{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:09:31Z","timestamp":1785312571306,"version":"3.55.0"},"reference-count":54,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Vitamins A and C (VitA+C) are pivotal biomolecules, with synergistic effects, especially in conjoint presence, on cellular pluripotency and regenerative capabilities. This randomized trial aimed to evaluate (VitA+C)\u2010augmented injectable platelet\u2010rich fibrin (i\u2010PRF) versus i\u2010PRF alone with a modified minimally invasive surgical technique (M\u2010MIST) in periodontal intraosseous defects in patients with stage III periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This parallel group, two\u2010arm, triple\u2010blinded, randomized controlled trial included patients with stage III grade B periodontitis (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a028) randomly allocated to the test (VitA+C\/i\u2010PRF+M\u2010MIST;\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a014) or the control (i\u2010PRF+M\u2010MIST;\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a014) group. The changes in radiographic linear defect depth (RLDD) (primary outcome), radiographic bone fill (RBF), and radiographic bone density (RBD) were recorded at baseline, 6, and 9 months. Clinical attachment level (CAL), probing depth (PD), gingival margin level (GML), plaque index (PI), and gingival index (GI; secondary outcomes) were recorded at baseline, 3 6, and 9 months. The in vitro release kinetics of VitA and VitC from the i\u2010PRF were characterized over 7 days using high\u2010performance liquid chromatography (HLPC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      VitA+C\/i\u2010PRF+M\u2010MIST demonstrated a significantly higher RLDD\u2010reduction at 6 months and a higher RBF percentage at 6 and 9 months compared with i\u2010PRF+M\u2010MIST (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05), with no intergroup differences regarding RBD. Both groups independently demonstrated significant improvements in CAL, PD, GML, RLDD, and BDA over time (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). Significantly higher CAL\u2010gain and PD\u2010reduction were evident in the VitA+C\/i\u2010PRF+M\u2010MIST group at 9 months (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>I\u2010PRF with M\u2010MIST significantly enhance periodontal clinical and radiographic parameters over time. Conjoint vitamin A\/C augmentation of i\u2010PRF at the described concentration results in significantly greater improvement in radiographic and clinical parameters of intraosseous defects compared with i\u2010PRF alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      This study was registered in the US National Institutes of Health Clinical Trials Registry (NCT05499598;\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/\">https:\/\/www.clinicaltrials.gov\/<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  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