|Year : 2013 | Volume
| Issue : 4 | Page : 416-420
Clinical evaluation of 0.2% hyaluronic acid containing gel in the treatment of gingivitis
Department of Periodontology and Implantology, Sr. Lecturer, S.G.T. Dental College and Hospital, Gurgaon, Haryana, India
|Date of Web Publication||17-Sep-2013|
701, Tower 7, Vipul Greens, Sohna Road, Sector 48, Gurgaon - 122 018, Haryana
Source of Support: None, Conflict of Interest: None
Background: Hyaluronic acid is an extracellular constitute of the connective tissue that acts as both a barrier to plaque bacteria and fulfils a variety of extracellular functions that are vital to the maintenance of healthy gingival tissue. Recently, 0.2% hyaluronic acid is introduced as an anti-inflammatory agent for topical application in the treatment of gingivitis. Aims: To evaluate the therapeutic efficacy of 0.2% hyaluronic acid containing gel as an adjunct to scaling. Materials and Methods: Fifty patients belonging to both gender and ages ranging 15-40 years diagnosed with plaque-induced gingivitis were included in the study. They were divided into two groups of 25 each; Group 1 (scaling and with 0.2% hyaluronic acid) and Group 2 (scaling alone). Plaque, gingival, and papillary bleeding index of each patient were recorded at baseline, 1, 2 and 4 week periods. Statistical analysis: Data was analyzed using Student's t test. Results: Comparison of the two treatment modalities revealed a statistically significant improvement in the clinical parameters for both groups at 4 th week with mean reductions in Gingival Index (GI) was 1.13 ± 0.22 (Group 1) and 0.85 ± 0.17 (Group 2), respectively, which was statistically highly significant (P ≤ 0.001), Papillary Bleeding Index (PBI) was 1.22 ± 0.31 and 0.83 ± 0.24, respectively, which was statistically highly significant (P < 0.001). Conclusions : 0.2% hyaluronic acid containing gel is an effective agent for treating plaque-induced gingivitis as an adjunct to scaling as compared to scaling alone.
Keywords: Gingivitis, hyaluronic acid gel, local drug delivery, matrix components, scaling
|How to cite this article:|
Jain Y. Clinical evaluation of 0.2% hyaluronic acid containing gel in the treatment of gingivitis. Med J DY Patil Univ 2013;6:416-20
| Introduction|| |
Plaque-generated inflammatory gingivitis is very common, and generally follows a cyclical or relapsing pattern. It is now unanimously acknowledged that despite its nature, often wrongly considered "trivial" by patients, the cyclical recurrence of episodes of gingivitis causes irreversible harm to the periodontal structures. Therefore maximum attention has to be given to gingivitis therapy.
Early stages of gingivitis may regress with correct oral hygiene, whereas the more advanced forms of gingival inflammation may not heal without specific dental treatment. As a part of non-surgical therapy, local drug therapy is a common mode of therapy. Topical delivery has the advantage of bringing a high concentration of drug where needed without exposing the whole body. The side effects of systemic antibiotic therapy and the possible failing compliance of the patient can be minimized by using locally applied antibiotics. Therefore, a positive influence on the subgingival biofilm may be accomplished with a local delivery of the antimicrobial drug.
In dental practice, the prescription of anti-inflammatory treatment is generally limited to mouthwashes, which contain no high-risk active constituents. But these preparations do not guarantee lengthy contact between the active constituent and the site of inflammation. The scarcity of topical preparations is probably due to the sensory unacceptability of the possible active constituents and partial ingestion of the drug. If viscous preparations (gels, pastes etc.), which adhere to the gingiva and therefore guarantee that the active constituent will perform its effect in situ for a lengthy period, are used instead of fluid mouthwash solutions, the amount ingested is likely to be greater. 
