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 Table of Contents  
Year : 2019  |  Volume : 11  |  Issue : 3  |  Page : 158-163

Effect of hyaluronan and metronidazole gels in management of chronic periodontitis

Department of Periodontics, College of Dentistry, Mustansiriyah University, Baghdad, Iraq

Date of Web Publication25-Jun-2019

Correspondence Address:
Dr. Athraa Ali Mahmood
College of Dentistry, Mustansiriyah University, Baghdad
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jioh.jioh_292_18

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Background: Sometimes, a combination of mechanical and chemical treatment provides good recovery such as metronidazole (MTZ) and hyaluronic acid (HA) topically that have recently been recognized as an adjunct therapeutic measure for periodontitis. Aims and Objectives: The objective is to estimate and compare the potential benefits of the effect of MTZ and HA gels on the clinical periodontal parameters. Materials and Methods: Chronic periodontitis patients were volunteered to partake in this research. They classified into three groups; 10 patients received root surface debridement (RSD) and 0.2% HA gel was additionally applied subgingival in test sites as the first group, the second group (10 patients) received RSD and MTZ gel was also added subgingival in test sites, and the last group consisting of 10-patient management with RSD alone. At the first visit, plaque index, gingival index, and periodontal pocket depth (PI, GI, and PPD) were recorded subsequently, and this represents 1st record which was done before periodontal treatment, while the 2nd record for indices was taken after 7 days. Results: Intragroup analysis of all the clinical periodontal parameters showed high significant (HS) results between baseline and 1 week at P < 0.01. In addition, on intergroup analysis, the results were significant at a second visit for GI and HS for PPD and not significant for PI. Conclusion: Local applications of MTZ and (0.2%) HA gels as an auxiliary to conventional periodontal therapy have a useful impact on clinical periodontal parameter during 7 days in chronic periodontitis patient.

Keywords: Chronic periodontitis, Hyaluronic acid, Metronidazole gel, Root planning, Scaling

How to cite this article:
Mahmood AA, Abdul-Wahab GA, Al-Karawi SI. Effect of hyaluronan and metronidazole gels in management of chronic periodontitis. J Int Oral Health 2019;11:158-63

How to cite this URL:
Mahmood AA, Abdul-Wahab GA, Al-Karawi SI. Effect of hyaluronan and metronidazole gels in management of chronic periodontitis. J Int Oral Health [serial online] 2019 [cited 2020 Apr 5];11:158-63. Available from:

  Introduction Top

Periodontitis is an inflammatory disease caused by particular microorganisms leading to progressive destruction of the periodontal ligament (PDL) and alveolar bone with the formation of the periodontal pocket, gingival recession, or both. Therefore, flexibility and tooth loss ensues.[1] The widespread type of periodontitis is the chronic one which is associated with the gathering of plaque and calculus.[1] The purpose of periodontal therapy, frequently by means of root surface debridement (RSD), is to remove the necrotic subgingival tissues that have been polluted by assumed anaerobic microorganisms.[1],[2] The using of RSD alone in the treatment of deep periodontal pocket may not give an absolute positive result in some patients due to difficulty in evacuation of microorganisms in this area that can leads to recurrence of periodontitis,[2],[3] so that the using of chemotherapeutic agents with RSD together can enhance the healing rate of periodontal pocket more than RSD alone.[4] Numerous investigations have reported clinical RSD effectiveness together with systemically or locally applied antimicrobial drugs such as metronidazole (MTZ) in the treatment of periodontal pocket.[5],[6],[7]

MTZ is a synthetic composite derivative of nitroimidazole class of antibiotic that restricts with bacterial DNA synthesis, causing cell death.[3],[8] It institutes one of the drugs that can be used in managing anaerobic microorganism and is prescribed in support of conventional periodontal therapy in systemic or local administration.[3],[9] A local type of MTZ present as gel form that forms reversed hexagonal liquid crystals when coming in contact with gingival crevicular fluid (GCF).[10] This can preserve a level of medication subgingivally for a long duration by preventing the gel from facile exit outside the pocket.[11] Moreover, the half-life of MTZ is about 8 h,[12] while the minimal inhibitory concentration (MIC) of MTZ is different according to the type of bacteria present in pocket; MIC of MTZ against Porphyromonas gingivalis did not exceed 1 μg/mL, while the MIC of MTZ against Prevotella intermedia was found about 8 μg/mL.[13]

