Journal of Maxillofacial and Oral Surgery

, Volume 19, Issue 1, pp 85–92 | Cite as

Is Impregnation of Xenograft with Caffeine Effective on Bone Healing Rate in Mandibular Defects? A Pilot Histological Animal Study

  • Sahand SamieiradEmail author
  • Vajiheh Mianbandi
  • Hamideh Salari Sedigh
  • Majid Hosseini-Abrishami
  • Farid Shiezadeh
  • Hossein Bagheri
  • Elahe Tohidi
  • Nasrollah Saghravanian
Original Article


Introduction and Aim

The aim of this study was to evaluate the effect of two concentrations of caffeine (1.5% and 3%) powder added to Bio-Oss xenograft on bone healing rate of iatrogenic mandibular defects in dogs.

Materials and Method

The researchers implemented a pilot study on ten male adult mongrel dogs. Two 4-mm circular critical-sized defects were trephined on each side of the mandibular body (a total of 4 defects for each dog). One of the defects remained empty as a control group. The other three defects in each case were randomly filled with 1.5% or 3% caffeinated Bio-Oss or pure Bio-Oss. The mandible specimens were sent for histological and histomorphometric assessments, 4 months postoperatively. Our predictor variable was the type of bone substitute. The study outcomes were new bone formation, angiogenesis, and fibrosis. The p value was set at 0.05 using SPSS 16.


The histological assessment showed that the administration of 1.5% caffeinated Bio-Oss to mandibular defects caused more angiogenesis and more new bone formation as well as less fibrosis compared to the other groups (p < 0.05).


This study suggested that the application of 1.5% caffeinated Bio-Oss in bone defects of dogs resulted in the higher new bone formation. However, further clinical trials are needed to support its relevancy.


Caffeine Bio-Oss Xenograft New bone formation 



The authors would like to appreciate the continued support of the Research Council of Mashhad University of Medical Sciences. We also thank the cooperation of Dr. Taghi Ghiasi (general pathologist) and Dr. Amin Rahpeyma (oral and maxillofacial surgeon) in this research.



Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical Approval

All procedures performed in this animal study were in accordance with the ethical standards of our institute. In addition, all applicable international, national, and institutional guidelines for the care and use of animals were followed.


