{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:39:51Z","timestamp":1791088791084,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,14]],"date-time":"2024-12-14T00:00:00Z","timestamp":1734134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cDunarea de Jos\u201d University, Galati, Romania"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: This study aimed to evaluate the role of A-PRF (advanced platelet-rich fibrin) in the enhancement of wound healing and protecting the periodontal health of mandibular second molars after the extraction of mandibular third molars. Additionally, the study assessed the levels of pro-inflammatory cytokines in the gingival crevicular fluid (GCF) of mandibular second molars as markers of inflammation. Materials and Methods: Twenty-five systemically healthy adult patients with bilateral removal of impacted mandibular third molars were included. Each patient received A-PRF in one extraction site, while the contralateral site served as a control. Periodontal parameters of the adjacent second molar, including probing depth (PD) and clinical attachment level (CAL), were measured in distal\u2013vestibular (DV) and distal\u2013lingual (DL) sites. Pain, swelling, and overall healing were subjectively evaluated. Levels of tumor necrosis factor-alpha (TNF-\u03b1), interleukin 1 beta (IL-1\u03b2), and interleukin 6 (IL-6) in the GCF were analyzed. Evaluations occurred at baseline and three months post-surgery. Results: A-PRF significantly improved PD (from 4.69 \u00b1 0.61 mm to 3.85 \u00b1 0.34 mm in DV, and from 4.71 \u00b1 0.65 mm to 3.79 \u00b1 0.27 mm in DL, respectively) and CAL (from 2.41 \u00b1 0.25 mm to 1.82 \u00b1 0.21 mm in DV, and from 2.40 \u00b1 0.36 mm to 1.75 \u00b1 0.19 mm in DL, respectively) of the adjacent second molar, compared to control sites, three months post-surgery. Pain and swelling scores were notably lower on the 7th postoperative day in the A-PRF group. A-PRF also reduced pro-inflammatory cytokines in GCF, significantly more than in control sites, at three months post-surgery. Conclusions: A-PRF enhances the periodontal and inflammatory status of adjacent teeth and wound healing after the extraction of mandibular third molars.<\/jats:p>","DOI":"10.3390\/medicina60122062","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T06:48:39Z","timestamp":1734331719000},"page":"2062","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Clinical and Molecular Impact of Advanced Platelet-Rich Fibrin on Pain, Swelling, and Distal Periodontal Status of Mandibular Second Molars After Mandibular Third-Molar Extraction"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2726-137X","authenticated-orcid":false,"given":"Ada","family":"Stefanescu","sequence":"first","affiliation":[{"name":"Faculty of Dental Medicine, \u201cDunarea de Jos\u201d University, Al. I. Cuza Street 35, 800216 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7779-8987","authenticated-orcid":false,"given":"Irina-Georgeta","family":"Sufaru","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, Grigore T. Popa University of Medicine and Pharmacy, Universitatii Street 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iulia","family":"Chiscop","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, \u201cDunarea de Jos\u201d University, Al. I. Cuza Street 35, 800216 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6872-8616","authenticated-orcid":false,"given":"Fabian Cezar","family":"Lupu","sequence":"additional","affiliation":[{"name":"Mechanical Engineering, Mechatronics and Robotics Department, \u201cGheorghe Asachi\u201d Technical University of Iasi, 700050 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Martu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Universitatii Street 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Oprisan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, Universitatii Street 16, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamel","family":"Earar","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, \u201cDunarea de Jos\u201d University, Al. I. Cuza Street 35, 800216 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1007\/s11136-018-1889-1","article-title":"Third molar removal and its impact on quality of life: Systematic review and meta-analysis","volume":"27","author":"Miranda","year":"2018","journal-title":"Qual. Life Res."