Dr. Lorenz Adlung

Important Takeaways:

1. Science communication
   Science communication is about communicating something complicated to people as simply as possible. It's not always easy to find the right language, as experts are very intensely involved in their subject and tend to use technical jargon. Lorenz Adlung emphasized the importance of always trying to communicate your research. For example it is easily possible to communicate via social media platforms, such as various Facebook groups or other text-based platforms. Nevertheless, apart from social media, we should also focus on offline events, as it is often easier to reach people when you speak face to face.
2. Trust model
   The trust model involves ability, integrity and benevolence. Ability stands for our professional competence to fulfill our tasks in the way we communicate. Integrity stands for honesty, openness and fairness, which must function both within the team and externally. Benevolence stands for doing things not only for oneself but also for others. As a team, we work together, support each other and help each other.

What We Integrated Into Our Project:
After the conversation with Lorenz Adlung, we gave a lot of thought to how we could best communicate our work to the outside world. How we can bring our science closer to people so that everyone feels involved. This conversation gave rise to many ideas in the Public Engagement Group (Link), which were successfully implemented. We also learned that it is important to look out for each other, that everyone in the team can always speak up if things are getting too much for them or if they don't understand something. The whole discussion helped us a lot to strengthen our presence in the team, but also for the general public.

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Dr. Mirko Himmel

Important takeaways

• Dr. Himmel stated that any intended misuse could be accomplished without utilizing our hydrogel or its constituents, and therefore, they do not present an additional threat. All of the project's techniques are already widely established and thus do not present an additional hazard.
• All activities follow the provisions outlined in the German Genetic Engineering Act (GenTG), specifically Article 1 G 2121-60-1 of 20 June 1990 I 1080.
• Dr. Mirko Himmel pointed out that Bacillus subtilis tends to produce spores, which are challenging to neutralize. Before we can start working with B. subtilis, we need to ascertain the efficacy of decontamination procedures in laboratory settings by testing their ability to eradicate it. He advised us to use an E. coli strain instead.

What We Integrated Into Our Project
After the safety discussion with Dr. Mirko Himmel we decided as a team to use the E. coli strains DH5α and Top10 instead of B. subtilis to minimize risks. You can read more about the workshop and the safety discussion with Dr. Mirko Himmel here.

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Prof. Dr. Simone Techert

Most Important Takeaways:

1. We got in touch with Simone Techert very early, as we knew that sooner or later we would reach the point in the laboratory where we wanted to photocrosslink our hydrogel and it was essential to talk to an expert in this field. Simone Techert gave us valuable advice on light sources for photocrosslinking and potential crosslinkers. One key take away is that for crosslinking, the number of photons is not that important, but the length of the irradiation. Red lasers are less suitable due to their low wavelength, but yellow or green lasers are more fitting.
2. Through Simone Techert we were able to find out that our initial crosslinker, ruthenium(III)bromide, is problematic to be used in a pharmaceutical context (see "Gefahrstoffkennzeichnung" for ruthenium(III)-bromid, https://www.chemie-schule.de/KnowHow/Ruthenium(III)-bromid). We therefore decided to use riboflavin, a non-toxic dityrosine photoinitiator.

What We Integrated Into Our Project:
Thanks to Simone Techert we were able to find the right light source for our crosslinking in advance. Even if we didn't get to that point, we know how we can progress there in the future. The interview also had a significant impact on our crosslinker selection. Due to the potential cytotoxicity/corrosive of Ru and persulfates, dityrosine photoinitiators including riboflavin or flavin mononucleotide will be used as alternatives Thanks to the tips, we were able to incorporate this into our lab plans which saved us many hours of work.

