Clinical Oral Investigations

, Volume 23, Issue 1, pp 369–379 | Cite as

Does the association of blood-derived growth factors to nanostructured carbonated hydroxyapatite contributes to the maxillary sinus floor elevation? A randomized clinical trial

  • Carlos Fernando de Almeida Barros Mourão
  • Emanuelle Stellet Lourenço
  • Jhonathan Raphael Barros Nascimento
  • Rafael Coutinho Mello Machado
  • Alexandre Malta Rossi
  • Paulo Emílio Corrêa Leite
  • José Mauro Granjeiro
  • Gutemberg Gomes Alves
  • Mônica Diuana Calasans-MaiaEmail author
Original Article



The combination of calcium phosphate with blood-derived growth factors (BDGF) has been widely used in bone regeneration procedures although its benefits are still unclear. The purpose of this study was to evaluate whether or not BDGF improves the efficacy of a modified carbonated calcium phosphate biomaterial in sinus floor augmentation.

Material and methods

Ten patients underwent 20 sinus floor augmentation procedures using nanostructured carbonated hydroxyapatite (cHA) microspheres alone or associated with BDGF in a randomized controlled clinical trial. The in vitro release of growth factors was assessed by an elution assay. Bone grafts were randomly implanted in the right and left maxillary sinuses of each participant, associated either with a 0.9% saline solution or BDGF. Bone gain was evaluated through cone beam tomography after 180 days.


Nine women and one man composed the sample. The blood-derived concentrates were able to release high levels of growth factors and cytokines. A significant clinical advantage was observed in the use of the BDGF after fibrin polymerization around the biomaterial microspheres, optimizing the surgical procedures, thereby reducing the time and displacement, and improving the adaptation of the biomaterial in the maxillary sinus. No synergistic effect was observed in bone formation when cHA was associated with BDGF (p > 0.05).


Equivalent new bone formation was observed for cHA in the presence or absence of the BDGF concentrate in bilateral sinus floor elevation after 6 months. Blood-derived growth factors did not improve bone repair when associated with calcium phosphate in sinus lift procedures.


Clinical trials Growth factors Biomaterials Sinus floor elevation 



Authors thank the Laboratório Nacional de Luz Síncrotron for the physicochemical evaluation of the biomaterials.


This study if financially supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), process no. E-26/110.303/2014, and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). INCT-REGENERA/CNPQ/FAPERJ.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/ national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical Standards (CONEP, Brazil no. 1.345.263).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

784_2018_2445_Fig7_ESM.gif (31 kb)
Supplementary Figure 1

Fourier-transformed infrared (FTIR) spectra of the nanostructured carbonated hydroxyapatite without thermal treatment. The arrows point to the carbonate and phosphate peaks and the presence of the H2O group, characterizing a non-sintered material. (GIF 31 kb)

784_2018_2445_MOESM1_ESM.tif (6.2 mb)
High resolution image (TIF 6383 kb)
784_2018_2445_Fig8_ESM.gif (21 kb)
Supplementary Figure 2

X-ray diffraction pattern (XRD) of nanostructured carbonated hydroxyapatite samples without thermal treatment. (GIF 20 kb)

784_2018_2445_MOESM2_ESM.tif (5.5 mb)
High resolution image (TIF 5657 kb)
784_2018_2445_Fig9_ESM.gif (69 kb)
Supplementary Figure 3

A. X-ray microtomography of the nanostructured carbonated hydroxyapatite sphere; B. Material volume (44.6%) C. Pores volume (55.4%). (GIF 69 kb)

784_2018_2445_MOESM3_ESM.tif (3.2 mb)
High resolution image (TIF 3289 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Carlos Fernando de Almeida Barros Mourão
    • 1
    • 2
  • Emanuelle Stellet Lourenço
    • 1
  • Jhonathan Raphael Barros Nascimento
    • 1
  • Rafael Coutinho Mello Machado
    • 1
  • Alexandre Malta Rossi
    • 3
  • Paulo Emílio Corrêa Leite
    • 4
  • José Mauro Granjeiro
    • 5
    • 6
  • Gutemberg Gomes Alves
    • 2
  • Mônica Diuana Calasans-Maia
    • 7
    Email author
  1. 1.Graduate Program in DentistryFluminense Federal UniversityRio de JaneiroBrazil
  2. 2.Department of Molecular and Cell Biology, Institute of BiologyFluminense Federal UniversityRio de JaneiroBrazil
  3. 3.Biomaterials Laboratory, Brazilian Center for Physical StudiesRio de JaneiroBrazil
  4. 4.Laboratory of Ultrastructure and Cellular Biology Hertha Meyer, Institute of Biophysics Carlos Chagas FilhoFederal University of Rio de JaneiroRio de JaneiroBrazil
  5. 5.Nacional Institute of Metrology, Quality and TechnologyRio de JaneiroBrazil
  6. 6.Dentistry SchoolFluminense Federal UniversityRio de JaneiroBrazil
  7. 7.Oral Surgery Department, Dentistry SchoolFluminense Federal UniversityRio de JaneiroBrazil

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