Hyaluronic acid (HA) is another chemotherapeutic agent that can be used in the treatment of pocket with RSD, where PDL contains huge amounts of matrix macromolecules such as collagen, noncollagenous proteins, and glycosaminoglycan. A major component of the extracellular matrix macromolecules of the periodontium is HA.[14] HA (hyaluronan or hyaluronate), is a linear polysaccharide, that is present in serum, humor vitreous, connective tissues, skin, as well as other tissues.[15] It goes about as an impedance to bacterial plaque development, so it helps the gingival tissues to remain upkeep without inflammation.[16] The high molecular weight HA (HMWHA) can perform an organized function in the response of inflammation. Hyaluronan synthase (HAS) enzymes (HAS1, HAS2, and HAS3) play a role in the synthesis of the HA, in different cells from the periodontal tissues. In tissue with chronic periodontal diseases, reactive oxygen species (ROS) have a function in HMWHA conversion to lower molecules weight HA (LMWHA). Superoxide-free radical and hydroxyl radical are examples of ROS which are produced throughout bacterial phagocytosis chiefly by recruited polymorphonuclear leukocytes as well as the remainder inflammatory cells.[17],[18],[19] The HA is present in the market in different forms (spray, gel, and mouthwash). The exogenous type of HA can be used locally to inflamed periodontal tissues which will be shown valuable influences in modifying and hastening of host tissue reaction because of the HA has plentiful biochemical and physiochemical characteristics in addition to the biocompatibility and the nontoxicity features of HA.[20]

The aim of this study was to estimate the effects of (0.2%) HA gel (Gengigel®, Ricerfarma S. R. L, Milano, Italy) and MTZ gel (MetrogylDenta) under well-ordered situations chronic periodontitis patients through 7 days subsequent to proficient oral hygiene session.

  Materials and Methods Top

This study took 1 year to complete from October 2015 to December 2016, where all 30 participants were interested and informed consents were taken from each one. This study was approved by the Ethics Committee of Mustansiriyah University, College of Dentistry (Ref no: MUCD/526/2015-16).

The patients were aged 33–51 years, nonsmokers, systemically healthy, cooperative; no pregnant and lactating females; and not receive previous periodontal treatment during the previous year or taking any antibiotics therapy during the past 3 months. Oral checkups of the patients were carried out at the dental clinics teaching hospital department of Periodontics of Mustansiriyah University (Iraq, Baghdad), under standard conditions which include using plane (flat surface) mouth mirrors (size 4 = 22 mm), William's periodontal probes (Hu-Friedy, UK), and dental chair with artificial light. All of the patients had chronic periodontitis, and they had at minimum five surfaces with periodontal pockets in their teeth (each pocket ≥5 mm); also, they minimally had remaining teeth 20.

The patients were separated into three equal groups randomly; each group consists of 10 patients as followings:

  • Group 1 (G1): treated with RSD and subgingival application of 1 mL from (0.2%) HA gel to the base of the pocket
  • Group 2 (G2): treated with RSD and subgingival application of 1 mL from MTZ gel to the base of the pocket
  • Group 3 (G3): treated with RSD alone.

At the 1st visit, plaque index, gingival index and periodontal pocket depth (PI, GI, PPD)[21],[22] were recorded subsequently, and this represents 1st record which was done before periodontal treatment, while the 2nd record of indices was taken after 7 days. Initial periodontal therapy including oral hygiene instructions (OHI) for self-performed plaque control (including interdental flossing and interdental tooth brushing), and motivation of the patient; in addition, the RSD was done with ultrasonic scaler and curettes for all patients. Then, the teeth in Group 1 and Group 2 were isolated with a cotton roll. The gel was administered to the periodontal pocket by a disposable bent syringe; the gel was pushed cautiously to the periodontal pockets by syringe with a blunt needle to fill the whole pocket with a gel up to the gingival margin. After that, (0.2%) HA and MTZ gels were given to the patients in Group 1 and Group 2, respectively, to be applied at home. The patients were instructed to put (1 mL) of gel in the inflamed site of gingiva 2 times daily. Furthermore, eating and tooth brushing was averted for 3 h after gel application.

