Project Description

DESCRIPTION

According to the latest alert from the International Diabetes Federation (IDF), there were 589 million adults with diabetes globally in 2024. Among them, approximately 25% suffer from impaired wound healing, and around 15% will develop severe complications such as diabetic foot ulcers. With the number of diabetic patients continuing to rise, this has become a major global health issue. When wound healing is disrupted by dysregulated VEGF/FGF signaling, leading to a vicious cycle of “persistent inflammation–infection–regeneration stagnation,” conventional wound dressings—lacking both anti-inflammatory and regenerative functions—fail to meet the clinical needs of diabetic wounds.

In response, our team has developed “Yeast Medics”, a thermosensitive wound dressing that integrates synthetic biology with biomaterials, aiming to reconstruct the wound microenvironment and promote inflammation resolution, antimicrobial defense, and tissue regeneration.

Unlike ordinary wounds, diabetic wounds are characterized by impaired fibroblast migration, which halts the regeneration process and transforms the expanding inflammatory response into a consequence of healing failure rather than a cause[1][2]. This distinct pathophysiological insight underpins our core design principle: a tripartite intervention—antibacterial infection control, anti-inflammatory modulation, and tissue regeneration—must be achieved simultaneously. To this end, we engineered Yarrowia lipolytica as a “living drug factory.” Through fine-tuned promoter systems, the yeast displays the antimicrobial peptide Pexiganan on its surface to lyse Staphylococcus aureus cell walls, secretes IL-4 and IL-10 to suppress excessive inflammation, and produces functional VEGF to correct defective angiogenesis[3][4].

To enable precise spatiotemporal delivery of therapeutic agents, we designed an innovative thermosensitive hydroxybutyl chitosan (HBC) hydrogel carrier. This hydrogel exhibits phase transition behavior: it remains injectable and fluid at 4 °C to fill irregular wound geometries, and rapidly solidifies into a 3D gel network upon contact with body temperature (37 °C)[5][6]. The engineered yeast is immobilized within the gel via surface peptide-mediated crosslinking.

This work is driven not only by clinical demand but also by personal motivation. Witnessing diabetic patients repeatedly hospitalized for foot ulcers, and seeing family members struggle with chronic, non-healing wounds that consume significant time, money, and emotional energy, we were compelled to act. Synthetic biology empowers us to reprogram living systems—transforming yeast into “micro medical soldiers” that dynamically execute tasks of infection control, inflammation regulation, and regeneration at the wound site. The thermoresponsive hydrogel provides programmable precision far beyond traditional dressings, enabling us to convert the wound microenvironment into a programmable therapeutic interface.