One in ten adults globally suffers from severe periodontitis, an inflammatory gum disease associated with worsening of other chronic inflammatory conditions such as diabetes, rheumatoid arthritis, and Alzheimer’s disease. Minimally-invasive non-surgical therapy (MINST) is a novel treatment for advanced periodontitis, shown to prevent tooth loss while avoiding complex surgeries. Recent evidence suggests that the ability to resolve inflammation is key to the success of MINST. Therefore, developing adjunctive therapies that activate inflammation-resolution pathways will widen the responsiveness to and increase the effectiveness of MINST.
This PhD project aims to explore an adjunctive therapies that may enhance MINST outcomes by activating inflammation-resolution pathways using a lipoxin-mimetic mouthwash, designed to promote inflammation resolution in oral tissues.
Preliminary data indicate that this intervention could improve clinical outcomes in MINST-treated patients. However, the underlying biological mechanisms remain unclear. This project will investigate how this adjunctive treatment modulates inflammation and resolution processes and identify biomarkers predictive of treatment response.
This project is highly translational, using patient samples from an ongoing clinical trial. Participants receive MINST alongside the lipoxin-mimetic mouthwash or a placebo. Samples—gingival crevicular fluid (GCF), saliva, and blood—will be collected at multiple time points.
Key methods:
• Lipid mediator profiling to assess inflammation and resolution
• Cytokine-bead arrays and ELISA to quantify cytokines, chemokines, and tissue repair/regeneration biomarkers
• Flow cytometry to monitor immune cell phenotype changes, focusing on pro-inflammatory vs. regulatory macrophages and neutrophils
• Bioassays (e.g. phagocytosis, efferocytosis, and scratch assays) to explore cellular repair/regeneration mechanisms
A biostatistician will assist in advanced data analysis, especially handling large datasets.
Year-by-year overview:
• Year 1: By the end of year 1, the student will have learnt about the molecular mechanisms related to inflammation-resolution, their implications in MINST outcomes and familiarised themselves with clinical trial design. Furthermore, they will have learnt some of the required techniques, including isolation and culture of primary human cells from blood and lipid mediator isolation from human samples.
• Year 2: Application of flow cytometry, cytokine assays, and analysis of patient samples to assess inflammatory status
• Year 3: Investigation of how adjunctive therapies influence tissue repair and regeneration
• Year 4: Statistical analysis, thesis writing, and manuscript preparation.
During the 3-month rotation project, baseline inflammation in patients (pre-treatment) will be characterised using cytokine and chemokine profiling. These findings will help identify biomarkers linked to patient responsiveness to MINST, with or without adjunctive treatments.