Tissue Engineering and Regenerative Medicine

, Volume 15, Issue 4, pp 503–510 | Cite as

Wicking Property of Graft Material Enhanced Bone Regeneration in the Ovariectomized Rat Model

  • Seunghyun Kim
  • Taeho Ahn
  • Myung-Ho Han
  • Chunsik BaeEmail author
  • Daniel S. OhEmail author
Original Article



Recruitment and homing cells into graft materials from host tissue is crucial for bone regeneration.


Highly porous, multi-level structural, hydroxyapatite bone void filler (HA-BVF) have been investigated to restore critical size bone defects. The aim was to investigate a feasibility of bone regeneration of synthetic HA-BVF compared to commercial xenograft (Bio-Oss). HA-BVF of 0.7 mm in average diameter was prepared via template coating method. Groups of animals (n = 6) were divided into two with normal (Sham) or induced osteoporotic conditions (Ovx). Subsequently, subdivided into three treated with HA-BVF as an experiment or Bio-Oss as a positive control or no treatment as a negative control (defect). The new bone formation was analyzed by micro-CT and histology.


At 4 weeks post-surgery, new bone formation was initiated from all groups. At 8 weeks post-surgery, new bone formation in the HA-BVF groups was greater than Bio-Oss groups. Extraordinarily greater bone regeneration within the Ovx-HA group than Sham–Bio-Oss or Ovx–Bio-Oss group (p < 0.05).


This study suggests that the immediate wicking property of HA-BVF from host tissue activates a natural healing cascade without the addition of exogeneous factors or progenitor cells. HA-BVF may be an effective alternative for repairing bone defects under both normal and osteoporotic bone conditions.


Bone regeneration Hydroxyapatite Osteoporosis Bone void filler 



This study was partially supported by Chonnam National University, 2016 and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by Ministry of Education (2017R1D1A1B03034829).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical statement

Animal experimental procedures were approved by the Institutional Animal Care and Use Committee of Chonnam National University (CNU IACUC-YB-R-2014-37) and the animals were cared for in accordance with the Guidelines for Animal Experiments of Chonnam National University.


