Find and verify problems

Background:

In the current context of increasing health challenges, we feel the urgency and importance of developing an effective relief product for itching caused by Staphylococcus aureus (Staphylococcus aureus for short). Staphylococcus aureus, as a common pathogen, widely exists in the natural environment and human skin. Its infection not only causes skin inflammation, redness and swelling, but also accompanies persistent and unbearable itching symptoms, which brings great trouble to the quality of life of patients.

Through online research, we found several reasons and needs why we needed to develop a new itch relief product.

The harm of Staphylococcus aureus causing itch

In the past 30 years, the prevalence of AD has gradually increased worldwide, and the prevalence of AD in children in developed countries has reached 10% to 20%. The increase of the prevalence of AD in China is later than that in western developed countries, Japan and South Korea, but it has increased rapidly in the past 10 years. According to the epidemiological survey conducted by Williams diagnostic criteria in China in 1998, the total prevalence rate of AD among school-age adolescents (6-20 years old) was 0.70%, and that among preschool children (1-7 years old) in 10 cities in 2002 was 2.78%. In 2012, the prevalence rate of children aged 3-6 in Shanghai was 8.3%. In 2014, using the diagnostic criteria of clinicians, the prevalence rate of AD in children aged 1-7 years in 12 cities in China reached 12.94%, and the prevalence rate of AD in infants aged 1-12 months was 30.48%.¹

Staphylococcus aureus is a Gram-positive bacteria present in 20-30% of healthy subjects. The prevalence of Staphylococcus aureus in AD skin can reach 30-100%. Staphylococcus aureus and Atopic Dermatitis: Mechanisms and Management and Colonization with Staphylococcus aureus in Atopic Dermatitis: A Review of the Literature mentions the presence of Staphylococcus aureus on the skin of about 70-90% of patients with atopic dermatitis.²

Insufficient functions of existing products

Although there are many kinds of itching relief products on the market, most of them tend to focus on broad spectrum itching relief, and their pertinence and effectiveness are still insufficient for itching caused by specific pathogens such as Staphylococcus aureus.

For existing hot products, drug resistance is the most important problem. Some products may contain hormonal components, long-term use may bring side effects, such as skin thinning, pigmentation, etc. Or a combination of drugs that is less effective and requires more hassle.

The need for medicine

Pursue the solution of the problem

Interviews

To gain a better understanding of Staphylococcus aureus infections in daily life, we interviewed Dr. Wang Xue and Dr. Tang Zongxiang, both of whom have extensive knowledge about the spread of Staphylococcus aureus. We learned that this bacterium is very common in humans. When Staphylococcus aureus causes itching, especially if it persists over a long period, people tend to scratch involuntarily, leading to skin damage and potentially more severe infections. The most common solution in daily life is the use of antibiotics, such as penicillin and cephalosporins, which aligns with our previous research findings.

The doctor also noted that antibiotics are unnecessary if the skin is not broken, and overuse of antibiotics can lead to antibiotic resistance. They informed us that there are currently no specific products on the market designed to address itching caused by Staphylococcus aureus. Dr. Tang pointed out that there are many factors that can cause itching, and suggested that we consider these other factors as well. He introduced us to a characteristic of traditional Chinese medicine—multi-target and multi-pathway approaches—where the combination of multiple herbs can enhance the effectiveness of the treatment. This could potentially become a direction for our future research.

From an evolutionary biological perspective, itching is a protective mechanism. However, pathological itching is persistent and can significantly affect normal life, making it necessary to address. The choice of product form should consider the mechanism and severity of the condition. Skincare products with lower concentrations of active ingredients are suitable for mild symptoms, while drugs with higher concentrations of active ingredients are appropriate for severe symptoms. Even though patients may not initially recognize the seriousness of their itching, they often seek medical help as symptoms worsen, making our product highly relevant. We can offer multiple solutions and forms to flexibly meet different needs, and integrate with existing products to enhance their practicality and market competitiveness.

In order to assist consumers at the onset of itching symptoms, we aim to integrate our product into daily necessities, to alleviate itching in everyday life and prevent more serious outcomes.

After conducting preliminary desk research, we have identified a significant issue that needs to be addressed - the problem of pruritus caused by Staphylococcus aureus. How can we effectively resolve this problem? Our team has reached out to multiple experts for conducting interviews.

Dr. Xing pointed out in the interview that in order to solve this problem, we first need to clarify the molecular mechanism of Staphylococcus aureus causing itch, so as to design solutions at the protein level to block this process.

Professor Yang pointed out that we can start with the existing plant-based small molecules, combined with the existing research on the molecular mechanism that causes itch, and design an experimental scheme to test the effectiveness of this small molecule on inhibiting itch.

In conclusion, we should first explore the molecular mechanism of Staphylococcus aureus causing itching, and then try to develop a method to screen the effectiveness of small molecules from the molecular mechanism, and obtain small molecules that can effectively reduce itching.

