Implementation

1. Background and Market Demand

There are nearly 588 million diabetic patients globally, of which up to 25% suffer from chronic non-healing wounds, facing risks of infection, gangrene, and even amputation (Dwivedi et al., 2024; Yadav et al., 2024). Current clinical treatment options have significant pain points: traditional therapies (such as debridement, dressing changes, antibiotic gauze) are cumbersome, inefficient, and exacerbate patient suffering (Peng et al., 2022); while advanced therapies are often difficult to popularize due to high costs, single functionality, or inability to dynamically respond to wound status.

The huge clinical demand and the shortcomings of existing solutions create an urgent need for an innovative treatment that can integratively address the three major challenges of infection, inflammation, and regeneration, and intelligently respond to the wound microenvironment. The goal of our "Yeast Medics" project is to precisely meet this market gap.

2. Product Application and Target Audience

Product Application:

"Yeast Medics" is an innovative injectable smart dressing based on engineered Yarrowia lipolytica and L-DOPA modified thermosensitive hydroxybutyl chitosan. Its core functions include:

Immediate Physical Antibacterial Action: Rapidly kills pathogens through antimicrobial peptides (Pexiganan) displayed on the yeast surface (Dumville et al., 2017).

Dynamic Anti-inflammatory Effect: Senses the high-glucose wound environment and programmatically releases the anti-inflammatory factor (IL-4) to resolve chronic inflammation (Hassanshahi et al., 2022).

Controllable Pro-regenerative Effect: Precisely releases the pro-angiogenic factor (VEGF) triggered by external infrared light to accelerate tissue repair (Crawford & Ferrara, 2009).

To ensure optimal and safe use of these advanced functions, we have developed a clear and concise instruction manual for patients and healthcare providers.

Target Audience:

Our direct users include endocrinology departments, burn units, wound care centers, and community health service centers at all levels of hospitals. The ultimate beneficiaries are hundreds of millions of patients worldwide suffering from chronic wounds associated with diabetes, particularly those who struggle to consistently access high-quality care due to mobility challenges, heavy financial burdens, or limited local medical resources.

3. Product Advantages

3.1 Integrated Collaborative Therapy, Mimicking Natural Healing Processes

Traditional dressings serve a very limited function, merely providing basic physical isolation between the wound and the external environment. Yeast Medics integrates triple functions—antimicrobial, anti-inflammatory, and regenerative—on a single platform. It intelligently activates these functions sequentially based on the healing process. This approach mimics and accelerates the body's natural healing cascade, overcoming a fundamental limitation of single-factor therapies: their inability to address the multifaceted demands of the entire healing process.

3.2 Intelligent Dynamic Response for Precision Medicine

The product functions not as a passive drug carrier but as a “living therapeutic factory.” Its therapeutic actions are dynamically controlled by the wound microenvironment (glucose concentration) and external commands (infrared light), enabling programmed and precise treatment. This maximizes efficacy while minimizing side effects, representing a new paradigm in chronic wound care.

3.3 User-Friendly Design, Significantly Reducing Patient Burden

Leveraging the “liquid-injection, body-temperature-gelling” properties of thermosensitive hydrogels, the product seamlessly conforms to any irregular or deep wound surface. Its simple application eliminates the secondary trauma and discomfort typically caused by conventional dressing changes. Combined with our planned smart delivery devices, it promises convenient, pain-free self-care at home, liberating patients and their families.

3.4 Outstanding Safety and Environmental Advantages

Biological Safety: Utilizes GRAS-certified lipolytic yeast chassis and ensures zero engineered yeast leakage through rigorous encapsulation technology, guaranteeing safe use (Sanya & Onésime, 2022).

Avoids Antibiotic Resistance: Employs antimicrobial peptides instead of traditional antibiotics, mechanistically circumventing the risk of developing resistant bacteria.

Green Production: The hydrogel's main component, chitosan, is sourced from renewable aquatic byproducts (e.g., snow crab shells, shrimp tails) and is biodegradable. The core active ingredient is produced through yeast fermentation, ensuring environmental sustainability (Sun et al., 2020).

3.5 Significant Potential Economic Advantages

Initial R&D relies on literature and molecular laboratories, resulting in extremely low development costs compared to traditional pharmaceutical companies. Once scaled for mass production, the per-treatment cost is projected to be lower than growth factor drugs requiring multiple applications or complex stem cell therapies. Additionally, it substantially reduces patient hospital visits and overall treatment duration, thereby lowering healthcare system expenditures and patients' socioeconomic burdens.

4. Challenges and Response Strategies

4.1 Clinical Translation and Regulatory Approval

Challenge: As a Class III medical device integrating synthetic biology and materials science, Yeast Medics faces a relatively complex approval pathway. Particularly concerning the local application of genetically engineered organisms, it requires demonstrating safety, efficacy, and quality control to regulatory authorities such as the National Medical Products Administration (NMPA) and the FDA.

Strategy: We will proactively engage in early communication with drug regulatory authorities to clarify product positioning and submission pathways. We plan to conduct comprehensive preclinical studies (including safety evaluations, pharmacodynamics, and pharmacokinetics) and progressively advance clinical trials (Phases I-III) to generate robust scientific data meeting regulatory requirements.

4.2 Manufacturing Process and Quality Control

Challenge: High-density fermentation of engineered yeast, efficient expression and presentation of target proteins, uniform modification of hydrogels, and the hybrid encapsulation process of yeast and hydrogels all require developing stable, scalable, GMP-compliant manufacturing workflows with stringent quality control standards.

