larger system where our product will be applied.

The timeline chart above illustrates the evolution of our design strategy, with key meetings playing a significant role in shaping our project's direction. Three crucial meetings stand out in particular.

At the project's outset, we conducted a comprehensive analysis to identify the issue we wanted to tackle. We also took stock of our available resources, including both knowledge and materials. This led us to focus on developing a biosensor capable of detecting biofilm formation on medical implants. As our research deepened, we started to define the core elements of our design. Our envisioned device would serve a dual purpose, both detecting biofilms and temporarily treating infections. To achieve this, we decided to utilize a cyclic-di-GMP promoter previously developed by the CUG China iGEM team in 2022, coupled with bacteriophage therapy.

Our project then split into two tracks: detection and treatment. With limited knowledge about phages, we sought guidance from a knowledgeable professor, which marked Meeting 1. This discussion provided valuable insights into phage design and sparked innovative ideas, such as attaching a protein for simultaneous detection and treatment. We also realized we could incorporate a protein that could aid in biofilm destruction. For the detection side, we were exploring options, including sensing analytes created by an expressed enzyme. While hydrogen peroxide and other redox molecules were considered, their lack of available sensing technologies proved a hurdle. Another avenue was to detect light emitted by bioluminescent or fluorescent proteins, leading to a series of discussions on measuring light and choosing the right light source. Meeting 2, where we engaged with a professor experienced in optogenetics and light sensing in biological contexts, was instrumental in our understanding of fluorescence as a reliable and easily measurable signal through optic fiber cables.

Subsequently, our design paths converged as we realized the necessity of creating a light expression system for sensing. We also recognized the importance of incorporating a control mechanism to verify the bacterial system's viability. This led to the development of a sensing plasmid, ensuring cyclic-di-GMP dependent green fluorescent protein activation, exclusively expressed upon biofilm formation and a continuous expression of red fluorescent protein as a system confirmation that our setup is alive and well.

With a final design in place, we began the process of ordering components, cloning, and testing. Simultaneously, we worked on an electronic sensor for light detection, initially considering optic fiber cables at the implant site. However, Meeting 3, where we consulted with an experienced orthopedic surgeon specializing in joint replacement surgeries, made us reassess our approach. We realized that a less invasive wearable device was necessary, given the mobility of joints and the risk of infection associated with invasive methods.

Understanding these practical constraints, we delved into wearable device design principles, gathering insights for future enhancements. Within the scope of our project, we couldn't identify a solution that could be feasibly tested with our available resources and timeframe. Consequently, we decided to retain the light sensor as a proof of concept, acknowledging the project's limitations and discussing potential avenues for improvement in our project documentation.

Stakeholder analysis

To identify who is involved in the problem around biofilm infections and in our project, and to understand their involvement in the landscape of our problem, our team completed a stakeholder analysis. The idea behind the analysis is to first identify which different stakeholders are involved in the project and which "stakeholder group" they belong to. The various identified stakeholders are shown in Figure 3.

Figure 3: The various stakeholder groups we've identified as being involved in our project, Bye-O-Film. We’ve also included various local stakeholders/organizations, such as the AJH (Aletta Jacobs School of Public Health), the HTRIC (Health Technology Research and Innovation Cluster), RIVM (Rijksinstituut voor Volksgezondheid en Milieu), MEBI (Meldpunt en Expertisecentrum Bijwerkingen Implantation) and the LROI (Landelijke Registratie Orthopedische Interventions). This figure was adapted from figure 10 of iGEM Groningen 2021 and figure 1 of iGEM Groningen 2022 ^[3,6]. This figure was made using BioRender.com.

Subsequently, an assessment is made for each stakeholder regarding the degree to which the project can impact their lives (interest/availability). Additionally, their power and ability to influence the project's outcome are evaluated and scored. Subsequently, stakeholders are categorized in a grid, where interest and availability increase from left to right, and influence rises from bottom to top. This grid guides decision-making on how to engage with stakeholders within each quadrant. For instance, it is advisable to proactively involve stakeholders located in the ‘Manage Closely’ quadrant in your project.

