Human Practices
Our project aims to advance biomanufacturing as a sustainable alternative to chemical manufacturing by developing a modular bacterial cellulose (BC) modification machine utilizing synthetic biology. We improved BC’s properties, making it more versatile and applicable in various fields.
By integrating Human Practices into every stage of our work, we shaped our bio-engineering design, improvement, and commercialization of our project and pioneered exploration on AI safety. Collaborating with industry experts, we ensured the project's global relevance and societal impact and the feasibility of our manufacturing processes. Our innovation opens new possibilities for BC’s use, starting with antimicrobial BC products, underscoring our commitment to sustainable biomanufacturing.
Framework of HP
Inspiration & Background
Initial InitiativeIn-depth background researchGroundbreaking InspirationIntegrated Human Practice
Initial design & StrategyProject refinementApplication scenario
Communications
Local EngagementSafety use of AI in SynbioFuture Outlook
Investigations & Reflections
Documentation
Referrence
PapersPictures
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During an outing where our teacher treated us to milk tea, one of our classmates suddenly inquired about the process of making coconut jelly in the tea, originally known as "Nata de Coco." The teacher explained that it was made from bacterial cellulose, sparking our classmate's curiosity. He subsequently conducted a thorough investigation, even interviewing representatives from Hainan Yeguo Food Co., Ltd. Through this, he gained insight into the current state of bacterial cellulose production techniques and its potential applications in society. Inspired by this, we decided to further explore the field of bacterial cellulose.
Nata de coco milk tea [9]
Cellulose (C6H10O5)n is a linear homopolysaccharide composed of β-D-glucopyranose units connected by β-1,4 glycosidic bonds. While bacterial cellulose, first discovered in 1880, is produced by bacteria such as Agrobacterium, Alcaligenes, Pseudomonas, Rhizobium, Sarcina, and Gluconacetobacter. Unlike plant-derived cellulose, bacterial cellulose is free of lignin and pectin, resulting in higher purity. It exhibits exceptional properties, including high water retention capacity, mechanical strength, crystallinity, and biodegradability. Moreover, bacterial cellulose is a renewable resource, and its production is environmentally friendly and non-toxic, making it a highly promising material for diverse applications across various fields.
Bacterial cellulose (BC). (A) Molecular structure of hydrated BC.(B) Typical microscopic BC fiber film morphology [11]
As a result, our team decided to focus on the highly functional bacterial cellulose. However, through both local and global research, we identified several functional limitations. Native bacterial cellulose exhibits properties that are difficult to manipulate, such as resistance to staining and inadequate mechanical strength. Therefore, modifying bacterial cellulose through composite formation is essential to enhance its properties and expand its applicability on a global scale.
Through our collaboration with Yuandong Bio as part of our Integrated Human Practices (IHP), we gained valuable expertise in a variety of methods for producing composite cellulose materials. These materials can be created through techniques such as solution blending, melt blending, and other advanced processing methods.
Composite cellulose materials are a vital class of bio-based composites created by integrating cellulose with other materials. These materials offer significant advantages, including renewability, biodegradability, and a role in reducing plastic pollution. They are also lightweight, strong, environmentally friendly, and exhibit good thermal stability and chemical resistance, all at a low cost. However, they come with challenges such as moisture sensitivity, processing difficulties, durability concerns, and variability in performance.
Referrence: [R6]
Interviewing Yuandong Biotechnology
Through peer-review research on the iGEM website, we discovered the bacterial cellulose modification design by Imperial College in 2014.
However, this system was difficult to achieve in 2014 due to the challenge of co-expressing and crosslinking Curli protein fibers and bacterial cellulose uniformly in E. coli. It was not until 2023, when the study titled "Bionanocomposites with Enhanced Physical Properties from Curli Amyloid Assemblies and Cellulose Nanofibrils" introduced a method of combining nanocellulose (a plant-based bacterial cellulose analogue) with Curli protein fibers[8]. The experiment demonstrated a sevenfold increase in mechanical strength when Curli and bacterial cellulose were mixed. Ultimately, we decided to advance the modification machine based on BC.