Explore the molecular mechanism

According to research³, Staphylococcus aureus secretes the V8 protease, which can cut the tail peptide of the EGFP receptor on the surface of human skin. When the target peptide is cut, it stimulates the nervous system to produce electrical signals, which in turn produces an itch sensation.

Design screening system

At the beginning of the experiment, we purified V8 protease in vitro, and tested its enzyme digestion activity with fluorescent substrates, so as to find substances that can inhibit the activity of V8 protease and inhibit itch sensation.

Optimize screening system

In our communication with Professor Shen Pi, Professor Shen believed that we could not only build an in vitro screening system, but we could also choose chassis to build an in vivo screening system. In vivo screening system has three advantages: it can realize the screening function, can be used as a monitoring system, and can have more optimization prospects.

With this suggestion in mind, we selected Escherichia coli as the chassis organism and constructed a model expressing V8 protease and its fluorescence reporting system. The fluorescence reporting system, called Flipcherry, consists of two parts: a B1-9 fragment containing sfcherry, and a B10-11 fragment containing the target cutting site of the V8 protease and connected by a linker. When the V8 protease in E. coli is expressed and activated, it cuts the target sequence in the fluorescence reporting system, causing the two parts to self-assemble into a complete, efficient fluorescent protein structure, which fluoresces red. The intensity of red fluorescence can be used to indicate the intensity of itch sensation.

By adding different foreign substances and observing the changes of red fluorescence, we can screen out those substances that can effectively reduce the intensity of red fluorescence, that is, compounds that can effectively relieve itching, as our products.

Grinding Solution

Overview

During the interview process, the critical perspectives raised by stakeholders on our project were of great help in improving it. We refined our solutions based on the feedback received and ensured efficient operations across departments by expanding our interview pool as much as possible.

In our project, summarizing stakeholders’ feedback and needs is crucial, as different groups have diverse priorities and perspectives on issues. For instance, doctors focused on our approach to alleviating itching, sharing clinical treatment information that guided us in identifying target populations. Meanwhile, project managers offered product design suggestions and aided in refining our initial business plan. This underscores that interviewing individuals from multiple industries helps us gain a broader and more comprehensive understanding of our project’s impact on the world.

Find the Direction of Development

At the beginning of the project, we planned to establish a low-cost screening platform to discover effective substances that can alleviate itching caused by Staphylococcus aureus. By adding different foreign substances and observing the changes in red fluorescence, we can screen out those substances that can effectively reduce the intensity of red fluorescence, that is, compounds that can effectively relieve itching.

At the same time, we wanted to give the project a richer meaning and ensure that our approach to solving the problem was novel and interesting, so we interviewed Professor Yang Jidong.

After listening to our introduction to the project, Professor Yang Jidong suggested that we should think in the direction of Chinese herbal medicine when screening natural extracts, which gave us the idea of combining the project with Chinese medical culture.

Enrich Project Connotation

Considering that members of the team have limited knowledge of TCM (traditional Chinese medicine), and TCM culture has a long history and a complex knowledge system, we then interviewed Yang Fan, an expert in the field of TCM, hoping to further understand TCM and get suggestions on the combination of our project and TCM.

Dr. Yang Fan expressed her affirmation of the necessity of our target problem and informed us that itching is a common clinical symptom, the root cause of repeated scratching behavior, an important factor leading to skin apparent damage, aggravating chronic inflammation and skin barrier destruction, which often affects the quality of life of patients. At present, the judgment of itching degree mainly depends on the description of patients. This inspired us to improve the project in the future, namely to create a product that can inhibit the initial stage of itching and reduce the damage caused by itching in patients.

At the same time, she also suggested that we expand the range of types of itch that can be detected, so that the E. coli platform we built can be applied to the search for drugs for more kinds of itch diseases, and help more people.

Perfect Business Plan

We interviewed Dr. Feng Chunbo and Ms. Cao Jinqiu in order to improve the commercial feasibility of our project, get suggestions on the application scenarios of the project, and learn more about the suggestions of skin care companies for our project. From the interviews, we realized that: when formulating the business plan, the audience should be clear, our products should have unique advantages compared with competitive products, and at the same time, we should consider the use of traditional Chinese medicinal materials, so as to help the local government upgrade its industrial direction and produce a lot of economic effects. These suggestions have greatly helped us refine our business plan and provide a path for us to find ways to improve in the future.

Educate the Public Effectively

We interviewed the popular science blogger Liu Pengxin, it is worth mentioning that he is also a professor of chemistry in our school. Considering his professionalism and rich experience in popularizing skin care products to the public, we sought his advice on the publicity of this project.