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Prof. Hyun Jong Lee

Most Important Takeaways:

1. In our e-mail exchange, Prof. Lee pointed out, that it is very important to choose the right buffer for skin applications. PBS and HEPES are suitable options, but a buffer that closely mimics the body’s natural buffers like a bicarbonate-based buffer adjusted to physiological pH would be even better.
2. He also reassured us that riboflavin could be a suitable photo-initiator for our reSkin hydrogel since it is non-cytotoxic and safe to use in hydrogels for open wound applications. A typical optimal concentration of riboflavin is around 0.01 %. It is important to keep in mind that riboflavin is sensitive to light and oxygen exposure. Prof. Hyun Jong Lee recommended to use riboflavin phosphate since it has similar photo-initiation effects and a better solubility. He also recommends to prepare fresh solutions for each experiment instead of using prepared stocks and to conduct the experiments promptly after preparing the solutions.
3. Due to the variability in material and chemical reactions, there is no formula to make up the perfect hydrogel for every approach. Therefore we will have to run a lot of tests to figure out which approach fits our system the best. Prof. Hyun Jong Lee provided a general guide to start with:
   • Start with a 0.01 % (w/v) final concentration of riboflavin
   • Wavelengths of 356 nm (UV light) and of 450 nm (blue light) are the most effective
   • We should test a range of irridation times from 1 up to 30 minutes. Since this is highly dependent on our light source’s intensity and the concentration of riboflavin we need to optimize these parameters through trial and error.

What We Integrated Into Our Project:
Prof. Hyun Jong Lee has helped us a lot to set up a plan for our crosslinking reaction. We learned about fitting buffers for our reaction and which photo-intiator to use. It was really hard to find a starting point concerning the concentration of the photo-initator, the wavelengths and the irridation time. Thanks to his recommendation we know how to get the crosslinking part of our project started.
We would like to thank Prof. Hyun Jong Lee for his help and support! Thanks to his tips we were able to work out a plan for crosslinking resilin and hyaluronic acid (link to project description with the plan). We greatly appreciate his interest in our project and his useful input!

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Prof. Brigida Bochicchio

Most Important Takeaways:

• Dr. Brigida Bochicchio told us that, in her experience, hydrogel formation is quite independent of concentration. The higher the concentration, the faster the hydrogel forms.
• According to Prof. Dr. Bochicchio, E. coli poses a suitable expression system. She has also successfully expressed resilin in E. coli in her working group and would therefore recommend this to us.
• In order to increase our resilin yield, we could use the concatamerization technique. Prof. Dr. Bochicchio's working group expressed a resilin sequence in a chimeric polypeptides containing elastin, collagen and resilin as well in low yield. In order to increase their yield of a different chimeric polypeptides containing resilin as well, they used concatamerization technique in collaboration with Professor Josè Carlos Rodriguez-Cabello of University of Valladolid in Spain (work in progress). In Italy, they have previously synthetized resilin-inspired peptides by Solid Phase Peptides Synthesis.
• Dr. Brigida Bochicchio thinks combining resilin and hyaluronic acid is an excellent idea.
• She thinks that our project has great potential.

What We Integrated Into Our Project:
The interview with Prof. Dr. Bochicchio has confirmed that we are on the right track with our project. Even if the expression of the 64 repeats of exon 1 of resilin is a significant challenge, our approach is fundamentally correct. We are pleased to hear that we have made the right and good decision despite our difficulties in producing resilin with E. coli as the expression system. This confirmation gave us new motivation to pursue a new approach.
From there on, we tried an adapted variant of the concatamerization technique to clone our 64 repeats of exon 1 of the Resilin gene. You can read more about the technique here.
We want to thank Prof. Dr. Brigida Bochicchio for the stimulating exchange and are very happy about her input and advice on our project. We are proud that we were able to inspire such an expert in hydrogels and elastomeric proteins and peptides for our project.

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Daniel Wedemeyer

Important takeaways:

1. Early difficulties
   Early on in our wet lab work, we encountered some difficulties with our restriction/ligation approach and told Daniel about them. He suggested two different concepts. The first one was the rolling circle amplification. For this concept, we would make the resilin sequence circular. The sequence needs to be long enough, but we already ordered 4 repeats by using different codons for the same amino acid. Only one primer should be then added to the circularised sequence as well as a special polymerase that amplifies circularised DNA without stopping. The product then should be a linearized product of the repeated sequence. It would be neccesary to try different amplification times to get the desired length of repeats. We would then need to clone this into our vector.
2. Oligo method
   The second concept is the Oligo method, which Daniel used in his undergraduate thesis to clone repeats. For this we would make six different oligos. The first oligo would be a full resilin exon and the other oligo would be the exon shifted by half. These form the middle of the sequence. This overlapping structure is created by overhangs and allows other middle oligos to extend the whole structure. After some time, the start and end oligos would be added, containing the restriction sites. They would perfectly overlap with the middle oligos and with each other. After choosing the right size, we would clean them and assemble the plasmid by a restriction ligation with the desired vector. (read more about the oligo method here)
3. E. coli strain
   He also helped us to search for the right E. coli strain, JM109, which needed to be recA-deficient, as other strains are more likely to destroy repeating constructs.