The insights derived from this final grid enabled us to determine the key stakeholders to prioritize in our project and to understand the dynamics of influence and interest across these various groups. We completed this stakeholder analysis as part of our preparations for stakeholder interviews. Our visual representation of the influence and interest of the stakeholders (figure 3) can be seen in Figure 4.

Figure 4: Stakeholder analysis of the stakeholders who are involved in our project Bye-O-Film. This figure was adapted from figure 11 of iGEM 2021 and figure 2 of iGEM 2022 ^[3,6]. This figure was made using BioRender.com

Engaging with stakeholders - AREA framework ^[7]

We used an email script similar to the ones used by previous Groningen iGEM teams (2021 and 2022) to contact the stakeholders ^[3,6]. Before each stakeholder meeting, we prepared questions to ask. In order to prepare for stakeholder interviews we communicated with an associate professor with expertise in lifecourse, self-management, and sociology to further improve upon our interview protocol. We ensured that our questions were tailored to the expertise of the specific stakeholder. We also asked stakeholders if they knew other relevant stakeholders we could contact. Through the so-called ‘stakeholders-know-more-stakeholders’ approach, we have been able to reach very interesting stakeholders that we hadn't identified before. How our interactions with different stakeholders have shaped our design choices throughout the project is shown in the progress timeline described above, figure 2. Summaries of the meetings we had with stakeholders can be found below, as well as the procedure we applied when talking to a stakeholder, figure 5. We used the AREA framework [AREA framework] for this, formulated by iGEM Exeter 2019 ^[7]. Using this structured approach, we ensured to maximize the value of the knowledge gathered, resulting in further project optimization. The framework is used to highlight the contribution of each meeting, articulate its impact on project adjustments, and outline our next steps.

Figure 5: Complete overview of our approach for contacting and interacting with stakeholders. Based on information from iGEM Groningen 2021 and 2022 ^[3-6]. This figure was adapted from figure 13 of iGEM Groningen 2021 ^[3]. This figure was made using BioRender.com

Figure 6: Bianca, Thomas and Mirela at the end of a successful meeting with a stakeholder.

One particularly interesting and important stakeholder we considered in our project is the end-user. The end-user is the patient (potentially) suffering from or more susceptible to developing a biofilm infection on their medical implant. Through our stakeholder interactions, we realized that our project might be particularly relevant to immunocompromised patients, as they are more likely to develop biofilm infections. With our project Bye-O-Film, we aim to represent the needs of a frequently overlooked group of people. Below, we outline the insights we gained from engaging with our primary stakeholder groups.

Medical professionals

Medical professionals play a crucial role in our project's development. They are some of the most important stakeholders due to their keen interest and significant influence. After all, they are the ones who interact with and treat the patients. Consulting them, especially regarding practicality and accuracy, is paramount.

Orthopedic surgeons and doctors are the ones hospitals turn to for guidance on the best monitoring and treatment practices based on their extensive knowledge. They also directly engage with patients and are responsible for surgeries and potentially installing monitoring devices. Their expertise in surgical practices and requirements makes their input invaluable when it comes to designing and improving our sensor.

Engaging with medical professionals helps us keep our project grounded and tailored to the needs of those who will use the device hands-on. It's essential that they can easily use and understand the device, and it should seamlessly fit into their existing practices.

To make sure our project is compatible with the current medical system, we interviewed the head of the orthopedics department at the University Medical Centre Groningen (UMCG) and asked for opinions and feedback. Here we realized that our design is not as patient-friendly as we thought, as devices using cables are generally not well suited for long-term usage, especially in highly mobile areas such as joints. We also received a lot of positive feedback regarding our design and confirmation that the issue we are tackling is indeed pressing.

We also had informal chats with medical students and physiotherapists to gain a broader understanding of how our device would function in the real world. We learned about the prosthetic joint surgery processes, the considerations for developing a medical device, and the need for more indirect patient monitoring due to staffing shortages. Overall, there's a growing need to ease the burden on the medical system, and our self-monitoring device could be part of the solution.

