Skip to main content

Advertisement

SpringerLink
Log in

An in vivo murine model for screening cranial bone regenerative materials: testing of a novel synthetic collagen gel

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Rapid and efficient animal models are needed for evaluating the effectiveness of many new candidate bone regenerative materials. We developed an in vivo model screening for calvarial bone regeneration in lipopolysaccharide (LPS)-treated mice, in which materials were overlaid on the periosteum of the calvaria in a 20 min surgery and results were detectable in 1 week. Intraperitoneal LPS injection reduced spontaneous bone formation, and local application of basic fibroblast growth factor (bFGF) increased the bone-forming activities of osteoblasts. A novel synthetic collagen gel, alkali-treated collagen (AlCol) cross-linked with trisuccinimidyl citrate (TSC), acted as a reservoir for basic substances such as bFGF. The AlCol–TSC gel in conjunction with bFGF activated osteoblast activity without the delay in osteoid maturation caused by bFGF administration alone. The AlCol–TSC gel may slow the release of bFGF to improve the imbalance between osteoid formation and bone mineralization. These findings suggest that our model is suitable for screening bone regenerative materials and that the AlCOl–TSC gel functions as a candidate reservoir for the slow release of bFGF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Takagi K, Urist M. The reaction of the dura to bone morphogenetic protein (BMP) in repair of skull defects. Ann Surg. 1982;196:100–9.

    Article  Google Scholar 

  2. Spicer PP, Kretlow JD, Young S, Jansen JA, Kasper FK, Mikos AG. Evaluation of bone regeneration using the rat critical size calvarial defect. Nat Protocols. 2012;7:1918–29.

    Article  Google Scholar 

  3. Lorenzo J, Horowitz M, Choi Y. Osteoimmunology: interactions of the Bone and Immune System. Endocr Rev. 2008;29:403–40.

    Article  Google Scholar 

  4. Taguchi T, Saito H, Uchida Y, Sakane M, Kobayashi H, Kataoka K, et al. Bonding of soft tissues using a novel tissue adhesive consisting of a citric acid derivative and collagen. Mater Sci Eng, C. 2004;24:775–80.

    Article  Google Scholar 

  5. Towler D. Fibroblast growth factor (FGF) and FGF families in bone. In: Bilezikian J, Raisz L, Martin T, editors. Principles of bone biology. 3rd edn., vol 2 San Diego: Academic Press; 2008. p. 1103–1132.

  6. Inoue M, Sasaki M, Nakasu A, Takayanagi M, Taguchi T. An antithrombogenic citric acid-crosslinked gelatin with endothelialization activity. Adv Healthc Mater. 2012;1:573–81.

    Article  Google Scholar 

  7. Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 1983;16:109–10.

    Article  Google Scholar 

  8. Parfitt A, Drezner M, Glorieux F, Kanis J, Malluche H, Meunier P, et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 1987;2:595–610.

    Article  Google Scholar 

  9. Saito H, Taguchi T, Aoki H, Murabayashi S, Mitamura Y, Tanaka J, et al. pH-responsive swelling behavior of collagen gels prepared by novel crosslinkers based on naturally derived di- or tricarboxylic acids. Acta Biomater. 2007;3:89–94.

    Article  Google Scholar 

  10. Villanueva A, Mathews C, Parfitt A. Relationship between the size and shape of osteoblasts and the width of osteoid seams in bone. In: Takahashi H, editor. Handbook of bone morphometry. 1st ed. Niigata: Nishimura; 1983. p. 191–6.

    Google Scholar 

  11. Morinobu M, Nakamoto T, Hino K, Tsuji K, Shen Z-J, Nakashima K, et al. The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein-induced bone formation. J Exp Med. 2005;201:961–70.

    Article  Google Scholar 

  12. Kikuchi T, Matsuguchi T, Tsuboi N, Mitani A, Tanaka S, Matsuoka M, et al. Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via toll-like receptors. J Immunol. 2001;166:3574–9.

    Article  Google Scholar 

  13. Takami M, Kim N, Rho J, Choi Y. Stimulation by toll-like receptors inhibits osteoclast differentiation. J Immunol. 2002;169:1516–23.

    Article  Google Scholar 

  14. Kawaguchi H, Kurokawa T, Hanada K, Hiyama Y, Tamura M, Ogata E, et al. Stimulation of fracture repair by recombinant human basic fibroblast growth factor in normal and streptozotocin-diabetic rats. Endocrinology. 1994;135:774–81.

