Clinical efficacy of hyaluronic acid in peri-implantitis treatment: a systematic review of clinical, radiographic, and biological outcomes
DOI:
https://doi.org/10.2340/biid.v13.45746Keywords:
hyaluronic acid, hyaluronan, periimplantitis, dental implant, peri-implantitisAbstract
Objective: This systematic review evaluated the impact of adjunctive hyaluronic acid (HA) on outcomes in the management of peri-implantitis, while characterizing the various protocols and formulations.
Materials and methods: In accordance with the PRISMA 2020 guidelines, a search was conducted across five databases up to February 10, 2025 to identify randomized controlled trials (RCTs) and non-randomized clinical studies including controlled studies and case series. A dual-pass screening and data extraction process was employed to ensure data accuracy. The risk of bias was evaluated using Cochrane Risk of Bias 2, Risk of Bias in Non-Randomized Studies of Interventions-I, and Joanna Briggs Institute tools. The certainty of evidence for key outcomes was graded with the GRADE approach.
Results: Six studies (four RCTs, one controlled pilot study with a split-mouth design, and one prospective case series) with 110 patients were included; sample sizes ranged from 5 to 63 participants, and follow-up periods ranged from 15 days to 12 months. The findings were heterogeneous; while some studies demonstrated statistically significant improvements in probing pocket depth (PPD) and bleeding on probing (BOP), other studies reported no significant difference compared to controls. Marginal bone loss (MBL) outcomes were inconsistent. HA demonstrated an anti-inflammatory effect by reducing interleukin-1 beta levels and showed some benefits against the peri-implantitis-associated bacterial community.
Conclusion: Adjunctive HA is associated with favorable effects on PPD and BOP, but with a low certainty of evidence, and may have a benefit in decreasing the levels of early-colonizing bacteria. Significant improvement in MBL was associated only with surgical approaches but with a very low certainty of evidence. The high degree of heterogeneity in study design, HA formulations, and treatment protocols, coupled with a high risk of bias, makes it difficult to draw a definitive conclusion. Well-designed RCTs are required to establish the clinical role of HA in the management of peri-implantitis.
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References
Levignac J. [Periimplantation osteolysis- periimplantosis – periimplantitis]. Rev Fr Odontostomatol. 1965;12(8):1251–60.
Berglundh T, Armitage G, Araujo MG, Avila-Ortiz G, Blanco J, Camargo PM, et al. Peri-implant diseases and conditions: consensus report of workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Clin Periodontol. 2018;45(Suppl 20):S286–91.
https://doi.org/10.1111/jcpe.12957 DOI: https://doi.org/10.1111/jcpe.12957
Dell’Olmo F, Blasi G, Monje A, Mariotti A, Valles C, Pascual A, et al. Periodontists’ trends in the management of peri-implant diseases. Int J Oral Maxillofac Implants. 2022;37(2):329–38.
https://doi.org/10.11607/jomi.9374 DOI: https://doi.org/10.11607/jomi.9374
Paula LG, Vieira JL, Santos DRM, Mendes PHC, Abdo VL, Duraes SVPB, et al. Peri‐implantitis: knowledge and attitudes of implantology clinicians regarding the disease management. Int J Dent Hyg. 2024;22(4):825–32.
https://doi.org/10.1111/idh.12797 DOI: https://doi.org/10.1111/idh.12797
Hong I, Koo KT, Oh SY, Park HW, Sanz-Martín I, Cha JK. Comprehensive treatment protocol for peri-implantitis: an up-to-date narrative review of the literature. J Periodontal Implant Sci. 2024;54(5):295–308.
https://doi.org/10.5051/jpis.2303360168 DOI: https://doi.org/10.5051/jpis.2303360168
Asparuhova MB, Kiryak D, Eliezer M, Mihov D, Sculean A. Activity of two hyaluronan preparations on primary human oral fibroblasts. J Periodontal Res. 2019;54(1):33–45.
https://doi.org/10.1111/jre.12602 DOI: https://doi.org/10.1111/jre.12602
Asparuhova MB, Chappuis V, Stähli A, Buser D, Sculean A. Role of hyaluronan in regulating self-renewal and osteogenic differentiation of mesenchymal stromal cells and pre-osteoblasts. Clin Oral Investig. 2020;24(11):3923–37.
https://doi.org/10.1007/s00784-020-03259-8 DOI: https://doi.org/10.1007/s00784-020-03259-8
Shirakata Y, Imafuji T, Nakamura T, Kawakami Y, Shinohara Y, Noguchi K, et al. Periodontal wound healing/regeneration of two-wall intrabony defects following reconstructive surgery with cross-linked hyaluronic acid-gel with or without a collagen matrix: a preclinical study in dogs. Quintessence Int. 2021;52(4):308–16.
https://doi.org/10.3290/j.qi.b937003
Shirakata Y, Imafuji T, Nakamura T, Shinohara Y, Iwata M, Setoguchi F, et al. Cross-linked hyaluronic acid gel with or without a collagen matrix in the treatment of class III furcation defects: a histologic and histomorphometric study in dogs. J Clin Periodontol. 2022;49(10):1079–89.
