Effect of Chlorhexidine Digluconate in Early Wound Healing of Human Gingival Tissues. A Histological, Immunohistochemical and Biomolecular Analysis.

Andrea Pilloni,Simona Ceccarelli,Daniela Bosco,Cinzia Marchese,Mariana A Rojas,Giulia Gerini,Lorenzo Marini

doi:10.3390/antibiotics10101192

Andrea Pilloni, Simona Ceccarelli + Show 5 more

Open Access

https://doi.org/10.3390/antibiotics10101192

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Journal: Antibiotics	Publication Date: Oct 1, 2021
Citations: 12	License type: CC BY 4.0

Affiliation: Sapienza University of Rome, Policlinico Umberto I

Abstract

Chlorhexidine digluconate (CHX) is considered the gold standard for oral cavity antiseptic treatment. Nevertheless, several in vitro studies have reported detrimental effects in oral tissue repair. The aim of the present study was to evaluate the in vivo effect of post-surgical CHX mouth rinse on gingival tissue (G) 24 h after injury. G biopsies were obtained in three patients 24 h after surgery with the indication of post-surgical 0.12% CHX use and were compared with those obtained from the same patients without any antiseptic use. Changes in collagen production, cell proliferation, and apoptosis were examined by histological and Ki-67/P53 immunohistochemical analysis. Fibrotic markers (COL1A1, αSMA), proapoptotic protein (BAX) expression, and wound healing-related gene modulation (RAC1, SERPINE1, TIMP1) were analyzed by quantitative real-time PCR analysis. CHX was able to reduce cellular proliferation and increase collagen deposition, proapoptotic molecule and fibrotic marker expression, and myofibroblast differentiation, reduce expression of RAC1 and trigger expression of SERPINE1 and TIMP1, showing “scar wound healing response” pattern. This study assessed for the first time the in vivo effects of CHX on gingival tissue. The demonstration of a CHX-induced fibrotic transformation, leading to scar repair, supports the need for new post-surgical clinical protocols based on a strategic and personalized use of CHX.

Highlights

Wound healing is a complex physiological process that depends on multiple factors [1]
Chlorhexidine digluconate (CHX) mouth rinse in the early phase of gingival tissue repair to understand its role on cell behavior, including (1) proliferation, (2) apoptosis, (3) fibrotic marker expression, (4) myofibroblast differentiation, and (5) early wound healing-related gene expression through a histological, immunohistochemical and biomolecular analysis of human gingival biopsies
24 h after injury, CHX is able to (a) reduce cell proliferation and increase the expression of proapoptotic molecules, (b) increase fibrotic marker expression and myofibroblast differentiation, (c) reduce expression of RAC1 gene, characterizing keratinocyte migration and proliferation, and the ability of the oral wound to respond to stress, and (d) trigger expression of SERPINE1 and TIMP1, which regulate scar wound healing

Summary

Introduction

Wound healing is a complex physiological process that depends on multiple factors [1]. The presence of oral biofilm, the main etiological factor of periodontal and peri-implant diseases, may jeopardize the repair process [2]. For this reason, especially after surgical procedures in which mechanical plaque control cannot be performed, the reduction of plaque accumulation by means of antimicrobial agents is extremely important [3]. Chlorhexidine digluconate (CHX), a bisbiguanide broad-spectrum antiseptic with antibacterial action, is widely used as a therapeutic agent in periodontology. Numerous studies have demonstrated the ability of CHX to reduce oral biofilm deposition [4,5,6]. By penetrating biofilms, CHX shows a bactericidal action [7], reaching a substantivity of 12 h [8]

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