    Google Scholar 

  15. Liang H, Pun S, Wronski TJ. Bone anabolic effects of basic fibroblast growth factor in ovariectomized rats. Endocrinology. 1999;140:5780–8.

    Google Scholar 

  16. Kaigler D, Wang Z, Horger K, Mooney D, Krebsbach P. VEGF scaffolds enhance angiogenesis and bone regeneration in irradiated osseous defects. J Bone Miner Res. 2006;21:735–44.

    Article  Google Scholar 

  17. Mansukhani A, Bellosta P, Sahni M, Basilico C. Signaling by fibroblast growth factors (Fgf) and fibroblast growth factor receptor 2 (Fgfr2)-activating mutations blocks mineralization and induces apoptosis in osteoblasts. J Cell Biol. 2000;149:1297–308.

    Article  Google Scholar 

  18. Tabata Y, Yamada K, Miyamoto S, Nagata I, Kikuchi H, Aoyama I, et al. Bone regeneration by basic fibroblast growth factor complexed with biodegradable hydrogels. Biomaterials. 1998;19:807–15.

    Article  Google Scholar 

  19. Kawaguchi H, Oka H, Jingushi S, Izumi T, Fukunaga M, Sato K, et al. A local application of recombinant human fibroblast growth factor 2 for tibial shaft fractures: a randomized, placebo-controlled trial. J Bone Miner Res. 2010;25:2735–43.

    Article  Google Scholar 

  20. Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000;21:115–37.

    Google Scholar 

  21. Nagayoshi M, Taguchi T, Koyama H, Takato T, Miyata T, Nagawa H. Enhanced neovascular formation in a novel hydrogel matrix consisting of citric acid and collagen. Ann Vascular Dis. 2011;4:196–203.

    Article  Google Scholar 

  22. Takayama T, Taguchi T, Koyama H, Sakari M, Kamimura W, Takato T, et al. The growth of a vascular network inside a collagen-citric acid derivative hydrogel in rats. Biomaterials. 2009;30:3580–7.

    Article  Google Scholar 

  23. Chikazu D, Taguchi T, Koyama H, Hikiji H, Fujihara H, Suenaga H, et al. Improvement in wound healing by a novel synthetic collage-gel dressing in genetically diabetic mice. Asian J Oral Maxillofac Surg. 2010;22:61–7.

    Article  Google Scholar 

  24. Saito H, Murabayashi S, Mitamura Y, Taguchi T. Unusual cell adhesion and antithrombogenic behavior of citric acid-cross-linked collagen matrices. Biomacromolecules. 2007;8:1992–8.

    Article  Google Scholar 

  25. Ehlers W, Karajan N, Markert B. A porous media model describing the inhomogeneous behaviour of the human intervertebral disc. Materialwiss Werkstofftech. 2006;37:546–51.

    Article  Google Scholar 

Download references

Acknowledgments

This study was supported in part by the Industrial Technology Research Grant Program of the New Energy and Industrial Technology Development Organization (NEDO) of Japan. This work was also supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to H.H.).

Author information

Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan

    Hisako Hikiji, Ken Tomizuka, Daichi Chikazu, Yoshiyuki Mori & Tsuyoshi Takato

  2. Department of Oral Functional Management, School of Oral Health Sciences, Faculty of Dentistry, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, 803-8580, Japan

    Hisako Hikiji

  3. Dentistry, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

    Ken Tomizuka

  4. Biomaterials Unit Nano-life Field, International Center for Materials Nanoarchitectonics, National Institute for Materials Science, Tsukuba, Japan

    Tetsushi Taguchi

  5. Translational Research Center, The University of Tokyo Hospital, Tokyo, Japan

    Hiroyuki Koyama

  6. Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Tokyo Medical University, Tokyo, Japan

    Daichi Chikazu

  7. Division of Tissue Engineering, Faculty of Medicine, The University of Tokyo, Tokyo, Japan

    Hiroyuki Koyama & Tsuyoshi Takato

Authors
  1. Hisako Hikiji
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ken Tomizuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tetsushi Taguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroyuki Koyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daichi Chikazu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshiyuki Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tsuyoshi Takato
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hisako Hikiji.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hikiji, H., Tomizuka, K., Taguchi, T. et al. An in vivo murine model for screening cranial bone regenerative materials: testing of a novel synthetic collagen gel. J Mater Sci: Mater Med 25, 1531–1538 (2014). https://doi.org/10.1007/s10856-014-5185-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-014-5185-5

Keywords

Search

Navigation