Description

Background

Diabetic chronic wounds, due to their complex pathological microenvironment, have become a global medical challenge. The accumulation of AGEs due to hyperglycemia, coupled with high oxidative stress and persistent inflammation, leads to stalled healing processes, causing immense physical and psychological suffering as well as significant economic burdens for patients(Porel et al., 2025). Existing treatment strategies fall into two categories, both with notable limitations:

1. Traditional Therapies: Complex Processes and Repetitive Progress

Debridement and Dressing Changes: The use of surgical blades to remove necrotic tissue during debridement makes frequent dressing changes not only painful but also result in secondary mechanical damage. This requires patients to make frequent trips to the hospital, consuming considerable time and effort.

Long-Term Antibiotic Use: Prolonged local application of antibiotics readily leads to the emergence of drug-resistant bacteria, disrupting the local microbial balance and complicating subsequent treatment(Nardulli et al., 2022).

Conventional dressings: Traditional gauze dressings merely cover wounds superficially, fail to maintain a moist environment, and poorly conform to irregular wound surfaces. Their functionality is severely limited, and removal often causes mechanical wound damage(Dwivedi et al., 2024).

2. Advanced Therapies: High Cost, Limited Functionality

Growth Factor Gels: While promoting healing, most contain only a single factor, failing to address the sequential multi-factor requirements throughout the entire healing process. They are also expensive, have a short half-life, and require frequent replacement(Jin et al., 2022).

Stem Cell Therapy: Issues include immune rejection, tumorigenic risks, and high costs. The injection procedure is complex, potentially affecting patient psychological well-being. More critically, the stability of this therapy's efficacy remains to be verified(Shi et al., 2024).

Novel Hydrogels: Most products remain passive carriers, capable only of sustained-release of preloaded drugs. They cannot intelligently respond to or actively regulate based on the dynamic changes in the wound microenvironment. Therefore, there is an urgent clinical need for an innovative solution that can simulate the body's natural healing process, dynamically respond to wound status, and automatically adjust treatment.

Solutions

Our Solutions: All-in-one Smart Treatment System

We have constructed an intelligent "living therapeutic factory" using synthetic biology techniques: an engineered yeast-hydrogel composite system designed to address the entire wound healing process using a single living biological material. This approach alleviates patients' financial burdens and psychological stress while tackling diabetic wounds—-a major complication of diabetes.

Img.2 A schematic diagram of "Yeast Medics"：Schematic illustration of the engineered yeast-based therapeutic strategy. The diagram depicts a wound site (lower part) covered by an L-HBC hydrogel (upper part). Engineered yeasts are securely integrated within the hydrogel matrix via surface-displayed antimicrobial peptide Pexiganan. These yeasts exert a dual therapeutic function: (1) they directly kill bacteria through the action of Pexiganan, and (2) they secrete immunomodulatory and pro-healing cytokines, specifically Interleukin-4 (IL-4) and Vascular Endothelial Growth Factor (VEGF), to promote wound repair.

1. Robust Stress-Tolerant Chassis: Yarrowia lipolytica Po1h

We selected Yarrowia lipolytica Po1h as the chassis. This strain, with both acidic and alkaline protease genes knocked out, serves as an ideal extracellular protein production system and is widely used in bioremediation. Beyond being a highly efficient protein-secreting "factory," it exhibits exceptional stress tolerance, perfectly withstanding the high-glucose, high-oxidative-stress microenvironment. Crucially, it can maintain viability even when using glucose as its sole carbon source. This intrinsic adaptation makes it particularly suited for managing the diabetic wound microenvironment.

Img.3 Technology Path of Yeast Medics

2. Dynamic Sensing and Programmatic Regulation

Our engineered yeast is designed to execute a precise "therapeutic program" through three layered mechanisms:

First Layer, Immediate Physical Antimicrobial Defense: By displaying the antimicrobial peptide Pexiganan on its surface, it eliminates primary skin pathogens like Staphylococcus aureus, establishing a robust physical barrier and fundamentally avoids antibiotic resistance issues(Maron et al., 2025).

Second Layer, Glucose-Sensitive Anti-Inflammatory Mechanism: Drives IL-4 expression via glucose-inducible promoters. When heightened inflammation leads to excessive wound exudate, elevated glucose levels in the microenvironment activate anti-inflammatory pathways. This promotes the polarization of macrophages from pro-inflammatory M1 to anti-inflammatory M2 types, effectively alleviating chronic inflammation(Hassanshahi et al., 2022).

