Skip to main content
SpringerLink
Log in

Bone formation in ectopic and osteogenic tissue induced by a novel BMP-2-related peptide combined with rat tail collagen

  • Research Paper
  • Published:
Biotechnology and Bioprocess Engineering Aims and scope Submit manuscript

Abstract

Bone morphogenetic proteins (BMPs) play an important role in regulating osteoblast differentiation and subsequent bone formation, mainly evidenced by the induced osteogenic ability of BMP-2 from BMPs. However, BMP-2 alone does not induce the expected efficacy due to its short retention in vivo. In this study, a novel BMP-2-related peptide (designated P24) derived from the “knuckle epitope” of BMP-2 was coupled covalently to type I collagen derived from rat tail and observed under scanning electron microscopy (SEM) in low vacuum mode. The BMP-2-related peptide/collagen composite was implanted in vivo into the pocket of the quadriceps musculature of Sprague-Dawley (SD) rats and then harvested 3 or 6 weeks after surgery. It was found that lyophilized collagen retained a porous network structure with an average inner-diameter of 90 ∼ 160 μm. Based on radiographic evaluation and histological examination, BMP-2-related peptide/collagen induced significant ectopic bone formation compared to that of rat tail collagen alone as a control. Our results indicate collagen served as a good carrier for newly synthesized BMP-2-related peptide and that the BMP-2-related peptide/collagen composite was an effective substitute in bone tissue engineering.

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

Access this article

Log in via an institution

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Similar content being viewed by others

References

  1. Groeneveld, E. H. and E. H. Burger (2000) Bone morphogenetic proteins in human bone regeneration. Eur. J. Endocrinol. 142: 9–21.

    Article  CAS  Google Scholar 

  2. Celeste, A. J., J. A. Iannazzi, R. C. Taylor, R. M. Hewick, V. Rosen, E. A. Wang, and J. M. Wozney (1990) Identification of transforming growth factor beta family members present in boneinductive protein purified from bovine bone. Proc. Natl. Acad. Sci. U S A. 24: 9843–9847.

    Article  Google Scholar 

  3. Malafaya, P., G. Silva, E. Baran, and R. Reis (2002) Drug delivery therapies II. Strategies for delivering bone regenerating factors. Curr. Opin. Solid St. Mat. Sci. 6: 297–312.

    Article  CAS  Google Scholar 

  4. Hosseinkhani, H., M. Hosseinkhan, A. Khademhosseini, and H. Kobayashi (2007) Bone regeneration through controlled release of bone morphogenetic protein-2 from 3-D tissue engineered nano-scaffold. J. Control. Release 17: 380–386.

    Article  Google Scholar 

  5. Saito, A., Y. Suzuki, S. I. Ogata, C. Ohtsuki, and M. Tanihara (2004) Prolonged ectopic calcification induced by BMP-2-derived synthetic peptide. J. Biomed. Mater. Res. A 70: 115–121.

    Article  Google Scholar 

  6. Seol, Y. J., Y. J. Park, S. C. Lee, K.H. Kim, J. Y. Lee, T.I. Kim, Y.M. Lee, Y. Ku, I.C. Rhyu, S.B. Han, and C.P. Chung (2006) Enhanced osteogenic promotion around dental implants with synthetic binding motif mimicking bone morphogenetic protein (BMP)-2. J. Biomed. Mater. Res. A 77: 599–607.

    Google Scholar 

  7. Lin, X. H., J. J. Elliot, D. L. Carnes, W.C. Fox, L.A. Pena, S.L. Campion, K. Takahashi, B.L. Atkinson, and P.O. Zamora (2006) Augmentation of osseous phenotypes in vivo with a synthetic peptide. J. Orthop. Res. 25: 531–539.

    Article  Google Scholar 

  8. Kim, C. S., J. I. Kim, J. Kim, S. H. Choi, J. K. Chai, C. K. Kim, and K. S. Cho (2005) Ectopic bone formation associated with recombinant human bone morphogenetic proteins-2 using absorbable collagen sponge and beta tricalciumphosphate as carriers. Biomaterials 26: 2501–2507.

    Article  CAS  Google Scholar 

  9. Duan, Z. X., Q. X. Zheng, X. D. Guo, Q. Yuan, and S. G. Chen (2007) Experimental research on ectopic osteogenesis of BMP-2-derived peptide P24 combined with PLGA copolymers. J. Huazhong Univ. Sci. Technol. Med. Sci. 27: 179–182.

    Article  CAS  Google Scholar 

  10. Yuan, Q., X. D. Guo, Q. X. Zheng, M. Zhao, Z. Q. Pan, S. G. Chen, and D. P. Quan (2007) Bioinspired growth of hydroxyapatite nanocrystals on PLGA-(PEG-ASP)n scaffolds modified with oligopeptide derived from BMP-2. Key Eng. Mater. 335: 1261–1264.

    Article  Google Scholar 

  11. Niu, X. F., Q. L. Feng, M. B. Wang, X. D. Guo, and Q. X. Zheng (2009) Porous nano-HA/collagen/PLLA scaffold containing chitosan microspheres for controlled delivery of synthetic peptide derived from BMP-2. J. Control. Release 134: 111–117.

    Article  CAS  Google Scholar 

  12. Yuan, Q., H. W. Lu, S. Tang, K. Liu, Z. Q. Pan, H. T. Pan, D. P. Quan, Q. X. Zheng, and X. D. Guo (2007) Ectopic bone formation in vivo induced by a novel synthetic peptide derived from BMP-2 using a porous collagen scaffold. J. Wuhan Univ. Technol. mater. Sci. Ed. 22: 701–705.

    Article  CAS  Google Scholar 

  13. Shin, H. S., S. B. Jo, and A. G. Mikos (2003) Biomimetic materials for tissue engineering. Biomaterials 24: 4353–4364.

    Article  CAS  Google Scholar 

  14. Panyam, J., M. M. Dali, S. K. Sahoo, W. X. Ma, S. S. Chakravarthi, G. L. Amidon, R. J. Levy, and V. Labhasetwar (2003) Polymer degradation and in vitro release of a model protein from poly(D,L-lactide-co-glycolide) nano-and microparticles. J. Control. Release 92: 173–187.

    Article  CAS  Google Scholar 

  15. Srouji, S., T. Kizhner, and E. Livne (2006) 3D scaffolds for bone marrow stem cell support in bone repair. Regen. Med. 1: 519–528.

    Article  CAS  Google Scholar 

  16. El-Ghannam, A. (2005) Bone reconstruction: From bioceramics to tissue engineering. Expert Rev. Med. Devices 2: 87–101.

    Article  Google Scholar 

  17. Glowacki, J. and S. Mizuno (2008) Collagen scaffolds for tissue engineering. Biopolymers 89: 338–344.

    Article  CAS  Google Scholar 

  18. Ottani, V., M. Raspanti, and A. Ruggeri (2001) Collagen structure and functional implications. Micron. 32: 251–260.

    Article  CAS  Google Scholar 

  19. Hollinger, J. O., J. M. Schmitt, D. C. Buck, R. Shannon, S. P. Joh, H. D. Zegzula, and J. Wozney (1998) Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration. J. Biomed. Mater. Res. (Appl. Biomater.) 43: 356–364.

    Article  CAS  Google Scholar 

  20. Franke, H., H. J. Galla, and C. T. Beuckmann (2000) Primary cultures of brain microvessel endothelial cells: A valid and flexible model to study drug transport through the blood-brain barrier in vitro. Brain Res. Prot. 5: 248–256.

    Article  CAS  Google Scholar 

  21. Bharagava, U., M. Bar-Lev, C. G. Bellows, and J. E. Aubin (1986) Ultrastructural analysis of bone nodules formed in vitro by isolated fetal rat calvaria cells. Bone 9: 155–163.

    Article  Google Scholar 

  22. Schmidmaier, G., P. Schwabe, C. Strobel, and B. Wildemann (2008) Carrier systems and application of growth factors in orthopaedics. Injury 39: 37–43.

    Article  Google Scholar 

  23. Chen, G. P., T. Ushida, and T. Tateishia (2001) Development of biodegradable porous scaffolds for tissue engineering. Mater. Sci. Eng. C 17: 63–69.

    Article  Google Scholar 

  24. Wozney, J. and H. Seeherman (2004) Protein-based tissue engineering in bone and cartilage repair. Curr. Opinion Biotechnol. 15: 392–398.

    Article  CAS  Google Scholar 

  25. Tabata, Y. (2003) Tissue regeneration based on growth factor release. Tissue Eng. 9: 5–15.

    Article  Google Scholar 

  26. Yamamoto, M., Y. Takahashi, and Y. Tabata (2003) Controlled release by biodegradable hydrogels enhances the ectopic bone formation of bone morphogenetic protein. Biomaterials 24: 4375–4383.

    Article  CAS  Google Scholar 

  27. Lee, C. H., A. Singla, and Y. Lee (2001) Biomedical applications of collagen. Int. J. Pharm. 221: 1–22.

    Article  CAS  Google Scholar 

  28. Uludag, H., T. Gao, T. J. Porter, W. Friess, and J. M. Wozney (2001) Delivery systems for BMPs: Factors contributing to protein retention at an application site. J. Bone Jt. Surg. 83A(Suppl. 1): 128–135.

    Google Scholar 

  29. Uludag, H., D. D’Augusta, R. Palmer, G. Timony, and J. Wozney (1999) Characterization of rhBMP-2 pharmacokinetics implanted with biomaterial carriers in the rat ectopic model. J. Biomed. Mater Res. 46: 193–202.

    Article  CAS  Google Scholar 

  30. Davis, A. R., C. M. Fouletier-Dilling, F. H. Gannon, Z. Gugala, and R. W. Lindsey (2007) Adenovirus BMP2-induced osteogenesis in combination with collagen carriers. Olmsted-Davis EA. Biomaterials 28: 4469–4479.

    Google Scholar 

  31. Geiger, M., R. H. Li, and W. Friess (2003) Collagen sponges for bone regeneration with rhBMP-2. Adv. Drug Deliv. Rev. 55: 1613–1629.

    Article  CAS  Google Scholar 

  32. Seo, Y. K., H. H. Youn, C. S. Park, K. Y. Song, and J. K. Park (2008) Reinforced bioartificial dermis constructed with collagen threads. Biotechnol. Bioproc. Eng. 13: 745–751.

    Article  CAS  Google Scholar 

  33. Tewes-Schwarzer, P. (1999) Manufacturing principles of freeze dried collagen sponges: Characteristics and applications. In: L. Rey and J. C. May (eds.). Freeze Drying/Lyophilization Pharmaceutical and Biological Products. Drugs Pharmaceut. Sci. Marcel Dekker, NY.

    Google Scholar 

  34. Vailhe, B., D. Vittet, and J. J. Feige (2001) In vitro models of vasculogenesis and angiogenesis. Lab. Invest. 81: 439–452.

    CAS  Google Scholar 

  35. Montanez, E., R. P. Casaroli-Marano, and S. Vilaro (2002) Comparative study of tube assembly in three-dimensional collagen matrix and on matrigel coats. Angiogenesis 5: 167–172.

    Article  CAS  Google Scholar 

  36. Sakou, T. (1998) