During the first step of the project-selecting of the topic, we were exposed to some terrible burn cases (For more details: Description) that inflicted great damage to physical and mental health of both the patients and people around them. With a desire to help these people, we decided to develop a cost-effective skin regeneration stent system that would make such affordable and effective treatment more accessible to more patients.

Early in our research and development period, we interviewed two firefighters to gain an insight into the actual work of firefighters, the degree of understanding and expectation of burn treatment, the burn cases and treatment that occurred around them, the understanding of the general public on burn knowledge, and the daily science popularization activities of the fire brigade. This touched us deeply, reinforcing our desire to produce a more affordable skin regeneration stent system so that more people can get better recovery at a lower cost.

We received outstanding advice and guidance from several doctors who know about the main drawback of the present available similar products-the expensive price, which led us to further make sure the core competency of the use of BC in our product. Their advice also assisted us in designing the application process and our hardware system, for instance, the assisted healing module, the negative pressure system, the antimicrobial module and so forth. In addition, the interview with Essex introduced a growth factor that had not been considered before-the bovine alkaline fibroblast growth factor bFGF to us, which has a very important role in dermal skin repair. Adding bFGF to our project further improved the curative effect of our skin regeneration stent system. Furthermore, the three communications with Prof.Liang provided a great help during the process of our experiments, solving instantly the problems we met.

To create a strong societal impact, our team has been in contact with firefighters, doctors, professors, industry and local K12 teachers. Each group suggested effective ways to create awareness and indicated where the development of educational materials and tools would be very beneficial. These stakeholders helped educate us about their purpose, viewpoints, the needs in China and around the globe, and their expectations about an ideal skin regeneration stent system. A particularly striking conversation with K12 teachers made us realize the lack of a comprehensive and systemic introduction of synthetic biology and burn prevention and solution, which informed the main goal of the design of our education part.

Moreover, we strived to make our work as inclusive as possible. For example, we have posted various contents about synthetic biology and burn prevention to our social media accounts, and translated them into different languages, allowing us to reach a larger, more diverse audience. In addition to these posts, we pursue different kinds of popular science activities to raise the interest of different people from diverse backgrounds and ages. Overall, with the help and guidance of our stakeholders across the globe, our team has created a cost-effective skin regeneration stent system, and has developed educational materials and tools to introduce relevant knowledge in synthetic biology and burns, all while taking sustainability and inclusivity into account for our values and goals.

Mr. Yang and Mr. Wu are firefighters with extensive work experience in the fire brigade of Shenzhen's Guangming District, where the former is mainly engaged in publicity work and the latter is the squad leader in the fire brigade.

We would like to know about the actual work of firefighters, the degree of understanding and expectation of burn treatment, the burn cases and treatment that occurred around them, the understanding of the general public on burn knowledge, and the daily science popularization activities of the fire brigade, which touched us deeply, reinforcing our desire to produce a more affordable skin regeneration stent system so that more people can get better recovery at a lower cost.

We briefly learned about the self-protection measures and equipment that firefighters usually use during the firefighting process, which contributed to the completion of the context of our popular science, as well as the simple first aid measures to be taken in case of accidents and mild burns (flowing water rinse for more than 15 minutes-apply scald cream-bandage wrapped around a circle, not too tight).

Mr. Wu also shared an example of a firefighter who suffered a scald on his back during a mission to extinguish a factory fire. Because the fire cloth on the back of the helmet was not worn well, and that firefighter’s head was too low, dripping molten iron flowed down the neck and caused burns. However, for the fact that the wound site was not obvious, after considering the efficacy and cost, he did not consider a treatment with a higher cost that was less likely to leave scars artificial stent to assist the skin graft, instead of which, he eventually chose a more economical plan. Furthermore, for the treatment of burns, Mr. Wu said that most firefighters probably have the same idea, that is, in addition to the treatment of the face regardless of the cost, in other parts of the body, even large wounds will take both cost and efficacy into consideration. This reinforces our project's desire to produce a more affordable skin regeneration stent system so that more people can get better recovery at a lower cost.

