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

Abstract

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 (G) tissues. Methods:In the present randomized, split-mouth, double-blind, clinical trial, G biopsies were obtained in eight patients 24 h post-surgery after HA application (HA group) and compared with those obtained from the same patients without HA application (no treatment; NT group). Clinical response was evaluated through the Early Wound Healing Score (EHS). Microvascular density (MVD), collagen content and cellular proliferation were evaluated through sirius red and Masson trichrome staining, and Ki-67 immunohistochemistry, respectively. To assess collagen turnover, MMP-1, MMP-2, MMP-9, TGF-β1 protein levels and LOX, MMP1, TIMP1, TGFB1 gene expression were analyzed by western blot and real time polymerase chain reaction. Results: Twenty-four hours after surgery, the EHS was significantly higher in the HA group. MVD, collagen content, and cell proliferation were not affected. LOX mRNA, MMP-1 protein, and TIMP1 gene expression were significantly upregulated in the HA compared to the NT group. Conclusions:The additional use of 0.8% HA gel does not modify new blood vessel growth in the early phase of gingival wound healing. Concerning the secondary outcomes, HA seems to enhance extracellular matrix remodeling andThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Glycosaminoglycans Modulate the Angiogenic Ability of Type I Collagen-Based Scaffolds by Acting on Vascular Network Remodeling and Maturation

“…GAGs highly modulate both endothelial cells migration, proliferation, and tube formation, but also vascular remodeling and maturation due to their effects on perivascular smooth muscles cells also [37,38]. Recently, Pilloni et al demonstrated that the addition of hyaluronic acid did not enhance the formation of new blood vessels in the early steps of reparative gingival angiogenesis, but enhanced extracellular matrix remodeling and collagen maturation, facilitating an accelerated wound healing inside human gingiva [39]. These findings are in accordance with ours.…”

Topical Adipose Mesenchymal Stem cell metabolites regulate the expression of MMP-1, MMP-9, EGF, TGF-β in oral mucosa ulcer rat model

“…This study showed that the AdMSCMs application increased TGF-β significantly, which indicated that the AdMSCMs involved in collagen turnover regulation and fibrogenesis and may accelerate collagen stabilization in the wound-healing process of oral ulcer ( Kim et al, 2013 , Pilloni et al, 2023 ). Collagen stabilization may facilitate nonscar formation in oral mucosal wound healing.…”

Transcriptomic profiling identifies differentially expressed genes and related pathways associated with wound healing and cuproptosis-related genes in Ganxi goats

“…TIMP-1 is produced by macrophages and connective tissue cells, while TIMP-3 exists only in ECMs and can induce cell apoptosis ( 28 ). The imbalance of dynamic MMPs/TIMPs expression is associated with many diseases, such as liver fibrosis ( 29 ), wound healing disorders ( 30 ), and multiple cancers ( 31 ), which are often associated with cuproptosis ( 7 ). Wound excipients containing copper and zinc have been shown to promote fibroblast proliferation, increase collagen fibers, new arterial and venous capillaries, and enhance the wound healing process ( 32 ).…”