Team:CCU Taiwan/Entrepreneurship

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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:


  • Patients with chronic wounds (including moderate, or heavy exudate chronic wounds, pressure ulcers, diabetic foot ulcers, etc.)
  • Patients with acute wounds (including moderate, or heavy exudate acute wounds, first- and second-degree burn sites, surgical incisions, etc.)

  • 2. Values

    We focused on the following values when designing our product:


  • Innovative
  • 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.

  • Multifunctional
  • The outer layer of PU film is waterproof, breathable, and blocks external infection.
  • Chitosan and alginate comprise the middle layer, with absorptive capacity up to 10 times the layer weight, it allows the wound to stay in a moist environment while absorbing redundant exudate.
  • The inner layer is made up of AMPs, AMPs linked with TAT, and collagen. Collagen speeds up the wound healing process while AMPs and AMPs with TAT tackle the intracellular and extracellular bacteria respectively, protecting the wound from potential infection.
  • User-friendly
  • PU film, the outer layer, with its adhesive characteristic, allows users to make the wound care process straightforward without special training required.

  • Customizable
  • The dressing can be tailor-made to fit the size of the wound.

  • Affordable
  • 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

  • Research and development to optimize AgenT Dressing
  • Understanding the cost structures and best market fit for our product.
  • Funding will be used to advance research and development of AgenT Dressing materials to be more eco-friendly.
  • Clinical trials and patents.
  • Mass production of the AgenT Dressing
  • Marketing and branding of the AgenT Dressing
  • Building long-term partnerships with customers and creating brand loyalty.

  • 7. Key Resources

  • Partnership establishment
  • Building partnerships with manufacturers and suppliers for raw material and mass production.
  • Building partnerships with medical care institutions and authorities for product distribution.
  • Investors will provide funds for product development and division.
  • Efficient manufacturing of AgenT Dressing.

  • 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

  • The combination of AMPs and AMPs with TAT can tackle a wide spectrum of both extracellular and intracellular bacteria.
  • Killing bacteria through innovative methods–AMP and TAT’s physical properties can reduce the likelihood of generating drug-resistance pathogens.
  • The outer layer (Polyurethane Film) being waterproof, breathable, and effectively blocks external contamination.
  • The middle layer, the absorptive layer (Chitosan), can absorb excess exudate while keeping the wound environment moist.
  • The inner layer, the collagen layer, can quicken the healing process and is less likely to leave scars.
  • Antimicrobial agents in AgenT Dressing can reduce the odor caused by bacterial flora on the wound.
  • AgenT Dressing is user-friendly, easy to operate without professional training.

  • Weakness

  • High cost of the raw material (collagen).
  • Few distributing channels due to Taiwanese regulations.

  • Opportunity

  • Superbugs have jeopardized ​​public health and became an international concern.
  • Abusing antibiotics has led to drug-resistance bacteria generation, leading to medical treatment failures.
  • Advanced medical care has increased health-related awareness among the general public.

  • Threat

  • Dressings with different antimicrobial substances are becoming more popular on the wound dressing market. For example, silver-impregnated is one of the most commonly used antimicrobial dressings [4].
  • The new technology, for example the photodynamic therapy (PDT) using Indocyanine green (ICG), may bypass the drug-resistance and kill bacteria through near-infrared light activation [5].
  • Competitor Analysis
  • Silver dressing
    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.
  • AgenT Dressing uses antimicrobial peptides (AMPs), which do not easily generate drug-resistant pathogens, as antimicrobial agents. To ensure the AMP can kill the bacteria both in and outside of the cell, we link TAT to the AMP. Once the dressing contacts the wound, the thrombin that naturally presents in the human body will cut the thrombin cleavage site and release the TAT-AMPs.


  • Market Survey (Click here for survey analysis report)

    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:

  • AgenT Dressing can reduce the generation of drug resistance.
  • The dressing can shorten the wound’s healing time.
  • Convenient and user-friendly.
  • The reasons that respondents choose “No” included:

  • Safety concerns of synbio products.
  • Prefer using traditional treatment methods (antibiotics) rather than using antimicrobial dressings.

  • 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:

  • AgenT Dressing is not likely to lead to the drug-resistant generation.
  • Having different options can reduce use of antibiotics.
  • The reasons that respondents choose “Antibiotics” for wound treatments included:

  • Antibiotics are more commonly used in medical treatments.
  • Antibiotics can efficiently kill the bacteria.
  • The reasons that respondents choose “Both (antibiotics and antimicrobial dressing)” for wound treatments included:

  • Following the prescriptions from the doctors.
  • Depend on the severity of the wound.

  • 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

  • Short-term Objectives
  • 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.

  • Long-term Goals
  • 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.