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

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.

Meta-Analysis of the Efficacy and Safety of Chlorhexidine for Ventilator-Associated Pneumonia Prevention in Mechanically Ventilated Patients

“…Six studies [ 14 – 16 , 18 , 19 , 21 ] reported the days in ICU, involving a total of 999 patients with mechanical ventilation, including 498 in the intervention group and 501 in the control group. Heterogeneity test results showed that heterogeneity existed among studies ( P =0.82, I 2 = 0%), so a fixed-effect model was adopted for analysis.…”

“…Oral care with chlorhexidine nursing solution can reduce oral bacterial colonization and the migration and colonization of microorganisms in the lung. Chlorhexidine gluconate contained in chlorhexidine nursing solution is a broadspectrum fungicide, which can combine with salivary glycoprotein, reduce tooth surface adsorption protein, and hinder the formation of plaque [12][13][14]. At physiological pH, chlorhexidine can be used as a preservative for oral care.…”

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

“…No postoperative chlorhexidine mouth rinse was prescribed during the first 24 h after surgery. 24 At 24 h, G biopsies were harvested at the level of the VRIs with a biopsy punch of 2.0 mm diameter, replicat-…”

3D Porous Collagen Matrices—A Reservoir for In Vitro Simultaneous Release of Tannic Acid and Chlorhexidine

“…Medical use of such antimicrobials extracted from plants, such as tannic acid, is frequently associated with synthetic antimicrobials. Among the latter, chlorhexidine digluconate ( CHDG ) is the most utilized biocide in clinical practice for skin antisepsis and in oral care products, being considered the gold standard for plaque control and for treating or preventing periodontal diseases in order to maintain oral cavity health [ 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. In fact, the broad-spectrum antimicrobial bioactivity of chlorhexidine ( CH ) has been reported in countless studies over a long period of time, more than six decades, but recent works are focused on designing novel CH -loaded carriers/materials/composites able to supply topically a tunable amount of active component ( CH –copper composite as micrometer sized particles with synergetically enhanced activity compared to that silver particles [ 43 ]; CH -loaded biocompatible gelatin fibers with antimicrobial activity demonstrated against both Gram-negative and Gram-positive bacteria [ 44 ]; CH -loaded nanocarriers— CH -containing shellac nanoparticles exhibiting enhanced bioactivity of CH [ 45 ], CH -loaded copolymer nanogel carriers superficially functionalized with a cationic polyelectrolyte with amplified and broad biocidal action [ 46 ], nanoparticles of amorphous calcium phosphate containing CH with a beneficial action of inhibiting collagen type I degradation and promoting its mineralization at the adhesive–dentin interface, with a direct consequence in slowing down the aging of the resin–dentine contact [ 47 ]; bioresorbable polylactide-based and collagen-based membranes previously soaked in CHDG solution displaying a certain retardation of bacterial colonization when the membranes were exposed to oral activity [ 48 ]).…”

“…In fact, the broad-spectrum antimicrobial bioactivity of chlorhexidine ( CH ) has been reported in countless studies over a long period of time, more than six decades, but recent works are focused on designing novel CH -loaded carriers/materials/composites able to supply topically a tunable amount of active component ( CH –copper composite as micrometer sized particles with synergetically enhanced activity compared to that silver particles [ 43 ]; CH -loaded biocompatible gelatin fibers with antimicrobial activity demonstrated against both Gram-negative and Gram-positive bacteria [ 44 ]; CH -loaded nanocarriers— CH -containing shellac nanoparticles exhibiting enhanced bioactivity of CH [ 45 ], CH -loaded copolymer nanogel carriers superficially functionalized with a cationic polyelectrolyte with amplified and broad biocidal action [ 46 ], nanoparticles of amorphous calcium phosphate containing CH with a beneficial action of inhibiting collagen type I degradation and promoting its mineralization at the adhesive–dentin interface, with a direct consequence in slowing down the aging of the resin–dentine contact [ 47 ]; bioresorbable polylactide-based and collagen-based membranes previously soaked in CHDG solution displaying a certain retardation of bacterial colonization when the membranes were exposed to oral activity [ 48 ]). In addition, other relatively newly obtained results deal specifically with CH action in treatment concerning curli production and biofilm formation ( E. colli ) [ 49 ], with new formulations of CH -based mouth rinse with bioactivity against pathogenic bacteria such as P. mutans and P. gingivalis [ 50 ], or in the wound healing of human gingival tissue that has been post-surgically affected [ 36 ]. Last but not least, other works proved that some enzymatically treated undesirable oral biofilms can be disrupted and removed under the action of low concentrations of aqueous CHDG solutions (<0.1%) [ 37 ], and, what is truly noteworthy, the bacteria ( P. aeruginosa , S. aureus ) killed by CHDG may behave similarly to zombie cells, which possess high biocidal activity against the next generation of viable bacteria [ 51 ].…”