Combined diode laser irradiation and nanohydroxyapatite for remineralization of demineralized enamel: a systematic review of in vitro evidence

Abstract Background Enamel demineralization, from early white spot lesions to porous subsurface mineral loss, is common, and non-invasive remineralization aims to restore lost mineral before cavitation. Nanohydroxyapatite (nHAp) and near-infrared diode laser irradiation have each shown remineralizing or surface-conditioning potential, and a small number of in vitro studies have combined them. Using the PICOS framework, this review asked whether, in human enamel specimens from permanent or primary teeth (P), combined diode laser irradiation and nHAp (I), compared with either modality alone or an untreated control, with or without other active remineralizing agents (C), improves surface microhardness (primary outcome) and mineral or elemental content and surface morphology (secondary outcomes) (O) in in vitro studies (S). A further objective was to map whether any study had addressed pre-existing enamel cracks or used volumetric outcome measures. Methods This review was reported in accordance with the PRISMA 2020 guidelines. It was not registered in a public register; a written protocol was prepared by the authors before data extraction and is available from the corresponding author upon request. PubMed/MEDLINE, Scopus, and Europe PMC were searched from inception to August 3, 2026, using a deliberately broad laser–apatite–enamel term combination, supplemented by reference-list and citation screening. Eligible studies were in vitro investigations applying a near-infrared diode laser (800–980 nm) in combination with nHAp to human enamel from permanent or primary teeth and reporting a quantitative structural, mineralogical, or mechanical outcome against a comparator arm. Two reviewers independently screened all records; one reviewer extracted the data and the second independently verified every extracted value. Disagreements were resolved by discussion. The risk of bias was assessed using a checklist adapted from the QUIN tool for in vitro dental research, and the certainty of evidence was assessed using an approach adapted from GRADE. Given the number and heterogeneity of eligible studies, the synthesis was narrative. Results Forty-nine records were identified and 32 unique records were screened; four in vitro studies met the eligibility criteria. All used artificially demineralized human enamel, from permanent (two studies) or primary (two studies) teeth, and applied a diode laser at 810–940 nm with an nHAp suspension or an nHAp-containing commercial product. Surface microhardness (four studies): three studies reported greater microhardness with the combined protocol than with nHAp alone, and than laser alone in the two that included a laser-only arm; the fourth found no between-group difference from either single modality and found a sodium fluoride comparator superior to all nHAp-containing groups. Mineral or elemental content (three studies; calcium and phosphorus weight percentages by energy-dispersive X-ray spectroscopy or an overall mineral index): nHAp-containing groups showed greater recovery than laser alone. Surface morphology was described only qualitatively. No study used pre-cracked enamel, volumetric outcomes, cyclic loading, or assessment beyond short-term storage. Risk of bias: randomization was reported in all four studies, whereas outcome-assessor blinding was reported in none and sample-size justification in one. The certainty of evidence was very low for both microhardness and mineral or elemental content. Conclusions The in vitro evidence on combining diode laser irradiation with nHAp consists of four small, heterogeneous studies, and its certainty is very low. It is compatible with an additive effect on the surface microhardness of demineralized enamel, but it does not establish superiority over either modality alone or over fluoride, and it provides no information on pre-existing enamel cracks or three-dimensional structural outcomes. Future studies should standardize laser and nHAp parameters, include an active fluoride comparator, blind outcome assessment, justify sample sizes, and use depth-resolved or volumetric outcomes.