To fulfill the above criteria, 0.2% hyaluronic acid gel (HA), a new commercially available gel that has an anti-inflammatory effect is used for topical application in periodontal therapy. The endogenous hyaluronan (HA) is a high-molecular weight (10,000-10,000,000 Da), non-sulfated polysaccharide component of the glycosaminoglycan family, which is present in the extracellular matrices of many tissues such as skin, synovial joints and periodontal tissues. Hyaluronan has been identified in all periodontal tissues, being particularly prominent in the non-mineralized tissues such as gingival and periodontal ligament. It is present in only low quantities in mineralized tissues such as cementum and alveolar bone.  Hyaluronan has many structural and physiological functions within tissues. It is also a key component in the series of stages associated with the wound-healing process in both mineralized and non-mineralized tissues. , It is evident that hyaluronan has a multifunctional role in wound-healing processes, with similar mechanisms of healing potentially existing within periodontal tissues. As a consequence of its non-toxicity, biocompatibility and numerous biochemical and physiochemical properties, the use of exogenous hyaluronan or hyaluronan-based biomaterials, applied topically to inflamed periodontal sites, would appear to offer beneficial effects in modulating and accelerating the host response, which has already been demonstrated in fields such as ophthalmology, dermatology and rheumatology. , But only a few studies could be found focusing the interest on results after the treatment with hyaluronan in dentistry. The topical application of a high-molecular weight exogenous hyaluronan-based gel has been proposed to have some potential in inducing periodontal healing in patients with inflammatory gingivitis, during both open and randomized, controlled double-blind studies conducted by Vangelisti et al  and Pagnacco et al.  But so far, comparison of the effect of 0.2% Hyaluronic Acid Containing gel in combination with other periodontal therapy such as scaling has not been evaluated. The purpose of the present study was to assess and compare the effectiveness of treatment of gingivitis with newly available 0.2% hyaluronic acid containing gel on plaque, gingival, papillary bleeding index as an adjunct to scaling.
| Material and Methods|| |
The study was conducted with a total sample size of 50 subjects comprising of both genders, in the age range of 15-40 years (average 30 years). Patients diagnosed with plaque-induced gingivitis were considered for the study. The samples were divided into two matching groups of 25 each; Group 1 (scaling and 0.2% hyaluronic acid containing gel) and Group 2 (scaling alone). The clinical parameter like plaque index, gingival index and papillary bleeding index of each patient were recorded at baseline, 1-week, 2-week and 4-week period.
- Subjects with good general and oral health
- Subjects who had not received any periodontal therapy for past 3 months
- Subjects with moderate gingivitis (at least 25% of test sites showing bleeding on probing)
- Ability of the subjects to attend the hospital at regular intervals and
- Subjects with full complement of teeth present except third molars.
- Subjects taking drugs that could affect the state of the gingival tissues
- Subjects undergoing orthodontic therapy
- Subjects with muco-gingival problems, pockets and attachment loss
- Subjects with five or more carious teeth that require immediate treatment
- Subjects using any other supplemental plaque control measures like interdental cleansing aids or mouthwashes
- Subjects with the habit of taking alcohol, smoking or chewing tobacco
- Subjects suffering from any systemic disease
- Subjects with chronic desquamative gingivitis
A proforma was prepared for the study so as to have a systematic and methodical recording of all the observation and information. After selecting the patients, preliminary information was recorded in proforma. Clinical examination was done in a dental chair under standard conditions of light, using mouth mirror and graduated Williams Periodontal Probe.
The subjects were informed about the study and their consent was obtained in a prescribed form to take part in the study. Approval for the study was also obtained from the institutional ethical committee.
Selected patients then divided into two treatment groups: Experimental group and Control group.
- Experimental group (Group 1) comprised of 25 patient for which scaling plus 0.2% hyaluronic acid containing gel was planned.
- Control group (Group 2) comprised of 25 patient for which scaling alone was done.
Gingival index, plaque index and papillary bleeding were recorded at baseline and then at 1, 2 weeks and 4 weeks after therapy. After recording these parameters at baseline, full mouth scaling was performed. After debridement, oral hygiene instruction was given to all the patients and Group 1 patient were given 0.2% hyaluronic acid containing gel and Group 2 were treated only with scaling and root planing.
A product for topical gingival use has been recently developed in gel form, containing the active constituent high-molecular weight, exogenous hyaluronic acid (mean m/w 1,500,000) at the concentration of 0.2%, in the form of its pure sodium salt obtained by the biotechnology method, which is nontoxic. It remains in situ as a result of increased adherence, its antibacterial and antiseptic activity boosted by the addition of 2,4-dichlorobenzene methanol, and the formulation consisted of a pleasant gel sweetened with the non-cariogenic sugar xylitol.  Gengigel® provides maximum adhesion and thus allows hyaluronic acid (which would otherwise be eliminated by constant salivary drainage) to remain in situ.
