Aim: The main purpose of the present study was to investigate the potential benefit of local use of hyaluronic acid as an adjunct to periodontal therapy, since commercial products of hyaluronic acid (HA), due to its anti-inflammatory and anti-bacterial actions and its significant role in wound repair, have been proposed as adjuncts to either nonsurgical or surgical periodontal therapy. Materials and methods: A total of 19 electronic databases were searched and the appropriate studies were identified with the use of specific eligibility criteria, according to PRISMA guidelines. Two reviewers independently screened and selected the studies and made the data extraction and the assessment of risk of bias, by using the Cochrane risk of bias tool. Results: Out of 3,186 papers, 38 randomized clinical trials (8 related to gingivitis therapy, 20 related to nonsurgical periodontal therapy, and 10 related to surgical periodontal therapy) were finally included in the review. The outcomes were categorized as primary (that answered the focus question) and secondary (regarding additional quality characteristics). The adjunct use of HA combined to all treatment modalities shows improvement of patients’ postoperative course, in terms of decreased inflammatory reactions, and changes in periodontal pocket depth and clinical attachment level. No side effects were reported in any of the included studies. Among the secondary outcomes were the variety of HA formulations and chemical forms, the variety in application, follow-up protocol and blinding design, the uneven geographic distribution of the studies, and the low bibliometric characteristics of most studies. Conclusion: Overall and despite the positive effects reported, further research is needed to define the ideal HA compound, formulation, and regimen characteristics for periodontal disease treatment. Clinical significance: The adjunct use of HA may lead in the reduction of the prescription of nonsteroid anti-inflammatory drugs and achieve improved clinical parameters, including periodontal probing depth, periodontal inflammation, and clinical attachment level.
Flemming HC, Wingender J. The biofilm matrix. Nat Rev Microbiol 2010;8(9):623–633. DOI: 10.1038/nrmicro2415.
Löe H, Theilade E, Jensen SB. Experimental gingivitis in man. J Periodontol 1965;36:177–187. DOI: 10.1902/jop.19184.108.40.206.
Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol 1999;4(1):1–6. DOI: 0.1902/annals.19220.127.116.11.
Albandar JM. A 6-year study on the pattern of periodontal disease progression. J Clin Periodontol 1990;17(7 Pt 1):467–471. DOI: 10.1111/j.1600-051x.1990.tb02346.x.
Lindhe J, Socransky SS, Nyman S, et al. “Critical probing depths” in periodontal therapy. J Clin Periodontol 1982;9(4):323–336. DOI: 10.1111/j.1600-051x.1982.tb02099.x.
Badersten A, Nilveus R, Egelberg J. Effect of nonsurgical periodontal therapy. II. Severely advanced periodontitis. J Clin Periodontol 1984;11(1):63–76. DOI: 10.1111/j.1600-051x.1984.tb01309.x.
Ramfjord SP, Knowles JW, Nissle RR, et al. Results following three modalities of periodontal therapy. J Periodontol 1975;46(9):522–526. DOI: 10.1902/jop.1918.104.22.1682.
Necas J, Bartosikova L, Brauner P, et al. Hyaluronic acid (hyaluronan): a review. Vet Med 2008;53(8):397–411. DOI: 10.17221/1930-VETMED.
Bukhari SNA, Roswandi NL, Waqas M, et al. Hyaluronic acid, a promising skin rejuvenating biomedicine: a review of recent updates and pre-clinical and clinical investigations on cosmetic and nutricosmetic effects. Int J Biol Macromol 2018;120(Pt B):1682–1695. DOI: 10.1016/j.ijbiomac.2018.09.188.
Håkansson L, Hällgren R, Venge P. Regulation of granulocyte function by hyaluronic acid. In vitro and in vivo effects on phagocytosis, locomotion, and metabolism. J Clin Invest 1980;66(2):298–305. DOI: 10.1172/JCI109857.
Dahiya P, Kamal R. Hyaluronic acid: a boon in periodontal therapy. N Am J Med Sci 2013;5(5):309–315. DOI: 10.4103/1947-2714.112473.
Bertl K, Bruckmann C, Isberg PE, et al. Hyaluronan in non-surgical and surgical periodontal therapy: a systematic review. J Clin Periodontol 2015;42(3):236–246. DOI: 10.1111/jcpe.12371.
Casale M, Moffa A, Vella P, et al. Hyaluronic acid: perspectives in dentistry. A systematic review. Int J Immunopathol Pharmacol 2016;29(4):572–582. DOI: 10.1177/0394632016652906.
Eliezer M, Imber J-C, Sculean A, et al. Hyaluronic acid as adjunctive to non-surgical and surgical periodontal therapy: a systematic review and meta-analysis. Clin Oral Investig 2019;23(9):3423–3435. DOI: 10.1007/s00784-019-03012-w.
Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6(7):e1000097. DOI: 10.1371/journal.pmed.1000097.
Higgins JP, Savović J, Page MJ, et al. Chapter 8: assessing risk of bias in a randomized trial 2021. Online information available at: www.training.cochrane.org/handbook.
Cardoso L, Silva R, de Almeida GGF, et al. A bibliometric model to analyze country research performance: scival topic prominence approach in tourism, leisure and hospitality. Sustainability (Switzerland) 2020; 12:1–27. DOI: 10.3390/su12239897.
Jentsch H, Pomowski R, Kundt G, et al. Treatment of gingivitis with hyaluronan. J Clin Periodontol 2003;30(2):159–164. DOI: 10.1034/j.1600-051x.2003.300203.x.
Pistorius A, Martin M, Willershausen B, et al. The clinical application of hyaluronic acid in gingivitis therapy. Quintessence Int 2005;36(7–8):531–538. PMID: 15999421.
Rodrigues SV, Acharya AB, Bhadbhade S, et al. Hyaluronan-containing mouthwash as an adjunctive plaque-control agent. Oral Health Prev Dent 2010;8(4):389–394. PMID: 21180677.
Sapna N, Vandana KL. Evaluation of hyaluronan gel (Gengigel(®)) as a topical applicant in the treatment of gingivitis. J Investig Clin Dent 2011; 2(3):162–170. DOI: 10.1111/j.2041-1626.2011.00064.x.
Sahayata VN, Bhavsar NV, Brahmbhatt NA. An evaluation of 0.2% hyaluronic acid gel (Gengigel ®) in the treatment of gingivitis: a clinical and microbiological study. Oral Health Dent Manag 2014;13(3):779–785. PMID: 25284557.
Gizligoz B, Ince Kuka G, Tunar OL, et al. Plaque inhibitory effect of hyaluronan-containing mouthwash in a 4-Day non-brushing model. Oral Health Prev Dent 2020;18(1):61–70. DOI: 10.3290/j.ohpd.a43936.
Al-Shabeeb AKH, Mohammed AN. Clinicalevaluation of 0.2% hyaluronic acid and its effect on the level of interleukine-1B in gingival crevicular fluid before and after treatment of plaque induced gingivitis. Ind J Public Health Res Develop 2019;10(2):659–664. DOI: 10.5958/0976-5506.2019.00368.1.
Abdulkareem AA, Al Marah ZA, Abdulbaqi HR, et al. A randomized double-blind clinical trial to evaluate the efficacy of chlorhexidine, antioxidant, and hyaluronic acid mouthwashes in the management of biofilm-induced gingivitis. Int J Dent Hyg 2020;18(3):268–277. DOI: 10.1111/idh.12432.
Engström PE, Shi XQ, Tronje G, et al. The effect of hyaluronan on bone and soft tissue and immune response in wound healing. J Periodontol 2001;72(9):1192–1200. DOI: 10.1902/jop.2000.72.9.1192.
Xu Y, Höfling K, Fimmers R, et al. Clinical and microbiological effects of topical subgingival application of hyaluronic acid gel adjunctive to scaling and root planing in the treatment of chronic periodontitis. J Periodontol 2004;75(8):1114–1118. DOI: 10.1902/jop.2004.75.8.1114.
Johannsen A, Tellefsen M, Wikesjö U, et al. Local delivery of hyaluronan as an adjunct to scaling and root planing in the treatment of chronic periodontitis. J Periodontol 2009;80(9):1493–1497. DOI: 10.1902/jop.2009.090128.