  1. 1.
    Petrie Aronin CE, Sadik KW, Lay AL, Rion DB, Tholpady SS, Ogle RC, et al. Comparative effects of scaffold pore size, pore volume, and total void volume on cranial bone healing patterns using microsphere-based scaffolds. J Biomed Mater Res A. 2009;89:632–41.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Guzmán R, Nardecchia S, Gutiérrez MC, Ferrer ML, Ramos V, del Monte F, et al. Chitosan scaffolds containing calcium phosphate salts and rhBMP-2: in vitro and in vivo testing for bone tissue regeneration. PLoS One. 2014;9:e87149.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Jabbarzadeh E, Starnes T, Khan YM, Jiang T, Wirtel AJ, Deng M, et al. Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: a combined gene therapy-cell transplantation approach. Proc Natl Acad Sci U S A. 2018;105:11099–104.CrossRefGoogle Scholar
  4. 4.
    Cha JK, Lee JS, Kim MS, Choi SH, Cho KS, Jung UW. Sinus augmentation using BMP-2 in a bovine hydroxyapatite/collagen carrier in dogs. J Clin Periodontol. 2014;41:86–93.CrossRefPubMedGoogle Scholar
  5. 5.
    Zhao J, Zhang Z, Wang S, Sun X, Zhang X, Chen J, et al. Apatite-coated silk fibroin scaffolds to healing mandibular border defects in canines. Bone. 2009;45:517–27.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Kim HJ, Kim UJ, Kim HS, Li C, Wada M, Leisk GG, et al. Bone tissue engineering with premineralized silk scaffolds. Bone. 2008;42:1226–34.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials. 2005;26:5474–91.CrossRefPubMedGoogle Scholar
  8. 8.
    Vats A, Tolley NS, Polak JM, Gough JE. Scaffolds and biomaterials for tissue engineering: a review of clinical applications. Clin Otolaryngol Allied Sci. 2003;28:165–72.CrossRefPubMedGoogle Scholar
  9. 9.
    Woodard JR, Hilldore AJ, Lan SK, Park CJ, Morgan AW, Eurell JA, et al. The mechanical properties and osteoconductivity of hydroxyapatite bone scaffolds with multi-scale porosity. Biomaterials. 2007;28:45–54.CrossRefPubMedGoogle Scholar
  10. 10.
    Zong C, Qian X, Tang Z, Hu Q, Chen J, Gao C, et al. Biocompatibility and bone-repairing effects: comparison between porous poly-lactic-co-glycolic acid and nano-hydroxyapatite/poly(lactic acid) scaffolds. J Biomed Nanotechnol. 2014;10:1091–104.CrossRefPubMedGoogle Scholar
  11. 11.
    Unger RE, Sartoris A, Peters K, Motta A, Migliaresi C, Kunkel M, et al. Tissue-like self-assembly in cocultures of endothelial cells and osteoblasts and the formation of microcapillary like structures on three-dimensional porous biomaterials. Biomaterials. 2007;28:3965–76.CrossRefPubMedGoogle Scholar
  12. 12.
    Zhang J, Zhou H, Yang K, Yuan Y, Liu C. RhBMP-2-loaded calcium silicate/calcium phosphate cement scaffold with hierarchically porous structure for enhanced bone tissue regeneration. Biomaterials. 2013;34:9381–92.CrossRefPubMedGoogle Scholar
  13. 13.
    Hofmann S, Hagenmüller H, Koch AM, Müller R, Vunjak-Novakovic G, Kaplan DL, et al. Control of in vitro tissue-engineered bone-like structures using human mesenchymal stem cells and porous silk scaffolds. Biomaterials. 2007;28:1152–62.CrossRefPubMedGoogle Scholar
  14. 14.
    Correia C, Bhumiratana S, Yan LP, Oliveira AL, Gimble JM, Rockwood D, et al. Development of silk-based scaffolds for tissue engineering of bone from human adipose-derived stem cells. Acta Biomater. 2012;8:2483–92.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Bohner M, Loosli Y, Baroud G, Lacroix D. Commentary: deciphering the link between architecture and biological response of a bone graft substitute. Acta Biomater. 2011;7:478–84.CrossRefPubMedGoogle Scholar
  16. 16.
    Hing KA, Annaz B, Saeed S, Revell PA, Buckland T. Microporosity enhances bioactivity of synthetic bone graft substitutes. J Mater Sci Mater Med. 2005;16:467–75.CrossRefPubMedGoogle Scholar
  17. 17.
    Lan Levengood SK, Polak SJ, Wheeler MB, Maki AJ, Clark SG, Jamison RD, et al. Multiscale osteointegration as a new paradigm for the design of calcium phosphate scaffolds for bone regeneration. Biomaterials. 2010;31:3552–63.CrossRefPubMedGoogle Scholar
  18. 18.
    Poole KE, Treece GM, Ridgway GR, Mayhew PM, Borggrefe J, Gee AH. Targeted regeneration of bone in the osteoporotic human femur. PLoS One. 2011;6:e16190.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Leppänen OV, Sievänen H, Jokihaara J, Pajamäki I, Kannus P, Järvinen TL. Pathogenesis of age-related osteoporosis: impaired mechano-responsiveness of bone is not the culprit. PLoS One. 2008;3:e2540.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Khosla S, Westendorf JJ, Oursler MJ. Building bone to reverse osteoporosis and repair fractures. J Clin Invest. 2008;118:421–8.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Dominguez LJ, Scalisi R, Barbagallo M. Therapeutic options in osteoporosis. Acta Biomed. 2010;81 Suppl 1:55–65.PubMedGoogle Scholar
  22. 22.
    Teófilo JM, Brentegani LG, Lamano-Carvalho TL. Bone healing in osteoporotic female rats following intra-alveolar grafting of bioactive glass. Arch Oral Biol. 2004;49:755–62.CrossRefPubMedGoogle Scholar
  23. 23.
    Okazaki A, Koshino T, Saito T, Takagi T. Osseous tissue reaction around hydroxyapatite block implanted into proximal metaphysis of tibia of rat with collagen-induced arthritis. Biomaterials. 2000;21:483–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Tami AE, Leitner MM, Baucke MG, Mueller TL, van Lenthe GH, Müller R, et al. Hydroxyapatite particles maintain peri-implant bone mantle during osseointegration in osteoporotic bone. Bone. 2009;45:1117–24.CrossRefPubMedGoogle Scholar
  25. 25.
    Xuan F, Lee CU, Son JS, Jeong SM, Choi BH. A comparative study of the regenerative effect of sinus bone grafting with platelet-rich fibrin-mixed Bio-Oss® and commercial fibrin-mixed Bio-Oss®: an experimental study. J Craniomaxillofac Surg. 2014;42:e47–50.CrossRefPubMedGoogle Scholar
  26. 26.
    Oh DS, Koch A, Eisig S, Kim SG, Kim YH, Kim DG, et al. Distinctive capillary action by micro-channels in bone-like templates can enhance recruitment of cells for restoration of large bony defect. J Vis Exp. 2015. Scholar
  27. 27.
    Starý V, Douděrová M, Bačáková L. Influence of surface roughness of carbon materials on human osteoblast-like cell growth. J Biomed Mater Res A. 2014;102:1868–79.CrossRefPubMedGoogle Scholar
  28. 28.
    Zhou H, Wu X, Wei J, Lu X, Zhang S, Shi J, et al. Stimulated osteoblastic proliferation by mesoporous silica xerogel with high specific surface area. J Mater Sci Mater Med. 2011;22:731–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Ito H, Sasaki H, Saito K, Honma S, Yajima Y, Yoshinari M. Response of osteoblast-like cells to zirconia with different surface topography. Dent Mater J. 2013;32:122–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Hollinger JO, Kleinschmidt JC. The critical size defect as an experimental model to test bone repair materials. J Craniofac Surg. 1990;1:60–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Gomes PS, Fernandes MH. Rodent models in bone-related research: the relevance of calvarial defects in the assessment of bone regeneration strategies. Lab Anim. 2011;45:14–24.CrossRefPubMedGoogle Scholar
  32. 32.
    Bosch C, Melsen B, Vargervik K. Importance of the critical size bone defect in testing bone-regenerating materials. J Craniofac Surg. 1998;9:310–6.CrossRefPubMedGoogle Scholar
  33. 33.
    Oh DS, Kim YH, Ganbat D, Han MH, Lim P, Back JH, et al. Bone marrow absorption and retention properties of engineered scaffolds with micro-channels and nano-pores for tissue engineering: a proof of concept. Ceram Int. 2013;39:8401–10.CrossRefGoogle Scholar

Copyright information

© The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.College of Veterinary MedicineChonnam National UniversityGwangjuRepublic of Korea
  2. 2.Department of Chemical EngineeringKyungil UniversityGyeongsanRepublic of Korea
  3. 3.Carroll Laboratory for Orthopedic SurgeryColumbia UniversityNew YorkUSA

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