What’s more, through the interview with Mr. Yang, we learned about some science popularization activities established by the Guangming District Fire Brigade. For example, they will carry out 119 fire protection publicity every month At that time, they will go to places where the crowd is relatively dense, such as supermarkets and so forth, to distribute popular science brochures and explain some basic fire safety knowledge, such as how to do a good job in personal fire safety protection, household electricity fire safety and other knowledge, and they will also give skill trainings to the community volunteer fire brigade and fire station from time to time. This is a significant inspiration to us in designing the fire knowledge science safety brochure and the support science course for primary and secondary school students (For more details: Education).

Fig.1 BNUZH-China communicated with the firefighters

Our project is aimed to cure the large wound of the patient, so the clinical experience and feedback of the doctor is very important and necessary for us.

Dr. Ma is a deputy chief physician of the Department of Burn and Plastic Surgery, Affiliated Hospital of Bengbu Medical College, Anhui Province. Because of his personal preference, his photo will not be exhibited on our wiki.

Our project is aimed to cure the large wound of the patient, so the clinical experience and feedback of the doctor is very important and necessary for us. Since this was an interview at an early stage of the project, we wanted to get a general idea of what treatments were available in the clinic and what needed to be improved.

Through the interviews, we learned the current treatment procedures of large wounds in clinic: debridement and infection control in the early stage and skin grafting first, flapping transplantation and other treatments in the later stage. We also learned that the tools often used in the process of debridement and infection control in the early stage: antibacterial dressings, oxygen-enriched products to kill anaerobic bacteria, negative pressure systems, which is of great help to our subsequent design of the use process of BCAID. We initially designed the application process of BCAID with reference to the clinical treatment steps. Furthermore, we communicate deeply on the use of the negative pressure systems, such as, the vsd negative pressure system widely used to prevent patients from being infected, which inspired us to add it into the application process of our product.

In addition, Dr. Ma mentioned some artificial dermal scaffolds that have been used to treat wounds nowadays. He indicated that the functionality of existing products has been clinically demonstrated, but there is a major problem of these products, that is, the high price, often making them difficult for patients to afford. Therefore, it is hoped that the skin tissue regeneration scaffold system prepared in this project can be better in functionality and cost-effectiveness, pointing the way to our project goal. During the communication with him, we have a clearer realization that the significance of our project is to explore BC as a skin regenerative scaffold. The structure of BC determines that it would have excellent performance as a dermal regenerative scaffold, and compared with competing products in the market that are made of collagen fibers, BC would have lower production cost and would not bring a huge treatment burden to patients, which is important for the promotion of the product. What’s more, the healing promoting module was added to this project inspired by him (For more details: Design), whose purpose is to increase the antimicrobial performance and healing capacity of the system, with the aim of shortening the treatment cycle of large wounds, relieving the patients from pain and improving treatment modalities.

Dr. L is a deputy chief physician of the Department of Burn and Plastic Surgery of a hospital in Shenzhen. Because of his personal preference, his photo and more personal information will not be exhibited on our wiki.

With the foundation of the former doctor, we could like to know more about the negative pressure system and some artificial dermal scaffolds that have been used in clinical treatment currently.

We learned about an artificial dermal scaffolds that Dr.L have used in the process of treating patients - integra from the United States, which is a kind of polymer fiber scaffold, mainly composed of a layer of scaffold and a layer of protective film. During the application process, it can induce and assist human body tissues such as nerve fibers to grow into the scaffold. When the scaffold is covered by its own tissues and the dermal regeneration completed, the surface protective film will be removed, and then skin grafting and other operations will be applied to the wound. Dr.L also introduced the use process of integra in more details: assess whether the wound needs to use artificial dermal stent - thorough debridement - use - after being replaced by the patient’s own tissue, tear off the surface film for epidermis grafting. The whole process often takes about 3-4 weeks.

Moreover, as mentioned by Dr.Ma, Dr.L also mentioned one drawback of this kind of products-the expensive price, which led us to further make sure the core competency of this product, that is, the high cost performance. After this communication, we carefully researched integra and deeply understood its raw materials, structure, price, application scenarios and clinical cases, which were basically consistent with Dr. Li's description. Based on the clinical operation process provided by Dr. Li and the official use process of integra product, we further defined the application scenario of BCAID, modified the application procedure of the product, and designed the supporting hardware in the application process. What’s more, Dr.L also mentioned other competing products of the same type in the market, such as Pelnac from Japan, Lando from China, and so forth, reminding us to pay more attention to the artificial dermal scaffolds that have been applied, especially Lando from China. Although the cost of Lando has been greatly reduced compared to Plenac and integra, it is still a very heavy financial burden for most people, and these artificial dermal stents are not covered by the Chinese health insurance system, which further determines the core competitiveness of our product. However, since he himself has not used these artificial dermal stent products, he suggested that we go to a doctor who has used these products for further understanding.