Experts & Researchers

Experts and Researchers are another important group of stakeholders. They have a high interest in our project, as our results and designs will be added to the scientific pool of information on the subject of infected implant treatment. They can also influence the outcome of our project through advice and guidance, as well as by sharing their experiences and providing highly valuable information. They are knowledgeable on the state-of-the-art developments in fields associated with the issue we are tackling. Consulting experts and researchers helps us make sure our project is accurate and feasible while providing a great source of inspiration and technical advice.

It was especially important for us to involve researchers and experts into the design process, as none of our team members had extensive knowledge of biofilms, phage therapy, or medical implants. As we progressed with the project we discovered new areas where some expert input was highly needed and the meetings we had proved to be invaluable to the final outcome.

We started off our journey by discussing with some professors within our faculty who were familiar with more integral concepts of our project, such as bacteriophages. We met with a professor who focuses on Molecular Evolution with knowledge of phage display and phage expression. The meeting helped us understand how phages work and what is possible to achieve within the project as far as phages are concerned.

Next, we met with a professor specializing in orthopedics and regenerative medicine from the University Medical Center Utrecht (UMCU). Here we learned a lot about biofilms, how they form, when is the best time to prevent their formation and what is the current state of the art in materials that can protect implants from getting infected. We also received valuable resources regarding wearable biosensors and current technologies we could incorporate into our design.

Another valuable meeting we had was with a professor from the University Medical Center Groningen (UMCG), specializing in biomaterial-related infections. In 2022 the ninth Thesinge (a village near Groningen) Biofilm meetup was organized. We learned that this professor was not only one of the main organizers but also one of the leading experts on biofilm in surgical applications. In conversation with the professor, we were told that non-material-based prevention methods are very much needed for implants since these implants are meant to be used long-term, while materials wear out with time. We were also faced with new questions, such as how large would our detection area be. An important takeaway was that fluorescence cannot be detected through the skin, so our sensor would have to be invasive.

Figure 7: Maartje, Mirela, Jelle, and Thomas after a meeting with a researcher of biofilm infections at the UMCG.

Around the same time, we were researching a detection method that would be biocompatible and easy to measure with the available lab resources. Once we settled on light detection, we planned another meeting with a professor from our university who focuses on Systems Biology and signaling networks, where a lot of experiments are based on light detection within living systems. Our takeaways from the meeting were that fluorescent light would provide high enough intensity for our measurements and it is possible to build a detection device using optic fiber. We also received valuable contacts that later helped us build our own sensor which we managed to test in the lab.

Armed with a lot of knowledge, it was time to start designing the setup of the electronic sensor. For this, we reached out to the Faculty Technical Service of the University of Groningen. This contact was instrumental in identifying the requirements for engineering a sound and working electrical circuit. They were also of considerate help in advising us, ordering the necessary equipment, and helping us in creating the right experiments to validate our design. Thanks to this collaboration we stepped outside of synthetic biology and developed new skills in electronics and engineering which helped us broaden the perspective of the project by using a multidisciplinary approach.

We also had multiple chats with other professors and students for small questions, ideas, and opinions. Each conversation helped us shape our final product and enhanced our knowledge and overall view of the issue.

Companies

Throughout our project, we actively engaged with a diverse array of (local) companies and innovation centers. Our primary objective was to gain a comprehensive understanding of advancements in biofilm detection and treatment technologies while establishing connections with relevant stakeholders.

Our initial point of contact was with local innovation and entrepreneurship hubs, most notably Campus Groningen. This dynamic hub is renowned as the epicenter of innovation in the Northern Netherlands, housing numerous companies, knowledge institutes, and a substantial student population. Discussions with Campus Groningen were aimed at identifying connections to relevant stakeholders specializing in biodetection, biofilm formation, bacteriophages, and medical implants. Their insightful recommendations opened doors to a network of fascinating organizations and companies operating in these domains.