From this interview, we got a constructive suggestion to help promote the idea of the project: teaching the public that blind sterilization is not always reasonable, which may lead to the overuse of antibiotics and other problems. This helped to refine the design logic of the project, as Staphylococcus aureus is widely present in our environment and we cannot completely eliminate them.

We believe that bacteria are also part of the human ecosystem, and by reducing their negative impact on our health, we can prevent more serious diseases from occurring. Therefore, our products are designed to control the flora rather than kill it. This also provided inspiration for our work in education. In community outreach, we popularized the methods of preventing Staphylococcus aureus infection to the public, so as to achieve the purpose of educating the public.

Stakeholders

Our team places a high priority on connecting with our stakeholders and interacts with them in a variety of ways, including emails, tours, and online and offline interviews. We record our interviews in a timely manner and quickly feed this information back to the entire team for improvement. This process shapes our interview forms and ensures that we are able to continuously optimize our communication and collaboration with our stakeholders.

Through exhaustive desk research and in-depth interviews, we gradually identified key stakeholders and built strong and deep relationships with them. In the process, we gained a deep understanding of their core concerns and values in their respective fields.

In total, we categorize stakeholders into these categories:

Informed consent form

In order to ensure the security of the interviewer’s personal information and the legitimacy of our information acquisition, our team developed an informed consent form. This consent form is intended to clarify the purpose of the interview, its content and how the data will be used, and to ensure that the interviewer is fully aware of the information and participates voluntarily.

How to Better Implement

1. Avoiding Long-Term Dependence on Antibiotics and Resistance Issues

Problem Background

Frequent use of antibiotics leads to resistance, which has become a significant challenge in the medical and public health domains.

Solution

Non-Antibiotic Approach to Itch Relief:

We propose addressing itch issues without antibiotics, specifically by using natural small molecules. This method effectively avoids the problem of resistance, garners broad public acceptance, and increases product adoption. Technological Advantage:

Using biotechnology to extract and optimize natural plant small molecules to ensure their efficacy and safety, making them a reliable alternative to antibiotics.

2. Raising Public Awareness about Staphylococcus aureus-Related Issues

Survey Data

• Nearly 90% of respondents are unaware of the cause of their itch.
• 66.7% endure the itch, waiting for it to naturally subside, 39.13% use over-the-counter itch relief, and 37.68% seek medical help.
• 66% consider it essential or significant to understand the dangers of Staphylococcus aureus.
• Nearly 80% believe there is a high or moderate necessity for skincare products addressing Staphylococcus aureus infection.

Survey Results Analysis

While most people are unaware that Staphylococcus aureus causes itching, there is a desire to understand this issue and its importance in daily skincare. Therefore, raising public awareness of the problems caused by Staphylococcus aureus and other itch-related issues is necessary, with reference to existing soothing skincare products.

Solution

Integration with Existing Skincare/Cosmetics:

Incorporate our product into existing skincare and cosmetic lines as a soothing cosmetic. This integration can greatly reduce the cost of educating the public on its standalone basis, allowing consumers to use our product naturally in their daily skincare routines.

3.Ensuring Product Safety

Problem Background

Product safety is a primary concern for any new technology application.

Solution

Third-Party Testing Institution Consultations:

By engaging with professional third-party testing institutions, we can more accurately position our product and ensure its safety throughout usage.

4. Integrating Medication Conveniently into Daily Life

Problem Background

To facilitate the convenient use of medication in daily routines.

Solution

Integration with Existing Products:

When consumers experience itchiness but cannot identify the cause, our product can be combined with existing skincare and cosmetic products. This allows it to be used in daily care routines, not only resolving itchiness but also providing a more convenient user experience. Hardware Innovation:

Medication-Infused Nail Wearables: Initially, we considered combining medication with nail wearables to administer the drug. However, due to its limited practicality and target audience, this plan was ultimately abandoned.

Head Scratcher with Roll-On Medication

The idea is to inject the medication into the head of the scratcher and deliver it through a roll-on mechanism. However, controlling the dosage was challenging, leading to modifications of this approach.

Combination of Manual and Electric Scratcher

• Manual Scratcher: Allows for precise medication delivery, with the user freely controlling the dosage.
• Electric Scratcher: Integrates massage functionality, offering both a principled and physical method for itch relief. This ensures comfort and effective itch relief without damaging the skin.

For more details, please refer to the Hardware.

Summary:

Through the above solutions, our project not only offers a convenient, non-antibiotic alternative using advanced technology but also raises public awareness about Staphylococcus aureus and itch-related issues by integrating with existing products. Additionally, the multi-layered safety checks and practical design ensure that the product is safe and easy to use.

Conclusion

Our Human Practice efforts have been instrumental in shaping a product that is not only scientifically sound but also resonates with the needs and preferences of our target stakeholders. Through active engagement with a diverse range of experts and the public, we have ensured that our project is well-positioned for successful implementation and societal impact.