Three dimensional (3D) gingival models in periodontal research: a systematic review

The aim of this study is to systematically appraise the evidence on available full thickness 3D gingival and mucosal models (3D culture in scaffold base system) and their application in periodontal and peri-implant research. This study involved a systematic review of twenty-two studies obtained from searching from five electronic databases: MEDLINE-OVID, EMBASE, EBSCOhost, Web of Science Core Collection and LILACS, as well as a hand search of eligible articles up to September 2022. A total of 2338 studies were initially identified, after removal of duplicates (573), abstracts/title selection (1765), and full text screening (95), twenty-two studies were included, thirty-seven models were identified. Several cellular markers were reported by the studies included. The expression of keratinocytes differentiation markers (K4, K5, K10, K13, K14, K16, K17, K18, K19, involucrin, laminin5), proliferation marker (Ki67, CD90), and vimentin, Type I, II and IV collagen produced by fibroblasts were investigated in thirty models. No quantitative analyses were performed, and results of the review confirmed a substantial level of heterogeneity across experiments. In conclusion, there is currently insufficient evidence to conclude that the available 3D gingival and mucosal models can entirely recapitulate the human gingival tissue/mucosa and provide a useful research tool for periodontal and peri-implant research. This review also highlighted the lack of a standardized protocol to construct and characterize 3D gingival models. A new protocol is proposed for the characterization of in vitro gingival models for future research.