https://doi.org/10.1111/jcpe.13694 DOI: https://doi.org/10.1111/jcpe.13694
Vela OC, Boariu MI, Iorio-Siciliano V, Vaduva A, Belova A, Stratul SI, et al. Histologic evaluation of early papilla healing after augmentation with injectable hyaluronic acid-a proof of concept. J Clin Med. 2024;13(14):4102.
https://doi.org/10.3390/jcm13144102 DOI: https://doi.org/10.3390/jcm13144102
Pilloni A, Marini L, Gagliano N, Canciani E, Dellavia C, Cornaghi LB, et al. Clinical, histological, immunohistochemical, and biomolecular analysis of hyaluronic acid in early wound healing of human gingival tissues: a randomized, split‐mouth trial. J Periodontol. 2023;94(7):868–81.
https://doi.org/10.1002/JPER.22-0338 DOI: https://doi.org/10.1002/JPER.22-0338
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):527–34.
https://doi.org/10.5005/jp-journals-10024-2294 DOI: https://doi.org/10.5005/jp-journals-10024-2294
Vela OC, Boariu M, Rusu D, Iorio-Siciliano V, Ramaglia L, Boia S, et al. Healing of periodontal suprabony defects following treatment with open flap debridement with or without hyaluronic acid (HA) application. Medicina (Kaunas). 2024;60(5):829.
https://doi.org/10.3390/medicina60050829 DOI: https://doi.org/10.3390/medicina60050829
Vajawat M, Rao DPC, Kumar GSV, Rajeshwari KG, Hareesha MS. Local delivery of hyaluronic acid as an adjunct to scaling and root planing in the treatment of chronic periodontitis in smokers and non-smokers: a clinical and microbiological study. J Indian Soc Periodontol. 2022;26(5):471–7.
https://doi.org/10.4103/jisp.jisp_308_21 DOI: https://doi.org/10.4103/jisp.jisp_308_21
Munn Z, Barker TH, Moola S, Tufanaru C, Stern C, McArthur A, et al. Methodological quality of case series studies: an introduction to the JBI critical appraisal tool. JBI Evid Synth. 2020;18(10):2127–33.
https://doi.org/10.11124/JBISRIR-D-19-00099 DOI: https://doi.org/10.11124/JBISRIR-D-19-00099
Sánchez-Fernández E, Magán-Fernández A, O’Valle F, Bravo M, Mesa F. Hyaluronic acid reduces inflammation and crevicular fluid IL-1β concentrations in peri-implantitis: a randomized controlled clinical trial. J Periodontal Implant Sci. 2021;51(1):63–74.
https://doi.org/10.5051/jpis.1903660183 DOI: https://doi.org/10.5051/jpis.1903660183
Soriano-Lerma A, Magán-Fernández A, Gijón J, Sánchez-Fernández E, Soriano M, García-Salcedo JA, et al. Short-term effects of hyaluronic acid on the subgingival microbiome in peri-implantitis: a randomized controlled clinical trial. J Periodontol. 2020;91(6):734–45.
https://doi.org/10.1002/jper.19-0184 DOI: https://doi.org/10.1002/JPER.19-0184
Rakašević D, Šćepanović M, Mijailović I, Mišić T, Janjić B, Soldatović I, et al. Reconstructive peri-implantitis therapy by using bovine bone substitute with or without hyaluronic acid: a randomized clinical controlled pilot study. J Funct Biomater. 2023;14(3):149.
https://doi.org/10.3390/jfb14030149 DOI: https://doi.org/10.3390/jfb14030149
De Araújo Nobre M, Carvalho R, Maló P. Non surgical treatment of periimplant pockets: an exploratory study comparing 0.2% chlorhexidine and 0.8% hyaluronic acid. Can J Dent Hyg. 2009;43(1):25–30.
Lopez MA, Manzulli N, D’Angelo A, Lauritano D, Papalia R, Candotto V. The use of hyaluronic acid as an adjuvant in the management of peri-implantitis. J Biol Regul Homeost Agents. 2017;31(4 Suppl 2):123–7.
Friedmann A, Jung R, Bilhan H, Ghawi-Begovic HA, Kauffmann F, Diehl D. Reconstructive surgical therapy of peri-implant defects with ribose cross-linked collagen matrix and crosslinked hyaluronic acid – a prospective case series. Clin Oral Investig. 2024;28(10):536.
https://doi.org/10.1007/s00784-024-05942-6 DOI: https://doi.org/10.1007/s00784-024-05942-6
Graves DT, Cochran D. The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol. 2003;74(3):391–401.
https://doi.org/10.1902/jop.2003.74.3.391 DOI: https://doi.org/10.1902/jop.2003.74.3.391
Neurath N, Kesting M. Cytokines in gingivitis and periodontitis: from pathogenesis to therapeutic targets. Front Immunol. 2024;15:1435054.
