Osseointegration of titanium scaffolds manufactured by selective laser melting in rabbit femur defect model

  • Aranka Ilea
  • Oana-Gabriela Vrabie
  • Anida-Maria Băbțan
  • Viorel Miclăuş
  • Flavia Ruxanda
  • Melinda Sárközi
  • Lucian Barbu-Tudoran
  • Voicu Mager
  • Cristian Berce
  • Bianca Adina BoșcaEmail author
  • Nausica Bianca Petrescu
  • Oana Cadar
  • Radu Septimiu Câmpian
  • Réka Barabás
Tissue Engineering Constructs and Cell Substrates Original Research
Part of the following topical collections:
  1. Tissue Engineering Constructs and Cell Substrates


The aim of this study was to assess the osseointegration of two series of titanium (Ti) scaffolds with 0.8 and 1 mm cell size obtained by Selective Laser Melting (SLM) technique. One of the series had the Ti surface unmodified, while the other had the Ti surface coated with silicon-substituted nano-hydroxyapatite (nano-HapSi). The scaffolds were implanted in the femur bone defects of 6 White Californian male rabbits: three animals were implanted with 0.8 mm cell size scaffolds and three animals with 1 mm cell size scaffolds, respectively. The bone fragments and scaffolds harvested at 2, 4 and 6 months were histologically analyzed using conventional light microscopy (LM) and scanning electron microscopy (SEM) for the qualitative evaluation of the bone tissue formed in contact with the scaffold. Both LM and SEM images indicated a better osseointegration for nano-HapSi coated Ti scaffolds. LM revealed that the compact bone formed in the proximity of nano-HapSi-coated scaffolds was better organized than spongy bone associated with unmodified scaffolds. Moreover, Ti scaffolds with meshes of 0.8 mm showed higher osseointegration compared with 1 mm. SEM images at 6 months revealed that the bone developed not only in contact with the scaffolds, but also proliferated inside the meshes. Nano-HapSi-coated Ti implants with 0.8 mm meshes were completely covered and filled with new bone. Ti scaffolds osseointegration depended on the mesh size and the surface properties. Due to the biocompatibility and favorable osseointegration in bone defects, nano-HapSi-coated Ti scaffolds could be useful for anatomical reconstructions.



This study was funded by the internal grant No 4995/20/08.03.2016 within the “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania and partially by PhD Grant of “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, No 3999/01.10.2016.

Compliance with ethical standards

Conflicts of interest

The authors declare no conflicts of interest with respect to the authorship and/or publication of this article.


