Effect of Applying 1% Metformin on Guided Bone Regeneration Processes with Bovine-Derived Xenografts
Abstract
:1. Introduction
2. Materials and Methods
2.1. Formulation of the 1% Metformin Solution
2.2. Ethics Committee
2.3. Experimental Animals
2.4. Anesthesia and Surgical Protocol
2.5. Euthanasia and Specimen Preparation
2.6. Histomorphometric Analysis
2.7. Statistical Analysis
3. Results
3.1. New Bone Formation
3.2. Xenograft Integration
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Elgali, I.; Omar, O.; Dahlin, C.; Thomsen, P. Guided bone regeneration: Materials and biological mechanisms revisited. Eur. J. Oral Sci. 2017, 125, 315–337. [Google Scholar] [CrossRef] [PubMed]
- Urban, I.A.; Monje, A. Guided Bone Regeneration in Alveolar Bone Reconstruction. Oral Maxillofac. Surg. Clin. North Am. 2019, 31, 331–338. [Google Scholar] [CrossRef]
- Viteri-Agustin, I.; Brizuela-Velasco, A.; Lou-Bonafonte, J.M.; Jimenez-Garrudo, A.; Chavarri-Prado, D.; Perez-Pevida, E.; Benito-Garzon, L.; Gruber, R. The Impact of Compaction Force on Graft Consolidation in a Guided Bone Regeneration Model. Int. J. Oral Maxillofac. Implant. 2020, 35, 917–923. [Google Scholar] [CrossRef] [PubMed]
- Archunan, M.W.; Petronis, S. Bone Grafts in Trauma and Orthopaedics. Cureus 2021, 13, 17705. [Google Scholar] [CrossRef] [PubMed]
- Rezuc, A.; Saavedra, C.; Maass, R.; Poblete, C.; Nappe, C. Histological comparison of DBBM and platelet rich fibrin for guided bone regeneration in a rabbit model. J. Oral Biol. Craniofacial Res. 2020, 10, 287–293. [Google Scholar] [CrossRef]
- Sheikh, Z.; Hamdan, N.; Ikeda, Y.; Grynpas, M.; Ganss, B.; Glogauer, M. Natural graft tissues and synthetic biomaterials for periodontal and alveolar bone reconstructive applications: A review. Biomater. Res. 2017, 21, 9. [Google Scholar] [CrossRef]
- Artas, G.; Gul, M.; Acikan, I.; Kirtay, M.; Bozoglan, A.; Simsek, S.; Yaman, F.; Dundar, S. A comparison of different bone graft materials in peri-implant guided bone regeneration. Braz. Oral Res. 2018, 32, e59. [Google Scholar] [CrossRef]
- Kuchler, U.; dos Santos, G.M.; Heimel, P.; Stähli, A.; Strauss, F.J.; Tangl, S.; Gruber, R. DBBM shows no signs of resorption under inflammatory conditions. An experimental study in the mouse calvaria. Clin. Oral Implant. Res. 2020, 31, 10–17. [Google Scholar] [CrossRef]
- Lindhe, J.; Lang, N.P.; Karring, T. Clinical Periodontology and Implant Dentistry; Wiley: Hoboken, NJ, USA, 2008. [Google Scholar]
- Kloss, F.R.; Kämmerer, P.W.; Kloss-Brandstätter, A. First Clinical Case Report of a Xenograft–Allograft Combination for Alveolar Ridge Augmentation Using a Bovine Bone Substitute Material with Hyaluronate (Cerabone® Plus) Combined with Allogeneic Bone Granules (Maxgraft®). J. Clin. Med. 2023, 12, 6214. [Google Scholar] [CrossRef]
- Rakašević, D.; Šćepanović, M.; Mijailović, I.; Mišić, T.; Janjić, B.; Soldatović, I.; Marković, A. Reconstructive Peri-Implantitis Therapy by Using Bovine Bone Substitute with or without Hyaluronic Acid: A Randomized Clinical Controlled Pilot Study. J. Funct. Biomater. 2023, 14, 149. [Google Scholar] [CrossRef]
- Gillman, C.E.; Jayasuriya, A.C. FDA-approved bone grafts and bone graft substitute devices in bone regeneration. Mater. Sci. Eng. C 2021, 130, 112466. [Google Scholar] [CrossRef]
- Solakoglu, Ö.; Heydecke, G.; Amiri, N.; Anitua, E. The use of plasma rich in growth factors (PRGF) in guided tissue regeneration and guided bone regeneration. A review of histological, immunohistochemical, histomorphometrical, radiological and clinical results in humans. Ann. Anat. Anat. Anz. 2020, 231, 151528. [Google Scholar] [CrossRef] [PubMed]