Fig.2 BNUZH-China communicated with Dr. L

Dr.Li is a deputy chief physician of the Department of Burn and Plastic Surgery, 301 PLA General Hospital, who specializes in comprehensive treatment of critical burns, electric shock injuries, frostbite, chemical burns, children's burns and burns combined with burns, chronic and refractory wound repair, burn wound surface scar restoration, and functional reconstruction. He is also a member of the Burn Surgery Branch of the Beijing Medical Association and a young member of the Burn Surgeon Branch of the Chinese Medical Doctor Association.

As being advised by Dr.L, we would like to know more about the artificial dermal scaffolds that have been applied, as well as the specific use process of these competing products.

We learned that Dr.Li once used Pelenac from Japan, is an artificial dermal stent that is widely used in wounds that are difficult to heal and difficult to skin graft, such as electric shock injuries and exposed wounds. Plenac also has a two-layer structure, with an outer silicone membrane and an inner layer of collagen sponge as a scaffold, while the outer silicone membrane acts as a moisturizer and seal.

Dr.Li also introduced the clinical use process of stent products: debridement (co-culture of secretions and antibiotics; Scrape off necrotic tissue on the operating table to determine whether it is scratching healthy tissue by whether it is bleeding; Repeated rinsing and disinfection of hydrogen peroxide, etc.) - covering the wound surface - bandaging treatment - after a week or two, there are granulation buds growing - granulation can be grafted and closed after covering the exposed area of the bone, which is very helpful for us to design the application process of our product itself in more detail and correctly.

In addition, Dr.Li solved the problem of immune rejection that had been plaguing us. We were afraid that allogeneic fibroblasts would bring immune burden to the patient and consulted him for this purpose. He replied that the immunogenicity of organs, tissues, and cells was decreasing one by one and that the fibroblasts themselves had low immunogenicity, suggesting that we didn’t need to concern too much about this issue. After the exchange, we continued to look for relevant information and the results we obtained confirmed his statement that the transplantation of allogeneic fibroblasts is not prone to immune exclusion, and we were surprised to find that allogeneic fibroblasts also have very great advantages in promoting wound healing, with their ability to produce important proteins such as collagen and fibronectin, which are important components of the extracellular matrix. We also found a number of cases where allogeneic fibroblast transplantation had been used to treat burn wounds with good curative effects^1,2.

Furthermore, Dr. Li also indicated that the healing process of large wounds needs to be very careful to avoid wound infection, which is a very important aspect in clinical practice, so he reminded us that we needed to pay attention to the antimicrobial module in the design to enhance the antimicrobial activity of the product during the whole cycle of wound healing. Following Dr. Li's suggestion, we added the design of initial modification by adding chitosan that has good antimicrobial ability after BC production. Chitosan, together with the original design of LL-37 secretion by trauma cells and the combination of negative pressure antimicrobial system for treatment, ensures the anti-infection performance of BCAID in the whole cycle of wound healing.

Dr. Li also emphasized that Pelenac can be used in combination with negative pressure system. In addition to its antibacterial activity, the mechanical force of Pelenac can also promote the secretion of cytokines, thus promoting granulation, which once again reinforced our idea of combining the application of BCAID with negative pressure technology. Inspired by Dr. Li, we followed up with a more careful research of the information about Pelenac, such as an in-depth understanding of the raw materials and properties of the two-layer structure, for the sake of perfecting the hardware design. We eventually designed a hardware system specifically for the BCAID application process, which could be adapted to the negative pressure system in the actual application. When selecting the second layer of protection material in addition to the BC stent, we first considered the silicone membrane used in the Pelenac. However, we later found that it was not suitable to be used with a negative pressure system. We finally chose a sterile surgical membrane, which is a widely used material in clinical practice, allowing wound exudate to drain, and can be better adapted to the negative pressure system.

