Osteogenic potential of mesenchymal stem cells derived from osteoporotic model cultured on microtextured titanium surfaces grades II, IV, and V

Authors

  • Rafael Almeida Rocha Universidade de Cuiabá. Programa de Pós Graduação em Ciências Odontológicas Integradas.
  • Matheus Dias Polegati Universidade Federal de Goiás. Faculdade de Odontologia.
  • Maria Vitória Barroso de Morais Universidade Federal de Goiás. Faculdade de Odontologia.
  • Letícia Faustino Adolpho Universidade de São Paulo. Bone Research Lab.
  • Eduardo Henrique Backes Universidade Federal de São Carlos. Departamento de Engenharia de Materiais.
  • Gileade Pereira Freitas https://orcid.org/0000-0002-1674-4667
  • Helena Bacha Lopes Universidade de Cuiabá. Programa de Pós Graduação em Ciências Odontológicas Integradas.

DOI:

https://doi.org/10.1590/1678-7765-2026-0531

Abstract

Osteoporosis may negatively affect bone healing and osseointegration, potentially influencing implant therapy outcomes. Surface characteristics and chemical composition of titanium implants play an important role in modulating osteogenic cellular responses under compromised systemic conditions. Objective  To evaluate the osteogenic behavior of mesenchymal stem cells from an osteoporotic animal model cultured on microtextured commercially pure titanium grade II (cpTi II), commercially pure titanium grade IV (cpTi IV), and Ti-6Al-4V alloy (Ti V) surfaces. Methodology  Mesenchymal stem cells were obtained from the bone marrow of ovariectomized rats and cultured on cpTi II, cpTi IV, and Ti V discs with microtextured surfaces. Surfaces were characterized by SEM to qualitatively assess the microtextured morphology and by 3D confocal laser scanning microscopy to quantify surface roughness. Chemical composition was assessed by energy-dispersive X-ray spectroscopy. Cell proliferation was evaluated after 1, 2, and 3 days, alkaline phosphatase (ALP) activity after 7 days, and mineralized extracellular matrix formation after 21 days. Data were statistically analyzed at a 5% significance level. Results  SEM and 3D confocal laser scanning microscopy images showed microtextured surfaces with irregular micrometric concavities in all titanium groups. EDS analysis confirmed titanium as the predominant element in all groups, whereas aluminum and vanadium were additionally detected on Ti V surfaces. Cell proliferation significantly differed between cpTi II and cpTi IV at days 2 and 3 (p<0.05). No significant differences were observed in ALP activity between the groups (p>0.05). However, cpTi II showed significantly greater mineralized extracellular matrix formation after 21 days than cpTi IV and Ti V (p<0.05). Conclusions  Within the limitations of this in vitro study, microtextured cpTi II surfaces promoted higher late-stage mineralized extracellular matrix formation than cpTi IV and Ti V under osteoporotic conditions despite similar early osteogenic marker levels (ALP activity).

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References

1- Albrektsson T, Wennerberg A. On osseointegration in relation to implant surfaces. Clin Implant Dent Relat Res. 2019;21(Suppl 1):4-7. doi: 10.1111/cid.12742

» https://doi.org/10.1111/cid.12742

2- Geetha M, Singh AK, Asokamani R, Gogia AK. Ti based biomaterials, the ultimate choice for orthopaedic implants - a review. Prog Mater Sci. 2009;54(3):397-425. doi: 10.1016/j.pmatsci.2008.06.004

3- Song T, Chen Z, Cui X, Lu S, Chen H, Wang H, et al. Strong and ductile titanium-oxygen-iron alloys by additive manufacturing. Nature. 2023;618(7963):63-8. doi: 10.1038/s41586-023-05952-6

» https://doi.org/10.1038/s41586-023-05952-6

4- Chouirfa H, Bouloussa H, Migonney V, Falentin-Daudré C. Review of titanium surface modification techniques and coatings for antibacterial applications. Acta Biomater. 2019;83:37-54. doi: 10.1016/j.actbio.2018.10.036