- Śmieszek, A.; Tomaszewski, K.A.; Kornicka, K.; Marycz, K. Metformin Promotes Osteogenic Differentiation of Adipose-Derived Stromal Cells and Exerts Pro-Osteogenic Effect Stimulating Bone Regeneration. J. Clin. Med. 2018, 7, 482. [Google Scholar] [CrossRef]
- Wang, P.; Ma, T.; Guo, D.; Hu, K.; Shu, Y.; Xu, H.H.; Schneider, A. Metformin induces osteoblastic differentiation of human induced pluripotent stem cell-derived mesenchymal stem cells. J. Tissue Eng. Regen. Med. 2018, 12, 437–446. [Google Scholar] [CrossRef]
- Zhang, R.; Liang, Q.; Kang, W.; Ge, S. Metformin facilitates the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells in vitro. Cell Biol. Int. 2020, 44, 70–79. [Google Scholar] [CrossRef] [PubMed]
- Sundar, R.; Rai, A.B.; Kumar, J.N.; Divakar, D.D. The role of Vitamin D as an adjunct for bone regeneration: A systematic review of literature. Saudi Dent. J. 2023, 35, 220–232. [Google Scholar] [CrossRef]
- Ursini, F.; Russo, E.; Pellino, G.; D’Angelo, S.; Chiaravalloti, A.; De Sarro, G.; Manfredini, R.; De Giorgio, R. Metformin and Autoimmunity: A “New Deal” of an Old Drug. Front. Immunol. 2018, 9, 1236. [Google Scholar] [CrossRef]
- Hundal, R.S.; E Inzucchi, S. Metformin: New understandings, new uses. Drugs 2003, 63, 1879–1894. [Google Scholar] [CrossRef] [PubMed]
- Feng, X.; Chen, W.; Ni, X.; Little, P.J.; Xu, S.; Tang, L.; Weng, J. Metformin, Macrophage Dysfunction and Atherosclerosis. Front. Immunol. 2021, 12, 682853. [Google Scholar] [CrossRef]
- Jing, Y.; Wu, F.; Li, D.; Yang, L.; Li, Q.; Li, R. Metformin improves obesity-associated inflammation by altering macrophages polarization. Mol. Cell Endocrinol. 2018, 461, 256–264. [Google Scholar] [CrossRef]
- Yan, Z.; Tian, X.; Zhu, J.; Lu, Z.; Yu, L.; Zhang, D.; Liu, Y.; Yang, C.; Zhu, Q.; Cao, X. Metformin suppresses UHMWPE particle-induced osteolysis in the mouse calvaria by promoting polarization of macrophages to an anti-inflammatory phenotype. Mol. Med. 2018, 24, 20. [Google Scholar] [CrossRef] [PubMed]
- Uddin, M.K.H.; Sadiq, M.S.K.; Ahmed, A.; Khan, M.; Maniar, T.; Mateen, S.M.; Saba, B.; Kashif, S.M.; Usman, S.; Najeeb, S.; et al. Applications of Metformin in Dentistry—A review. J. Taibah. Univ. Med. Sci. 2023, 18, 1299–1310. [Google Scholar] [CrossRef] [PubMed]
- Pradeep, A.; Rao, N.S.; Naik, S.B.; Kumari, M. Efficacy of Varying Concentrations of Subgingivally Delivered Metformin in the Treatment of Chronic Periodontitis: A Randomized Controlled Clinical Trial. J. Periodontol. 2013, 84, 212–220. [Google Scholar] [CrossRef] [PubMed]
- Pradeep, A.R.; Patnaik, K.; Nagpal, K.; Karvekar, S.; Ramamurthy, B.L.; Naik, S.B.; Suke, D.; Singh, P.; Raju, A. Efficacy of locally-delivered 1% metformin gel in the treatment of intrabony defects in patients with chronic periodontitis: A randomized, controlled clinical trial. J. Investig. Clin. Dent. 2016, 7, 239–245. [Google Scholar] [CrossRef]
- Yıldırım, T.T.; Dündar, S.; Bozoğlan, A.; Karaman, T.; Kahraman, O.E.; Özcan, E.C. The effects of metformin on the bone filling ration around of TiAl6Va4 implants in non diabetic rats. J. Oral Biol. Craniofac. Res. 2020, 10, 474–477. [Google Scholar] [CrossRef] [PubMed]
- Bastos, M.F.; Serrão, C.R.; Miranda, T.S.; Cruz, D.F.; Malta, F.d.S.; Duarte, P.M. Effects of metformin on bone healing around titanium implants inserted in non-diabetic rats. Clin. Oral Implant. Res. 2017, 28, E146–E150. [Google Scholar] [CrossRef]
- Velasco, A.B.; Garrudo, A.J.; Agustín, I.V.; Prado, D.C.; Pevida, E.P.; Pereira, M.D.; Vadillo, O.M.; de la Pinta, I.B.; Valiente, Y.C.; Mendez, E.S.; et al. Diseño de un compactador de precisión para su uso en regeneración ósea guiada en el área de la cirugía oral. DYNA-Ing. E Ind. 2019, 94, 53–58. [Google Scholar] [CrossRef]