Our iGEM team Peer-review of Imperial College 2014
Addressing the significant challenge of stringent chemical conditions and essential temperature requirements, our team has designed an innovative strategy that employs a bio-based modular modification "machine" or system, instead of relying on traditional chemical methods, to overcome these obstacles.
This system is composed of three modules:
Illurstration for 3 modules of our BC modificaiton system
This design perfectly solves the challenge of naturally binding POIs to BC.
In the future, each of these three modules can be independently upgraded and iterated. We could use high-throughput screening to find more scaffold molecules that bind to BC, discover new SpyCatcher-SpyTag pairs, and create protein pools with different POIs that can all work together in BC.
In summary, our modular system paves the way for endless innovations with BC, transforming a simple material into a versatile platform with real-world applications.
During our interview with Professor Hong Feng's team (State Key Laboratory For Modification of Chemical Fibers and Polymer Materials[SKLFPM]）, we presented the details of our project. Professor Hong expressed concern regarding the crosslinking strength between protein fibers and bacterial cellulose, emphasizing that insufficient crosslinking could compromise the integrity of subsequent composite connections [R1]. We took this feedback seriously and engaged in further in-depth discussions to address the issue.
Webminar with SKLFPM
With the previous concern in mind, we consulted Dr. Chen from Yuandong Bio, an expert in the field.
Dr. Chen confirmed that the relationship between protein fibers and bacterial cellulose is encapsulation rather than simple crosslinking. This encapsulation ensures that the crosslinking strength is sufficient to support subsequent connections, thereby mitigating potential issues in the composite material.
Curli proteins serve as a universal scaffold, and when embedded with curli fibers, they can be integrated with bacterial cellulose.
One of the challenges with bacterial cellulose is that attaching proteins or any other functional molecules to its surface is quite difficult. However, when curli fibers are combined with bacterial cellulose, the composite acts as a versatile “scaffold”, allowing for the easy attachment of a wide variety of functional entities. This versatility opens up new possibilities for bacterial cellulose to be functionalized in ways that were previously challenging or even impossible, making it a highly adaptable material for diverse applications. Referrence：R[6]
In summary, the crosslinking between BC and curlis fibers is embedding relationship, it makes our composite modification machicine have a high crosslinking strength and can easily attach to a wide variety of functional entities.
After those Human practices with experts from the previous academic and industrial fields, we have refined the design of our project and have become more confident about the feasibility and future prospects of our project.
We first decided to use Green Fluorescent Protein (GFP), known for its strong visual effects, as our initial POI (Protein of Interest) to validate the engineering feasibility of our machine by the Wetlab team. Subsequently, to give our machine practical significance and inspire confidence for future users, we decided to explore its commercialization potential. We selected antimicrobial peptides as the first application-focused POI for our modification machine. Through brainstorming, we explored various application scenarios for antimicrobial peptide-integrated bacterial cellulose, ranging from antimicrobial dressings to antibacterial sanitary pads. Mr. Kang, who is an entrepreneur and a former investor in bio-technology, facilitates our brainstorming. Recognizing the multiple commercialization possibilities of antimicrobial peptides as a functional protein, we communicated this decision to the Wetlab team, asking them to prioritize the bioengineering design and synthesis of the entire machine using antimicrobial peptides as the POI.
Brainstorming of application senarios and selection using Business Model Canvas
Through extensive IHP work with experts across various potential application scenarios, we conducted an initial feasibility analysis and ultimately selected outdoor antimicrobial products as the first category for commercialization. Below is the IHP and feasibility analysis we conducted through our IHP efforts:
Due to the excellent antimicrobial properties of antimicrobial peptides and the superb biocompatibility of bacterial cellulose, we initially aimed to create antimicrobial dressings using bacterial cellulose combined with antimicrobial peptides. To assess the feasibility and prospects of our product, we consulted with burn specialists.