  1. 1.
    Li JP, Habibovica P, van del Doel M, Wilson CE, de Wijn JR, van Blitterswijk CA et al. Bone ingrowth in porous titanium implants produced by 3D fiber deposition. Biomaterials. 2007;28:2810–2820.CrossRefGoogle Scholar
  2. 2.
    Ozcan M, Hammerle C. Titanium as a reconstruction and implant material in dentistry: advantages and pitfalls. Mater (Basel). 2012;5:1528–1545.CrossRefGoogle Scholar
  3. 3.
    Yoo JJ, Park YJ, Rhee SH, Chun HJ, Kim HJ. Synthetic peptide-conjugated titanium alloy for enhanced bone formation in vivo. Connect Tissue Res. 2012;53:359–365.CrossRefGoogle Scholar
  4. 4.
    Taniguchi N, Fujibayashi S, Takemoto M, Sasaki K, Otsuki B, Nakamura T et al. Effect of pore size on bone ingrowth into porous titanium implants fabricated by additive manufacturing: an in vivo experiment. Mater Sci Eng C Mater Biol Appl. 2016;59:690–701.CrossRefGoogle Scholar
  5. 5.
    Salou L, Hoornaert A, Louarn G, Layrolle P. Enhanced osseointegration of titanium implants with nanostructured surfaces: an experimental study in rabbits. Acta Biomater. 2015;11:494–502.CrossRefGoogle Scholar
  6. 6.
    Wieding J, Lindner T, Bergschmidt P, Bader R. Biomechanical stability of novel mechanically adapted open-porous titanium scaffolds in metatarsal bone defects of sheep. Biomaterials. 2015;46:35–47.CrossRefGoogle Scholar
  7. 7.
    Ban J, Kang S, Kim J, Lee K, Hyunpil L, Vang M et al. MicroCT analysis of micro-nano titanium implant surface on the osseointegration. J Nanosci Nanotechnol. 2015;15:172–175.CrossRefGoogle Scholar
  8. 8.
    Deppe H, Grunberg C, Thomas M, Sculean A, Benner KU, Bauer FJ. Surface morphology analysis of dental implants following insertion into bone using scanning electron microscopy: a pilot study. Clin Oral Implants Res. 2015;26:1261–1266.CrossRefGoogle Scholar
  9. 9.
    Yong-Dae K, Yang DH, Lee DW. A titanium surface-modified with nano-sized hydroxyapatite and simvastatin enhances bone formation and osseointegration. J Biomed Nanotechnol. 2015;11:1007–1015.CrossRefGoogle Scholar
  10. 10.
    Horasawa N, Yamashita T, Uehara S, Udagawa N. High-performance scaffolds on titanium surfaces: osteoblast differentiation and mineralization promoted by a globular fibrinogen layer through cell-autonomous BMP signaling. Mater Sci Eng C Mater Biol Appl. 2015;46:86–96.CrossRefGoogle Scholar
  11. 11.
    Svanborg LM, Meirelles L, Stenport VF, Kjellin P, Currie F, Andersson M et al. A Evaluation of bone healing on sandblasted and acid etched implants coated with nanocrystalline hydroxyapatite: an in vivo study in rabbit femur. Int J Dent Article. 2014;197581:1–7. Scholar
  12. 12.
    Hirota M, Shima T, Sato I, Ozawa T, Iwai T, Ametani A et al. Development of a biointegrated mandibular reconstruction device consisting of bone compatible titanium fiber mesh scaffold. Biomaterials. 2016;75:223–236.CrossRefGoogle Scholar
  13. 13.
    Garcia-Gareta E, Hua J, Blunn GW. Osseointegration of acellular and cellularized osteoconductive scaffolds: is tissue engineering using mesenchymal stem cells necessary for implant fixation? J Biomed Mater Res A. 2014;103:1067–1076.CrossRefGoogle Scholar
  14. 14.
    Sivolella S, Brunello G, Ferroni L, Berengo M, Meneghello R, Savio G et al. A novel in vitro technique for assessing dental implant osseointegration. Tissue Eng Part C Methods, 2015;
  15. 15.
    Hirota M, Hayakawa T, Shima T, Ametani A, Tohnai I. High porous titanium scaffolds showed higher compatibility than lower porous beta-tricalcium phosphate scaffolds for regulating human osteoblast and osteoclast differentiation. Mat Sci Eng C Matter. 2015;49:623–631.CrossRefGoogle Scholar
  16. 16.
    Yan C, Hao L, Hussein A, Young P. Ti–6Al–4V triply periodic minimal surface structures for bone implants fabricated via selective laser melting. J Mech Behav Biomed. 2015;51:61–73.CrossRefGoogle Scholar
  17. 17.
    Sirin HT, Vargel I, Kutsal T, Korkusuz P, Piskin E. Ti implants with nanostructured and HA-coated surfaces for improved osseointegration. Artif Cells Nanomed Biotechnol. 2016;44:1023–1030.CrossRefGoogle Scholar
  18. 18.
    Dancu AC, Barabas R, Bogya ES. Adsorption of nicotinic acid on the surface of nanosized hydroxyapatite and structurally modified hydroxyapatite. Cent Eur J Chem. 2011;9:660–669.Google Scholar
  19. 19.
    Zhang LC, Attar H, Calin M, Eckert J. Review on manufacture by selective laser melting and properties of titanium based materials for biomedical applications. Mater Technol. 2016;31:66–76.CrossRefGoogle Scholar
  20. 20.
    Jian YT, Yang Y, Tian T, Stanford C, Zhang XP, Zhao K. Effect of pore size and porosity on the biomedical properties and compatibility of porous NiTi alloys. PloS ONE. 2015;10:e0128138.CrossRefGoogle Scholar