- Anderson, T.W.; Darling, D.A. A Test of Goodness of Fit. J. Am. Stat. Assoc. 1954, 49, 765–769. [Google Scholar] [CrossRef]
- Bonett, D.G. Meta-analytic interval estimation for bivariate correlations. Psychol. Methods 2008, 13, 173–181. [Google Scholar] [CrossRef]
- Levene, H. Robust tests for equality of variances. In Contributions to Probability and Statistics; Springer: Berlin/Heidelberg, Germany, 1960; pp. 278–292. [Google Scholar] [CrossRef]
- Moore, D.S. Introduction to the Practice of Statistics; WH Freeman and company: New York, NY, USA, 2009. [Google Scholar]
- Wilcoxon, F. Individual comparisons by ranking methods. In Breakthroughs in Statistics: Methodology and Distribution; Springer: Berlin/Heidelberg, Germany, 1992; pp. 196–202. [Google Scholar] [CrossRef]
- Kruskal, W.H.; Wallis, W.A. Use of Ranks in One-Criterion Variance Analysis. J. Am. Stat. Assoc. 1952, 47, 583. [Google Scholar] [CrossRef]
- Jung, R.E.; Windisch, S.I.; Eggenschwiler, A.M.; Thoma, D.S.; Weber, F.E.; Hämmerle, C.H.F. A randomized-controlled clinical trial evaluating clinical and radiological outcomes after 3 and 5 years of dental implants placed in bone regenerated by means of GBR techniques with or without the addition of BMP-2. Clin. Oral Implant. Res. 2009, 20, 660–666. [Google Scholar] [CrossRef]
- Jung, R.E.; Kovacs, M.N.; Thoma, D.S.; Hämmerle, C.H.F. Guided bone regeneration with and without rhBMP-2: 17-year results of a randomized controlled clinical trial. Clin. Oral Implant. Res. 2022, 33, 302–312. [Google Scholar] [CrossRef] [PubMed]
- Jung, R.E.; Glauser, R.; Schärer, P.; Hämmerle, C.H.F.; Sailer, H.F.; Weber, F.E. Effect of rhBMP-2 on guided bone regeneration in humans: A randomized, controlled clinical and histo-morphometric study. Clin. Oral Implant. Res. 2003, 14, 556–568. [Google Scholar] [CrossRef] [PubMed]
- Jung, J.; Park, J.S.; Dard, M.; Al-Nawas, B.; Kwon, Y.-D. Effect of enamel matrix derivative liquid combined with synthetic bone substitute on bone regeneration in a rabbit calvarial model. Clin. Oral Investig. 2021, 25, 547–554. [Google Scholar] [CrossRef] [PubMed]
- Miller, R.J. The Use of Enamel Matrix Derivative in Two-Stage Guided Bone Regeneration Procedures. Clin. Adv. Periodontics 2015, 5, 184–191. [Google Scholar] [CrossRef]
- Mitra, D.K.; Donde, R.J.; Desai, A.B.; Ghangrekar, K.P.; Potdar, P.N.; Shetty, G.P. A comparative study of demineralized freeze-dried bone allograft alone and with 1% metformin in the treatment of intrabony defects in patients with chronic periodontitis: A randomized clinical trial. J. Indian Soc. Periodontol. 2023, 27, 70–75. [Google Scholar] [CrossRef]
- Jiating, L.; Buyun, J.; Yinchang, Z. Role of Metformin on Osteoblast Differentiation in Type 2 Diabetes. Biomed. Res. Int. 2019, 2019, 9203934. [Google Scholar] [CrossRef]
- Tamimi, F.M.; Torres, J.; Tresguerres, I.; Clemente, C.; López-Cabarcos, E.; Blanco, L.J. Bone augmentation in rabbit calvariae: Comparative study between Bio-Oss® and a novel β-TCP/DCPD granulate. J. Clin. Periodontol. 2006, 33, 922–928. [Google Scholar] [CrossRef] [PubMed]
- Torres, J.; Tamimi, F.M.; Tresguerres, I.F.; Alkhraisat, M.H.; Khraisat, A.; Lopez-Cabarco, E.; Blanco, L. Effect of solely applied platelet-rich plasma on osseous regeneration compared to Bio-Oss: A morphometric and densitometric study on rabbit calvaria. Clin. Implant. Dent. Relat. Res. 2008, 10, 106–112. [Google Scholar] [CrossRef]
- Zhou, X.; Zhang, Z.; Li, S.; Bai, Y.; Xu, H. Osteoconduction of different sizes of anorganic bone particles in a model of guided bone regeneration. Br. J. Oral Maxillofac. Surg. 2011, 49, 37–41. [Google Scholar] [CrossRef]
