Soft tissue attachment of human gingival fibroblasts to titanium dioxide nanotubes compared to commercially pure titanium and its alloys: a systematic review

Abstract

Objective: This systematic review was conducted to evaluate the attachment of human gingival fibroblasts (HGFs) of the soft tissue, to titanium dioxide nanotubes (TNTs) compared to commercially pure titanium (cp-Ti) and its alloys, in in-vitro studies. It is postulated that the nanotopography of the TNTs provide cells with a biomimetic environment, allowing HGFs to form more focal adhesion (FA) attachment sites at the tubule edges. Method: A comprehensive literature search was conducted on MEDLINE, DOSS, EMBASE and Google Scholar from January 2012 to January 2022. The identified studies were screened based on titles and abstracts for inclusion criteria. The relevant studies underwent data extraction. The risk of bias was assessed through the Office of Health Assessment and Translation (OHAT) tool. Results: This systematic review included four studies evaluating cell proliferation, protein expression, gene expression and cell morphology of HGFs evocative of stronger and mature soft tissue attachment. A significant increase in the cell proliferation at TNTs compared to cp-Ti, at day 7 for three studies and at day 14, for one study was evident. In addition, a significant increase in the type 1 collagen protein expression at TNTs compared to cp-Ti, at day 6 for one study and day 7 for two studies. Enhanced cellular extensions from HGFs attached onto TNTs, compared to cp-Ti was observed in all four studies. All the primary effects evaluated suggest the formation of better interlaced fibers giving a stronger adhesion than the parallel ones which is the most relevant outcome of this research. Conclusion: HGFs showed enhanced contact guidance onto TNTs but a true biological attachment was not confirmed. This review involved invitro studies which lack methodological rigor to compare among studies, lack information and have small sample sizes limiting effectiveness of parametric tests. The results may be unpredictable when translated to in-vivo studies mainly affected by confounding factors. Further research is needed to determine the precise mechanism of mechanical attachment between the soft tissue and the transmucosal surfaces.