Harnessing immunomodulation to reprogramme macrophage function and restore healing in fracture-related infection

When a person has an open fracture, such as after a serious accident, the broken bone is exposed to dirt and bacteria. Up to one in three of these injuries can lead to a fracture-related infection. These infections are very hard to treat and can cause long hospital stays, repeated surgeries, and long-term problems with walking or using the injured limb. Even with modern surgery and antibiotics, we have not become better at preventing or treating these infections over the last 20 years. A major challenge is that bacteria can form biofilms, sticky layers that protect them from antibiotics. These bacteria can also hide inside bone cells and immune cells, making them even harder to kill. This means patients may have infections that stop the bone from healing properly, leading to non-union, where the bone does not join back together. This project aims to test a new treatment, specialised pro-resolving mediators (SPMs) to help bones heal and fight bacteria. SPMs are natural molecules made from healthy fats that help end inflammation and promote healing. They guide immune cells to clear damaged tissue without weakening normal defenses. By testing this treatment in the laboratory, including animal model of infection, the project will explore whether this approach can kill bacteria more effectively and help bones heal faster. If successful, it could lead to better treatments for people with severe open fractures.