Integration into our project:
Thanks to Daniel, we got some more ideas and came up with a new lab plan focusing on the Oligo method. The rolling circle amplification required special enzymes and it was not quite clear how we would get our linearized product into a vector, as there are no restriction sites and a PCR is still not possible because of the repeats.
As he already had used the Oligo method successfully and kindly provided us with his protocols from his bachelor thesis, we decided to lay our hope in this special cloning method. We developed our own oligos and assembly protocols, which was very effective. We also bought the E. coli strain JM109 which is recA-deficient and would not destroy our repeat construct.

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Dr. Tobias Gutowski and Christian Sommer

Important Takeaways - Part I

• We learned how the UKE deals with medication shortages and what solutions have been developed to prevent shortages from reaching patients. For example, the fully digital UKE medication process provides information and time advantages that enable ward pharmacists and attending physicians to ensure that patients continue to receive the best possible drug therapy.
• We also learned that the hospital pharmacy is only responsible for supplying wound dressings and plasters that contain active ingredients and are, therefore, pharmacy-only. Other wound dressings and plasters are considered medical products and are procured via the central purchasing department.

Important Takeaways - Part II

• Packaging:
  Dr. Tobias Gutowski recommended packing each hydrogel dressing individually in an aluminum package to prevent the hydrogel from losing liquid. In addition, our team's assessment was confirmed that storage at 2-8 °C is most likely best to keep the activity of the bromelain low and prevent digestion of the resilin in the hydrogel.
• Water qualities:
  Dr. Tobias Gutowski also specifically pointed out to us that different qualities of water exist and that these can be crucial, especially in an open wound. He advises using water for injection purposes (aqua ad iniectabilia) due to the damaged skin barrier.
• Sterilization:
  Dr. Tobias Gutowski emphasized the importance of sterilizing our reSkin hydrogel wound dressing so that it bears no threat of an infection of the burn wound. There are a few possibilities how to sterilize: classic autoclaving, radiation sterilization, ethylene oxide, and working utterly sterile from the outset. However, predicting which sterilization method is the most suitable for our product is not necessarily possible. It simply makes sense to try different techniques and check which one does the least damage to our hydrogel and its components.
• Improving the solubility of astaxanthin and vitamin E:
  As Dr. Tobias Gutowski has already worked on improving the solubility of extremely lipophilic substances in his doctoral thesis, we were particularly interested to see whether he could help us improve the solubility of our lipophilic components astaxanthin and vitamin E. Dr. Tobias Gutowski explained to us that the solubility of these active ingredients initially depends on their concentration in the hydrogel. If we only need low concentrations to achieve the desired effect, it is possible that both components can be dissolved in the hydrogel without further steps, but it may take a little more time. Dr. Gutowski explained the solubilization via amorphous dispersion and the possibilities of removing the solvent again: spray drying and freeze drying. He drew our attention to polymeric solubilizers with an amphiphilic chemical structure specially developed for solid solutions. Due to its bifunctional character, a matrix polymer can serve for solid solutions and dissolve poorly soluble drugs in aqueous media. In addition, such a solubilizer can increase the bioavailability of poorly soluble drugs.
• Patent:
  Dr. Tobias Gutowski is so enthusiastic about our idea and project that he advised us to apply for a patent.

What We Integrated Into Our Project:
Considering the input, we plan to produce our hydrogel with water for injection. We will test different sterilization methods and their effects on our hydrogel components. We also want to check if solubilizers are suitable for improving the solubility of astaxanthin and vitamin E in our hydrogel. For the case that the hydrogel reaches the market, we already have an idea for suitable packaging and storage conditions.

