Clinical, histological, immunohistochemical and biomolecular analysis of hyaluronic acid in early wound healing of human gingival tissues: a randomized, split‐mouth trial

Background: Hyaluronic acid (HA) exerts a fundamental role in tissue repair. In vitro and animal studies demonstrated its ability to enhance wound healing. Nevertheless, in vivo human studies evaluating mechanisms involved in oral soft tissue repair are lacking. The aim of this study was to evaluate the in vivo effect of HA on early wound healing of human gingival tissues (G). Methods: In the present randomized, split-mouth, double-blind, clinical trial, G biopsies were obtained in eight patients 24 hours after surgery after HA application (treatment group-HA) and compared with those obtained from the same patients without HA application (no treatment group-NT). Clinical response was evaluated through Early Wound Healing Score (EHS). Microvascular density (MVD), collagen content and cellular proliferation were evaluated through Sirius red, Masson trichrome staining and Ki67 immunohistochemistry, respectively. To assess collagen turnover, MMP-1, MMP-2, MMP-9, TGF-β1 protein levels and LOX, MMP-1, TIMP-1, TGF-β1 gene expression were analysed by Western Blot and Real Time PCR. Results: Twenty-four hours after surgery, EHS was significantly higher in HA group. MVD, collagen content and cell proliferation were not affected. LOX mRNA, MMP-1 protein and TIMP-1 gene expression were significantly up-regulated in HA compared to NT group. Conclusions: The additional use of 0.8% HA gel does not modify the new blood vessels growth in the early phase of gingival wound healing. Concerning the secondary outcomes, HA seems to enhance extracellular matrix remodelling and collagen maturation, that could drive the early wound healing of gingival tissues to improve clinical parameters. This article is protected by copyright. All rights reserved.