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Simultaneous treatment of infection and fracture healing with a phage cocktail and mesenchymal stem cell composite hydrogel in fracture-related infections

Code: BC-DTP_2026_20

Title: Simultaneous treatment of infection and fracture healing with a phage cocktail and mesenchymal stem cell composite hydrogel in fracture-related infections

Primary Supervisor: Hamish Simpson

Email: hamish.simpson@qmul.ac.uk

Institute: Blizard Institute

Secondary Supervisor: Jerry Tsang

Email: j.tsang@qmul.ac.uk

Institute: Blizard Institute

Lay Summary:

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 that combines two tools: mesenchymal stem cells (MSCs) and bacteriophages. MSCs help bone heal and may also fight bacteria. Bacteriophages are natural viruses that attack harmful bacteria, including those inside biofilms. The research team will place MSCs and bacteriophages inside a soft, safe gel called a hydrogel, which can be applied directly to the fracture. By testing this treatment in the laboratory and in an animal model of infection, the project will explore whether this combined 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.

Aims:

Primary Aim: To evaluate the effectiveness of a composite MSC–phage hydrogel in simultaneously controlling infection and promoting bone healing following open fractures. Objectives: In vitro studies 1) To assess the bacterial growth on the surface of clinical grade titanium implant material under static and dynamic flow conditions using confocal fluorescence microscopy in different time intervals, 2) To MSC growth on implants material surfaces under static condition using time lapse microscope, 3) To study the competitive colonization of materials surfaces by MSCs and bacteria in static condition using timelapse microscopy, and d) To compare the antibacterial effect of hydrogels loaded with MSCs and phage cocktails individually and together on bacterial biofilms on the implant surface using scanning electron microscopy (SEM), bacterial viability and biofilm matrix staining. In vivo studies 1) To assess the control of infection and the progression of healing in an FRI model with hydrogels of both MSCs and Phage cocktails individually and together on using bioluminescent bacteria and X-ray, Micro-CT imaging, histomorphometry. 

References: 

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