Supervisor Database Search

• genetics, genomics and molecular biology
• cell and developmental biology/regenerative medicine

• Dentistry

• Immunology

Traditional dentistry is expensive, invasive and relies on an outmoded mechanical understanding of dental disease, rather than solutions that harness cell biology and the regenerative-capacity of teeth. As a result, the key-direction of my research targets the development of minimally-invasive biologically-focused ‘fillings’ that preserve tooth vitality (i.e. the ‘nerve’ or pulp); research that is shifting the paradigm from expensive high technology dentistry, with accompanying high failure rates, to smart restorations targeted at biological processes. This provides impact at a tooth level (regenerating rather than removing pulps), patient level (quality-of-life, pain, outcome) and population level (saving money and retaining teeth). Key to my research has been discovery to application, with laboratory-based dental-pulp-cell projects identifying the pro-regenerative effects of epigenetic-modification during pulp inflammation and repair using pharmacological inhibitors, with later translation of the findings to an animal/human models after inhibitor-integration into fillings. Novel lab and clinical projects have also used biological inflammatory biomarkers (matrix-metalloproteinases [MMPs] and epigenetic-related) as next-generation diagnostic aids for predicting pulpitis and outcome and well as the effects of individual-MMPs on regeneration. Clinical studies are ongoing on evaluating experimental novel dental-fillings as well as qualitative studies analysing the attitudes and barriers of general dentists to applying these new treatments.

Extensive previous research from our group has established a potential use for pharmacological epigenetic modifiers in regenerative endodontics (Duncan et al., 2013; Kearney et al., 2023). This includes histone deacetylase inhibitors (HDACis), which have been shown to increase rat and human dental pulp cell (DPC) mineralisation without affecting cell viability (Duncan et al., 2016), and DNA methyltransferase inhibitors (DNMTis), which have demonstrated similar pro-mineralisation effects in human DPCs at low concentrations (Kearney et al., 2023). Additionally, a role for non-coding RNAs such as microRNAs (miRNAs) in epigenetically-mediated regulation of DPC mineralisation has highlighting several therapeutic targets for further investigation (Kearney et al., 2023).

In order to further the translational development of therapeutic interventions involving pharmacological epigenetic modifiers, an effective delivery system is required (Kearney et al., 2018). Within regenerative endodontics, there is great potential for the use of a biocompatible scaffold material in pulpotomy procedures within which DPCs, growth factors and, potentially, therapeutic agents could be integrated prior to transplantation into the pulp chamber. This scaffold would provide a 3D framework which facilitates cellular attachment, proliferation and differentiation, while also possessing important qualities such as biocompatibility, biodegradability and low immunogenicity. While the use of scaffolds in other areas of regenerative medicine is well-established, research within dentistry and the development of commercial products is comparatively nascent. Previous studies have shown promising results for naturally-derived scaffolds, such as platelet-rich plasma (PRP) (Torabinejad et al., 2015) and collagen (Nakashima et al., 2017); however, much remains to be elucidated before these can be brought to clinical reality. In particular, further research is required to determine the optimum collagen scaffold and the means by which therapeutic agents, such as pharmacological epigenetic modifiers, could be incorporated into a scaffold material, along with DPCs and relevant growth factors, in order to promote dental pulp repair mechanisms in vivo.

The overall aim of this potential translational PhD project is to integrate the previously identified pro-mineralisation and regenerative properties of pharmacological inhibitors into bespoke bioactive collagen scaffolds and dental materials and assess pulp regenerative processes in vitro and in vivo with a view to developing next-generation targeted biomaterials.

Professor Oran Kennedy, RCSI, Dublin