Pilloni A, Annibali S, Dominici F, et al. Evaluation of the efficacy of an hyaluronic acid-based biogel on periodontal clinical parameters. A randomized-controlled clinical pilot study. Ann Stomatol (Roma) 2011;2(3-4):3–9. PMCID: PMC3314319.
Koshal A, Bolt R, Galgut P. A comparison in postoperative healing of sites receiving non-surgical debridement augmented with and without a single application of hyaluronan 0.8% gel. DENTAL TRIBUNE Middle East & Africa Edition 2012. Online information Available at: http://www.takara-net.com.
Gontiya G, Galgali SR. Effect of hyaluronan on periodontitis: a clinical and histological study. J Indian Soc Periodontol 2012;16(2):184–192. DOI: 10.4103/0972-124X.99260.
Bevilacqua L, Eriani J, Serroni I, et al. Effectiveness of adjunctive subgingival administration of amino acids and sodium hyaluronate gel on clinical and immunological parameters in the treatment of chronic periodontitis. Ann Stomatol (Roma) 2012;3(2):75–81. PMCID: PMC3476496.
Chauhan AS, Bains VK, Gupta V, et al. Comparative analysis of hyaluronan gel and xanthan-based chlorhexidine gel, as adjunct to scaling and root planing with scaling and root planing alone in the treatment of chronic periodontitis: a preliminary study. Contemp Clin Dent 2013;4(1):54–61. DOI: 10.4103/0976-237X.111619.
Eick S, Renatus A, Heinicke M, et al. Hyaluronic acid as an adjunct after scaling and root planing: a prospective randomized clinical trial. J Periodontol 2013;84(7):941–949. DOI: 10.1902/jop.2012.120269.
Rajan P, Baramappa R, Rao NM, et al. Hyaluronic acid as an adjunct to scaling and root planing in chronic periodontitis. A randomized clinical trail. J Clin Diagn Res 2014;8(12):11–14. DOI: 10.7860/JCDR/2014/8848.5237.
Polepalle T, Srinivas M, Swamy N, et al. Local delivery of hyaluronan 0.8% as an adjunct to scaling and root planing in the treatment of chronic periodontitis: a clinical and microbiological study. J Indian Soc Periodontol 2015;19(1):37–42. DOI: 10.4103/0972-124X.145807.
Sharma V, Gupta R, Dahiya P, et al. Comparative evaluation of coenzyme Q10-based gel and 0.8% hyaluronic acid gel in treatment of chronic periodontitis. J Indian Soc Periodontol 2016;20(4):374–380. DOI: 10.4103/0972-124X.183097.
Shah SA, Vijayakar HN, Rodrigues SV, et al. To compare the effect of the local delivery of hyaluronan as an adjunct to scaling and root planing versus scaling and root planing alone in the treatment of chronic periodontitis. J Indian Soc Periodontol 2016;20(5):549–556. DOI: 10.4103/0972-124X.201695.
Mallikarjun S, Neelakanti A, Babu HM, et al. Neutrophil elastase levels in the gingival crevicular fluid following hyaluronan gel application in the treatment of chronic periodontitis: a randomized split-mouth study. Indian J Dent Res 2016;27(4):397–404. DOI: 10.4103/0970-9290.191889.
Omer, B, Satti A, Gismalla, B, et al. The effect of local application of hyaluronan gel as an adjunctive to scaling and root planing in chronic periodontitis patients. African J Dent 2018;6(5):163–170. ISSN: 3216-0216.
Al-Shammari NM, Shafshak SM, Ali MS. Effect of 0.8% hyaluronic acid in conventional treatment of moderate to severe chronic periodontitis. J Contemp Dent Pract 2018;19(5):527–534. PMID: 29807962.
Lobato JCRF, Dos Santos Vilhena MA, Izidoro C, et al. Single application of 0.8% hyaluronic acid as a coadjuvant of nonsurgical treatment in nonsmoking patients with periodontitis: A split-mouth, randomized, controlled pilot clinical trial. J Indian Soc Periodontol 2019; 23(6):545–548. DOI: 0.4103/jisp.jisp_674_18.