Dr. Li raised several concerns regarding the antimicrobial dressings made from antimicrobial peptides combined with bacterial cellulose:
Dr. Zheng also expressed several concerns:
Interview with Dr. Zheng
Through these interviews, we have engaged in reflection.
Due to the challenges in approval, high costs, and lack of competitive advantages compared to silver ion antimicrobial gels, we have ultimately decided to give up the development of antimicrobial adjunct products.
For more detailed interview Referrence, please click here: Interview Referrence[2] , Interview Referrence [3]
In recent years, there has been an increased focus among Chinese women on hygiene products, with greater emphasis on hygiene, safety, and skin-friendliness. It became the trend to pursue by major manufacturers. Given that antimicrobial peptide-combined bacterial cellulose offers good antimicrobial and biocompatibility properties, we believe that using it to make antimicrobial sanitary pads is a highly promising option. To validate the feasibility of this idea, we conducted an interview with YiRu Biotech in hopes of receiving further guidance.
Mr. Wang from YiRu Biotech provided us with valuable advice.
He suggested:
After interviewing YiRu Biotech, we ultimately decided to give up the idea of using antimicrobial peptide-combined bacterial cellulose for manufacturing antimicrobial sanitary pads.
For more detailed interview Referrence, please click here: Interview Referrence [5]
Disision making meeting for sanitary pads proposal of our team memebers
Ultimately, after discussion, we found that high-end, eco-friendly, antimicrobial outdoor products, such as bandages, have promising entrepreneurial prospects. Therefore, we decided to pursue this path for commercialization. Additionally, we conducted an interview with Bloomage Biotech to gain a deeper understanding of the pilot-scale platform for commercialization. For specific details, please refer to the Entrepreneurship section.
Our visit to Bloomage Biotech
Ultimately, we selected high-end outdoor antimicrobial products as our first application scenario. Our entrepreneurship taskforce team will provide a detailed market analysis and proof of concept (POC) validation on the Entrepreneurship page. Please refer to the Entrepreneurship page for further details.
Our team participated in the 11th China iGEMer Communication Conference (CCiC), held at Xi'an Jiaotong-Liverpool University in Suzhou. This prestigious event brought together nearly 300 iGEM teams from across China, providing us with a platform to share our project and learn from the latest advancements in synthetic biology. We had the opportunity to listen to insightful presentations from leading experts and gain a deeper understanding of the current trends and challenges in the field of synthetic biology.
One of the key takeaways from the conference was the valuable feedback we received from experts and scholars regarding our project on modified bacterial cellulose. For instance, the Peking iGEM GPA team from Peking University advised us to be mindful of issues related to antibacterial peptide autophagy and the connections between our three components.
Through this conference, we proudly presented our project to the entire Chinese iGEM community,emphasizing that our work is focused on addressing global challenges. We are committed to providing sustainable solutions in synthetic biology, and all our approaches revolve around this core theme.
Professor Zhang Weiwen from Tianjin University delivered a keynote lecture at the CCiC conference on biosafety in synthetic biology. His insights on the application of AI in synthetic biology, as well as the dual-use nature of AI technology and the importance of responsible innovation, provided us with significant inspiration and reflection. In response, we conducted discussions and social experiments on the safe use of AI in the AI x Synbio field. And we plan to do an social experiments with on-site iGEMers on Jambree by live-stage interactive session. For more details, please explore our safety page on AI safety.
In recent years, numerous companies have been exploring synthetic biology techniques for the biosynthesis and modification of materials, marking a major trend for the future. Our project is closely aligned with this movement, as it focuses on a composite modificaiton system designed for the modification of bio-based materials. This system represents a state-of-the-art modification platform that not only addresses current development trends but also embodies a responsible innovation for both society and the global community.