One notable company we contacted via this network was Bioprex, a notable player in the field. They specialize in developing novel antimicrobial coatings for biomedical devices. Their unique coatings effectively eliminate bacteria upon contact, preventing biofilm formation and ensuring the absence of body fluid contamination. We explored the diverse stages of a company’s development and learned about their position in the market. We discovered that their operational model involves providing specialized coatings. A Toll-manufacturer then takes on the task of applying these coatings to substrates, typically obtained from implant manufacturers. These implant manufacturers subsequently carry out clinical studies and facilitate the entry of products into the market. Regrettably, we were unable to arrange an in-person meeting with them.

Our interactions extended to another entrepreneurial hub, Pharma Connect Capital. Pharma Connect Capital is an organization dedicated to investing in startup ventures throughout the Northern Netherlands with a focus on drug development, delivery technologies, biomarkers, and diagnostics. Their insights and introductions to potential stakeholders further enriched our understanding of the dynamic landscape of innovation in these areas. This contact led to the fruitful introduction to Detact Diagnostics.

Detact Diagnostics has developed a broadly applicable diagnostic test for detecting bacterial infections on the basis of the presence of bacterial peptidases. More notably, Detact Diagnostics is also developing a product that aims to tackle the same problem as Bye-O-Films, namely periprosthetic joint infections (PJIs). The opportunity to learn about the establishment and growth of their startup offered a valuable perspective on their journey of entering medical diagnostic tools into the market in this specialized field. This interaction also gave us the opportunity to learn alternative approaches to our problem statement.

In summary, our interactions with these entities not only broadened our understanding of biofilm-related technologies but also forged essential connections within the industry, contributing to the success and depth of our project's endeavors.

The general public and peers

Considering the general public and university students as stakeholders is crucial for several reasons. Public perception profoundly influences the success and adoption of our innovative solution for implant-related infections. Engaging the general public empowers us to address their concerns, gather valuable feedback, and align our project with societal values and expectations. This involvement also raises awareness about implant-related infections, biosensors, and phage therapies, potentially garnering support, funding, and interest in our initiative. Actively involving the general public enhances transparency and taps into the collective intelligence and potential contributions of a broader audience, ultimately enriching our project's impact and sustainability.

The general public may have concerns about the safety of GMOs used in the biosensor and potential long-term environmental impacts. Questions may arise regarding the biosensor's detection methods, safety measures for GMOs, and overall efficacy. However, Bye-O-Film offers numerous aspects of interest to the general public, including improved healthcare approaches, awareness about managing implant-related infections, potential reductions in antibiotic resistance concerns, and enhanced patient-centric care. The development of customizable biosensors provides tailored solutions across various industries, extending beyond healthcare. Our project is likely to intrigue those fascinated by cutting-edge medical advancements, particularly given its focus on addressing global public health threats related to drug-resistant microorganisms. Bye-O-Film's mission holds the potential to revolutionize biofilm management practices, benefiting individuals with medical implants while also contributing to advancements in biosensor design and phage therapy. All of this occurs while raising awareness about infection-related complications in the general public and the scientific community.

For our peers and university students, who are also part of the general public, concerns may revolve around the safety of wearable biosensors, the use of GMOs, and the comfort associated with continuous glucose monitoring. However, Bye-O-Film offers a unique opportunity for university students, especially those in healthcare and biosciences courses, to gain hands-on experience with cutting-edge technology and research. It underscores the importance of interdisciplinary approaches in healthcare, aligning with the academic journey of these students.

To ensure our peers remain informed, we've organized workshops, seminars, and presentations to share our progress, results, and challenges. For instance, we hosted a Design-thinking workshop and presented our project at our university's Groningen Biomolecular Sciences and Biotechnology symposium. We also arranged interviews with the magazine Lifelines of the Life Sciences Study Association G.L.V. Idun, aiming to reach out to our peers and promote the iGEM community. Lastly, we also aimed to educate the public, of all ages. We have written a blog series in understandable language for the general public on the Dutch biotecnologie.nl science website. We also set out to educate young pupils by giving lessons about the potential of simple laboratory techniques to answer simple scientific questions. Lastly, we also believe it is important to show what can be done in the course of an iGEM project and to highlight our results and findings. Therefore, we will organize a Groningen symposium for all relevant students and researchers to not only present our results but to educate the participants about the possibilities of synthetic biology, particularly within the scope of iGEM. More details about our efforts can be read on the [collaborations] page.

