Bioactive materials for post-operative healing and pain relief following palatal epithelialized graft harvesting: A meta-analysis of randomized clinical trials

Background/purpose: Palatal epithelial graft harvesting requires secondary healing, and various materials have been used to accelerate this and reduce discomfort. However, comparisons against standardized controls remain limited, especially in randomized clinical trials. This meta-analysis assessed the efficacy of bioactive materials of hyaluronic acid, platelet-rich fibrin, collagen, and cyanoacrylate in promoting healing and reducing pain after epithelial graft harvesting. Materials and methods: Clinical trials were identified from PubMed, Scopus, Web of Science and Embase up to August 2024. The efficacies of bioactive materials were assessed using Review Manager Analysis, with odds ratios calculated for complete wound healing and mean differences in Visual Analog Scale (VAS) scores for pain. Results: Of 787 references, 9 clinical trials met eligibility: 6 on healing and 7 on pain. Meta-analysis showed significant improvement in complete epithelialization for the overall materials vs. control (OR = 4.28). Subgroup analysis showed improvements for HA (OR = 4.80) and PRF (OR = 12.81), but not cyanoacrylate. Similar results were seen for VAS pain scores on days 1-3 and day 7, with benefits for the overall materials and individually for HA, PRF, and collagen, except cyanoacrylate. High heterogeneity was found on days 1-3 (I2 = 66) and day 7 (I2 = 90 %). Subgroup analysis reduced most heterogeneity, except for HA on days 1-3 (I2 = 91 %). Conclusion: HA, PRF, and collagen may relief pain, and HA and PRF might aid healing after epithelialized gingival graft harvest (no trials recruited in evaluating the collagen's effect on wound healing). Cyanoacrylate may not support pain relief or healing. Further trials are needed. <feminine ordinal indicator> 2025 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).