{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:13:52Z","timestamp":1778742832378,"version":"3.51.4"},"reference-count":23,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"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":["Clin Adv Periodontics"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n The basic fibroblast growth factor (FGF\u20102) drug formulation, human recombinant FGF\u20102 and hydroxypropylcellulose, developed in Japan, has been confirmed to induce effective periodontal regeneration. However, in cases with minimal residual bone walls or vertical bone defects fused with furcation involvement, FGF\u20102 alone does not achieve ideal periodontal regeneration. Therefore, it is necessary to attempt to use FGF\u20102 in combination with bone grafting materials. Beta\u2010tricalcium phosphate (\u03b2\u2010TCP) has been developed as a bone graft material and has a long history of use. Its advantage lies in its ability to be absorbed early during wound healing and replaced by bone. In this study, we examined the effectiveness of the smallest particle\u2010sized \u03b2\u2010TCP in combination with FGF\u20102 for the severe deep and wide combined one\u2010 to three\u2010walled bone defect and Class II furcation involvement.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n FGF\u20102 with \u03b2\u2010TCP was applied to an intrabony defect and Class II furcation involvement of a 40\u2010year\u2010old female patient with aggressive periodontitis (stage III and grade C). As far as possible, the incision line was not placed over the bone defect. The interdental papillae were dissected using a simplified papilla preservation technique. Full\u2010thickness buccal and lingual mucoperiosteal flaps were reflected. After thorough debridement, FGF\u20102 with small\u2010particle \u03b2\u2010TCP was applied to the bone defects.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Radiographic examination at 1 month demonstrated early radiographic bone fill. Over time, layered bone\u2011like radiopacity was observed extending from the remaining bone wall. In addition, by 6 months, a distinctive protruding bone\u2011like radiopacity arising from the alveolar crest of the adjacent tooth was observed extending toward the defect. At 41 months, substantial radiographic bone fill was evident. While Class II furcation involvement showed overall improvement, some sites exhibited only limited reparative changes.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The combination of FGF\u20102 and small\u2011particle \u03b2\u2011TCP may promote periodontal regeneration in severe intrabony and furcation defects, although definitive confirmation of complete regeneration requires further investigation.<\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n The optimal \u03b2\u2011TCP particle size for use with FGF\u20112 remains unclear. In this study, the smallest available \u03b2\u2011TCP granules were incorporated into the hydroxypropylcellulose\u2011based FGF\u20112 formulation, functioning as a dispersed, space\u2011maintaining scaffold.<\/jats:p>\n <\/jats:list-item>\n \n Periodontal tissue regeneration using the smallest and rapidly absorbable \u03b2\u2011TCP granules in combination with FGF\u20112 demonstrated favorable healing in complex, deep vertical bone defects and Class II furcation lesions.<\/jats:p>\n <\/jats:list-item>\n \n Although larger \u03b2\u2011TCP granules are generally considered advantageous because their greater porosity allows easier migration of undifferentiated mesenchymal cells from existing bone walls or periodontal ligament remnants, the small\u2011particle \u03b2\u2011TCP used with the FGF\u20112 formulation behaved differently. When mixed with FGF\u20112, the granules are suspended within the base carrier, creating a highly porous structure that facilitates mesenchymal cell migration.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Plain language summary<\/jats:title>\n Severe periodontal disease often destroys the bone supporting teeth, creating complex defects specifically between tooth roots that are notoriously difficult to treat and often lead to tooth extraction. The periodontal tissue regenerative drug using FGF\u20102 (basic fibroblast growth factor), one of the cell growth factors, helps promote the formation of new blood vessels and periodontal tissues, but it is often insufficient on its own for large or complex bone defects. In this case study, the combination of the gel\u2011based FGF\u20112 formulation with small granules of beta\u2011tricalcium phosphate (\u03b2\u2011TCP) supported periodontal tissue regenerative healing. The key to this favorable healing response appears to be the combination itself: although the small\u2011particle \u03b2\u2011TCP remains dispersed within the FGF\u20112 gel rather than forming a densely packed structure, this structure creates necessary space. This spacing likely allows the patient's own repair cells to migrate easily from the surrounding bone into the defect, facilitating effective natural healing and saving the tooth.