Statistical analysis

Statistical analytical methods of the study results were performed using the Statistical Package for the Social Sciences (SPSS®) version 21, 2012 (IBM® Corp., Armonk, NY, USA) and statistical tests were one-way ANOVA test (is used to calculate means between two or more groups), least significant difference (LSD) test (for multiple comparisons between each two groups), and Paired t-test (for the comparison of intragroup).

  Results Top

The mean of PLI was reduced from 1.21 ± 0.17 in the 1st visit to 0.67 ± 0.19 in the 2nd visit in Group 1, while for Group 2, the mean in 1st visit was 1.17 ± 0.13 and 2nd visit was 0.63 ± 0.15 but in Group 3, 1st visit was 1.10 ± 0.16 and 2nd visit was 0.69 ± 0.18. There was decreased in the mean of GI to reach 0.57 ± 0.25, 0.63 ± 0.17, and 0.70 ± 0.21 in the 2nd record for Group 1, Group 2, and Group 3, respectively. In addition, the resulting exhibit that there was reduced in the mean PPD for all groups in the 2nd record as shown in [Table 1].
Table 1: Descriptive statistical results of the clinical parameter of each group

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In general, the comparison of intragroup showed that there was highly significant (HS) difference in all clinical periodontal parameters between 1st and 2nd visit using t-test for all groups as shown in [Table 2].
Table 2: Comparison between first and second visit using t-test for each group

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For intergroup comparisons among groups in different visits, by ANOVA test; there was nonsignificant (NS) difference at P ≥ 0.05 among as well as within groups for PI, GI, and PPD at 1st visit, and for PI at 2nd visit, whereas, there was significant (S) difference at P ≤ 0.05 among as well as within groups for GI and HS difference at P ≤ 0.01 among and within groups for PPD in the 2nd visit, as shown in [Table 3].
Table 3: ANOVA test for clinical parameters for each visit

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While the results of LSD test for multiple comparisons between each two groups, there was NS difference at P ≥ 0.05 between Group 1 and Group 2 for GI, while significant difference at P ≤ 0.05 between Group 1 and Group 3 and Group 2 and Group 3 for GI and between Group 1 and Group 2 and Group 2 and Group 3 for PPD were revealed, whereas there was an HS difference at P ≤ 0.01 between Group 1 and Group 3 [Table 4].
Table 4: Least significant difference test to compare the means of clinical parameter among groups

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  Discussion Top

At the time of the starting point of the investigation, NS differences were revealed in PI, GI, and PPD in the subjects of all groups, permitting the proposal of the resemblance of the patient population.

Owing to microorganism presence in subepithelial connective tissue and crevicular epithelial cells, RSD alone not sufficient to eradicate them. Furthermore, the side effects of antibiotic systemically along with the possible bad compliance of the patient can be reduced by consuming local antibiotic as in toothpaste, mouthwashes, and gel form or sustained-release drug supplying agents locally.[23],[24],[25],[26] Hence, this study analyzed the possible beneficial effects of HA (Group 1) and MTZ gel (Group 2) as additional local application during RSD on the clinical periodontal parameters up to 1 week and compared to RSD alone (Group 3). There was an HS reduction in all clinical parameters for all groups at the 2nd visit.

The outcomes of this study estimated that the patients managed with RSD having a statistically HS difference in all parameters (P < 0.01) from baseline up to 1 week. Scaling is effective in decreasing PI as well as GI, and it is the best successful management since years. These outcomes may be due to regional debridement, reduces the bacterial accumulation of periodontal tissue, and in this manner preparing such conductive situation for contaminated periodontal soft tissue to recover.[1],[27],[28]

Endogenous HA is present naturally in human connective tissue. In addition, we can increase the healing effect of HA by adding it as a gel to the infected area (gingivitis) which can reduce the bleeding, GCF, and lysosomal enzymes (hyaluronidase as well as chondroitinase) without causing immunoreaction as a negative side effect.[29] As a result of the auxiliary influence of HA gel after RSD, group 1 showed a statistically HS difference between GI and PI (P < 0.01) from baseline to 1 week in this research. This result is in conformity with Pagnacco et al., in 1997,[30] and Gontiya and Galgali, in 2012.[31] The buildup of extracellular connective tissue matrix is recognized to be augmented by HA gel giving rise to healthy periodontium, an analytical study that was done by Pirnazar et al., 1999, they found that recombinant HA exerted varied bacteriostatic effects on bacterial strains, including Aggregatibacter actinomycetemcomitans, Staphylococcus aureus, and Propionibacterium acnes relying on its molecular weight as well as concentration. The elevated concentrations of HMWHA (4000–20,000,000 Da) had the greatest bacteriostatic effect.[32],[33]

