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Overview
Our antimicrobial dressing–AgenT Dressing–was developed to tackle the superbug issue. After discussing with medical professionals and being encouraged by entrepreneurs, we realized our project could go beyond the iGEM competition and make a real impact on the medical industry and public health. Our project not only focuses on experimental endeavors but is also highly aware of other aspects in a way to fully understand our targeted customers and the market.
Our team is dedicated to raising awareness among the general public on accountability for using medical substances. From the marketing end, we dove into market research; while from the user end, we conducted surveys and consulted with experts to understand user preferences and practical/professional demands. After painting a bigger picture, we strategized a complete implementation plan for our product–AgenT Dressing, including mapping out a business canvas, conducting SWOT analysis, understanding cost structures, and setting up short-term objectives and long-term goals to ensure project execution.
We could not have possibly done all the above without the help of experts from various fields whom we sought for professional advice on our project.
Team Composition
iGEM CCU_Taiwan is a multidisciplinary team consisting of 24 passionate students from 6 departments pooling talents together to address one of the most crucial global health crises–superbugs. We have divided the team into three groups: Wet Lab, Dry Lab, and Human Practice. Wet Lab is in charge of testing and experimental work, Dry Lab for modeling, designing a product, and setting up our Wiki page, and lastly, Human Practice to take the results and impact beyond the lab.
Defining Problem
In 1928, the discovery of the antibiotic penicillin effectively controlled bacterial infections and greatly improved patients’ survival rate. However, the improper use of antibiotics led to the development of drug resistance in bacteria. Superbugs–such as Methicillin-resistant Staphylococcus aureus (MRSA)–were born.
From a recent global survey, at least 700,000 people die of antibiotic-resistant infections every year, because the available antimicrobial drugs have become less effective at killing resistant pathogens [1]. According to the WHO, if we keep neglecting these urgent issues, antimicrobial resistance could force up to 24 million people into extreme poverty by 2030. By 2050, drug-resistant diseases could cause 10 million deaths each year [2].
Groups highly susceptible to superbug infections include: (1) patients with chronic wounds are prone to be infected because of their weak immune systems, such as pressure ulcers, diabetes mellitus, etc., while (2) patients without proper treatment of acute wounds are likely to develop bacterial infections as well.
Solution
To bypass the antibiotics resistance of superbugs, we found that antimicrobial peptide (AMP) kills superbugs through a physical mechanism that is different from antibiotics. Considering dealing with the latent superbugs, we generate cell-permeable AMPs through linking AMPs with cell-penetrating peptide, TAT. Patients with weak immunity, chronic disease, and/or receiving improper wound treatments are at a high risk of superbugs infection through open wounds, thus we designed the AgenT Dressing to optimize wound care while solving the underlying superbug issue.
Process
While surveying antimicrobial substances that may support or even replace antibiotics to deal with superbugs, we found that biosynthetic AMPs are a promising candidate, because of their physical mechanism. We also found that the cell-penetrating peptides may carry AMPs into macrophages to clear latent superbugs without causing damage to the cells. We applied AMPs and TAT linked with AMPs (TAT-AMPs) to deal with the superbug infection and latency, respectively. The short cationic peptides AMPs can kill extracellular superbugs through a physical mechanism that causes holes in the bacterial membrane. TAT-AMPs can translocate into cell membranes to tackle the intracellular bacterial latency.
To confirm the possible application of AMPs and TAT-AMPs on human wounds, we conducted four major experiments to ensure the efficiency and safety of the AgenT Dressing, namely the minimal inhibitory concentration (MIC), Hemolysis, Cytotoxicity, and cell penetration ability test [3]. The MIC is performed to examine the antimicrobial efficiency of AMPs. The Hemolysis and Cytotoxicity examine the biosafety of AMPs. Combining the result from these three assays, we could define the minimal dosage of AMPs that is functional and safe on the dressing. Finally, the cell penetration ability test is to confirm the ability of TAT, the selected cell-penetrating peptide.
Innovation
Antimicrobial agents: AMP and TAT-AMP
AMPs alone can kill a wide spectrum of bacteria outside the cell membranes, but not intracellular ones. TAT can translocate cargo across the cell membrane. Therefore, we linked AMP with TAT to carry the AMPs into cells to tackle intracellular bacteria, achieving both intra- and extracellular sterilization.
Regulatable AMP releasing mechanism
In the long run, the constitutively activated AMPs could attack other molecules on the wound due to positively charged characteristics. Due to AMP’s natural mechanism, we designed regulatable AMPs by linking AMPs with a thrombin cleavable collagen-binding domain (CBD). This design allows the dressing to release AMPs only when contacting the blood in the wound and also helps AMPs to anchor on the collagen layer.
AgenT Dressing Design
AgenT Dressing is a three-layer antimicrobial dressing. Each layer is designed for specific functions to attain optimal sterilization of wound care.
Outer Layer
Polyurethane Film, acts as a bacterial barrier, blocking out external contamination while the material is breathable and waterproof.
Middle layer
The mixture of alginate and chitosan is lyophilized to form a flexible absorption layer to absorb excessive wound exudate while keeping the wound moist.
Inner layer
Collagen, as the base of the inner layer, can stimulate the deposition and organization of newly formed collagen fiber and granulation tissue in the wound bed. Binding with the collagen, antimicrobial agents can achieve both intra- and extracellular sterilization.