5- Pandey C, Rokaya D, Bhattarai BP. Contemporary concepts in osseointegration of dental implants: a review. Biomed Res Int. 2022;2022:6170452. doi: 10.1155/2022/6170452

» https://doi.org/10.1155/2022/6170452

6- Siqueira R, Ferreira JA, Rizzante FA, Moura GF, Mendonça DB, Magalhães D, et al. Hydrophilic titanium surface modulates early stages of osseointegration in osteoporosis. J Periodontal Res. 2021;56(2):351-62. doi: 10.1111/jre.12827

» https://doi.org/10.1111/jre.12827

7- Giro G, Chambrone L, Goldstein A, Rodrigues JA, Zenóbio E, Feres M, et al. Impact of osteoporosis in dental implants: a systematic review. World J Orthop. 2015;6(2):311-5. doi: 10.5312/wjo.v6.i2.311

» https://doi.org/10.5312/wjo.v6.i2.311

8- Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet. 2019;393(10169):364-76. doi: 10.1016/S0140-6736(18)32112-3

» https://doi.org/10.1016/S0140-6736(18)32112-3

9- Nakhaei Amroodi MN, Maghsoudloo M, Amiri S, Mokhtari K, Mohseni P, Pourmarjani A, et al. Unraveling the molecular and immunological landscape: exploring signaling pathways in osteoporosis. Biomed Pharmacother. 2024;177:116954. doi: 10.1016/j.biopha.2024.116954

» https://doi.org/10.1016/j.biopha.2024.116954

10- Belibasakis GN, Manoil D. Microbial community-driven etiopathogenesis of peri-implantitis. J Dent Res. 2021;100(1):21-8. doi: 10.1177/0022034520949851

» https://doi.org/10.1177/0022034520949851

11- Sachelarie L, Scrobota I, Cioara F, Ghitea TC, Stefanescu CL, Todor L, et al. The influence of osteoporosis and diabetes on dental implant stability: a pilot study. Medicina (Kaunas). 2025;61(1):74. doi: 10.3390/medicina61010074

» https://doi.org/10.3390/medicina61010074

12- Adolpho LF, Gomes MP, Freitas GP, Bighetti-Trevisan RL, Ramos JI, Campeoti GH, et al. Jaboticaba peel extract attenuates ovariectomy-induced bone loss by preserving osteoblast activity. Biology (Basel). 2024;13(7):526. doi: 10.3390/biology13070526

» https://doi.org/10.3390/biology13070526

13- Freitas GP, Souza AT, Lopes HB, Trevisan RL, Oliveira FS, Fernandes RR, et al. Mesenchymal stromal cells derived from bone marrow and adipose tissue: isolation, culture, characterization and differentiation. Bio Protoc. 2020;10(4):e3534. doi: 10.21769/BioProtoc.3534

» https://doi.org/10.21769/BioProtoc.3534

14- Frumkin N, Iden JA, Schwartz-Arad D. Effect of osteopenia and osteoporosis on failure of first and second dental implants: a retrospective observational study. Int J Implant Dent. 2024;10(1):40. doi: 10.1186/s40729-024-00556-9

» https://doi.org/10.1186/s40729-024-00556-9

15- Bandyopadhyay A, Mitra I, Goodman SB, Kumar M, Bose S. Improving biocompatibility for next generation of metallic implants. Prog Mater Sci. 2023;133:101053. doi: 10.1016/j.pmatsci.2022.101053

» https://doi.org/10.1016/j.pmatsci.2022.101053

16- Brizuela A, Herrero-Climent M, Rios-Carrasco E, Rios-Santos JV, Pérez RA, Manero JM, et al. Influence of the elastic modulus on the osseointegration of dental implants. Materials (Basel). 2019;12(6):980. doi: 10.3390/ma12060980

» https://doi.org/10.3390/ma12060980

17- Sarraf M, Rezvani Ghomi E, Alipour S, Ramakrishna S, Liana Sukiman N. A state-of-the-art review of the fabrication and characteristics of titanium and its alloys for biomedical applications. Biodes Manuf. 2022;5(2):371-95. doi: 10.1007/s42242-021-00170-3