We actively engage with our peers to share project progress. Engaging them in discussions to gather feedback and insights can be valuable for refining our project. Collaborating with peers who have expertise in related fields fosters a multidisciplinary approach to problem-solving. A highlight is for example the survey carried out among fellow students to ask about their experiences wearing a continuous glucose monitor for their course. Furthermore, sharing our project's documentation and findings through easily accessible channels such as a project website or social media is essential. Building trust and understanding with the general public can benefit from engagement through social media. Platforms like LinkedIn, Instagram, and Facebook provide opportunities to share informative content, host live Q&A sessions, and address questions and concerns promptly. Similarly, maintaining a close connection with university students is vital. Sharing project updates and insights on university social media channels helps maintain student engagement.

Bye-O-Film has initiated three surveys to gather valuable feedback:

Patients' experience with biofilm infections on implants Survey, the purpose of which was to reach our end-user and collect their experiences with having a medical implant and dealing with an infection.
The General Public Survey on GMOs in Therapeutics gauges public opinion on genetically modified organisms (GMOs) in therapeutic applications, enabling Bye-o-film to address public concerns effectively.
The Survey for University Students (Food and Metabolism Course at the University of Groningen) focuses on students who have used continuous glucose monitors, collecting feedback on usability and comfort, and guiding improvements in wearable biosensors.

You can read more about the approach and results of the surveys on the [survey] page. Bye-O-Film's pioneering approach not only promises improved patient outcomes but also catalyzes raising awareness and engaging the general public and university students. Through proactive social media outreach, meaningful interaction with stakeholders, and insightful surveys, the project seeks to create a collaborative ecosystem where science, technology, and public understanding converge to address critical healthcare challenges

End user - Patients

Patients at high risk of developing biofilm-related infections on their implants represent a significant and steadily growing demographic within the realm of healthcare. This vulnerable group primarily consists of individuals with chronic diseases and compromised immune systems, and the prevalence of non-communicable diseases is further contributing to the expanding number of patients susceptible to biofilm-related infections. Despite constituting a mere 2% of individuals undergoing joint-replacement surgeries, these patients merit the unwavering attention of the scientific community to enhance their healthcare journey. Our perspective extends beyond the physical implications of surgery and recovery, encompassing the mental and emotional toll of potential infections. This includes the burden of revision surgeries, escalating healthcare expenditures, prolonged hospitalization, and, tragically, the risk of mortality, not only for the patients themselves but also for their families.

In our endeavor to connect with this patient demographic, we initiated outreach efforts toward relevant patient advocacy groups. Regrettably, our attempts to establish collaboration with Joint Replacement Patient Advocacy and the online community BoneSmart ^[2] were unfruitful. Nevertheless, we remained determined to engage with our target audience. Our approach shifted towards conducting a survey and establishing personal contacts with potential participants. The survey aimed to collect general insights into the concerns of this afflicted group and identify willing participants for in-depth interviews. For comprehensive information about our survey, please refer to the [survey] page.

Patients susceptible to biofilm-related infections understandably may harbor apprehensions regarding the effectiveness and invasiveness of potential treatments. The prospect of revision surgeries and prolonged antibiotic regimens can be daunting, leading to a heightened sense of uncertainty. Concerns may also encompass the introduction of genetically modified organisms into their bodies, with questions arising about unforeseen side effects or interactions with pre-existing health conditions or medications. Additionally, patients may express reservations regarding the invasiveness of the proposed device and its potential impact on their daily lives, including fears of hindering mobility or comfort.

Despite these valid concerns, our project offers a multitude of benefits to these patients. Firstly, our biosensor's capacity for early detection holds the promise of substantially improving treatment outcomes, thereby minimizing pain, discomfort, and the necessity for invasive procedures. Secondly, the utilization of phages as a targeted therapeutic approach carries the potential to reduce reliance on antibiotics, mitigating the risk of antibiotic resistance and its associated complications. Thirdly, the convenience of real-time monitoring through a wearable device empowers patients to proactively manage their health, thereby enhancing overall well-being and peace of mind.

