Injectable platelet-rich fibrin (i-PRF) has the capacity to release great amounts of several growth factors, as well as to stimulate increased fibroblast migration and the expression of collagen, transforming growth factor β, and platelet-derived growth factor. Consequently, i-PRF can be used as a bioactive agent to promote periodontal tissue regeneration. We aim to compare and evaluate the effectiveness of i-PRF in periodontal tissue regeneration. We will conduct an electronic search in the following databases: PubMed, Cochrane Library, Google Scholar, Semantic Scholar, Scopus, and Web of Science. Papers will be restricted to those in English and to those that are randomized controlled trials comparing PRF or any other biomaterial with i-PRF for periodontal regeneration during dental treatment. The included papers in this review and the reference lists of pertinent reviews will be manually searched. The selection of studies, data extraction, and assessment will be carried out separately by 2 reviewers using the Risk of Bias 2 tool for the included research. The success of i-PRF will be evaluated by comparing the mean difference in periodontal regeneration of soft and hard tissues in terms of gingival recession, probing pocket depth, clinical attachment level, bone gain, and gingival width. The combined effect size measurements and the associated 95% CIs will be estimated using a random-effects model. The synthesis or work for this systematic review started in October 2023 and will last until December 2025. i-PRF may play a role in dentistry and could enhance soft and hard tissue regeneration. PROSPERO CRD42023464250; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=464250. PRR1-10.2196/65137.
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