  21. 21.
    Markhoff J, Wieding J, Weissmann V. Influence of different three-dimensional open porous titanium scaffold designs on human osteoblasts behavior in static and dynamic cell investigations. Mater (Basel). 2015;8:5490–5507.CrossRefGoogle Scholar
  22. 22.
    Vasconcellos LM, Leite DO, Oliveira FN, Carvalho YR, Cairo CA. Evaluation of bone ingrowth into porous titanium implant: histomorphometric analysis in rabbits. Braz Oral Res. 2010;24:399–405.CrossRefGoogle Scholar
  23. 23.
    Schätzle M, Zinelis S, Markic G, Eliades G, Eliade T. Structural, morphological, compositional, and mechanical changes of palatal implants after use: a retrieval analysis. Eur J Orthod. 2017;39:579–585.CrossRefGoogle Scholar
  24. 24.
    Le Guehennec L, Lopez-Heredia MA, Enkel B, Weiss P, Amourig Y, Layrolle P. Osteoblastic cell behaviour on different titanium implant surfaces. Acta Biomater. 2008;4:535–543.CrossRefGoogle Scholar
  25. 25.
    Xie H, Ji Y, Tian Q, Wang X, Zhang N, Zhang Y et al. Autogenous bone particle/titanium fiber composites for bone regeneration in a rabbit radius critical-size defect model. Connect Tissue Res. 2017;58:553–561.CrossRefGoogle Scholar
  26. 26.
    Antonov B, Bochev I, Mourdjeva M, Kinov P, Tzvetanoc L, Sheitanov I et al. Porous coated titanium implants do not inhibit mesenchimal stem cells proliferation and osteogenic differentiation. Biotechnol Biotec Eq. 2014;27:4290–4293.CrossRefGoogle Scholar
  27. 27.
    Yoo JJ, Park YJ, Rhee SH, Chun HJ, Kim HJ. Scanning electron microscope (SEM) evaluation of the interface between a nanostructured calcium-incorporated dental implant surface and the human bone. Mater (Basel). 2017;10:E1438.CrossRefGoogle Scholar
  28. 28.
    Lim JY, Donahue HJ. Cell sensing and response to micro- and nanostructured surfaces produced by chemical and topographic patterning. Tissue Eng. 2007;13:1879–1891.CrossRefGoogle Scholar
  29. 29.
    Nouri A, Hodgson PD, Wen C. Biomimetic porous titanium scaffolds for orthopaedic and dental applications. In: Mukherjee A, ed. Biomimetics, Learning from nature. Croatia: InTechOpen. 2010; p. 415–450.Google Scholar
  30. 30.
    Gligor I, Soritau O, Todea M, Berce C, Vulpoi A, Marcu T et al. Porous c.p. titanium using dextrin as space holder for endosseous implants. Part Sci Technol. 2012;31:357–365.CrossRefGoogle Scholar
  31. 31.
    Hrabe NW, Heinl P, Bordia RK, Korner C, Fernandes RJ. Maintenance of a bone collagen phenotype by osteoblast-like cells in 3D periodic porous titanium (Ti-6Al-4 V) structures fabricated by selective electron beam melting. Connect Tissue Res. 2013;54:351–360.CrossRefGoogle Scholar
  32. 32.
    de Oliveira MV, Moreira AC, Pereira LC.Porosity characterization of sintered titanium scaffolds for surgical implants. Mater Sci Forum. 2008;591-593:36–41.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Aranka Ilea
    • 1
  • Oana-Gabriela Vrabie
    • 2
  • Anida-Maria Băbțan
    • 1
  • Viorel Miclăuş
    • 3
  • Flavia Ruxanda
    • 3
  • Melinda Sárközi
    • 4
  • Lucian Barbu-Tudoran
    • 5
    • 6
  • Voicu Mager
    • 7
  • Cristian Berce
    • 8
  • Bianca Adina Boșca
    • 9
    Email author
  • Nausica Bianca Petrescu
    • 1
  • Oana Cadar
    • 10
  • Radu Septimiu Câmpian
    • 1
  • Réka Barabás
    • 4
  1. 1.Department of Oral Rehabilitation, Oral Health and Dental Office Management, Faculty of Dentistry“Iuliu Hațieganu” University of Medicine and PharmacyCluj-NapocaRomania
  2. 2.Faculty of Dentistry“Iuliu Hațieganu” University of Medicine and PharmacyCluj-NapocaRomania
  3. 3.Department of Histology and EmbriologyFaculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine Cluj-NapocaCluj-NapocaRomania
  4. 4.Department of Chemistry and Chemical Engineering, Faculty of Chemistry and Chemical EngineeringHungarian Line of Study, “Babeş Bolyai” University Cluj-NapocaCluj-NapocaRomania
  5. 5.Department of Molecular Biology and Biotechnology, Faculty of Biology“Babeş Bolyai” University Cluj-NapocaCluj-NapocaRomania
  6. 6.National Institute for Research and Development of Isotopic and Molecular TechnologiesCluj-NapocaRomania
  7. 7.Postdoctorand of Technical University of Cluj-NapocaCluj-NapocaRomania
  8. 8.Biobase Department of “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-NapocaCluj-NapocaRomania
  9. 9.Department of Histology, Faculty of Medicine“Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-NapocaCluj-NapocaRomania
  10. 10.INCDO-INOE 2000, Research Institute for Analytical InstrumentationCluj-NapocaRomania

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