- Kurian, I.G.; Dileep, P.; Ipshita, S.; Pradeep, A.R. Comparative evaluation of subgingivally-delivered 1% metformin and Aloe vera gel in the treatment of intrabony defects in chronic periodontitis patients: A randomized, controlled clinical trial. J. Investig. Clin. Dent. 2018, 9, e12324. [Google Scholar] [CrossRef] [PubMed]
- Pankaj, D.; Sahu, I.; Kurian, I.G.; Pradeep, A.R. Comparative evaluation of subgingivally delivered 1.2% rosuvastatin and 1% metformin gel in treatment of intrabony defects in chronic periodontitis: A randomized controlled clinical trial. J. Periodontol. 2018, 89, 1318–1325. [Google Scholar] [CrossRef] [PubMed]
- Pradeep, A.; Nagpal, K.; Karvekar, S.; Patnaik, K.; Naik, S.B.; Guruprasad, C. Platelet-Rich Fibrin With 1% Metformin for the Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Controlled Clinical Trial. J. Periodontol. 2015, 86, 729–737. [Google Scholar] [CrossRef] [PubMed]
- Bigham-Sadegh, A.; Oryan, A. Selection of animal models for pre-clinical strategies in evaluating the fracture healing, bone graft substitutes and bone tissue regeneration and engineering. Connect. Tissue Res. 2015, 56, 175–194. [Google Scholar] [CrossRef] [PubMed]
- Majzoub, Z.; Berengo, M.; Giardino, R.; Aldini, N.N.; Cordioli, G. Role of Intramarrow Penetration in Osseous Repair: A Pilot Study in the Rabbit Calvaria. J. Periodontol. 1999, 70, 1501–1510. [Google Scholar] [CrossRef]
- Lundgren, D.; Lundgren, A.K.; Sennerby, L.; Nyman, S. Augmentation of intramembraneous bone beyond the skeletal envelope using an occlusive titanium barrier. An experimental study in the rabbit. Clin. Oral Implant. Res. 1995, 6, 67–72. [Google Scholar] [CrossRef]
Metformin | Control | Total | ||
---|---|---|---|---|
NBF % | ROI1 | 57.745 ± 9.832 [55.785] | 46.748 ± 15.796 [49.290] | 52.240 ± 13.917 [52.773] |
ROI2 | 36.058 ± 7.420 [33.992] | 28.646 ± 10.803 [25.593] | 32.352 ± 9.737 [32.192] | |
BBC % | ROI1 | 64.93 ± 10.77 [64.47] | 61.26 ± 12.37 [58.7] | 63.09 ± 11.36 [63.91] |
ROI2 | 52.31 ± 7.92 [52.99] | 51.35 ± 8.63 [48.39] | 51.83 ± 8.02 [50.36] |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Montalbán-Vadillo, O.; Pérez-Pevida, E.; Viteri-Agustín, I.; Chávarri-Prado, D.; Estrada-Martínez, A.; Diéguez-Pereira, M.; Sánchez-Lasheras, F.; Brizuela-Velasco, A. Effect of Applying 1% Metformin on Guided Bone Regeneration Processes with Bovine-Derived Xenografts. J. Clin. Med. 2024, 13, 2973. https://doi.org/10.3390/jcm13102973
Montalbán-Vadillo O, Pérez-Pevida E, Viteri-Agustín I, Chávarri-Prado D, Estrada-Martínez A, Diéguez-Pereira M, Sánchez-Lasheras F, Brizuela-Velasco A. Effect of Applying 1% Metformin on Guided Bone Regeneration Processes with Bovine-Derived Xenografts. Journal of Clinical Medicine. 2024; 13(10):2973. https://doi.org/10.3390/jcm13102973
Chicago/Turabian StyleMontalbán-Vadillo, Oier, Esteban Pérez-Pevida, Iratxe Viteri-Agustín, David Chávarri-Prado, Alejandro Estrada-Martínez, Markel Diéguez-Pereira, Fernando Sánchez-Lasheras, and Aritza Brizuela-Velasco. 2024. "Effect of Applying 1% Metformin on Guided Bone Regeneration Processes with Bovine-Derived Xenografts" Journal of Clinical Medicine 13, no. 10: 2973. https://doi.org/10.3390/jcm13102973
APA StyleMontalbán-Vadillo, O., Pérez-Pevida, E., Viteri-Agustín, I., Chávarri-Prado, D., Estrada-Martínez, A., Diéguez-Pereira, M., Sánchez-Lasheras, F., & Brizuela-Velasco, A. (2024). Effect of Applying 1% Metformin on Guided Bone Regeneration Processes with Bovine-Derived Xenografts. Journal of Clinical Medicine, 13(10), 2973. https://doi.org/10.3390/jcm13102973