},{"key":"ref_2","first-page":"CD004345","article-title":"Surgical techniques for the removal of mandibular wisdom teeth","volume":"7","author":"Bailey","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2780","DOI":"10.6061\/clinics\/2021\/e2780","article-title":"Preemptive use of intravenous ibuprofen to reduce postoperative pain after lower third molar surgery: A systematic review of randomized controlled trials","volume":"76","author":"Silva","year":"2021","journal-title":"Clinics"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pardo, A., Signoriello, A., Corr\u00e0, M., Favero, V., De\u2019Manzoni Casarola, R., and Albanese, M. (2023). Six-Month Soft Tissues Healing after Lower Third Molar Extraction: Comparison of Two Different Access Flaps. J. Clin. Med., 12.","DOI":"10.3390\/jcm12227017"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Caymaz, M.G., and Buhara, O. (2021). Association of Oral Hygiene and Periodontal Health with Third Molar Pericoronitis: A Cross-Sectional Study. Biomed Res. Int., 2021.","DOI":"10.1155\/2021\/6664434"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Poszytek, D., and G\u00f3rski, B. (2023). Relationship between the Status of Third Molars and the Occurrence of Dental and Periodontal Lesions in Adjacent Second Molars in the Polish Population: A Radiological Retrospective Observational Study. J. Clin. Med., 13.","DOI":"10.3390\/jcm13010020"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/S1079-2104(98)90029-4","article-title":"Platelet-rich plasma: Growth factor enhancement for bone grafts","volume":"85","author":"Marx","year":"1998","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1563\/AAID-JOI-D-10-00155","article-title":"Optimizing platelet-rich plasma gel formation by varying time and gravitational forces during centrifugation","volume":"39","author":"Jo","year":"2013","journal-title":"J. Oral Implantol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1080\/14712598.2021.1945030","article-title":"Progress in the use of plasma rich in growth factors in ophthalmology: From ocular surface to ocular fundus","volume":"22","author":"Anitua","year":"2022","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1563\/aaid-joi-D-14-00138","article-title":"Advanced platelet-rich fibrin: A new concept for cell-based tissue engineering by means of inflammatory cells","volume":"40","author":"Ghanaati","year":"2014","journal-title":"J. Oral Implantol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/jre.12714","article-title":"Effects of L-PRF and A-PRF+ on periodontal fibroblasts in in vitro wound healing experiments","volume":"55","author":"Pitzurra","year":"2020","journal-title":"J. Periodontal Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s00068-017-0785-7","article-title":"Reduction of relative centrifugal forces increases growth factor release within solid platelet-rich-fibrin (PRF)-based matrices: A proof of concept of LSCC (low speed centrifugation concept)","volume":"45","author":"Kubesch","year":"2019","journal-title":"Eur. J. Trauma Emerg. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1080\/09537104.2017.1293812","article-title":"The impact of the centrifuge characteristics and centrifugation protocols on the cells, growth factors, and fibrin architecture of a leukocyte- and platelet-rich fibrin (L-PRF) clot and membrane","volume":"29","author":"Pinto","year":"2018","journal-title":"Platelets"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s40778-016-0034-8","article-title":"Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and Regeneration","volume":"2","author":"Masoudi","year":"2016","journal-title":"Curr. Stem Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.joms.2017.06.004","article-title":"Use of Leukocyte- and Platelet-Rich Fibrin in the Treatment of Medication-Related Osteonecrosis of the Jaws","volume":"76","author":"Maluf","year":"2018","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2147\/TCRM.S298147","article-title":"Effects of Impacted Lower Third Molar Extraction on Periodontal Tissue of the Adjacent Second Molar","volume":"17","author":"Zhang","year":"2021","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"61","DOI":"10.4067\/S0718-381X2017000100009","article-title":"Evaluation of 1211 third molars positions according to the classification of Winter, Pell & Gregory","volume":"11","author":"Primo","year":"2017","journal-title":"Int. J. Odontostomat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1902\/jop.2005.76.10.1729","article-title":"Factors affecting the outcomes of coronally advanced flap root coverage procedure","volume":"76","author":"Huang","year":"2005","journal-title":"J. Periodontol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1097\/MRR.0b013e3282fc0f93","article-title":"Reliability and validity of the visual analogue scale for disability in patients with chronic musculoskeletal pain","volume":"31","author":"Boonstra","year":"2008","journal-title":"Int. J. Rehabil. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3470","DOI":"10.1002\/sim.3634","article-title":"The design and analysis of split-mouth studies: What statisticians and clinicians should know","volume":"28","author":"Lesaffre","year":"2009","journal-title":"Stat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e230","DOI":"10.18295\/squmj.2019.19.03.009","article-title":"Complications of Third Molar Extraction: A retrospective study from a tertiary healthcare centre in Oman","volume":"19","author":"Sayed","year":"2019","journal-title":"Sultan Qaboos Univ. Med. J."