GROWTH FACTOR LOADED BIOMATERIALS FOR PERIODONTAL TISSUE REGENERATION: A SYSTEMATIC REVIEW OF PRECLINICAL STUDIES ON ANIMAL MODELS
Keywords:
biomaterials, tissue regeneration, growth factor, scaffold
Abstract
Over the past decade, numerous biomaterials have been developed for periodontal tissue regeneration. The aim of this systematic review was to evaluate the application of growth factor–loaded biomaterials for the regeneration of the periodontal complex in preclinical animal studies. The review was conducted in accordance with PRISMA guidelines. A computerized search of SCOPUS, PubMed, and Web of Science was performed, including English-language articles published between 2015 and 2025. From an initial yield of 173 articles, 12 studies met the inclusion criteria after screening titles, abstracts, and full texts. All included studies demonstrated successful regeneration of the three key periodontal tissues – alveolar bone, cementum, and periodontal ligament – in animal models. With one exception, the studies were short-term, with histological evaluations performed up to 12 weeks. The biomaterials used ranged from relatively simple systems to complex multiphasic scaffolds. Six studies employed biomaterials loaded with a single growth factor, while the remaining six used combinations of two or more growth factors. Fibroblast growth factor (FGF) was the most frequently used growth factor, followed by bone morphogenetic proteins (BMPs). The findings indicate that scaffolds are the most commonly used biomaterial platform, and that FGF- and BMP-based systems are predominant. Notably, simpler biomaterial and growth factor combinations often achieve regenerative outcomes comparable to more complex scaffold designs but remain robust, especially when the goal is functional regeneration.
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2. H.N. Woo, Y.J. Cho, S. Tarafder, C.H. Lee, The recent advances in scaffolds for integrated periodontal regeneration, Bioact Mater, 6 (2021) 10, 3328-3342, doi: 10.1016/j.bioactmat.2021.03.012
3. Y. Liang, X. Luan, X. Liu, Recent advances in periodontal regeneration: A biomaterial perspective, Bioact Mater, 5 (2020) 2, 297-308, doi: 10.1016/j.bioactmat.2020.02.012
4. K. Hynes, D. Menicanin, J. Han, V. Marino, K. Mrozik, S. Gronthos, P.M. Bartold, Mesenchymal stem cells from iPS cells facilitate periodontal regeneration, J Dent Res, 92 (2013) 9, 833-9, doi: 10.1177/0022034513498258
5. S.S. Ghosh, P. Gopinath, A. Ramesh. Adenoviral vectors: a promising tool for gene therapy, Appl Biochem Biotechnol, 133 (2006) 1, 9-29, doi: 10.1385/abab:133:1:9. PMID: 16622281.
6. P. C. Chang, J. A. Cirelli, Q. Jin, Y. J. Seol, J. V. Sugai, N. J. D'Silva, T. E. Danciu, L. A. Chandler, B. A. Sosnowski, W. V. Giannobile, Adenovirus encoding human platelet-derived growth factor-B delivered to alveolar bone defects exhibits safety and biodistribution profiles favorable for clinical use, Human Gene Therapy 20 (2008), 486–496.
7. P. Aprile, D. Letourneur, T. Simon-Yarza, Membranes for Guided Bone Regeneration: A Road from Bench to Bedside, Adv Healthc Mater, 9 (2020) 19, 2000707, doi: 10.1002/adhm.202000707
8. Y. Zhang, R. J. Miron, S. Li, B. Shi, A. Sculean, X. Cheng, Novel MesoPorous BioGlass/silk scaffold containing adPDGF-B and adBMP7 for the repair of periodontal defects in beagle dogs, J Clin Periodontol, 42 (2015) 3, 262-71, doi: 10.1111/jcpe.12364
9. K. Matsuse, Y. Hashimoto, S. Kakinoki, T. Yamaoka, S. Morita, Periodontal regeneration induced by porous alpha-tricalcium phosphate with immobilized basic fibroblast growth factor in a canine model of 2-wall periodontal defects, Med Mol Morphol, 51 (2018) 1, 48–56, doi:10.1007/s00795-017-0172-9. PMID: 29079935
10. T. Momose, H. Miyaji, A. Kato, K. Ogawa, T. Yoshida, E. Nishida, S. Murakami, Y. Kosen, T. Sugaya, M. Kawanami, Collagen Hydrogel Scaffold and Fibroblast Growth Factor-2 Accelerate Periodontal Healing of Class II Furcation Defects in Dog. Open Dent J, 10 (2016), 347–359, doi:10.2174/1874210601610010347, PMID: 27583044, PMCID: PMC4974830
11. T. Ding, J. Li, X. Zhang, L. Du, Y. Li, D. Li, B. Kong, S. Ge, Super-assembled core/shell fibrous frameworks with dual growth factors for in situ cementum-ligament-bone complex regeneration. Biomater Sci, 8 (2020) 9, 2459–2471, doi:10.1039/d0bm00102c, PMID: 32191780
12. S. Sowmya, U. Mony, P. Jayachandran, S. Reshma, R.A. Kumar, H. Arzate, S.V. Nair, R. Jayakumar, Tri-Layered Nanocomposite Hydrogel Scaffold for the Concurrent Regeneration of Cementum, Periodontal Ligament, and Alveolar Bone. Adv Healthc Mater, 6 (2017) 7, doi:10.1002/adhm.201601251, PMID: 28128898
13. K.H. Chien, Y.L. Chang, M.L. Wang, J.H. Chuang, Y.C. Yang, M.C. Tai, C.Y. Wang, Y.Y. Liu, H.Y. Li, J.T. Chen, S.Y. Kao, H.L. Chen, W.L. Lo, Promoting Pluripotent Induced Stem Cell-driven Biomineralization and Periodontal Regeneration in Rats with Maxillary-Molar Defects using Injectable BMP-6 Hydrogel, Sci Rep, 8 (2018) 1, doi:10.1038/s41598-017-18415-6.