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cap.70074","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:02:09Z","timestamp":1778742129000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fibroblast growth factor\u20102 with beta\u2010tricalcium phosphate for the deep and wide intrabony defect reaching the apex and Class II furcation involvement of a mandibular molar"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5658-8681","authenticated-orcid":false,"given":"Shinichi","family":"Takayama","sequence":"first","affiliation":[{"name":"Takayama Dental Clinic Shiga Japan"},{"name":"Department of Periodontology and Regenerative Dentistry, Graduate School of Dentistry The University of Osaka Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoaki","family":"Iwayama","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Regenerative Dentistry, Graduate School of Dentistry The University of Osaka Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0331-3478","authenticated-orcid":false,"given":"Masahide","family":"Takedachi","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Regenerative Dentistry, Graduate School of Dentistry The University of Osaka Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/j.1600-0765.1997.tb00577.x","article-title":"Effects of basic fibroblast growth factor on human periodontal ligament cells","volume":"32","author":"Takayama S","year":"1997","journal-title":"J Periodontal Res"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1902\/jop.2002.73.12.1467","article-title":"Effects of basic fibroblast growth factor on human gingival epithelial cells","volume":"73","author":"Takayama S","year":"2002","journal-title":"J Periodontol"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0131870","article-title":"Action mechanism of fibroblast growth factor\u20102 (FGF\u20102) in the promotion of periodontal regeneration in beagle dogs","volume":"10","author":"Nagayasu\u2010Tanaka T","year":"2015","journal-title":"PLoS One"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1902\/cap.2012.120014","article-title":"Successful case of periodontal tissue repair with fibroblast growth factor\u20102: long\u2010term follow\u2010up and comparison to enamel matrix derivative","volume":"3","author":"Ninomiya M","year":"2013","journal-title":"Clin Adv Periodontics"},{"issue":"2","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/cap.10127","article-title":"Efficacy of FGF\u20102 in periodontal regeneration in a case of severe intrabony defect and furcation involvement with 15\u2010month follow\u2010up","volume":"11","author":"Takayama SI","year":"2021","journal-title":"Clin Adv Periodontics"},{"issue":"5","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1177\/0022034516632497","article-title":"A randomized clinical trial evaluating rh\u2010FGF\u20102\/\u03b2\u2010TCP in periodontal defects","volume":"95","author":"Cochran DL","year":"2016","journal-title":"J Dent Res"},{"key":"e_1_2_10_8_1","first-page":"1","article-title":"Saving a hopeless tooth with a four\u2010wall bone defect: a case report","volume":"23","author":"Nagahara T","year":"2024","journal-title":"Clin Adv Periodontics"},{"issue":"6","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/jcpe.13619","article-title":"Comparison of periodontal wound healing\/regeneration by recombinant human fibroblast growth factor\u20102 combined with \u03b2\u2010tricalcium phosphate, carbonate apatite, or deproteinized bovine bone mineral in a canine one\u2010wall intra\u2010bony defect model","volume":"49","author":"Shirakata Y","year":"2022","journal-title":"J Clin Periodontol"},{"issue":"7","key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"500","DOI":"10.5005\/jp-journals-10024-3534","article-title":"Evaluating and comparing the effectiveness of Nano\u2010HA and HA + \u03b2\u2010TCP with A\u2010PRF clinically and radiographically in the treatment of human infrabony defects","volume":"24","author":"Aishwarya R","year":"2023","journal-title":"J Contemp Dent Pract"},{"issue":"6","key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"721","DOI":"10.4012\/dmj.2010-033","article-title":"Effect of \u03b2 tricalcium phosphate particle size on recombinant human platelet\u2010derived growth factor\u2010BB\u2010induced regeneration of periodontal tissue in dog","volume":"29","author":"Irokawa D","year":"2010","journal-title":"Dent Mater J"},{"issue":"4","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1016\/j.actbio.2009.10.023","article-title":"Comparative study on bone regeneration by synthetic octacalcium phosphate with various granule