18- Lee SA, Yi YJ, Won S, Chang NH, Kim JH. Prognostic factors influencing implant survival and marginal bone loss in patients with osteoporosis or osteopenia medication. J Korean Assoc Oral Maxillofac Surg. 2025;51(1):17-25. doi: 10.5125/jkaoms.2025.51.1.17

» https://doi.org/10.5125/jkaoms.2025.51.1.17

19- Ma Y, Yang Z, Yu B, Lyu K, Wu J, Chen B, et al. Biomechanical analysis of axial-radial integrated functional gradient material implants in healthy and osteoporotic bones. Dent Mater J. 2025;44(2):179-89. doi: 10.4012/dmj.2024-222

» https://doi.org/10.4012/dmj.2024-222

20- Probst M, Probst F, Tröltzsch M, Bruckbauer M, Marka AW, Andreisek G, et al. Retrospective analysis of dental implant stability in relation to mandibular bone density and cortical thickness in osteopenic and osteoporotic patients. J Clin Med. 2025;14(4):1339. doi: 10.3390/jcm14041339

» https://doi.org/10.3390/jcm14041339

21- Tshephe TS, Akinwamide SO, Olevsky E, Olubambi PA. Additive manufacturing of titanium-based alloys: a review of methods, properties, challenges, and prospects. Heliyon. 2022;8(3):e09041. doi: 10.1016/j.heliyon.2022.e09041

» https://doi.org/10.1016/j.heliyon.2022.e09041

22- Tardelli JD, Dos Reis AC. Influence of surface electric charge of Ti implants on osteoblastic interaction: a systematic review. Saudi Dent J. 2022;34(5):335-45. doi: 10.1016/j.sdentj.2022.04.003

» https://doi.org/10.1016/j.sdentj.2022.04.003

23- Zhao G, Schwartz Z, Wieland M, Rupp F, Geis-Gerstorfer J, Cochran DL, et al. High surface energy enhances cell response to titanium substrate microstructure. J Biomed Mater Res A. 2005;74(1):49-58. doi: 10.1002/jbm.a.30320

» https://doi.org/10.1002/jbm.a.30320

24- Jemat A, Ghazali MJ, Razali M, Otsuka Y. Surface modifications and their effects on titanium dental implants. Biomed Res Int. 2015;2015:791725. doi: 10.1155/2015/791725

» https://doi.org/10.1155/2015/791725

25- Lotz EM, Cohen DJ, Schwartz Z, Boyan BD. Titanium implant surface properties enhance osseointegration in ovariectomy induced osteoporotic rats without pharmacologic intervention. Clin Oral Implants Res. 2020;31(4):374-87. doi: 10.1111/clr.13575

» https://doi.org/10.1111/clr.13575

26- Niinomi M, Nakai M, Hieda J. Development of new metallic alloys for biomedical applications. Acta Biomater. 2012;8(11):3888-903. doi: 10.1016/j.actbio.2012.06.037

» https://doi.org/10.1016/j.actbio.2012.06.037

27- Geng T, Wang Y, Lin K, Zhang C, Wang J, Liu Y, et al. Strontium-doping promotes bone bonding of titanium implants in osteoporotic microenvironment. Front Bioeng Biotechnol. 2022;10:1011482. doi: 10.3389/fbioe.2022.1011482

» https://doi.org/10.3389/fbioe.2022.1011482

28- Jillek B, Szabó P, Kopniczky J, Krafcsik O, Szabó I, Patczai B, et al. Characterizing surface morphological and chemical properties of commonly used orthopedic implant materials and determining their clinical significance. Polymers (Basel). 2024;16(9):1193. doi: 10.3390/polym16091193

» https://doi.org/10.3390/polym16091193

29- Mishra T, Kukreja BJ, Patel R, Ghadage M, Dalave P, Kumari S, et al. In vitro evaluation of titanium exfoliation during simulated surgical insertion of dental implants. J Pharm Bioallied Sci. 2024;16(Suppl 4):S3383-5. doi: 10.4103/jpbs.jpbs_856_24