To further explore the diverse possibilities for our composite machine’s future development, particularly its integration with various biological modification methods, we engaged in discussions with Yiru Biology. During these discussions, Dr. Jiawei Wang provided us with broader strategies to enhance the properties of bacterial cellulose.
In chemical modifications, esterification reactions, utilizing anhydrides such as acetic anhydride or benzoyl anhydride, can improve cellulose's solubility and thermal stability, while also imparting new functionalities such as water resistance and corrosion resistance. Acetylation, where cellulose reacts with acetic acid to produce cellulose acetate, enhances water solubility and optical properties, making it widely applicable in textiles and coatings. Carbonization, involving the treatment of cellulose with nitric acid to produce nitrocellulose, imparts flammability and fire resistance, commonly used in explosives and film production. Hydroxyl modifications through aminolysis or amidation can increase the reactivity and functionality of cellulose, facilitating the development of biocompatible materials.
In biological modifications, enzymatic modification employs specific enzymes such as cellulases or Acetobacter xylinum to improve cellulose solubility and biodegradability, contributing to the development of biodegradable materials. Microbial methods use bacteria or fungi to degrade and modify cellulose, generating novel bio-based materials, enhancing biocompatibility, and promoting the recycling and reuse of waste.
By exploring these modification methods, we have gained a clearer understanding of how to further expand the potential of bacterial cellulose modification within our composite modificaiton machine. This will not only broaden the application scenarios but also advance the development of environmentally friendly optimization techniques, potentially replacing chemical methods with biological ones.
We have systematically cataloged all IHP activities conducted with external experts. The guidance provided by IHP has been instrumental across various stages of our wetlab experiments, entrepreneurial initiatives, and safety considerations. Each activity has been assigned a Referrence number, accompanied by detailed reflections. The insights and decisions outlined on this page are predominantly shaped by the contributions from our IHP engagements, which have significantly influenced our strategic thinking and actions. Relevant citations to IHP activities have been integrated into the main content of this page.
Professor at Donghua University
Dr. Hong Feng, a Professor and PhD advisor in the fields of biochemical and molecular biology, and biomedical sciences, is the Director of the Bacterial Nanocellulose Manufacturing and Composite Technology Research Base. He is also the head of the Sino-Swiss Industrial Biotechnology International Cooperation Research Laboratory, the leader of the Microbial Engineering and Industrial Biotechnology Research Group, and a leading figure in industrial microbiology, biomaterials, and textile biotechnology.
Dr. Hong was a visiting scholar at Cornell University’s biomedical program (2016-2017) and a postdoctoral researcher in the Department of Applied Microbiology at Lund University in Sweden (1999-2001). He currently serves as a committee member of the Bio-medical Composite Materials Division of the China Composite Materials Society, an academic committee member of the International Series Conference on Bacterial Nanocellulose, a director of the Shanghai Society of Biological Engineering, a committee member of the Biotechnology and Engineering Professional Committee of the Shanghai Chemical and Chemical Engineering Society, an advisor to the Guangdong Province Bioindustry Association, and a member of the American Chemical Society (ACS). He is also an expert reviewer for the National Science and Technology Awards, key international science and technology cooperation projects from the Ministry of Science and Technology, and science and technology achievement evaluations from the Ministry of Education, as well as a reviewer for the National Natural Science Foundation of China projects. He is on the editorial boards of journals such as Cellulose Science and Technology and Biomaterials and Tissue Engineering Bulletin and serves as a reviewer for over 60 international journals. In recent years, he has led and undertaken major projects including key national research and development plans, general projects from the National Natural Science Foundation, and special projects from the National Advanced Functional Fiber Innovation Center. His related achievements have won the Shanghai Science and Technology Invention Award (First Prize) and the "Textile Light" Science and Technology Progress Award (First Prize) from the China National Textile Industry Council. He has been engaged in research on industrial microorganisms and biomaterials, focusing on the efficient and cost-effective production of bacterial cellulose (BC) for medical applications, and has conducted exploratory and original work in this area.