Application of Gengigel®
After the recording of clinical parameters by the main investigator, the Gengigel application was applied topically onto the cotton bud applicator and applied onto the gingival surface with gentle pressure. The application of the gel was repeated by the patient using the gel tube supplied to each patient in the similar manner twice daily for 28 days after regular oral hygiene regimen. After application, patients were instructed to avoid eating, drinking or rinsing for 1 hour.
The duration of the study was 4 weeks. Clinical parameters were recorded at 1 week, 2 week and then at 4 weeks. Subjects returned to the dental clinic at 1, 2, 4 week as appointed and same experimental procedures were conducted and same clinical parameters were evaluated and recorded and these were submitted for statistical evaluation. Collected data was analyzed and different subgroups were compared using Student's t test. The statistical analysis is shown in [Table 1]. The mean value and p value were calculated.
|Table 1: Comparison of Mean Change for only Scaling, and Scaling + 0.2% Hyaluronic acid Gel (Gengigel®) for all Indices from Baseline to 4 Week |
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| Results|| |
There were no dropout cases and all the 50 subjects maintained their appointments. Mean plaque score for Group 1 at baseline was 2.99 ± 0.37, at 1 week was 2.58 ± 0.58, at 2 week mean was 2.53 ± 0.56 and at 4 week was 2.60 ± 0.47. Mean plaque index score for Group 2 at baseline was 3.16 ± 0.42, at 1 week was 2.38 ± 0.40, at 2 week 2.19 ± 0.54 and at 4 week 2.30 ± 0.36, respectively. Unpaired t-test revealed the plaque index score with mean values at baseline between Group 1 and Group 2 was 2.99 ± 0.37 and 3.16 ± 0.42, respectively, which was statistically non-significant (0.19) and at 4 week was 2.60 ± 0.47 and 2.30± 0.54, respectively, which was also statistically non-significant (0.11).
Mean gingival index score for Group 1 at baseline was 1.54 ± 0.14, at 1 week was 1.15 ± 0.16, at 2 week was 1.12 ± 0.19 and at 4 week was 1.13 ±0.22. Mean gingival index score for Group 2 at baseline was 1.51 ± 0.24, at 1 week was 0.98 ± 0.23, 2 week was 0.97 ± 0.29 and at 4 week was 0.85 ± 0.17.
The mean reduction in gingival index score at baseline between Group 1 and Group 2 was 1.54 ± 0.14 and 1.51 ± 0.24, respectively, which was statistically non-significant (0.92), at 4 week was 1.13 ± 0.22 and 0.85 ± 0.17, respectively, which was statistically highly significant (0.001).
Mean papillary bleeding index score for Group 1 at baseline was 1.81 ± 0.32, at 1 week was 1.22 ± 0.22, at 2 week 1.24 ± 0.27 and at 4 week 1.22 ± 0.31. Mean papillary bleeding index score for Group 2 at baseline was 1.77 ± 0.53, at 1 week 0.94 ± 0.27, 2 week mean score was 0.92 ± 0.22 and at 4 week 0.83 ± 0.24.
The mean reduction in papillary bleeding index score between Group 1 and Group 2 at baseline was 1.81 ± 0.32 and 1.77 ± 0.53, respectively, which was statistically non-significant (0.77), at 4 week was 1.22 ± 0.31 and 0.83 ± 0.24, respectively, which was statistically highly significant (0.001). The overall mean reductions in plaque, gingival and papillary bleeding index scores between Group 1 and Group 2 from baseline to 4 week are presented in [Table 1] and [Figure 1], [Figure 2], [Figure 3].
|Figure 1: Showing Plaque Index at Baseline, 1 Week, 2 Week and 4 Week between Group 1 and Group 2|
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|Figure 2: Showing Gingival Index at Baseline, 1 Week, 2 Week and 4 Week between Group 1 and Group 2|
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|Figure 3: Showing Papillary Bleeding Index at Baseline, 1 Week, 2 Week and 4 Week between Groups 1 and Group 2|
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| Discussion|| |
Plaque is intimately related to the production and progress of dental caries and inflammatory gingival and periodontal disease. In 1965, Loe et al. conducted the classic study demonstrating the cause and effect relationship between plaque accumulation and the development of gingivitis in humans. 
Wu and Savitt (2002)  reported that in conjunction with mechanical methods, oral hygiene products containing chemotherapeutic agents with a variety of antimicrobial mechanism have been desirable and beneficial. Recent pharmacological research on periodontal disease intervention has shifted from an antimicrobial to an anti-inflammatory approach to therapy.