» https://doi.org/10.4103/jpbs.jpbs_856_24

30- Echeverry-Rendón M, Galvis O, Quintero Giraldo D, Pavón J, López-Lacomba JL, Jiménez-Piqué E, et al. Osseointegration improvement by plasma electrolytic oxidation of modified titanium alloys surfaces. J Mater Sci Mater Med. 2015;26(2):72. doi: 10.1007/s10856-015-5408-4

» https://doi.org/10.1007/s10856-015-5408-4

31- Lemos CA, Oliveira AS, Faé DS, Oliveira HF, Del Rei Daltro Rosa CD, Bento VA, et al. Do dental implants placed in patients with osteoporosis have higher risks of failure and marginal bone loss compared to those in healthy patients? A systematic review with meta-analysis. Clin Oral Investig. 2023;27(6):2483-93. doi: 10.1007/s00784-023-05005-2

» https://doi.org/10.1007/s00784-023-05005-2

32- Liu J, Kim EK, Ni A, Kim YR, Zheng F, Lee BS, et al. Multiscale characterization of ovariectomized rat femur. J Biomech. 2021;122:110462. doi: 10.1016/j.jbiomech.2021.110462

» https://doi.org/10.1016/j.jbiomech.2021.110462

33- Yan R, Li J, Wu Q, Zhang X, Hu L, Deng Y, et al. Trace element-augmented titanium implant with targeted angiogenesis and enhanced osseointegration in osteoporotic rats. Front Chem. 2022;10:839062. doi: 10.3389/fchem.2022.839062

» https://doi.org/10.3389/fchem.2022.839062

34- Medeiros FC, Kudo GA, Leme BG, Saraiva PP, Verri FR, Honório HM, et al. Dental implants in patients with osteoporosis: a systematic review with meta-analysis. Int J Oral Maxillofac Surg. 2018;47(4):480-91. doi: 10.1016/j.ijom.2017.05.021

» https://doi.org/10.1016/j.ijom.2017.05.021

35- Black DM, Rosen CJ. Clinical practice. Postmenopausal osteoporosis. N Engl J Med. 2016;374(3):254-62. doi: 10.1056/NEJMcp1513724

» https://doi.org/10.1056/NEJMcp1513724

36- Coelho MC, Guedes de Mello LG, Suguimoto SP, Fernandes RR, Bombonato-Prado KF. Effect of different osteogenic media and saline solutions on the osteogenesis protocol using MC3T3-E1 subclones. Braz J Sci. 2025;4(1):1-11. doi: 10.14295/bjs.v4i1.662

» https://doi.org/10.14295/bjs.v4i1.662

37- Amarasekara DS, Kim S, Rho J. Regulation of osteoblast differentiation by cytokine networks. Int J Mol Sci. 2021;22(6):2851. doi: 10.3390/ijms22062851

» https://doi.org/10.3390/ijms22062851

38- Birmingham E, Niebur GL, McHugh PE, Shaw G, Barry FP, McNamara LM. Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. Eur Cell Mater. 2012;23:13-27. doi: 10.22203/eCM.v023a02

» https://doi.org/10.22203/eCM.v023a02

39- Lopes HB, Rios TL, Adolpho LF, Souza AT, Lopes UM, Backes EH, et al. Evaluation of osteoblastic differentiation induced by microtextured titanium surface produced by laser metal fusion 3D printing. Mater Res. 2024;27:e20230448. doi: 10.1590/1980-5373-MR-2023-0448

» https://doi.org/10.1590/1980-5373-MR-2023-0448

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Published

2026-10-26

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Section

Original Articles

How to Cite

Rocha, R. A., Polegati, M. D., Morais, M. V. B. de, Adolpho, L. F., Backes, E. H., Freitas, G. P., & Lopes, H. B. (2026). Osteogenic potential of mesenchymal stem cells derived from osteoporotic model cultured on microtextured titanium surfaces grades II, IV, and V. Journal of Applied Oral Science, 34, e20260531. https://doi.org/10.1590/1678-7765-2026-0531