Scar-free healing frostbite: the promise of sine-like skin

Frostbite is a severe cold injury that affects millions of globally, often leading to long-term recovery, scars and long-term complications of recovery, scars and long-term complications such as chronic pain and dysfunction. Injury often begins with cold-induced cell death, local inflammation and tissue ischemia, which destroys the ability of skin to heal. Current therapies (such as calcium channel blockers) work in preventing scar formation and often fail to address potential damage to skin cells and extracellular matrix (ECM). These shortcomings underscore the urgent need for innovative therapies that accelerate healing, reduce inflammation and restore normal skin function. Research on new therapies is crucial to address the complex pathology of frostbite and its long-term effects.

On October 4, 2024, researchers from the Beijing United Medical College Hospital and the National Center for Protein Science (Beijing) published a study in proteins and cells (doi: 10.1093/procel/pwae055) exploring the potential of skin skeletons derived from human-induced pluripotent stem cells (HIPSCs) to treat fragile peels. This study provides valuable insights into the regeneration capacity of these skin organs and their potential to promote scarless wound healing.

The researchers developed a mouse model of frostbite to better understand the healing process and cellular responses. They used single-cell transcriptomics to track dynamic changes in various cell types, including monocytes, macrophages, epidermal cells and fibroblasts. Analysis shows that in the early stages of frostbite, obvious inflammation and tissue damage are characterized by increased immune cell infiltration and destruction of ECM. To address these problems, the researchers designed HIPSC-derived skin organs, combined with gelatin-hydregel, and transplanted them into mice caused by frostbite. The results show that these skin organoids significantly accelerate wound healing by reducing early inflammation by reducing inflammatory cytokines (e.g., CCL4 and IL6) and promoting the proliferation of epidermal stem cells. Later in the healing process, organoids regulate the integrin α5β1-FAK pathway, reducing the transition from fibroblasts to myofibroblasts and remodeling ECM to prevent abnormal scar formation. It is worth noting that organoids restore physiological ECM, paving the way for scar-free healing. This breakthrough not only addresses the unique challenges of frostbite, but also provides potential solutions for the treatment of a range of other complex skin injuries.

Dr. Ling Leng, one of the corresponding authors, highlights the importance of their findings: Our study shows that skin organs can effectively regulate inflammatory responses and promote rapid wound healing for frostbite injuries. This opens up new possibilities for the treatment of complex wounds and the prevention of long-term complications.

The use of skin athletes in frostbite treatment represents a significant advance in regenerative medicine. By accelerating wound healing and inhibiting scar formation, these skin organs offer promising solutions to patients with severe frostbite. Their ability to regulate inflammation and restore normal skin function fills a critical gap in current treatments, which often fail to address long-term complications. Future research will focus on optimizing techniques for skin organ transplantation and expanding its potential to treat other complex skin conditions, such as burns and chronic wounds. This breakthrough has the potential to improve frostbite wound care, improve patient outcomes and improve quality of life.