Clinical, Microbiological, and Biochemical Outcomes of Hyaluronic Acid in Non-Surgical Periodontal Therapy: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Research Question
2.2. Search Strategy
2.3. Screening and Selection
- P (Population): patients diagnosed with periodontal disease;
- I (Intervention): adjunctive use of HA gel in support of SRP;
- C (Comparison): SRP alone;
- O (Outcome): clinical, microbiological, and biochemical parameters.
2.4. Risk of Bias Assessment
2.5. Data Extraction
2.6. Data Analysis
2.7. Grading the Body of Evidence
3. Results
3.1. Study Flow Chart
3.2. Study Characteristics
3.3. Microbiological Analysis
Biochemical Analysis
3.4. Risk of Bias Assessment
3.5. Meta-Analysis
3.6. Grading the Body of Evidence
4. Discussion
4.1. Clinical Parameters
4.2. Microbiological and Biochemical Analysis
4.3. Formulation of HA and Its Clinical Impact
4.4. Study Limitations
4.5. Implications for Future Research
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
RCT | Randomized Clinical Trial |
NI | No Information |
PD | Probing Depth |
PPD | Pocket Probing Depth |
CAL | Clinical Attachment Level |
BOP | Bleeding On Probing |
SRP | Scaling and Root Planing |
HA | Hyaluronic Acid |
PI | Plaque Index |
RAL | Relative Attachment Level |
GCCI | Gingival Color Change Index |
EIBI | Eastman Interdental Bleeding Index |
PBI | Papillary Bleeding Index |
GI | Gingival Index |
FMPS | Full Mouth Plaque Score |
GRH | Gingival Recession level |
API | Approximal Plaque Index |
REC | Recession |
MSBI | Mean Sulcus Bleeding Index |
FMPS | Full Mouth Plaque Score |
FMBS | Full Mouth Bleeding Index |
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Database | Search Terms | Boolean Operators | Notes |
---|---|---|---|
PubMed, Cochrane Library, Scopus, Web of Science | (“Periodontitis”[MeSH] OR non-surgical periodontal therapy OR periodontal disease) AND (“Hyaluronic Acid”[MeSH] OR hyaluronan OR hyaluronate) | AND, OR | Up to January 2025 |
PubMed, Cochrane Library, Scopus, Web of Science | (“Hyaluronic Acid”[MeSH] OR hyaluro*) AND (“Periodontal Diseases”[MeSH] OR periodont*) AND non-surgical | AND, OR | Up to January 2025 |
PubMed, Cochrane Library, Scopus, Web of Science | (“Hyaluronic Acid” OR hyaluro*) AND (Periodontitis OR periodont*) AND non-surgical | AND, OR | Up to January 2025 |
First Author and Year | Study Design | Study Design | Country | Sample Size and Sex | Mean Age/Rang (Years) | Test and Control Interventions | Follow-Up | Outcome |
---|---|---|---|---|---|---|---|---|
Xu 2004 [18] | RCT | Split-mouth | China | 20 (11 M, 9 F) | 48.6 | 1 SRP 2 SRP + 1 mL 0.2% HA gel | 6 and 12 wks | BOP, CAL, PD |
Johannsen 2009 [19] | RCT | Split-mouth | Sweden | 12 (sex not stated) | 42–63 | 1 SRP 2 SRP + 0.2 mL + 0.8% HA gel | 12 wks | BOP, PI, CAL, PD |
Koshal 2012 [20] | RCT | Random assignment | Africa | 52 (sex not stated) | / | 1 SRP + placebo 2 SRP + HA | 12 wks | GI, PD |
Chauhan 2013 [21] | RCT with biochemical analysis | Random assignment | India | 11 (sex not stated) | 30–65 | 1 SRP 2 SRP + HA gel 3 SRP + HA gel + CHX gel | 6 and 12 wks | PD, CAL, PI |
Eick 2013 [22] | RCT with microbiological analysis | Random assignment | Switzerland | 34 (sex not stated) | 41–72 | 1 SRP 2 SRP + 0.8% HA gel in office + 0.2% HA gel at home | 12, 24, 36 wks | BOP, PI, CAL, PD |
Rajan 2014 [23] | RCT | Split-mouth | India | 33 (15 M, 18 F) | NI | 1 SRP 2 SRP + 0.2% HA gel | 4 and 12 wks | GI, PI, BOP, PPD, CAL |
Polepalle 2015 [24] | RCT | Split-mouth | India | 18 (11 M, 7 F) | 30–60 45 | 1 SRP 2 SRP + 0.2 mL 0.8% HA gel | 4 and 12 wks | PI, BOP, PPD, CAL, CFU |
Shah 2016 [25] | RCT | Split-mouth | India | 9 (sex not stated) | 30–60 45 | 1 SRP 2 SRP + 0.8% HA gel + periodontal dressing | 4 and 12 wks | GI, PI, PPD, RAL |
