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Combination of leukocyte and platelet–rich fibrin and demineralized bovine bone graft enhanced bone formation and healing after maxillary sinus augmentation: a randomized clinical trial

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Abstract

Background and objective

The resorption of alveolar ridge bone and maxillary sinus pneumatization are challenges to implant-supported prosthetic rehabilitation. Bone regeneration using bone substitutes and growth factors are alternatives for maxillary sinus augmentation (MSA). Therefore, we sought to evaluate the effects of the association between leukocyte and platelet–rich fibrin (L-PRF) and deproteinized bovine bone mineral (DBBM) in MSA procedures.

Materials and methods

Thirty-six maxillary sinuses from 24 individuals were included in this randomized clinical trial. The maxillary sinuses were randomly grafted with LPRF and DBBM (test group) or grafted only with DBBM (positive control). Dental implants were installed in the test group following two periods of evaluation: after 4 (DBBM+LPRF4) and 8 (DBBM+LPFR8) months of sinus graft healing, while the control group received implants only after 8 months. Cone beam computed tomography (CBCT) was taken 1 week after surgery (T1) and before implant placement (T2). Bone samples were collected during implant placement for histomorphometric and immunohistochemical (IHC) analysis. The primary implant stability was assessed by resonance frequency analysis.

Results

CBCT analysis demonstrated a significant decrease in bone volume from T1 to T2 in all groups without differences among them. Histologically, the test group showed significantly increase in bone neoformation in both periods of evaluation (LPRF+DBBM4: 44.70±14.01%; LPRF+DBBM8: 46.56±12.25%) compared to the control group (32.34±9.49%). The control group showed the highest percentage of residual graft. IHC analysis showed increased staining intensity of osteocalcin (OCN), vascular endothelial growth factor (VEGF), and runt related transcription factor 2 (RUNX-2) in LPRF+DBBM4 group, and osteopontin (OPN) in the L-PRF+DBBM8. Primary implant stability was successfully achieved (above 60 in implant stability quotient) in all the evaluated groups.

Conclusion

Combination of L-PRF and DBBM increased and accelerated new bone formation allowing early implant placement probably due to the higher protein expression of RUNX2, VEGF, OCN, and OPN. These data suggest that the use of L-PRF might be an interesting alternative to use in combination with DBBM for augment the maxillary sinuses allowing the installation of appropriate length implants in shorter period of time.

Clinical relevance

This study showed improvement in bone neoformation and accelerated healing when associating L-PRF and DBBM for maxillary sinus augmentation procedures.

Trial registration

This study was registered before participant recruitment in Brazilian Registry of Clinical Trials (ReBEC - RBR-95m73t).

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Data availability

The data used to support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to thank Geistlich Pharma AG® (Wolhusen, Switzerland) for the free donation of Bio-Oss® and BioGide® membranes, and Neodent® (Curitiba, PR, Brazil) for the donation of the implants.

Funding

Carolina M. de Almeida Malzoni and Elton Carlos Pichotano were supported by grant provided by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior).

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Authors and Affiliations

  1. Department of Diagnosis and Surgery, School of Dentistry at Araraquara, São Paulo State University – UNESP, Rua Humaitá, 1680, Araraquara, SP, 14801-903, Brazil

    Carolina Mendonça de Almeida Malzoni, Elton Carlos Pichotano, Luiz Guilherme Freitas de Paula, Elcio Marcantonio Jr & Daniela Leal Zandim-Barcelos

  2. Private practice, School of Medicine of Ribeirão Preto, Sao Paulo University – USP, Ribeirao Preto, Sao Paulo, 14040-904, Brazil

    Ricardo Violante de Souza

  3. Department of Basic Sciences, School of Dentistry at Araçatuba, São Paulo State University – UNESP, Araçatuba, SP, 16015-050, Brazil

    Roberta Okamoto

  4. Tissue Engineering and Biophotonics, King’s College London Dental Institute, Guy’s Hospital, London, UK

    Rupert S. Austin

  5. Department of Diagnosis and Surgery, School of Dentistry at Araçatuba, Sao Paulo State University – UNESP, Rua Jose Bonifacio, 1193, Vila Mendonça, Araçatuba, SP, 16015-050, Brazil

    Rafael Scaf de Molon

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  1. Carolina Mendonça de Almeida Malzoni
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Contributions

Carolina Mendonca de Almeida Malzoni: methodology, conceptualization, formal analysis, writing — original draft, writing — review and editing, visualization, final approval of the submitted version; Elton Carlos Pichotano: methodology, formal analysis, writing — review and editing, visualization, final approval of the submitted version; Luis Guilherme Freitas de Paula: methodology, conceptualization, supervision, formal analysis, writing — review and editing, visualization, final approval of the submitted version; Ricardo Violante de Souza: methodology, formal analysis, writing — review and editing, visualization, final approval of the submitted version; Roberta Okamoto: methodology, formal analysis, writing — review and editing, visualization, final approval of the submitted version; Elcio Marcantonio Jr: methodology, conceptualization, supervision, formal analysis, writing — review and editing, visualization, final approval of the submitted version; Rupert S. Austin: methodology, formal analysis, writing — review and editing, visualization, final approval of the submitted version; Rafael Scaf de Molon: methodology, formal analysis, writing — original draft, writing — review and editing, visualization, final approval of the submitted version; Daniela Leal Zandim-Barcelos: methodology, formal analysis, conceptualization, supervision, writing — review and editing, visualization, final approval of the submitted version

Corresponding authors

Correspondence to Rafael Scaf de Molon or Daniela Leal Zandim-Barcelos.

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The authors declare no competing interests.

Ethical approval

This study was approved by the Human Research Ethics Committee of the School of Dentistry at Araraquara (CAAE #41357514.5.0000.5416) and was performed in accordance with the principles stated in the Declaration of Helsinki in 1964. Furthermore, this clinical trial was registered before participant recruitment in Brazilian Registry of Clinical Trials (ReBEC - RBR-95m73t).

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de Almeida Malzoni, C.M., Pichotano, E.C., Freitas de Paula, L.G. et al. Combination of leukocyte and platelet–rich fibrin and demineralized bovine bone graft enhanced bone formation and healing after maxillary sinus augmentation: a randomized clinical trial. Clin Oral Invest 27, 5485–5498 (2023). https://doi.org/10.1007/s00784-023-05167-z

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