Central to our mission is a profound empathy for the lives touched by implant-related infections. It encompasses the grandmother who aspires to dance with her grandchildren once more, the athlete resolute in returning to the field, and countless individuals yearning for relief from chronic pain. Their narratives, aspirations, and unwavering resilience serve as the driving force behind our unwavering commitment to our end users. Each statistic, figure, and chart is a poignant reflection of real people grappling with genuine challenges. It serves as a constant reminder that our mission extends beyond the confines of scientific inquiry; it is intrinsically tied to our shared humanity. By keeping these individuals at the forefront of our efforts, we draw inspiration to innovate, summon the courage to persevere, and find the motivation to transform lives. Together, we are dedicated to crafting a world where biofilm-related infections cease to impede the pursuit of these cherished dreams and aspirations.

Problem and engineering analysis

Our human practices efforts culminated in a comprehensive overview of the desires and needs of our stakeholders, a knowledge-informed idea about the requirements of our biosensor and the electronic sensor, and finally, a concrete idea about which functions the Bye-O-Film product should entail, to relate back to figure 1, we find ourselves in the top of the pyramid. To summarize our efforts in the Human Practices area and to transform this knowledge into an overview we performed a problem and engineering analysis [add link to Problem and engineering analysis]

Besides once again defining our project description through the lens of human practices, we characterize our stakeholders, try to identify their expectations, and denote the implications for our project. We then proceed to put these elements into a cause-and-effect diagram. Ultimately, focusing on the design of the electrical sensor, we describe what our final design should look like, and should include. While also specifying what our design should not be.

Outreach & Education

To explore our efforts in outreach and education, we invite you to check out the [Team: Collaborations] page. Here, you will find an array of collaborative initiatives and educational projects that our iGEM team has actively engaged in, contributing to our commitment to scientific advancement and public understanding of synthetic biology. Discover how we've partnered with other teams, educational institutions, and organizations to broaden the impact of our work.

Responsibly Interacting with Stakeholders

When engaging with stakeholders, you are collecting data. Personal data that might be collected needs to be dealt with in a responsible way. Therefore, it is important to consider possible data security challenges that may come up during your Human Practices work. An overview of the considerations we considered, based on information described by iGEM Groningen 2021, is presented in Figure 8 below.

Figure 8: Overview of data collection awareness considerations when engaging with stakeholders. Based on information from iGEM Groningen 2021 ^[3,4]. This figure was made using BioRender.com

To ensure that these considerations are taken into account during our stakeholder interactions, we adapted the overview figure designed by iGEM Groningen 2021. This figure (Figure 9) describes the aspects of data storage, data collection, and relevant regulations that we considered during our project.

Figure 9: A visual representation of the measures we implemented to secure data protection and informed consent during our stakeholder interviews. Based on information from iGEM Groningen 2021 and 2022 ^[3-6]. Adapted from figure 18 of iGEM Groningen 2021 ^[3]. This figure was made using BioRender.com

The figure above outlines the measures taken to ensure responsible engagement with stakeholders during our project. It highlights key decisions related to data collection and storage. First, we avoided asking questions that could pose a high safety risk, as this data was not deemed beneficial to addressing the problem and could breach privacy. Vulnerable research participants were not engaged, as working with them entailed additional ethical challenges in obtaining informed consent.

We also prioritized the protection of personally identifiable information, refraining from including names in internal notes and consulting stakeholders on the inclusion of such data in summaries. To support data security, interactions were conducted through trusted, password-protected platforms, and collected data was password-protected whenever possible. Throughout and before stakeholder interviews, we provided a comprehensive explanation of the project's objectives and asked for permission to take notes and share the interview results and summaries on the wiki.

In addition to data protection, we considered regulatory compliance under the Dutch General Data Protection Regulation (GDPR). After a comprehensive assessment, it was determined that the project's data collection and stakeholder engagement practices aligned with the Dutch GDPR, eliminating the need for a Data Protection Impact Assessment (DPIA) and the appointment of a Data Protection Officer (DPO). These measures collectively aimed to ensure responsible and ethical stakeholder engagement in the project