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(3):158–163. DOI: 10.4103/jioh.jioh_292_18.
Ibraheem LM, Abdulhameed BS, Wifaq MA, et al. The effect of Hyaluronic Acid as an Adjunct after Scaling and Root Planning in the Treatment of Chronic Periodontitis. Indian J Public Health Res Develop. 2020;11:357–363. DOI: 10.37506/ijphrd.v11i10.11174.
Aydinyurt HS, Akbal D, Altindal D, et al. Evaluation of biochemical and clinical effects of hyaluronic acid on non-surgical periodontal treatment: a randomized controlled trial. Ir J Med Sci 2020;189(4):1485–1494. DOI: 10.1007/s11845-020-02230-6.
Galli F, Zuffetti F, Capelli M, et al. Hyaluronic acid to improve healing of surgical incisions in the oral cavity: a pilot multicentre placebo-controlled randomised clinical trial. Eur J Oral Implantol 2008;1(3):199–206. PMID: 20467622.
Fawzy El-Sayed KM, Dahaba MA, Aboul-Ela S, et al. Local application of hyaluronan gel in conjunction with periodontal surgery: a randomized controlled trial. Clin Oral Investig 2012;16(4):1229–1236. DOI: 10.1007/s00784-011-0630-z.
Briguglio F, Briguglio E, Briguglio R, et al. Treatment of infrabony periodontal defects using a resorbable biopolymer of hyaluronic acid: a randomized clinical trial. Quintessence Int 2013;44(3):231–240. DOI: 10.3290/j.qi.a29054. PMID: 23444204.
Kumar R, Srinivas M, Pai J, et al. Efficacy of hyaluronic acid (hyaluronan) in root coverage procedures as an adjunct to coronally advanced flap in Millers Class I recession: a clinical study. J Indian Soc Periodontol 2014;18(6):746–750. DOI: 10.4103/0972-124X.147411.
Gupta S, Kediege SD, Gupta A, et al. Evaluation of Gengigel® application in the management of furcation with coronally advanced flap through surgical re-entry: a split mouth clinical study. J Clin Diagn Res 2017;11(1):ZC27–ZC32. DOI: 10.7860/JCDR/2017/21938.9169.
Pilloni A, Schmidlin PR, Sahrmann P, et al. Effectiveness of adjunctive hyaluronic acid application in coronally advanced flap in Miller class I single gingival recession sites: a randomized controlled clinical trial. Clin Oral Investig 2019;23(3):1133–1141. DOI: 10.1007/s00784-018-2537-4.
Reddy SP, Koduganti RR, Panthula VR, et al. Efficacy of low-level laser therapy, hyaluronic acid gel, and herbal gel as adjunctive tools in gingivectomy wound healing: a randomized comparative clinical and histological study. Cureus 2019;11(12):e6438. DOI: 10.7759/cureus.6438.
Marwa M, Mai SA, Eatmad AS. Clinical evaluation of hyaluronan gel alone or in combination with platelet-rich fibrin (PRF) in periodontal regenerative surgery. Al-Azhar Dent J Girls 2020;7:273–279. DOI: 10.21608/ADJG.2020.7697.1091.
Pilloni A, Rojas MA, Marini L, et al. Healing of intrabony defects following regenerative surgery by means of single-flap approach in conjunction with either hyaluronic acid or an enamel matrix derivative: a 24-month randomized controlled clinical trial. Clin Oral Investig 2021(8);25:5095–5107. DOI: 10.1007/s00784-021-03822-x.
Mamajiwala AS, Sethi KS, Raut CP, et al. Clinical and radiographic evaluation of 0.8% hyaluronic acid as an adjunct to open flap debridement in the treatment of periodontal intrabony defects: randomized controlled clinical trial. Clin Oral Investig 2021;25(9):5257–5271. DOI: 10.1007/s00784-021-03834-7.
Mühlemann HR, Son S. Gingival sulcus bleeding: a leading symptom in initial gingivitis. Helv Odontol Acta 1971;15(2):107–113. PMID: 5315729.
Miller PD. A classification of marginal tissue recession. Int J Periodontics Restorative Dent 1985;5(2):8–13. PMID: 3858267.