Fig.3 BNUZH-China communicated with Dr. Li Dongjie

Mr. Fang is the general manager of Zhuhai Essex Biotechnology, Ms. Song is the marketing operations director of Zhuhai Essex Biotechnology, and Mr. Zhu is the corporate communications manager of Zhuhai Essex Biotechnology. Zhuhai Essex Biotechnology is a company mainly engaged in the research, development, production and sales of genetically engineered drugs. Two national first-class genetic engineering new drugs and a series of biological drugs have been successfully developed. The company's main products are bFGF series, which mainly include Beifuji, Beifushu and Beifuxin. The successful development of bFGF series has enabled the company to enter the world's advanced ranks.

We would like to know more about bFGF in order to decide whether to add it into our product or not, as well as some professional opinion towards our project from industry who specializes in wound healing.

During our online communication and offline interactions with Zhuhai Essex Biotechnology, we learned about a growth factor that had not been considered-the bovine alkaline fibroblast growth factor bFGF, which was first found in the pituitary gland of cattle. It is a trace protein with a combination of 155 amino acids, widely used in the repair of burn large areas of defects, laser surgery, fundus injuries, mouth ulcers and other wounds. Since Essex used bFGF as the main ingredient in their core repair products , we learned that bFGF has an outstanding performance on injury repair and security during the communnication with the three experts. In the application of bFGF for more than 20 years, it has not actively caused cancer. What’s more, bFGF has a very important role in dermal repair. Mrs. Song attach great importance to dermal repair, because the dermis is usually difficult to repair on its own in large wounds, and epidermal repair can only occur after dermal regeneration. And the previous growth factor we originally considered-EGF-focus more on epidermal repair than dermal regeneratio. After the communication, we had a deeper understanding of bFGF and decided to add this growth factor to our program to work together with EGF (For more details: Design), both of which give our scaffold system better pro-healing properties .

We also learned that topical bFGF products need to be changed every day for the fact that the promotion effect produced by one use is difficult to maintain, in this case, our idea of using Adeno-associated virus (type 6, AAV6) can overcome these limitations in use, which clarifies another core competitiveness of our stents with other competitors of the same type on the market, that is, our scaffold has a relatively long-term and stable therapeutic effect and it also saves manpower.

Ms. Song, as a product technician, also mentioned the safety of AAV, prompting us to pay more attention to gain an in-depth understanding of the relevant principles and think about the specific application process. So we further confirmed the safety of AAV and designed a more rational application scheme. She also alerted us to the fixation of BC stent in the wound during application, which we had not considered before, inspiring us to refine the application process of our product (For more details: Implementation).

Fig.4 BNUZH-China visited Essex and communicated projects with experts

Prof. Liang successively served as the project scientist at UC Irvine School of Medicine and the principle investigator of Shenzhen Institute of Digital Life before. Now he is a Distinguished Associate Professor of BNUZH Biotechnology Research Center, who is mainly engaged in the research of cell biology, especially on the field of exosomes.

We would like to learn about the feasibility of some parts of our project, as well as solving some theoretical and pragmatic questions appeared during the process of the experiments.

First of all, we concerned about whether our desired prokaryotic proteins (three cellulase genes: Cex, CenA and Bglx ) could express successfully in eukaryotic cells, Prof. Liang suggested that we needed to pay attention to the selection of signal peptides and the effect of eukaryotic modifications (especially glycosylation) on the activity of prokaryotic proteins, and shared some relevant essays with us. Based on this, we reviewed more information and found relevant articles showing that the activity of our desired protein was basically unaffected by glycosylation when expressed in eukaryotic cells^3-5. And then, under the suggestion of Prof. Liang, we changed the prokaryotic signal peptide to eukaryotic signal peptide to ensure that the three genes could be expressed in fibroblast, a eukaryotic cell.

In addition, regarding the light control module in the scaffolding system, we were reminded to make sure that the blue and red light needed was sufficient to penetrate the skin to activate the light control system, as well as to confirm the safety of using red and blue light. We reviewed more information to confirm that the two types of light we used are able to reach the dermis safely⁶. And he also reminded us to start the building of a light-controlled and stable fibroblast cell line as early as possible since it may need a long time.