Recently, exogenous hyaluronic acid known to have an anti-inflammatory effect is introduced as topical applicant for the treatment of gingivitis. The topical application of a high-molecular weight hyaluronan-based gel (Gengigel®) has been proposed to have some potential in inducing periodontal healing in patients with inflammatory gingivitis. , It is also beneficial in accelerating the healing of periodontal wounds following surgery.  Endogenous HA is a glycosaminoglycan of high-molecular weight of the extracellular matrix involved in growth and inflammation / repair. It plays an important role in post-inflammatory tissue regeneration, facilitating cell migration and differentiation during tissue formation and repair. It is used topically as an anti-inflammatory and anti-edematous agent. , Brandimorte  stated that it can be used in patients with periodontal disease, especially gingivitis. It also reduces the severity of gingival inflammatory infiltrate in periodontal patients as mentioned by Mesa et al.  Gengigel (0.2% hyaluronic acid), which is used in the treatment of gingivitis, proved practically tasteless, and very easy to spread in a thin, even layer on the gingivae and also produced a prolonged sensation of "smoothness" of the gingivae, which suggests that the gel may remain in situ for an equal length of time.  Gengigel has also been used subgingivally in the treatment of chronic periodontitis.
In the present study, an attempt has been made to evaluate the effectiveness of Gengigel (0.2% hyaluronic acid) in the treatment of plaque-induced gingivitis with or without scaling when applied topically. The study period of 4 weeks follows the recommendations of Chilton and Fleiss  to undertake trials regarding gingival inflammation with a study period longer than 2 weeks and Jentsch H et al.,  who compared clinical parameters between Gengigel and placebo gel group in gingivitis cases for a period of 3 weeks. The clinical parameters such as plaque index, gingival index and papillary bleeding index were recorded at '0' day, 7 th day, 14 th day and 28 th day. Any adverse reaction to the gel were recorded.
There was a consistent reduction in plaque score, gingival score and papillary bleeding score at different time intervals from '0' to 28 th day in each group. In the scaling group (control group), the mean reduction in plaque score from '0' to 28 th day was from 3.16 ± 0.42 to 2.30 ± 0.36. This was consistent with the findings of Pagnacco A et al.  and Suresh and Vandana,  who reported reduction in plaque score from baseline to end of the study period in scaling group. In the scaling and topical application of Gengigel group (Experimental group), the mean reduction in plaque score from '0' to 28 th day was from 2.99 ± 0.37 to 2.60 ±0.47. This finding was similar to that of Pagnacco A et al.,  who reported decrease in plaque score using Gengigel and placebo gel after scaling at the end of the study period. In the scaling group (Control group), the mean reduction in gingival score from '0' to 28 th day was from 1.51 ± 0.24 to 0.85 ±0.17. This was consistent with the findings of other workers  who showed reduction in gingival index score in the group treated by scaling at the end of study period. In the scaling and topical application of Gengigel group (Experimental group), the mean reduction in gingival score from '0' to 28 th day was from 1.54 ± 0.14 to 1.13 ± 0.22. The mean reduction in papillary bleeding index score between Group 1 and Group 2 at baseline was 1.81 ± 0.32 and 1.77 ± 0.53, respectively, which was statistically non-significant (0.77), at 4 week was 1.22 ± 0.31 and 0.83 ± 0.24, respectively, which was statistically highly significant (0.001).
No adverse effects were observed on clinical examination and as reported by the patients. These findings were similar to the findings of Pagnacco A et al.  and Vangelisti R et al.  Patients also presented the compliance with the regular use of Gengigel, proving the practicality of Gengigel and its excellent acceptability, including acceptability of its sensory characteristics. Gengigel as a product for oral use has been evaluated by skin irritation test, sensitizing potentiality and percutaneous absorption test and has been proved to be a safe non-irritant product. 
Although, present study was short term and with small sample size, but adjunctive use of 0.2% hyaluronic acid gel (Gengigel® ) evaluated in this study was safe and provided good results. It is the first topically applied anti-inflammatory product that has been specifically developed for dental use. It can reduce the tendency to relapse in patients with plaque-induced gingivitis. However, this study must be interpreted with due consideration to its limitations viz. relatively small sample size and short evaluation period. Also, further large-scale randomized, controlled clinical trials into the therapeutic effects of 0.2% hyaluronic acid gel (Gengigel® ) must be carried out in the future.
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[Figure 1], [Figure 2], [Figure 3]