  1. 1.
    Khojasteh A, Fahimipour F, Jafarian M, Sharifi D, Jahangir S, Khayyatan F et al (2017) Bone engineering in dog mandible: coculturing mesenchymal stem cells with endothelial progenitor cells in a composite scaffold containing vascular endothelial growth factor. J Biomed Mater Res B Appl Biomater 105(7):1767–1777CrossRefGoogle Scholar
  2. 2.
    Jafarian M, Eslaminejad MB, Khojasteh A, Abbas FM, Dehghan MM, Hassanizadeh R et al (2008) Marrow-derived mesenchymal stem cells-directed bone regeneration in the dog mandible: a comparison between biphasic calcium phosphate and natural bone mineral. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105(5):e14–e24CrossRefGoogle Scholar
  3. 3.
    Khojasteh A, Dashti SG, Dehghan MM, Behnia H, Abbasnia P, Morad G (2014) The osteoregenerative effects of platelet-derived growth factor BB cotransplanted with mesenchymal stem cells, loaded on freeze-dried mineral bone block: a pilot study in dog mandible. J Biomed Mater Res B Appl Biomater 102(8):1771–1778CrossRefGoogle Scholar
  4. 4.
    Wang F, Li Q, Wang Z (2017) A comparative study of the effect of Bio-Oss® in combination with concentrated growth factors or bone marrow-derived mesenchymal stem cells in canine sinus grafting. J Oral Pathol Med 46(7):528–536CrossRefGoogle Scholar
  5. 5.
    Singh J, Takhar RK, Bhatia A, Goel A (2016) Bone graft materials: dental aspects. J Nov Res Healthc Nurs 3:99–103Google Scholar
  6. 6.
    Macedo RM, Lacerda SA, Brentegani LG, Bombonato-Prado KF, Prata CA (2011) Osteointegration of autogenous bone graft associated with osteoblastic cells under treatment with caffeine. Implant Dent 20(5):369–373CrossRefGoogle Scholar
  7. 7.
    Duarte PM, Marques MR, Bezerra JP, Bastos MF (2009) The effects of caffeine administration on the early stage of bone healing and bone density: a histometric study in rats. Arch Oral Biol 54(8):717–722CrossRefGoogle Scholar
  8. 8.
    Lacerda SA, Matuoka RI, Macedo RM, Petenusci SO, Campos AA, Brentegani LG (2010) Bone quality associated with daily intake of coffee: a biochemical, radiographic and histometric study. Braz Dent J 21(3):199–204CrossRefGoogle Scholar
  9. 9.
    Macedo RM, Brentegani LG, Lacerda SAD (2015) Effects of coffee intake and intraperitoneal caffeine on bone repair process-a histologic and histometric study. Braz Dent J 26(2):175–180CrossRefGoogle Scholar
  10. 10.
    Khojasteh A, Behnia H, Hosseini FS, Dehghan MM, Abbasnia P, Abbas FM (2013) The effect of PCL-TCP scaffold loaded with mesenchymal stem cells on vertical bone augmentation in dog mandible: a preliminary report. J Biomed Mater Res B Appl Biomater 101(5):848–854CrossRefGoogle Scholar
  11. 11.
    Lipton RB, Diener H-C, Robbins MS, Garas SY, Patel K (2017) Caffeine in the management of patients with headache. J Headache Pain 18(1):107CrossRefGoogle Scholar
  12. 12.
    Samieirad S, Afrasiabi H, Tohidi E, Qolizade M, Shaban B, Hashemipour MA et al (2017) Evaluation of caffeine versus codeine for pain and swelling management after implant surgeries: a triple blind clinical trial. Journal of Craniomaxillofac Surg 45(10):1614–1621CrossRefGoogle Scholar
  13. 13.
    Zhou Y, Guan X, Zhu Z, Guo J, Huang Y, Hou W et al (2010) Caffeine inhibits the viability and osteogenic differentiation of rat bone marrow-derived mesenchymal stromal cells. Br J Pharmacol 161(7):1542–1552CrossRefGoogle Scholar
  14. 14.
    Tsuang Y-H, Sun J-S, Chen L-T, Sun SC-K, Chen S-C (2006) Direct effects of caffeine on osteoblastic cells metabolism: the possible causal effect of caffeine on the formation of osteoporosis. J Orthop Surg Res 1(1):1CrossRefGoogle Scholar
  15. 15.
    Lucaciu O, Gheban D, Soriţau O, Băciuţ M, Câmpian RS, Băciuţ G (2015) Comparative assessment of bone regeneration by histometry and a histological scoring system/Evaluarea comparativă a regenerării osoase utilizând histometria şi un scor de vindecare histologică. Romanian Rev Lab Med 23(1):31–45Google Scholar
  16. 16.
    Liu H-Y, Zheng H, Hou X-P, Zhong W-J, Ying X-X, Chai S-L et al (2014) Bio-Oss® for delayed osseointegration of implants in dogs: a histological study. Br J Oral Maxillofac Surg 52(8):729–734CrossRefGoogle Scholar
  17. 17.
    Antunes AA, Oliveira Neto P, de Santis E, Caneva M, Botticelli D, Salata LA (2013) Comparisons between Bio-Oss® and Straumann® Bone Ceramic in immediate and staged implant placement in dogs mandible bone defects. Clin Oral Implant Res 24(2):135–142CrossRefGoogle Scholar
