{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T12:25:05Z","timestamp":1767615905377,"version":"3.48.0"},"reference-count":24,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Dentistry, Universitas Indonesia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Periodontal disease, characterized by progressive destruction of tooth-supporting tissues, often results in substantial alveolar bone loss, necessitating regenerative interventions such as guided bone regeneration (GBR). Insulin-like growth factor 2 (IGF-2) has emerged as a promising biomolecule for periodontal regeneration because of its osteogenic and immunomodulatory properties. Materials and Methods: A comprehensive literature search was conducted across five electronic databases (Scopus, ScienceDirect, PubMed, Wiley, and EBSCO). Studies examining the use of IGF-2 in periodontal or alveolar bone regeneration, including randomized controlled trials, animal studies, and in vitro experiments, were included. Results: Three studies met the inclusion criteria. In vitro, IGF-2 was associated with enhanced osteogenic differentiation and mineralization of mesenchymal stem cells, along with upregulation of key osteogenic markers. In animal models, IGF-2 treatment was associated with increased osteogenesis, greater bone volume, and a shift in macrophage polarization toward a less inflammatory phenotype. However, heterogeneity in study designs, protocols, and outcome measures limited direct comparisons. Conclusions: In vitro, IGF-2 was associated with enhanced osteogenic differentiation and mineralization of mesenchymal stem cells, accompanied by upregulation of key osteogenic markers. In animal models, IGF-2 treatment was associated with increased osteogenesis, greater bone volume, and a shift in macrophage polarization toward a less inflammatory phenotype.<\/jats:p>","DOI":"10.3390\/medicina62010114","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T10:03:48Z","timestamp":1767607428000},"page":"114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Insulin-like Growth Factor 2 (IGF-2) in Periodontal Regeneration: A Systematic Review"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-0409","authenticated-orcid":false,"given":"Karina Natalie","family":"Kuntjoro","sequence":"first","affiliation":[{"name":"Periodontology Specialist Program, Faculty of Dentistry, Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4660-3045","authenticated-orcid":false,"given":"Yuniarti","family":"Soeroso","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Faculty of Dentistry, Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8767-0941","authenticated-orcid":false,"given":"Fatimah Maria","family":"Tadjoedin","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Faculty of Dentistry, Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5495-4625","authenticated-orcid":false,"given":"Nik Madihah Nik","family":"Azis","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3586-8788","authenticated-orcid":false,"given":"Nadhia Anindhita","family":"Harsas","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Faculty of Dentistry, Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"ref_1","unstructured":"Newman, M.G., Klokkevold, P.R., Elangovan, S., Kapila, Y., Carranza, F.A., and Takei, H. 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