Professor Hong Feng and the doctoral students in his team provided profound insights into our questions. Dr. Xu elaborated on the advantages and disadvantages of template modification versus traditional modification methods. He pointed out that while traditional methods are relatively simple to operate, they have a greater environmental impact. In contrast, the new modification methods emphasize large-scale application and have stronger environmental protection advantages. Dr. Liu discussed the future development prospects of bacterial cellulose, especially its potential applications in tissue engineering scaffolds, as well as in electronics and energy fields. Dr. Yang further noted that despite the challenges of low production efficiency and high costs in mass production of bacterial cellulose, these issues are gradually being addressed through dynamic production and innovative techniques utilizing low-cost biomass materials. Additionally, managing waste and by-products generated during production to reduce environmental impact remains an urgent issue to be solved.
Head Nurse and Chief Nurse
Li Hua was graduated from the Army Medical University, she has led two provincial and ministerial-level research projects and has published over 20 papers in core journals. She has also directed four national-level continuing medical education projects and one continuing education project in Chongqing. She has achieved five new business and technology innovations at the Army Medical University. She is a committee member of the Rehabilitation Nursing Group of the Burn Surgery Branch of the Chinese Medical Association, a committee member of the Burn Surgery Branch of the China Medical Promotion Committee, and a committee member of the Burn Branch of the Chinese Society of Medical Education. Doctor Li serves as an editorial board member for Chinese Journal of Burns and Journal of Nursing Science. She has been honored with the "Advanced Individual in Quality Nursing Services" award in Chongqing and recognized as an outstanding head nurse at the university.
Dr. Li provided a detailed response regarding the background of burn and wound management. She explained that burns can result from various causes, including thermal, chemical, and electrical sources. Despite the diverse nature of burns, they ultimately all involve wound repair. Following emergency treatment, appropriate dressings are chosen based on the different stages of wound healing, such as the infection stage, granulation stage, and epithelialization stage.
We then inquired about the current status of wound dressings. Dr. Li explained that there are many types of dressings available, including liquid, solid, and gel forms. Both imported and domestic dressings have their advantages and disadvantages. While domestic dressings are continuously innovating, they tend to be more expensive and are not widely covered by health insurance. Overall, new dressings like silver-containing ones have strong antimicrobial effects and are widely used in clinical settings. However, they come with potential risks of toxicity, high costs, and suboptimal patient experience.
Lastly, regarding antimicrobial peptide dressings, Dr. Li expressed a somewhat pessimistic outlook on their market prospects. She believes that antimicrobial properties should be a basic requirement for dressings rather than a distinguishing advantage. Furthermore, antimicrobial peptides are currently used less in clinical settings and are more commonly found in cosmetic products like face masks, where their antimicrobial effectiveness may not be significant and their costs are high. In contrast, while silver-containing dressings are expensive, they extend the intervals between dressing changes and improve the overall patient experience.
Associate Chief Physician, Burn Department
Dr. Zheng Wang is an Associate Chief Physician in the Burn Department at Harbin Fifth Hospital. He specializes in the treatment of burns, scalds, frostbite, electrical injuries, as well as scar and scar revision surgery.
We began our interview with Dr. Zheng to gain insights into the basic procedures for burn management. According to Dr. Zheng, the standard treatment process in the burn department includes disinfection, debridement, and dressing. Antimicrobial dressings are primarily used to prevent infection, followed by the application of adjunctive materials that promote wound healing.
Dr. Zheng then discussed the current status of wound dressings and their pros and cons. The available dressings include both imported and domestic products. With the advancement of domestic dressings, silver ion dressings have become a major choice due to their excellent antimicrobial properties and suitability for large wound areas. However, some silver ion dressings are not yet covered by health insurance, and their high cost, short antimicrobial duration, and frequent need for replacement lead to a suboptimal patient experience. Future improvements in dressings should focus on affordability, extended replacement intervals, suitability for large wounds, and minimal harm to the body.