Furthermore, we discussed how to package lentiviruses and the possibility of stabilizing with lentiviruses. After looking at the plasmid map we initially identified, Prof. Liang suggested that we separated the three cellulases into three plasmids for expression, as packaging the three genes simultaneously is close to the upper limit of lentiviral packaging and there may be no guarantee that all genes can be successfully expressed.(For more details: Engineering Success)

More importantly, Prof. Liang thought that the first thing our project needed to verify was the cytocompatibility of BC, therefore he reminded us to complete the experiments related to BC membrane and cell co-culture as soon as possible so that the project design would be more convincing. Based on his suggestion, we adjusted the experimental plan and immediately started the co-culture experiments, and the results proved that BC has good cytocompatibility .

Fig.5 BNUZH-China communicated with Prof. Liang

Ms. Wang is a biology teacher at Cuiyuan middle school in Shenzhen and has a wealth of knowledge and experience to teach middle school students. Moreover, she is also a very experienced homeroom teacher who has been managing and leading the best classes at Cuiyuan Middle School for many years.

We would like to know about the understanding of middle school students on knowledge of burn injuries and synthetic biology, and so perfect our context and forms of our education part.

We learned that high school students are exposed to non-specific immunity in the immune system and animal cell cultures for skin transplantation and they got some knowledge relevant to burn recovery, but do not gain an in-depth, systematic understanding of burn prevention and recovery. As for synthetic biology, the concept is not proposed and systematically introduced in the classroom, but there will be contents related to synthetic biology in the study of gene engineering, cell engineering, and genetics. As to junior high school students, they rarely have the opportunity to learn about burns in school, unless they have to complete homework of the online safety platform. As to synthetic biology knowledge is very far from students, it is only possible to mention a few words when talking about prospects in biology class. This information has greatly promoted the content of our education, especially when setting up popular science links for high school student.

In addition, for the popular science form of our project, Ms. Wang also put forward the following suggestions, such as taking examples that are closely related to the audience, using the form of Q version comics, and considering the introduction of problems-the introduction of basic methods and principles of learning-understanding the relevant applications (examples) when teaching. The members in our team who participated in the summer teaching program took Ms. Wang's suggestion into consideration and designed the curriculum , which got a good effect of science popularization.

Fig.6 BNUZH-China communicated with Ms. Wang

Mr. Zhang Junguo is a biology teacher and researcher in Shenzhen, who refers to professionals engaged in education teaching and scientific research for basic education, shouldering various teaching and research activities.

We would like to know about the understanding of students of all grades on knowledge of burn and synthetic biology, and perfect our context and forms of our education part.

We learned about how much primary and secondary school students in Shenzhen learn about the knowledge of burn. Students will have relevant knowledge since the school will accept the government, social media and some social organizations to popularize relevant common sense. Anyhow, the knowledge is mainly at the early warning level, in order to reduce the potential threat of students in the high incidence of burns. Importantly, schools will arrange fire lectures to popularize relevant common sense, such as introducing prevention and post-injury treatment methods when being burnt and so forth. The scope of above lectures is relatively wide, not only including the knowledge about burn injuries, so the understanding of students about burn is relatively scattered. As for synthetic biology, because it is an emerging subject, there are few of relevant contents in the middle school textbooks and tests. In addition, it is often used to broaden students’ horizon in classes. It is subject to the middle school curriculum, so students’ in-depth understanding of synthetic biology is not enough. This information is helpful when we designed our education plan, considering what context should be included.

Regarding popular science, Mr. Zhang feels that various factors should be considered for different groups of people. "The way of science popularization pays attention to the form, what kind of group is facing, what content appeared at that time, so that relevant popular science content adopted. For example, in the teaching process, it is necessary to start from the needs of students, and through the emergence of cases, which will make students be more interested. If you only talk about the theoretical part, it may be more boring. The more feasible way is to connect the various popular science knowledge through a story, and students will be more willing to explore.” This information has greatly promoted the content of our education, especially when setting up popular science links for students.

Furthermore, the media promotion is relatively widespread, but the effectiveness is worth investigating. "For example, the Little Red Book is equivalent to a tool book in use, that is, people will only find what they need solely when using it, such as where to play will search for strategies, so the effect of casting a wide net will not necessarily be good, and it must be aimed at the audience." If the public account is widely oriented to the group, big data may not necessarily match the corresponding group. " These words woke us up, encouraging us to find more specific and effective ways to popularize relevant information to different kinds of people.

Fig.7 BNUZH-China communicated with Mr. Zhang