Exploiting dentine extracellular matrix components for treating apical periodontitis

Virdee, Satnam Singh ORCID: 0000-0002-8046-1805 (2025). Exploiting dentine extracellular matrix components for treating apical periodontitis. University of Birmingham. Ph.D.

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Abstract

Conventional antimicrobial only approaches for treating apical periodontitis have consistently demonstrated limited successful treatment outcomes over the last five decades. This has resulted in growing interests for more biologically driven treatment strategies. One such approach is exploiting endogenous bioactive dentine extracellular matrix components (dECM) to upregulate the intrinsic regenerative capacity of recently discovered periapical lesion derived-mesenchymal stem cells (PL-MSCs). This mechanism is hypothesised to improve upon clinical outcomes when compared with a conventional approach. The overall aim of the present thesis was to therefore provide proof of concept for a biologically based regenerative clinical protocol for treating apical periodontitis that can be used in mature permanent teeth. Several in vitro and in vivo methodologies underpinned by systematic reviews and surveys were utilised, all of which culminated in a pilot triple blinded paralleled group randomised controlled clinical trial. Briefly, a series of in vitro investigations where sodium hypochlorite (NaOCl) was used at concentrations as low as 0.5 – 1.5% was found to inhibit release of dECMs, even after mechanically re-instrumenting the dentine. Treatment with 17% EDTA alone was thus considered the optimal irrigant regime for solubilising bioactive proteins from within the dentine matrix. This therapeutic protocol contrasted current trends in antimicrobial irrigant regimes, as evidenced in the national survey, and thus was tested in vitro against an E.faecalis biofilm and found to possess antimicrobial capabilities when combined with mechanical debridement. Furthermore, bioavailability was demonstrated in vitro for dECMs to interact with periradicular inflammatory tissues in mature permanent teeth with subsequent topical application to PL-MSC cultures revealing upregulation of regenerative events at just picogram levels. This included increases in proliferation, migration, mineralisation and osteogenic differentiation without effecting cell viability. As some of these effects in vivo are likely to be undetectable using currently available clinical techniques, the process of sampling and analysing biomarkers from within periradicular tissue fluid was optimised. When clinically implemented, the proposed therapeutic irrigation protocol resulted in similar root canal treatment success rates to conventional regimes with no significant differences in pain scores or periradicular tissue-derived biomarker activity. The therapeutic potential for irrigant regimes that promote dECM release to treat periradicular disease has thus been demonstrated warranting the need for more extensive clinical investigation.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):

Supervisor(s)	Email	ORCID
Tomson, Phillip	UNSPECIFIED	orcid.org/0000-0001-5408-7744
Grant, Melissa	UNSPECIFIED	orcid.org/0000-0003-1154-7266
Camilleri, Josette	UNSPECIFIED	orcid.org/0000-0003-3556-6365
Cooper, Paul	UNSPECIFIED	orcid.org/0000-0003-1305-7287