<i>In vitro</i> biofilm models to study dental caries: a systematic review

The aim of this systematic review is to characterize and discuss key methodological aspects of <i>in vitro</i> biofilm models for caries-related research and to verify the reproducibility and dose-response of models considering the response to anti-caries and/or antimicrobial substances. Inclusion criteria were divided into Part I (PI): an <i>in vitro</i> biofilm model that produces a cariogenic biofilm and/or caries-like lesions and allows pH fluctuations; and Part II (PII): models showing an effect of anti-caries and/or antimicrobial substances. Within PI, 72.9% consisted of dynamic biofilm models, while 27.1% consisted of batch models. Within PII, 75.5% corresponded to dynamic models, whereas 24.5% corresponded to batch models. Respectively, 20.4 and 14.3% of the studies reported dose-response validations and reproducibility, and 32.7% were classified as having a high risk of bias. Several <i>in vitro</i> biofilm models are available for caries-related research; however, most models lack validation by dose-response and reproducibility experiments for each proposed protocol.本项系统综述旨在阐明并探讨体外（in vitro）龋病相关生物膜模型的核心方法学要点，并针对抗龋和/或抗菌物质的响应效应，验证相关模型的可重复性与剂量-反应关系。本次研究的纳入标准分为两部分：第一部分（PI）为可形成致龋生物膜和/或龋样损害、且能够模拟pH波动的体外生物膜模型；第二部分（PII）为可体现抗龋和/或抗菌物质作用效应的模型。在PI范畴内，动态生物膜模型占比72.9%，分批式模型占比27.1%；在PII范畴内，动态模型占比75.5%，分批式模型占比24.5%。分别有20.4%与14.3%的研究报道了剂量-反应验证与可重复性验证工作，另有32.7%的研究被归类为偏倚风险较高。当前已有多款适用于龋病相关研究的体外生物膜模型，但绝大多数模型未针对各自拟定的实验方案开展剂量-反应与可重复性验证实验。