Strategy: We will establish strategic partnerships with mature bioprocessing companies and medical device manufacturers to jointly develop scalable processes. Implement a comprehensive quality control system spanning plasmids, strains, intermediates, and finished products to ensure efficacy, safety, and consistency across all batches.

4.3 Physician Acceptance and Patient Education

Challenge: Healthcare providers and patients may harbor inherent caution and skepticism toward “live bacteria” therapies. Demonstrating significant advantages over conventional treatments and educating clinicians on proper usage (e.g., infrared light application) are critical for market adoption.

Strategy: Establish authoritative academic evidence and expert consensus through publishing high-impact research papers, participating in specialized conferences, and collaborating with leading wound care experts on clinical studies. Develop clear physician operating guidelines and patient education materials. Complement these with community outreach activities to educate patients about synthetic biology, fostering public confidence in using these products.

5. Future Plans and Outlook

5.1 Near-Term Plans (1-3 Years): Complete Proof-of-Concept and Preclinical Studies

We plan to complete the construction and functional validation of all engineered strains in the near future. Our immediate next steps include integrating the optimized promoters with their respective target genes to assess the system's full therapeutic efficacy. We intend to continue refining the hydrogel formulation and encapsulation process while conducting experiments to evaluate the hydrogel's in vitro antibacterial, anti-inflammatory, and pro-angiogenic effects. While our current prototype requires replacement every 3 days and we have individually confirmed the efficacy of the yeast and the hydrogel, our immediate next step is to evaluate the combined therapy's effects across all three therapeutic dimensions. After clarifying the efficacy of the combined yeast-hydrogel therapy, we will conduct efficacy and safety evaluations using animal models (diabetic mouse wound models). We will apply for relevant invention patents and publish research findings.

5.2 Mid-Term Plan (3-5 years): Advance Clinical Trials and Product Registration

We plan to industrialize our product, establishing a pilot production system compliant with GMP standards. Apply for and initiate clinical trials. Maintain ongoing communication with regulatory authorities to submit product registration applications. Explore collaborative development and commercialization opportunities with major pharmaceutical or medical device companies. We also plan to collaborate with CMOs (Contract Manufacturing Organizations) and CROs (Contract Research Organizations) to enhance the professionalism of our products.

5.3 Long-Term Plan (5+ years): Market Promotion and Application Expansion

Following product registration approval, commence commercial production and sales. Initially focus on the domestic market, targeting key hospitals and wound treatment centers. Our hardware team has developed a robotic arm capable of performing disinfection, UV sterilization, infrared heating, and automated wound medication application. As long as patients have a refrigerator at home to meet the 4°C storage requirement for medications, they can use the system independently at home. Furthermore, as the robotic arm undergoes further development, it will be capable of performing additional actions and treating a wider variety of wounds.

Through these steps, we firmly believe "Yeast Medics" has the potential to revolutionize existing diabetic wound care models. It offers patients worldwide an integrated, intelligent, and user-friendly solution that ultimately alleviates suffering and financial burdens while creating significant social and market value.

References

[1] International Diabetes Federation. (2025). IDF diabetes atlas: 11th edition.

[1] Crawford, Y., & Ferrara, N. (2009). VEGF inhibition: Insights from preclinical and clinical studies. Cell and Tissue Research, 335(1), 261–269. https://doi.org/10.1007/s00441-008-0675-8

[2] Dumville, J. C., Lipsky, B. A., Hoey, C., Cruciani, M., Fiscon, M., & Xia, J. (2017). Topical antimicrobial agents for treating foot ulcers in people with diabetes. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD011038.pub2

[3] Dwivedi, J., Sachan, P., Wal, P., Wal, A., & Rai, A. K. (2024). Current State and Future Perspective of Diabetic Wound HealingTreatment: Present Evidence from Clinical Trials. Current Diabetes Reviews, 20(5), e280823220405. https://doi.org/10.2174/1573399820666230828091708

[4] Hassanshahi, A., Moradzad, M., Ghalamkari, S., Fadaei, M., Cowin, A. J., & Hassanshahi, M. (2022). Macrophage-Mediated Inflammation in Skin Wound Healing. Cells, 11(19), 2953. https://doi.org/10.3390/cells11192953

[5] Peng, W., Li, D., Dai, K., Wang, Y., Song, P., Li, H., Tang, P., Zhang, Z., Li, Z., Zhou, Y., & Zhou, C. (2022). Recent progress of collagen, chitosan, alginate and other hydrogels in skin repair and wound dressing applications. International Journal of Biological Macromolecules, 208, 400–408. https://doi.org/10.1016/j.ijbiomac.2022.03.002

[6] Sanya, D. R. A., & Onésime, D. (2022). New roles for Yarrowia lipolytica in molecules synthesis and biocontrol. Applied Microbiology and Biotechnology, 106(22), 7397–7416. https://doi.org/10.1007/s00253-022-12227-z

[7] Sun, M., Wang, T., Pang, J., Chen, X., & Liu, Y. (2020). Hydroxybutyl Chitosan Centered Biocomposites for Potential Curative Applications: A Critical Review. Biomacromolecules, 21(4), 1351–1367. https://doi.org/10.1021/acs.biomac.0c00071

[8] Yadav, J. P., Singh, A. K., Grishina, M., Pathak, P., Verma, A., Kumar, V., Kumar, P., & Patel, D. K. (2024). Insights into the mechanisms of diabetic wounds: Pathophysiology, molecular targets, and treatment strategies through conventional and alternative therapies. Inflammopharmacology, 32(1), 149–228. https://doi.org/10.1007/s10787-023-01407-6