https://doi.org/10.3389/fimmu.2024.1435054 DOI: https://doi.org/10.3389/fimmu.2024.1435054
Renvert S, Hirooka H, Polyzois I, Kelekis-Cholakis A, Wang HL. Diagnosis and non-surgical treatment of peri-implant diseases and maintenance care of patients with dental implants – consensus report of working group 3. Int Dent J. 2019;69(Suppl 2):12–17.
https://doi.org/10.1111/idj.12490 DOI: https://doi.org/10.1111/idj.12490
Polymeri A, van der Horst J, Anssari Moin D, Wismeijer D, Loos BG, Laine ML. Non-surgical peri-implantitis treatment with or without systemic antibiotics: a randomized controlled clinical trial. Clin Oral Implants Res. 2022;33(5):548–57.
https://doi.org/10.1111/clr.13914 DOI: https://doi.org/10.1111/clr.13914
Noelken R, Al-Nawas B. Bone regeneration as treatment of peri-implant disease: a narrative review. Clin Implant Dent Relat Res. 2023;25(4):696–709.
https://doi.org/10.1111/cid.13209 DOI: https://doi.org/10.1111/cid.13209
Sanz-Martín I, Cha JK, Sanz-Sánchez I, Figuero E, Herrera D, Sanz M. Changes in peri-implant soft tissue levels following surgical treatment of peri-implantitis: a systematic review and meta-analysis. Clin Oral Implants Res. 2021;32(Suppl 21):230–44.
https://doi.org/10.1111/clr.13840 DOI: https://doi.org/10.1111/clr.13840
Risolo M, Cevik-Aras H, Sayardoust S. The effect of reconstructive techniques as treatment modality for peri-implant osseous defects – a systematic review and meta-analysis. Acta Odontol Scand. 2023;81(7):569–77.
https://doi.org/10.1080/00016357.2023.2243325 DOI: https://doi.org/10.1080/00016357.2023.2243325
Carvalho ÉBS, Romandini M, Sadilina S, Sant’Ana ACP, Sanz M. Microbiota associated with peri-implantitis – a systematic review with meta-analyses. Clin Oral Implants Res. 2023;34(11):1176–87.
https://doi.org/10.1111/clr.14153 DOI: https://doi.org/10.1111/clr.14153
Ting M, Craig J, Balkin BE, Suzuki JB. Peri-implantitis: a comprehensive overview of systematic reviews. J Oral Implantol. 2018;44(3):225–47.
https://doi.org/10.1563/aaid-joi-D-16-00122 DOI: https://doi.org/10.1563/aaid-joi-D-16-00122
Chun Giok K, Menon RK. The microbiome of peri-implantitis: a systematic review of next-generation sequencing studies. Antibiotics (Basel). 2023;12(11):1610.
https://doi.org/10.3390/antibiotics12111610 DOI: https://doi.org/10.3390/antibiotics12111610
Liu S, Li M, Yu J. Does chlorhexidine improve outcomes in non-surgical management of peri-implant mucositis or peri-implantitis?: a systematic review and meta-analysis. Med Oral Patol Oral Cir Bucal. 2020;25(5):e608–15.
https://doi.org/10.4317/medoral.23633 DOI: https://doi.org/10.4317/medoral.23633
Zhao P, Wang Q, Zhang P, Zhou X, Nie L, Liang X, et al. Clinical efficacy of chlorhexidine as an adjunct to mechanical therapy of peri-implant disease: a systematic review and meta-analysis. J Oral Implantol. 2021;47(1):78–87.
https://doi.org/10.1563/aaid-joi-D-19-00213 DOI: https://doi.org/10.1563/aaid-joi-D-19-00213
Ye M, Liu W, Cheng S, Yan L. Efficacy of adjunctive chlorhexidine in non-surgical treatment of peri-implantitis/peri-implant mucositis: an updated systematic review and meta-analysis. Pak J Med Sci. 2023;39(2):595–604.
https://doi.org/10.12669/pjms.39.2.7253 DOI: https://doi.org/10.12669/pjms.39.2.7253
Rosa A, Pujia AM, Arcuri C. Hyaluronic acid combined with ozone in dental practice. Biomedicines. 2024;12(11):2522.
https://doi.org/10.3390/biomedicines12112522 DOI: https://doi.org/10.3390/biomedicines12112522
López-Valverde N, López-Valverde A, Blanco Rueda JA. Role of hyaluronic acid in the treatment of peri-implant diseases: results of a meta-analysis. Front Oral Health. 2025;6:1564599.
https://doi.org/10.3389/froh.2025.1564599 DOI: https://doi.org/10.3389/froh.2025.1564599
Bokor B, Objelean A, Campian RS. Current trends of hyaluronic acid use as a therapeutic strategy in peri-implantitis: a scoping review. Oral. 2025;5(3):68.
https://doi.org/10.3390/oral5030068 DOI: https://doi.org/10.3390/oral5030068
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