Sharma 2016 [26] | RCT | Split-mouth | India | 24 (sex not stated) | 25–55 40 | 1 SRP + d coenzyme Q gel 2 SRP + 0.8% HA gel 3 SRP alone | 1, 2, 6 wks | PI, EIBI, GCCI, PD, CAL |
Al-Shammari 2018 [27] | RCT with biochemical analysis | Split-mouth | Kingdom of Saudi Arabia | 24 (14 F, 10 M) | 24–57 40.5 | 1 SRP alone 2 SRP + 0.8% HA | 6 and 12 wks | PI, GI, PBI, PPD, CAL, human beta defensin-2 (hBD-2) expression |
Lobato 2019 [28] | RCT | Split-mouth | India | 16 | 41–68 54.5 | 1 SRP 2 SRP + 0.8% HA | 6 and 12 wks | FMPS, GI, BOP, PD CAL |
Aydinyurt 2020 [29] | RCT with biochemical analysis | Random assignment | Turkey | 96 (40 M, 56 F) | 22–55 38.5 | 1 SRP + saline irrigation 2 SRP + 0.2% HA gel 3 SRP + 0.2% HA hydrogel mouth rinse 4 SRP + 0.2% HA hydrogel mouth rinse + 0.2% HA gel | 1, 2, 4 wks | PI, GI, BOP, PD, GRH, CAL, biochemicals (ADA, CAT, GSH) |
Nguyen 2021 [30] | RCT with microbiological analysis | Split-mouth | Vietnam | 34 | ni | 1 SRP + 0.9% NaCl solution rinse 2 SRP + 0.9% NaCl solution rinse + 1 mL 0.2% HA gel | 1, 2, 3, 6 wks | PI, GI, PPD, CAL, BOP |
Olszewska 2021 [31] | RCT | Random assignment | Poland | 100 (51 F, 49 M) | 25–65 45 | 1 SRP + HA gel (1.6% reticular HA + 0.2% HA natural) 2 SRP alone | 12 wks | API, BOP, PPD, CAL |
Vajawat 2022 [32] | RCT with microbiological analysis | Split-mouth | India | 24 | 35–65 50 | 1: SRP + placebo 2: SRP + 0.8% HA gel | 4, 12 wks | CAL, PD, BI, GI, PI |
Mazloum 2023 [33] | RCT | Random assignment | Lebanon | 75 | 20–60 40 | 1 SRP + 0.8% HA gel 2 SRP + with red i-PRF 3 SRP alone | 4, 8, 12 wks | CAL, PD, PI, GI, BOP |
Bertl 2024 [34] | RCT | Random assignment | Sweden | 56 (37 F, 19 M) | 35–75 55 | 1 SRP + 0.3% HA gel 2 SRP + saline solution | 12, 24, 36, 48 wks | PPD, PI, GI, BOP, CAL |
Jaafar 2024 [35] | RCT | Random assignment | Malaysia | 36 (25 F, 11 M) | 30–60 45 | 1 SRP + 0.8% HA gel 2 SRP alone | 12 wks | PI, PD, CAL, BOP, REC |
El Emam 2024 [36] | RCT | Random assignment | Egypt | 28 (14 M, 14 F) | 28–40 34 | 1 SRP + local 0.2% HA gel 2 SRP alone | 12 wks | PI, BI, CAL, MSBI, PD |
Ramanaus kaite 2023 [37] | RCT | Random assignment | Lithuania | 21 | 30–72 | 1 SRP alone 2 SRP+ crosslinked HA gel baseline | 12 and 24 wks | PD, CAL, BOP, PI |
Iorio-Siciliano 2025 [38] | RCT | Random assignment | Italy | 38 (14 M, 24 F) | Test 49.3 ±11.6 Control 50.8 ± 10.8 | 1 SRP 2 SRP + HA | 4, 12, 24 wks | PD, FMPS, FMBS, CAL |
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Share and Cite
Pardo, A.; Magnani, V.; Montagna, P.; Ala, A.; Brancato, G.; Melloni, F.; Lombardo, G.; De Santis, D. Clinical, Microbiological, and Biochemical Outcomes of Hyaluronic Acid in Non-Surgical Periodontal Therapy: A Systematic Review and Meta-Analysis. Appl. Sci. 2025, 15, 5975. https://doi.org/10.3390/app15115975
Pardo A, Magnani V, Montagna P, Ala A, Brancato G, Melloni F, Lombardo G, De Santis D. Clinical, Microbiological, and Biochemical Outcomes of Hyaluronic Acid in Non-Surgical Periodontal Therapy: A Systematic Review and Meta-Analysis. Applied Sciences. 2025; 15(11):5975. https://doi.org/10.3390/app15115975
Chicago/Turabian StylePardo, Alessia, Veronica Magnani, Pietro Montagna, Andrea Ala, Gabriele Brancato, Federica Melloni, Giorgio Lombardo, and Daniele De Santis. 2025. "Clinical, Microbiological, and Biochemical Outcomes of Hyaluronic Acid in Non-Surgical Periodontal Therapy: A Systematic Review and Meta-Analysis" Applied Sciences 15, no. 11: 5975. https://doi.org/10.3390/app15115975
APA StylePardo, A., Magnani, V., Montagna, P., Ala, A., Brancato, G., Melloni, F., Lombardo, G., & De Santis, D. (2025). Clinical, Microbiological, and Biochemical Outcomes of Hyaluronic Acid in Non-Surgical Periodontal Therapy: A Systematic Review and Meta-Analysis. Applied Sciences, 15(11), 5975. https://doi.org/10.3390/app15115975