In vitro modelling of the oral mucosal response to denture wear

Analysis of how tissue responds to the repeated physical pressure associated with functional dentures
A set of dentures being held by hands wearing white gloves 
Funded by: Haleon PLC
Duration: 18 months
Location: Plymouth
Project partner: Haleon PLC

Project aims

At least half of removable denture wearers face physical, social or clinical challenges (Singh H et al 2014) or poor denture status (Kosuru KRV et al 2017). Whilst the quality and fit of the removable prothesis are key, the changes that occur in the oral mucosa and the underlying tissues almost certainly play a role in treatment outcomes as these would play a critical role when distributing occlusal loads during mastication (Chen J et al 2015).
What is lacking in the literature are studies on the effect of physical forces during mastication in vivo including cyclical pressure changes on the oral mucosa The aim of the project is to develop 3 dimensional oral mucosal models (OMM) that will allow a detailed analysis of the histological and molecular responses to the physical forces associated with functional dentures.

Methodology

OMMs will be constructed using collagen gels seeded with fibroblasts and overlaid with oral epithelial cells before allowing the layer to mature and differentiate at an air liquid interface for 14 days. The OMM construct will then be transferred to a cell culture chamber, allowing different pressure regimes to be applied to the air above the model for up to 7 days at forces relevant to those in the oral cavity.
At different time points following the pressure stimulus, part of the OMM with be subjected to standard histological processing, immunohistochemical analysis of cytokeratin 13 and E-cadherin and electron microscopy. OMMs left at atmospheric pressure with serve as a negative control. Conditioned media and the remaining part of the OMM will also be harvested. Any cell death will be examined using a lactate dehydrogenase assay and expression of several genes and proteins will be examined using ELISA and qPCR including the inflammatory markers and markers of fibroblast activation.
 

Simon Whawell, Professor of Integrated Oral Sciences and the project lead:

"Dentures can obviously have a hugely positive impact on people who lose teeth or need to have them removed as a result of disease or trauma. However, the impact of wearing dentures on the inside of people’s mouths hasn’t been extensively tested. By creating models in the lab, we can accurately mimic the physical effects of dentures – and the adhesives used with them – to understand this process more clearly. With an ageing population and more people likely to need dentures in the future, it is a critical piece of work with the potential to benefit patients, dentists and the companies involved in creating these dentures."
Simon Whawell looking at a medical model of the human face and teeth
This research is being performed in collaboration with world-leading consumer health study, Haleon, who are contributing to the funding of this study. 
Dr Anousheh Alavi, Global Medical Affairs Director for Oral Health at Haleon, commented:
“It is important to remember our duty of care continues beyond the provision of  bespoke dentures for our patients. Carrying out further research on the impact of dentures on the tissues that support them is essential for optimising their function and comfort. We should also help maintain the oral health of patients who have experienced tooth loss. It is a privilege to be part of this exciting research and I look forward to seeing how the findings pave the way for further research.”

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