Third Layer, Infrared-Triggered Regeneration Promotion: Controls VEGF expression via a thermosensitive promoter. After inflammation fades and microenvironment ROS levels decrease, the hydrogel receives brief localized infrared light exposure, activating massive VEGF expression to powerfully initiate angiogenesis and tissue regeneration processes(Crawford & Ferrara, 2009).

3. Intelligent Carrier

We developed a thermosensitive hydrogel based on hydroxybutyl chitosan and bio-inspiredly modified it with L-DOPA. This achieves a convenient “liquid-injection, body-temperature-gelling" application method, perfectly conforming to irregular and deep wounds. L-DOPA modification significantly enhances tissue adhesion, preventing detachment during daily activities while markedly improving photothermal conversion efficiency. This enables faster and more efficient infrared triggering, thereby enhancing treatment convenience and patient compliance.

Vid.1 The state change of hydrogel

Future Perspectives

The Yeast Medics project embraces synthetic biology principles to create a truly economical, safe, eco-friendly, and human-centered medical product.

Our product offers significant economic advantages. The dressings require no complex storage conditions, significantly reducing hospital operational costs. Combined with our proprietary smart delivery device, patients can conveniently and painlessly self-medicate at home. This not only alleviates the burden on healthcare systems but also liberates patients and their families from the hassle of frequent hospital visits and waiting times.

Regarding safety and environmental sustainability, we have established dual safeguards. Rigorous encapsulation technology ensures zero yeast leakage, while the use of antimicrobial peptides inherently avoids the risk of antibiotic resistance. Our material selection also embodies green principles: the hydrogel's main component, chitosan, is sourced from renewable aquatic byproducts like snow crab shells and shrimp tails, and is fully biodegradable. Its core active ingredients (IL-4, VEGF) are directly produced by yeast, reducing pollution and energy consumption from chemical synthesis at the source.

Ultimately, these technological innovations serve a greater purpose: human-centric care. Yeast Medics significantly alleviates patients' psychological anxiety and financial burdens. Through technological means, it empowers patients with autonomy over their care, enabling them to face illness with greater dignity and composure while embracing life.

References

[1]Armstrong, D. G., Tan, T.-W., oulton, A. J. M., & Bus, S. A. (2023). Diabetic Foot Ulcers: A Review. JAMA, 330(1), 62. https://doi.org/10.1001/jama.2023.10578

[2]Cai, Y., Yang, X., Chen, S., Tian, K., Xu, S., Deng, R., Chen, M., Yang, Y., & Liu, T. (2023). Regular consumption of pickled vegetables and fermented bean curd reduces the risk of diabetes: A prospective cohort study. Frontiers in Public Health, 11, 1155989. https://doi.org/10.3389/fpubh.2023.1155989

[3]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

[4]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

[5]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

[6]Jin, L., Guo, X., Gao, D., Liu, Y., Ni, J., Zhang, Z., Huang, Y., Xu, G., Yang, Z., Zhang, X., & Jiang, X. (2022). An NIR photothermal-responsive hybrid hydrogel for enhanced wound healing. Bioactive Materials, 16, 162–172. https://doi.org/10.1016/j.bioactmat.2022.03.006

[7]Maron, B., Zanchi, C., Johnston, P., Rolff, J., Friedman, J., & Hayouka, Z. (2025). Uncovering the genetic basis of Staphylococcus aureus resistance to single antimicrobial peptides and their combinations. iScience, 28(6), 112671. https://doi.org/10.1016/j.isci.2025.112671

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

[9]Nardulli, P., Hall, G. G., Quarta, A., Fruscio, G., Laforgia, M., Garrisi, V. M., Ruggiero, R., Scacco, S., & De Vito, D. (2022). Antibiotic Abuse and Antimicrobial Resistance in Hospital Environment: A Retrospective Observational Comparative Study. Medicina, 58(9), 1257. https://doi.org/10.3390/medicina58091257

[10]Porel, P., Kaur, M., Sharma, V., & Aran, K. R. (2025). Understanding molecular mechanism of diabetic wound healing: Addressing recent advancements in therapeutic managements. Journal of Diabetes & Metabolic Disorders, 24(1), 76. https://doi.org/10.1007/s40200-025-01588-7

[11]Shi, Y., Wang, S., Liu, D., Wang, Z., Zhu, Y., Li, J., Xu, K., Li, F., Wen, H., & Yang, R. (2024). Exosomal miR-4645-5p from hypoxic bone marrow mesenchymal stem cells facilitates diabetic wound healing by restoring keratinocyte autophagy. Burns & Trauma, 12, tkad058. https://doi.org/10.1093/burnst/tkad058