Dentinal tubule penetration of nanoparticle-incorporated calcium hydroxide as an intracanal medicament: a systematic review

Abstract

Calcium hydroxide is widely used as an intracanal medicament due to its antimicrobial properties and its ability to neutralize bacterial by-products. However, its clinical efficacy may be compromised by poor penetration into dentinal tubules, especially in deeper dentin. Nanoparticle-incorporated calcium hydroxide has been introduced to improve intratubular diffusion, physicochemical behaviour and antimicrobial efficacy. This systematic review aimed to evaluate the available evidence comparing dentinal tubule penetration of nanoparticle-incorporated calcium hydroxide with conventional calcium hydroxide. This review was registered prospectively (Open Science Framework, DOI: https://doi.org/10.17605/OSF.IO/9AWH6 ) and reported in accordance with PRISMA 2020. A systematic search was conducted in PubMed, Scopus and Web of Science for studies published between January 2010 and April 2026. In vitro and ex vivo studies assessing nanoparticle-incorporated or nano-modified calcium hydroxide as an intracanal medicament, compared against conventional calcium hydroxide and reporting dentinal tubule penetration or depth-related intradentinal outcomes were included. Study selection, full-text screening and data extraction were performed independently and in duplicate by two reviewers with disagreements resolved by discussion or third-reviewer adjudication. Methodological quality was assessed using a modified in vitro quality-assessment checklist across eight pre-defined domains. Given the substantial methodological heterogeneity anticipated across studies in microscopy techniques, medicament formulations, vehicles and incubation protocols, a quantitative meta-analysis was not undertaken. Twelve studies, all in vitro or ex vivo laboratory investigations on extracted human teeth, met the inclusion criteria: four evaluated pure nano-calcium hydroxide, six evaluated nano-modified or combination formulations, and two evaluated nanoparticle-based delivery systems. Most included studies reported greater measured penetration parameters for nanoparticle-based calcium hydroxide formulations than conventional calcium hydroxide, particularly in the coronal and middle thirds, although direct comparison across studies is limited by methodological heterogeneity. Penetration in the apical third was comparatively lower across formulations. One study reported no statistically significant difference in penetration depth between nano-calcium hydroxide and conventional calcium hydroxide despite significantly superior endotoxin reduction with the nano formulation. Nano-modified formulations, including those combined with titanium dioxide nanoparticles, silver nanoparticles and polymeric delivery systems such as PLGA, also demonstrated greater measured penetration and, in several studies, enhanced antimicrobial or endotoxin-neutralizing activity. Twelve studies were judged to be at overall low ( n = 2) or unclear ( n = 10) risk of bias, no study was judged high risk overall. A quantitative meta-analysis was not feasible because of methodological and outcome heterogeneity across microscopy techniques, medicament formulations, vehicles and incubation protocols. Within the limitations of the available evidence, derived exclusively from in vitro and ex vivo studies with considerable methodological heterogeneity, nanoparticle-incorporated calcium hydroxide appears to provide greater dentinal tubule penetration than conventional calcium hydroxide and may offer additional antimicrobial and biological advantages. However, dentinal tubule penetration is a surrogate laboratory outcome and no included study evaluated clinical healing or treatment success. These findings should not be interpreted as evidence of superior clinical effectiveness and well-designed animal and clinical studies are needed to determine whether these laboratory benefits translate into improved endodontic outcomes. By promoting deeper medicament penetration and, in several studies, enhanced antibacterial and endotoxin-neutralizing properties, nano-modified formulations may have the theoretical potential to improve endodontic treatment outcomes. However, as the current evidence is confined entirely to in vitro and ex vivo models with reduced apical penetration and considerable methodological inconsistency across investigations, this remains a laboratory-based hypothesis. Standardized in vivo and clinical studies are essential before any recommendation for clinical adoption can be made.