sizes","volume":"6","author":"Murakami Y","year":"2010","journal-title":"Acta Biomater"},{"issue":"11","key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1902\/jop.2011.110023","article-title":"Enhanced \u03b2\u2010tricalcium phosphate blended clot adhesion to EDTA biomodulated periodontally affected root surfaces: in vivo scanning electron microscopy evaluation","volume":"82","author":"Gamal AY","year":"2011","journal-title":"J Periodontol"},{"issue":"12","key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1902\/jop.2001.72.12.1702","article-title":"The simplified papilla preservation flap in the regenerative treatment of deep intrabony defects: clinical outcomes and postoperative morbidity","volume":"72","author":"Cortellini P","year":"2001","journal-title":"J Periodontol"},{"key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1600-0765.1999.tb02277.x","article-title":"Regeneration of periodontal tissues by basic fibroblast growth factor","volume":"34","author":"Murakami S","year":"1999","journal-title":"J Periodont Res"},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1177\/00220345010800121001","article-title":"Periodontal regeneration by FGF\u20102 (bFGF) in primate models","volume":"80","author":"Takayama S","year":"2001","journal-title":"J Dent Res"},{"issue":"1","key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1034\/j.1600-0765.2003.00640.x","article-title":"Recombinant human basic fibroblast growth factor (bFGF) stimulates periodontal regeneration in class II furcation defects created in beagle dogs","volume":"38","author":"Murakami S","year":"2003","journal-title":"J Periodontal Res"},{"key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1177\/0022034510384616","article-title":"FGF\u20102 stimulates periodontal regeneration: results of a multi\u2010center randomized clinical trial","volume":"90","author":"Kitamura M","year":"2011","journal-title":"J Dent Res"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1002\/jbmr.2738","article-title":"Randomized placebo\u2010controlled and controlled non\u2010inferiority phase III trials comparing trafermin, a recombinant human fibroblast growth factor 2, and enamel matrix derivative in periodontal regeneration in intrabony defects","volume":"31","author":"Kitamura M","year":"2016","journal-title":"J Bone Miner Res"},{"issue":"7","key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/JPER.20-0481","article-title":"Impact of adjunctive procedures on recombinant human fibroblast growth factor\u20102\u2010mediated periodontal regeneration therapy: a retrospective study","volume":"92","author":"Nakayama Y","year":"2021","journal-title":"J Periodontol"},{"issue":"1","key":"e_1_2_10_21_1","first-page":"91","article-title":"Periodontal surgery using rhFGF\u20102 with deproteinized bovine bone mineral or rhFGF\u20102 alone: 2\u2010year follow\u2010up of a randomized controlled trial","volume":"48","author":"Aoki H","year":"2020","journal-title":"J Clin Periodontol"},{"key":"e_1_2_10_22_1","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.reth.2022.06.001","article-title":"An exploratory clinical trial to evaluate the safety and efficacy of combination therapy of REGROTH\u00ae and Cytrans\u00ae granules for severe periodontitis with intrabony defects","volume":"21","author":"Kitamura M","year":"2022","journal-title":"Regen Ther"},{"key":"e_1_2_10_23_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.bbrc.2010.11.032","article-title":"Effects of concomitant use of fibroblast growth factor (FGF)\u20102 with beta\u2010tricalcium phosphate (\u03b2\u2010TCP) on the beagle dog 1\u2010wall periodontal defect model","volume":"403","author":"Anzai J","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3390\/ma15020655","article-title":"The application of beta\u2010tricalcium phosphate in implant dentistry: a systematic evaluation of clinical studies","volume":"15","author":"Roca\u2010Millan E","year":"2022","journal-title":"Materials (Basel)"}],"container-title":["Clinical Advances in Periodontics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cap.70074","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cap.70074","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cap.70074","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:02:12Z","timestamp":1778742132000},"score":1,"resource":{"primary":{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/10.1002\/cap.70074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":23,"alternative-id":["10.1002\/cap.70074"],"URL":"https:\/\/doi.org\/10.1002\/cap.70074","archive":["Portico"],"relation":{},"ISSN":["2573-8046","2163-0097"],"issn-type":[{"value":"2573-8046","type":"print"},{"value":"2163-0097","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]},"assertion":[{"value":"2025-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cap.70074"}}