Finally, we inquired about Dr. Zheng’s opinion on our product. Dr. Zheng mentioned that he had read about antimicrobial peptide dressings in journals and believes they have potential. However, due to their limited clinical use and lack of extensive data support, further market research and clinical trials are necessary before they can be introduced to the market. Dr. Zheng emphasized that antimicrobial properties and biocompatibility are crucial characteristics for dressings, but these effects still require additional clinical validation.
Bloomage Biotech Technology Co., Ltd.
Founded in 2000, Bloomage Biotech Technology Co., Ltd. is a global leader in the research, development, and production of hyaluronic acid (HA). The company specializes in the development of bio-based materials, with products widely applied in medical, healthcare, and beauty fields. Bloomage is dedicated to providing high-quality biotechnology solutions to users around the world.
In our discussion with Bloomage Biotech Technology Co., Ltd., we gained in-depth insights into their core research and development achievements in the field of collagen. Bloomage Biotech provided detailed information about several key products, including 1% sodium hyaluronate solution and low molecular weight sodium hyaluronate solution, highlighting the unique technological advantages of these products.
They also shared their experiences in overcoming challenges related to cost, improving efficiency, and ensuring quality control in large-scale production. This information has been invaluable for our commercialization team, providing substantial guidance and support for the development of future pilot platforms.
Shanghai Yiru Biotechnology Co., Ltd.
Founded in 2021, Shanghai Yiru Biotechnology Co., Ltd. is committed to Biotech manufacturing, low-carbon cycle, and recycling, with a focus on maximizing material innovation through synthetic biology. The company utilizes natural fiber waste materials, including straw, coffee grounds, oat husks, and distiller's grains, to cultivate a new generation of innovative biomaterials using unique processes.
Firstly, Professor Wang Jiawei provided a detailed explanation of current bio-based material modification technologies, outlining their advantages and disadvantages. He noted that while common methods each have their own benefits, they generally face issues with material solubility and resistance to degradation.
Next, we inquired about how companies should address the ethical and safety issues associated with synthetic biology technologies. Professor Wang emphasized the need to tackle these concerns from multiple angles, including legal considerations, company policies, project management, and human resource management. He also provided examples of safety issues encountered in real-world production settings.
Through this interview, we gained insights into the current technological landscape of the bio-cellulose industry and learned more about addressing biological safety issues.
Guangzhou Yuandong Biotechnology Co., Ltd.
Established on January 16, 2024, Guangzhou Yuandong Biotechnology Co., Ltd. is dedicated to developing high-performance bio-based materials for advanced manufacturing.
Firstly, we interviewed Professor Chen from Yuandong Biotechnology regarding AI safety issues. He provided in-depth advice on our proposed AI safety concepts. Professor Chen argued that implementing tiered management for AI users could be seen as an unfair practice that conflicts with the principle of knowledge democratization. He suggested that the correct approach is to ensure the directional safety and proper functioning of AI and large language models, rather than restricting individual access to AI. Additionally, he recommended improving AI applications through downstream control measures and using high-quality training datasets. Given the limitations of individual capabilities, he emphasized the need for public institutions to establish principled regulations for AI.
Moreover, Professor Chen made detailed adjustments to our terminology, advising that our system should be referred to as a composite system. He explained that modification provides diversity and future optimization potential for the composite system. He also clarified that protein fibers and bacterial cellulose are connected through embedding, which is not merely cross-linking. This method ensures that the connection strength is sufficient to support subsequent components for further reactions.
In our HP and IHP work, we have meticulously produced, documented, and archived all relevant materials, including interview outlines, interview records, and work documents. We believe that comprehensive and well-organized documentation will provide valuable first-hand information for those who may Referrence our team's project in the future.