  18. 18.
    Araújo MG, Linder E, Lindhe J (2011) Bio-Oss® collagen in the buccal gap at immediate implants: a 6-month study in the dog. Clin Oral Implant Res 22(1):1–8CrossRefGoogle Scholar
  19. 19.
    Araújo MG, Lindhe J (2009) Ridge preservation with the use of Bio-Oss® collagen: a 6-month study in the dog. Clin Oral Implant Res 20(5):433–440CrossRefGoogle Scholar
  20. 20.
    Bassi APF, Carvalho PSPD (2011) Repair of bone cavities in dog’s mandible filled with inorganic bovine bone and bioactive glass associated with platelet rich plasma. Braz Dent J 22(1):14–20CrossRefGoogle Scholar
  21. 21.
    Piattelli M, Favero GA, Scarano A, Orsini G, Piattelli A (1999) Bone reactions to anorganic bovine bone (Bio-Oss) used in sinus augmentation procedures: a histologic long-term report of 20 cases in humans. Int J Oral Maxillofac Implants 14(6):835–840PubMedGoogle Scholar
  22. 22.
    Kim JJ, Schwarz F, Song HY, Choi Y, Kang KR, Koo KT (2017) Ridge preservation of extraction sockets with chronic pathology using Bio-Oss® Collagen with or without collagen membrane: an experimental study in dogs. Clin Oral Implant Res 28(6):727–733CrossRefGoogle Scholar
  23. 23.
    Polyzois I, Renvert S, Bosshardt DD, Lang NP, Claffey N (2007) Effect of Bio-Oss® on osseointegration of dental implants surrounded by circumferential bone defects of different dimensions: an experimental study in the dog. Clin Oral Implant Res 18(3):304–310CrossRefGoogle Scholar
  24. 24.
    Aludden H, Mordenfeld A, Hallman M, Dahlin C, Jensen T (2017) Lateral ridge augmentation with Bio-Oss alone or Bio-Oss mixed with particulate autogenous bone graft: a systematic review. Int J Oral Maxillofac Surg 46(8):1030–1038CrossRefGoogle Scholar
  25. 25.
    Bonardi JP, dos Santos Pereira R, Lima FB, Faverani LP, Griza GL, Okamoto R et al (2018) Prospective and randomized evaluation of ChronOS and Bio-Oss in human maxillary sinuses: histomorphometric and immunohistochemical assignment for Runx 2, vascular endothelial growth factor, and osteocalcin. J Oral Maxillofac Surg 76(2):325–335CrossRefGoogle Scholar
  26. 26.
    Sawynok J (2011) Caffeine and pain. Pain 152(4):726–729CrossRefGoogle Scholar
  27. 27.
    Ng N, Kaye EK, Garcia RI (2014) Coffee consumption and periodontal disease in males. J Periodontol 85(8):1042–1049CrossRefGoogle Scholar
  28. 28.
    Conlisk AJ, Galuska DA (2000) Is caffeine associated with bone mineral density in young adult women? Prev Med 31(5):562–568CrossRefGoogle Scholar
  29. 29.
    Cooper C, Atkinson EJ, Wahner HW, O’Fallon WM, Riggs BL, Judd HL et al (1992) Is caffeine consumption a risk factor for osteoporosis? J Bone Miner Res 7(4):465–471CrossRefGoogle Scholar
  30. 30.
    Ferreira Bastos M, Barreto Menezes DJ, Pinho Bezerra J, Braz C, Kelmy C, Silva Fonseca PF et al (2014) Impact of caffeine and/or estrogen deficiency on trabecular bone area and healing: a study in rats. Int J Oral Maxillofac Implants 29(1):221–231CrossRefGoogle Scholar
  31. 31.
    Johansson C, Mellström D, Lerner U, Österberg T (1992) Coffee drinking: a minor risk factor for bone loss and fractures. Age Ageing 21(1):20–26CrossRefGoogle Scholar
  32. 32.
    Tiwari KK, Chu C, Couroucli X, Moorthy B, Lingappan K (2014) Differential concentration-specific effects of caffeine on cell viability, oxidative stress, and cell cycle in pulmonary oxygen toxicity in vitro. Biochem Biophys Res Commun 450(4):1345–1350CrossRefGoogle Scholar

Copyright information

© The Association of Oral and Maxillofacial Surgeons of India 2019

Authors and Affiliations

  • Sahand Samieirad
    • 1
    • 2
    Email author
  • Vajiheh Mianbandi
    • 2
  • Hamideh Salari Sedigh
    • 3
  • Majid Hosseini-Abrishami
    • 1
    • 2
  • Farid Shiezadeh
    • 1
  • Hossein Bagheri
    • 4
  • Elahe Tohidi
    • 5
  • Nasrollah Saghravanian
    • 1
  1. 1.Oral and Maxillofacial Diseases Research CenterMashhad University of Medical SciencesMashhadIran
  2. 2.Oral and Maxillofacial Surgery Department, Mashhad Dental SchoolMashhad University of Medical SciencesMashhadIran
  3. 3.Department of Clinical Sciences, Faculty of Veterinary MedicineFerdowsi University of MashhadMashhadIran
  4. 4.Dental Materials Research Center, Faculty of DentistryMashhad University of Medical SciencesMashhadIran
  5. 5.Oral and Maxillofacial RadiologistMashhadIran

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