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Prof. Dr. rer. nat. Johanna Brandner

Most Important Takeaways:

1. Woundhealing
   There are so many different cell types and molecules that have to interact at the right time for wound healing to take place. If one component doesn't work properly, it can derail repeatedly and there are so many different reasons that causes it to happen. It is also important to look at the components individually beforehand. Even if they make sense as part of the overall concept, they may act different from what expected, especially the pH value is important. In the case of a wound, it is better to have a slightly acidic pH. Substances that you initially think could be positive for wound healing sometimes show the opposite effect at certain time points or in the wrong concentrations.
2. Wound treatment in recent years
   A general breakthrough in terms of wound healing in recent years has been the move from dry treatment to moist treatment. Wounds can only heal well if they are moist. Since too much moisture on the other hand could slow down the healing process as well, a hydrogel is exactly the right approach to achieve moist wound healing in a balanced way.

What We Integrated Into Our Project:
Prof. Dr. rer. nat. Johanna Brandner has once again shown us the importance of our components. This has led us to re-read studies on the individual components that we want to incorporate into our hydrogel. We have planned in more detail to test the components individually in different concentrations, but also together. She was also able to confirm that a hydrogel could be an ideal wound dressing, as this would be a method of providing the wound with optimal conditions.

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Agnes Süselbeck

Most Important Takeaways:

1. The right way to communicate science
   1. What we first did not think of is the fact that certain terms can interpreted differently in distinct fields. Agnes Süselbeck pointed out that there are a few wordings in our project description and survey for burn wounded people that we should work on to make it clear for everyone. For example:
      1. The term hydrogel we previously used has a different meaning in the medical workspace. In a medical envionment it simply describes a gel in a tube. The better fitting term in a medical context would be “wound dressing”.
      2. There is a palette of products for burn-wound treatment already in use in the everyday care of patients. Especially the NexoBrid Hydrogel has a few similarities with our reSkin Hydrogel. We must definitely emphasize the differences between the two products, such as the consistency or the efficiency of bromelain, as NexoBrid uses a very high concentration here while we tend to use a lower one, which then saves ressources.
   2. She also encouraged us to create another anonymous survey for experts in wound treatment and helped us phrasing the questions.
2. Concretization of the application of our hydrogel
   There were a lot of aspects that we hadn't even thought about, but in hindsight are essential for the development of our product. The questions focused a lot on consistency and application, such as whether the hydrogel is stable enough, even when it gets squeezed. How often does the hydrogel actually need to be changed? Is it necessary to apply it together with a bandage? She also asked about contraindication and impacts on intact/ healthy skin and she thinks it is particularly important that our hydrogel can be used by any specialist. Since Agnes Süselback is very experienced in wound treatment she has used a lot of different products with different applications. For her it would be best if a product has no negative contraindications or impacts on intact skin.

What We Integrated Into Our Project:
Following the talk with Agnes Süselbeck we had a lot to think about and to work on. We updated and improved our project description and our survey for burn injured people to make it unambiguously and easier to understand. We also informed ourselves more about current burn wound treatment with a book recommendation of her (”Moderne Wundversorgung”, Kerstin Protz (Moderne Wundversorgung - 9783437278877 | Elsevier GmbH)) and about NexoBrid. Reading this literature, we learned that modern wound care materials such as foam, alginate, hydrocolloids/hydrogels, silicone and hydrofiber do not stick to the wound and thus enable painless, atraumatic dressing changes. There was also information about hydrogels in tube form and their effect on a wound. These gels rehydrate dry and barely exuding wounds and help to soften and detach dead, dry tissue components. This promotes cell formation and accelerates the healing process. It is generally said that a dry environment tends to hinder the formation of new cells and that a moist environment has a beneficial effect on the healing process. Wound dressings that keep the wound constantly moist and prevent the formation of scabs are particularly suitable for burn wound teatment.For our project, this means that the idea fulfills the optimal conditions and would be ideally suited for burns. In practice, however, we have to make a lot of adjustments and ensure that we add the right concentrations of components to create ideal measures.
All her questions about the application of reSkin made us realize how much we still have to consider. We are still far from being able to answer all the questions she had, but are definitely incorporating her expertise and tips into our further development. We would like to thank Agnes Süselbeck and the Heidekreis Klinikum Walsrode and Soltau for their help and support! They have made a significant contribution to the shape of our project and have also supported us by taking part in our project promotion video. We greatly appreciate the interest in our project, their useful input and their help with sharing our idea!