14. M. Hua, J. Xiang, J. Wu, W. Yang, Growth factors-encapsulated triphasic scaffolds of electrospun polylactic acid–polycaprolactone (PLA-PCL) nanofibrous mats combined with directionally freeze-dried chitosan hydrogel for periodontal tissue regeneration, Mater Adv, 4 (2023), 4798–4811, doi:10.1039/D3MA00465A.
15. M. Yu, D. Luo, J. Qiao, J. Guo, D. He, S. Jin, L. Tang, Y. Wang, X. Shi, J. Mao, S. Cui, Y. Fu, Z. Li, D. Liu, T. Zhang, C. Zhang, Z. Li, Y. Zhou, Y. Liu, A hierarchical bilayer architecture for complex tissue regeneration, Bioact Mater, 16 (2021) 10, 93–106, doi:10.1016/j.bioactmat.2021.08.024, PMID: 34901532, PMCID, PMC8636921
16. J. Anzai, T. Nagayasu-Tanaka, A. Terashima, T. Asano, S. Yamada, T. Nozaki, M. Kitamura, S. Murakami, Long-term Observation of Regenerated Periodontium Induced by FGF-2 in the Beagle Dog 2-Wall Periodontal Defect Model, PLoS One, 11 (3026) 7, e0158485, doi:10.1371/journal.pone.0158485, PMID: 27391131, PMCID: PMC4938520
17. T. Nagayasu-Tanaka, J. Anzai, S. Takaki, N. Shiraishi, A. Terashima, T. Asano, T. Nozaki, M. Kitamura, S. Murakami, Action Mechanism of Fibroblast Growth Factor-2 (FGF-2) in the Promotion of Periodontal Regeneration in Beagle Dogs, PLoS One, 10 (2015) 6, e0131870, doi:10.1371/journal.pone.0131870, PMID: 26120833, PMCID: PMC4488280
18. R.Y. Huang, W.C. Tai, M.H. Ho, P.C. Chang, Combination of a biomolecule-aided biphasic cryogel scaffold with a barrier membrane adhering PDGF encapsulated nanofibers to promote periodontal regeneration. J Periodontal Res. 2020 Feb 24;55(4):529–538.
19. M. Kiyota, T. Iwata, N. Hasegawa, S. Sasaki, Y. Taniguchi, Y. Hamamoto, S. Matsuda, K. Ouhara, K. Takeda, T. Fujita, H. Kurihara, H. Kawaguchi, N. Mizuno, Periodontal tissue regeneration with cementogenesis after application of brain-derived neurotrophic factor in 3-wall inflamed intra-bony defect, J Periodontal Res, 59 (2024) 3, 530–541, doi:10.1111/jre.13244, PMID: 38501357
20. F. Mukasheva, L. Adilova, A. Dyussenbinov, B. Yernaimanova, M. Abilev, D. Akilbekova, Optimizing scaffold pore size for tissue engineering: insights across various tissue types, Front Bioeng Biotechnol, 12 (2024), 1444986, doi:10.3389/fbioe.2024.1444986, PMID: 39600888, PMC11588461.
21. Y. Ma, X. Wang, T. Su, F. Lu, Q. Chang, J. Gao, Recent Advances in Macroporous Hydrogels for Cell Behavior and Tissue Engineering, Gels, 8 (2022) 10, 606, doi:10.3390/gels8100606, PMID: 36286107, PMCID: PMC9601978.
22. E. Mijiritsky, H.D. Assaf, O. Peleg, M. Shacham, L. Cerroni, L. Mangani, Use of PRP, PRF and CGF in Periodontal Regeneration and Facial Rejuvenation—A Narrative Review, Biology (Basel), 10 (2021) 4, 317, doi:10.3390/biology10040317, PMID: 33920204, PMCID: PMC8070566
Published
2026-04-09
How to Cite
1.
Urška Škof, Schara R. GROWTH FACTOR LOADED BIOMATERIALS FOR PERIODONTAL TISSUE REGENERATION: A SYSTEMATIC REVIEW OF PRECLINICAL STUDIES ON ANIMAL MODELS. MatTech [Internet]. 2026Apr.9 [cited 2026Jul.16];60(2):283–291. Available from: https://mater-tehnol.si/index.php/MatTech/article/view/1634
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