},{"key":"ref_22","first-page":"E520","article-title":"Variations of interleukin-6 after surgical removal of lower third molars","volume":"11","year":"2006","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Castagna, V., Pardo, A., Lanaro, L., Signoriello, A., and Albanese, M. (2022). Periodontal Healing after Lower Third Molars Extraction: A Clinical Evaluation of Different Flap Designs. Healthcare, 10.","DOI":"10.3390\/healthcare10081587"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"154","DOI":"10.22146\/majkedgiind.37414","article-title":"Effect of advanced platelet-rich fibrin applications on periodontal regeneration in infrabony pocket treatment","volume":"4","author":"Suwondo","year":"2018","journal-title":"Maj. Kedokt. Gigi Indones."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"217","DOI":"10.4103\/ccd.ccd_7_19","article-title":"Different regenerative responses of two platelet concentrates in the treatment of human periodontal infrabony defects: A clinico-radiographic study","volume":"11","author":"Upadhyay","year":"2020","journal-title":"Contemp. Clin. Dent."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pitzurra, L., Vasdravellis, D., Rosema, N.A.M., Bizzarro, S., and Loos, B.G. (2023). Effects of Advanced Platelet Rich Fibrin (A-PRF+), Enamel Matrix Derivative (EMD) and Open Flap Debridement on clinical and wound healing parameters in molar furcation sites: A case series from a RCT study. Front. Dent. Med., 4.","DOI":"10.3389\/fdmed.2023.1223217"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.5005\/jp-journals-10024-2666","article-title":"Effect of Advanced Platelet-rich Fibrin on Wound Healing after Third Molar Extraction: A Split-mouth Randomized Double-blind Study","volume":"20","author":"Zahid","year":"2019","journal-title":"J. Contemp. Dent. Pract."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.joms.2014.11.013","article-title":"Evaluation of treatment outcome after impacted mandibular third molar surgery with the use of autologous platelet-rich fibrin: A randomized controlled clinical study","volume":"73","author":"Kumar","year":"2015","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1016\/j.joms.2017.05.034","article-title":"Local Application of Platelet-Rich Fibrin During Lower Third Molar Extraction Improves Treatment Outcomes","volume":"75","author":"He","year":"2017","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s10006-022-01075-w","article-title":"Advanced platelet-rich-fibrin (A-PRF+) has no additional effect on the healing of post-extraction sockets of upper third molars. A split mouth randomized clinical trial","volume":"27","author":"Pereira","year":"2023","journal-title":"Oral Maxillofac. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jormas.2020.04.008","article-title":"Advanced-PRF: Clinical evaluation in impacted mandibular third molar sockets","volume":"122","author":"Gupta","year":"2021","journal-title":"J. Stomatol. Oral Maxillofac. Surg."},{"key":"ref_32","first-page":"97","article-title":"Study regarding the IL1-A and IL1-B levels in gingival crevicular fluid in patients with chronic periodontitis and osteoporosis","volume":"8","author":"Ursarescu","year":"2016","journal-title":"Rom. J. Oral Rehabil."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/s41590-020-0741-2","article-title":"The mesenchymal context in inflammation, immunity and cancer","volume":"21","author":"Koliaraki","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3261","DOI":"10.1038\/s41467-018-05800-6","article-title":"Resolution of chronic inflammatory disease: Universal and tissue-specific concepts","volume":"9","author":"Schett","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kargarpour, Z., Nasirzade, J., Panahipour, L., Miron, R.J., and Gruber, R. (2021). Platelet-Rich Fibrin Decreases the Inflammatory Response of Mesenchymal Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111333"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40729-016-0052-4","article-title":"Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF)","volume":"2","author":"Masuki","year":"2016","journal-title":"Int. J. Implant. Dent."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.trsl.2021.05.001","article-title":"Diabetic wound healing in soft and hard oral tissues","volume":"236","author":"Ko","year":"2021","journal-title":"Transl. Res."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/12\/2062\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:55:37Z","timestamp":1760115337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/12\/2062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,14]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["medicina60122062"],"URL":"https:\/\/doi.org\/10.3390\/medicina60122062","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,14]]}}}