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Dr. med. Sophie Schleußer

Important Takeaways and aspects of burn injuries:

1. The first 48 hours after burn injury:
   Correct assessment and treatment are essential. If burns are minor they should be cooled slightly and be kept clean to prevent progressive tissue damage and infections. If burns cover a larger area of the body or are located in vulnerable parts of the body such as the face or the genital region, they need special treatment in a burn care unit. In every case the assessment of burns should be done by a specialist as even minor burns can have serious consequences. If treated incorrect burn injuries can cause infection and scarring or can even be life threatening. In general small superficial burns are debrided, desinfected and kept moist for 24-48 hours. Then, the wounds are reassessed, redebrided and treated according to their final degree of tissue damage. Patients with minor burns in the outpatient sector are instructed to moisten the wound dressings with antiseptic solutions themselves before reevaluation at the clinic after 24 hours. This can be quite time-consuming and is not managed sufficiently by everyone. So unfortunately some patients allow the dressing to dry which can increase tissue damage because there is no evaporative cooling effect during those first 24 hours after injury. Removal of the wound dressing is painful because the dressing is sticking to the wound and second debridement is much harder because fibrinous coating and newly dead skin are not moist enough.
2. Differentiation between superficial and 2nd degree burns
   Superficial second degree burns appear with blistered skin and a red woundbed which is very painful. Deep second degree burns appear white or with impaired capillary perfusion. In principle, there are no problems to differentiate between those stages. However, burns almost always come in mixed patterns or in combination of serveral degrees of tissue damage which can make assessment difficult. The decision whether surgery is needed and which parts of the burn need surgical debridement and skin grafts is made after 24-48 hours. At that point the extent and depth of tissue damage will most likely not change anymore. Dr. Schleußer is of the opinion that clinical assessment and experience are the most important tools and that a product that could show the difference between the different burn depths is not absolutely necessary.
3. Treatment methods
   Deep burns or full thicknes burns in particular are difficult to treat as they do not heal on their own. The layers of skin are dead layers of skin and have to be surgically removed and be replaced with skin grafts. Skin grafts can only replace epidermal layers of the skin and do not contain any functional components such as thermoreceptors, sweat glands, oil glands, hair follicles or sufficient connective tissue. Patients who underwent those surgeries because of large full thicknes burns lack sensitivity, skin elasticity, sebaceous glands and the ability of temperature regulation and sweating. Also, the transplanted skin is not as mechanically resilient as normal skin and is prone to excessive scarring - which of course can considerably restrict the patient and affects their quality of life tremendously. Patients also need to wear compression garments for at least 1 year after a skin transplant which is very uncomfortable. Among other things, the skin dries more quickly due to the lack of sebaceous glands and is also more affected by UV-radiation. Patients burn more easily because they lack temperature sensation and do not realise when they get in contact with too hot or too cold substances. Experience has also been gained with products, that enable enzymatic debridenent with bromelain. The enzymatic activity is supposed to remove dead cells from the wound bed to possibly avoid surgery. Enzymatic debridement is not suitable for large body-surfaces and all types of burns. Treatment can be painful and is only applied to sedated patients at the burn care unit. According to Dr. Schleußers experience enzymatic debridement does not fully replace surgical debridement.

What We Integrated Into Our Project:
We learned a lot from Sophie Schleußer and are grateful for her expertise and honest views on our project! After the interview, the decision regarding the bromelain concentration in our hydrogel was one of the main factors that influenced our project. As a high concentration can cause pain, it makes sense for us to use a lower concentration that still has a slightly debriding effect. A concentration that is still effective, but not dangerous or painful if left on the wound for a long time. Patients who are not severely burned are instructed to keep the wound moist and then have to moisten the dressing themselves with antiseptic solutionsserasept. Our hydrogel would be a helpful idea here, as it could keep the wound moist without the patient having to keep dripping moisture. At the same time, with its slightly enzymatic capabilities, new forming dead skin could alread detach while the dressing is still on be removed beforehandand make the following debridement less painful and complicated. In conclusion, we realized that we needed a product that might not help in all phases of recovery, but in the first critical phase of 24-48 hours after burn injury.
Again we want to thank Dr. Schleußer for her time and input to improve and sharpen the vision of reSkin.