Market Overview
Business Canvas
1. Target Customers
The antimicrobial agents in AgenT Dressing can tackle a wide spectrum of bacteria. Our target customers can be divided into two main segments:
2. Values
We focused on the following values when designing our product:
AgenT Dressing offers a new treatment option for patients who suffer from bacterial infections while reducing the likelihood of generating drug resistance pathogens by using low-cytotoxicity Antimicrobial Peptides (AMPs) and TAT-AMP.
PU film, the outer layer, with its adhesive characteristic, allows users to make the wound care process straightforward without special training required.
The dressing can be tailor-made to fit the size of the wound.
The raw materials of the AgenT Dressing (7.5×7.5 cm2) only costs about 2 USD, compared to over 10 USD for silver-based dressings providing the same sort of physical protection.
3. Distribution Channels
AgenT Dressing will be distributed through the hospital or other health care providers.
4. Customer Relationships
We conducted a market survey for the general public to understand customer-end preferences. In the future, we plan on establishing long-term partnerships, for example, directly providing samples to hospitals for practical assessments.
5. Revenue Streams
Revenue will be gained from the sales by distributing to hospitals or other health care providers.
6. Key Activities
7. Key Resources
8. Key Partners
Our key partners Including investors, healthcare providers, government, and manufacturers.
9. Cost Structure - Cost of the raw materials
(1 USD = 27.64 NTD; Date: September 11, 2021)
SWOT analysis
Strength
Weakness
Opportunity
Threat
Silver ions in the silver dressing interfere with the respiratory chain in the cytochromes of micro bacteria and also interfere with components of the microbial electron transport system, bind DNA, and inhibit DNA replication, disturbing the survival of bacteria [6]. The price varied from approximately 12.9 USD.
We conducted the survey to the general public by using google form to understand the market of antimicrobial dressing in Taiwan.
a. Purchase Preference
After introducing the innovations of our product, we included this and the next question to determine whether our AgenT Dressing has a market fit and to determine public preference.
89% (299 responses) responded Yes while 11% (37 responses) responded No.
b. Reasons of Purchase Preference
The reasons that respondents choose “Yes” included:
The reasons that respondents choose “No” included:
c. Wound Treatment Preferences
This question was intended to take a glimpse into the public opinion on choosing antibiotics, antimicrobial dressings, or both for wound treatments.
37.5% (126 responses) Antimicrobial dressing, 6.3% (21 responses) Antibiotics, 54.5% (183 responses) Both, and 1.8% (6 responses) Prefer not to answer.
d. Reasons for Wound Treatment Preferences
The reasons that respondents choose “Antimicrobial dressing” for wound treatments included:
The reasons that respondents choose “Antibiotics” for wound treatments included:
The reasons that respondents choose “Both (antibiotics and antimicrobial dressing)” for wound treatments included:
e. Prefered Price (1 USD = 27.64 NTD; Date: September 11, 2021)
To understand how much people are willing to pay for the AgenT Dressing (10x10 cm2), in the future, our team will set the market price of the dressing between 12.5 to 16 USD which meets the preferred and reasonable price.
36% (121 responses) 9-12.5 USD, 39.6% (133 responses) 12.5-16 USD, 16.7% (56 responses) 16-20 USD, 2.7% (9 responses) 20-23.5 USD, 0.3% (1 response) ≥ 23.5 USD, and 4.8% (16 responses) prefer not to answer.
Future Work
Targeting the Taiwanese market as our short-term objective. Optimizing hard power such as product development, logistics, and cost structures to gain market competitiveness. Meanwhile focusing on soft power such as marketing & branding, developing partnerships to enhance brand loyalty, and creating two-way communication with our customers. The top priorities are to reduce drug-resistance pathogens caused by bacterial infections and to raise public awareness on superbugs issues.
Expanding to the international market is our long-term goal. During this stage, we will focus on product diversification and partnerships. When designing, we hope to provide a variety of products based on different wound types to achieve optimal wound care while taking local culture/regulations into consideration. Establishing partnerships with biotechnology and pharmaceutical companies, suppliers, and medical care institutions, developing international production lines or divisions.
References:
1. Antimicrobial resistance: a global threat (2021, UNEP)
2. New report calls for urgent action to avert antimicrobial resistance crisis (2019, WHO)
3. Kimmelman, J., & Federico, C. (2017). Consider drug efficacy before first-in-human trials. Nature News, 542(7639), 25.
4. Chuangsuwanich, A., Chortrakarnkij, P., & Kangwanpoom, J. (2013). Cost-effectiveness analysis in comparing alginate silver dressing with silver zinc sulfadiazine cream in the treatment of pressure ulcers. Archives of plastic surger, 40(5), 589.
5. Wong, T. W., Liao, S. Z., Ko, W. C., Wu, C. J., Wu, S. B., Chuang, Y. C., & Huang, I. (2019). Indocyanine Green—Mediated Photodynamic Therapy Reduces Methicillin-Resistant Staphylococcus aureus Drug Resistance. Journal of clinical medicine, 8(3), 411.
6. Barnea, Y., Weiss, J., & Gur, E. (2010). A review of the applications of the hydrofiber dressing with silver (Aquacel Ag®) in wound care. Therapeutics and clinical risk management, 6, 21.