In addition, all the patients in Group 2 showed statistically significant improvements in GI and PI at the pursued visit, in comparison to the starting levels. Throughout the study, PI and GI showed reasonable reading, giving an indication that patients comply with OHI.[34] Furthermore, MTZ specifically has bactericidal action against anaerobic microorganisms, that are well known to be the chief pathogens related to periodontitis; so, it can be using in the management of patients with chronic periodontitis.[35],[36] It is well-founded that in systematized biofilms, the antibiotic is less effective on the microorganisms and the agent's penetration into the biofilm is inadequate.[37] Accordingly, the elimination of the former biofilm, could lead to superior efficacy of the antimicrobials directed against microorganisms subgingivally and consequently enhanced healing response.[38]

The intercomparison groups showed that there was a significant difference at (P < 0.05) in GI at a deferent time interval when compare. The results are in conformity with Pagnacco et al., in 1997[30] who revealed that HA gel is effective in the reduction of symptoms after an oral hygiene visit and promoting rapid healing. In addition, this study agreed with Jentsch et al., 2003[29] of enhanced gingival health after the addition of different HA formulations supragingival in patients had gingivitis. Besides, agreement with studies which was done by Johannsen et al., 2009[39] and Gontiya and Galgali 2012[31] who also applied an HA gel in the subgingival area, established HS perfection of GI and bleeding on probing (BOP) in the HA group when compared with RSD alone However, Xu et al., 2004[40] show no difference in BOP between HA test and control groups after management. It maybe estimated that the use of HA is very substantial for healing as well as clinical consequences, particularly in the earliest periods after management, as speculated in this research. In the present study, intercomparison groups showed an NS difference of PI among all groups. Researches by Jentsch et al. and Pagnacco et al. also indicated that (0.2%) HA gel had an NS influence on PI.[29],[30]

In this study, the PPD was reduced in Group 2 after management with MTZ. This can be related to the increase in the inflammatory response in the gingival connective tissues subjacent to the junctional epithelium, and this leads to a reduction in the number of subgingival bacteria.[41],[42] Griffiths et al. 2000[43] who established that MTZ gel created significantly improved outcomes related to reductions of PPD as well as gain in CAL when perfumed with RSD that in agreement with the results of this study.

The clinical improvement that includes a reduction in PPD in Group 3 resulted from local etiologic elements eradication, there is a suggestion that RSD can be evolved a host stimulus systemically and locally which can help in eradicating local inflammation as well as accelerating tissue healing.[44]

This study showed a significant decrease in PPD for all groups, but the inter groups comparison showed that the reduction of PPD for Group 1 was significantly higher than Group 2 and Group 3 and this result was in agreement with Johannsen et al., in 2009,[39] because HA has anti-inflammatory influence (through the scavenger effect of exogenous HA by infiltrating prostaglandins, metalloproteinase as well as additional bioactive molecules), also HA has anti-edematous effect for the treatment of periodontal disease so that it could be used as an adjunct to RSD due to its acceleration in tissue healing properties due to the equilibrium between the free radicals/ROS and antioxidants is the major prerequisite for healthy periodontal tissue.[14],[29],[45] The HA represents a significant factor in postinflammatory tissue regeneration, growth, development, and repair of periodontal tissue and periodontal disease treatment if HA was administered to periodontal wound sites. Furthermore, HA appears as a diagnostic inflammatory indicator in GCF.[14] Topical application of subgingivally HA gel can be used as an antimicrobial agent as an adjunct to RSD[29],[39] In addition, HA has osteoinductive properties as well.[46]

  Conclusion Top

The grades of this study signpost the possible enhancement of clinical periodontal parameter using (0.2%) HMWHA or MTZ gel as an additional means to RSD over 7 days in the management of chronic periodontitis.


We would like to thank Mustansiriyah University ( Baghdad-Iraq for its support in the present work.

Also, we would like to thank assistant prof. Eman N. Najee (Department of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq).

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2], [Table 3], [Table 4]


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