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Hospitation

A distressing start to our time at the hospital
Our internship turned out to be a highly intense experience, which was both physically and emotionally demanding, but also very educational. On arrival we were immediately faced with the different kinds of injuries the accident and burns ward as well as the intensive care unit for severely burnt patients deal with every day.
During the morning briefing all the doctors go over their cases together, showing detailed pictures of the injuries, which helps them evaluate wound healing and plan the next steps for the patients. To them it is part of their routine, but for us seeing and discussing such images for the first time was distressing. It prepared us, however, for our stay at the two different wards.

Part I: Intensive care unit for severely burnt patients
On our first day, we plunged in right at the deep end. We were sent to the intensive care unit for severely burnt patients. It accommodates four people in separate rooms of which three were occupied at the time. To reduce the risk of contamination, everybody who enters the unit has to change clothes and shoes as well as put on a surgical cap, and disinfect their hands. This has to be done several times a day: every time someone enters or leaves the unit, and also after visiting a patient in one of the intensive care rooms.
Only one patient was awake at the time, but we had no oppotunity for a conversation. The other two had been flown in from abroad on the previous day and had suffered burns of the highest degree all over their bodies, apparently due to an explosion in a house (presumably due to gas). We were allowed to witness the change of the wound dressings and bedspreads, which is an exhausting task performed by several people working together. As students we were not qualified to treat the patients ourselves, but we helped a little by passing along material.
The treatment of these patients bears a lot of hurdles. The difficulties arise due to several things. First, because of the risk of contamination everybody in the room has to wear additional protective gear consisting of a plastic coat, two pairs of gloves on top of each other, a surgical mask, and a fresh surgical cap. Second, when the skin gets burned severely, the body temperature drops dramatically, because the metabolism breaks down – this is why the room was heated to 37 degrees centigrade at all times. Third, since the patients were unconscious, they had to be moved from side to side by medical staff. All of this put together transforms the change of wound dressings in intensive care into an arduous task, which may actually result in people blacking out, if they aren’t used to the exertion.
The care of the severely burnt is an all-day job, that demands constant attention – alarms went off permanently so someone had to rush. Despite the efforts of everybody involved, one of the burn victims succumbed to their injuries on the second day. The other victim, whose burns were not quite as severe as the first ones’, was scheduled for surgery to remove the lost skin. During the operation, however, lab results from a blood sample came in: there were all kinds of multi-resistant bacteria – such as E. coli, staphylococci and others – already in the blood stream. According to the staff, patients from abroad tend to bring these with them, because of an over-use of antibiotics. And once the bacteria are in the blood, unfortunately there isn’t much that can be done to save the patient, we were told.
Although the intensive care unit deals with cases that don’t relate so much to our own project (because the burns are much worse than reSkin is intended for) it certainly was the most profound experience of our internship. We have the highest respect for the people working there, fighting for patients’ lives and yet often having to accept defeat.

Part II: Accident and burns ward
On the second day we accompanied the doctors on their visit to all the patients on the accident and burns ward. Altogether there were more than 30 people. There was a high demand for beds that day, so everybody who could be dismissed was. It took several hours and a lot of walking to see and talk to every patient. At times there was a whole throng of staff walking along and squeezing into the rooms, because apart from us all the nurses on duty came along to be informed.
During the rounds we were just silent observers, but afterwards we had the chance to speak to an 18-year-old patient who had burned his hand with boiling fat. His injury combined 2a and 2b burns and thus was exactly the kind of case we intend reSkin for. After introducing ourselves and our project, he agreed to show us his hand and answer some of our questions.
His 2b burns had been treated with a split-skin graft (a skin transplant taken from his thigh), and his 2a burns had been covered with an artificial skin called Suprathel, which serves as a wound and burn dressing. This is the current golden standard in burn wound treatment.
The patient elaborated that his wound had to be disinfected on a regular basis. For this, the covers had to be removed and put back on again every time. While the part with the transplant as well as untreated areas were painful, the part covered with the artificial skin was feeling fine, he said. Since the accident happened six days ago, he was also in need of physiotherapy to prevent the hand from going stiff.

Résumé
Our stay at UKSH has given us the chance to experience the difficulties of medical staff as well as of patients who are concerned with burn wounds. We are extremely grateful for this opportunity and want to thank all of the staff at UKSH for their time and advice. We presented reSkin in front of the doctors during one morning meeting and got very informative feedback. Everybody was highly interested in our project and asked a lot of questions about our methods and intended area of application, which showed us that there is indeed a need for improvements.
However, every doctor had some slightly different views on what our product should be able to do. While some would welcome an antiseptic dressing that would seal off the wound and thus abolish the need for several layers, others were concerned about the possibility of excess wound fluid that might wash our hydrogel off the skin. The head physician also made us aware of the fact that there are already a lot of products out there, so ours would need an edge to stand out.
Talking to a patient and seeing for ourselves how exactly burn wounds are being treated was a valuable insight for us. It made us realise that reSkin could indeed become a very good addition in the process, possibly coming in handy with diagnostics during the first 48 hours after the accident just as intended. A real asset, however, is preparing the burnt skin for further treatment by moisturising and assisting with blood circulation, while the use of mild enzymes will take off the dead skin, which will be absorbed into the hydrogel.
We learned that there isn’t one perfect product to treat burn wounds yet, but also that there are several areas of application in which a hydrogel might be of real value. So, setting out with reSkin is a very good starting point - but it also has the potential to become more, if our hydrogel could be designed to be loaded with drugs according to individual needs during different phases of treatment.
Our two days in hospital were very educational, even if extremely exhausting. We would do it again any time and would therefore encourage coming iGEM teams to get firsthand experience in the field. We would recommend to do it right in the beginning of the project, though, so there will be enough time to act on the experience gained and the advice given.

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Surveys for medical experts and burn patients

1. Important findings:
   1. Survey for medical experts
      The most important thing in treating a burn in the first 48 hours is cleaning the wound, usage of antiseptic and traumatic wound care and pain treatment. It is not always easy to distinguish directly between 2a and 2b in the treatment of burns. Antiseptic hydrogels have already been used, as well as spacer meshes and silicone-based foam dressings. In general, treatment with such products is seen as positive. In the opinion of our interviewees, an ideal product for wound care would be a hydrocolloid with a cooling and anti-septic effect, which can also remain on the skin for up to 2-3 days. A hydrokolloid bandage is a special wound dressing that contains gel-forming agents which create a moist environment to promote healing.
   2. Survey of patients
      All people who answered this survey had wound infections as a result of their burns and had to be treated as in patients between the ages of 2 to 8 months. The injuries more often occur in children at a younger age (0 to 10 months) but also in youth and adulthood. Injuries often covered over 50% of the body. The regular treatment methods consist of skin grafts and wound dressings. There are hardly any patients who have had positive experiences with these methods. Statements like: “The graft is as tough as leather and requires therapeutic treatment even after more than 30 years, it has to be constantly lubricated and has a low-threshold risk of injury” (translated to English) , or: “Itching could not be alleviated and permanent pain” (translated to English) were made. The interviewees had little to no experience with hydrogels and only one interviewee already had experience with bromelain. Here, we have especially asked about experiences with NexoBrid. NexoBrid is one of the few companies that integrate bromelain into their product for the treatment of burns. The difference here is that the wound dressing is a paste, that is applied directly to the wound. The patient described the treatment as OK, but the wound did not heal and changing the wound dressing was painful, because of the texture. The participants also described their general wishes for improving wound treatment. In general, they would prefer wound care treatments with an oily effect, cooling and anaesthetic effect, to use it for other cronic skin diseases (e.g. acne) and generally more patient education regarding burns.
2. What we would like to integrate into our project:
   Thanks to the many responses, we realized even more how important it is to talk to the people concerned. As a team, we can't know what is really needed and how we can really improve something applicable. Above all, we want to focus even more on wound infections, as everyone, who took part in the survey, was affected by them. We also feel that the idea of making the hydrogel flexible and elastic has been confirmed, as the application should be as smooth and painless as possible. We also learned from the surveys that it is important that a lot still needs to happen in general wound care. It will never be simple to develop the perfect product that can really help with every problem. All this led us to the idea that it is important for the future to be able to load other components into our hydrogel, depending on patients' wishes or application requirements.

anonymoussurvey-patients-english.pdf

anonymoussurvey-patients-german.pdf

anonymoussurvey-specialist-english.pdf

anonymoussurvey-specialist-german.pdf

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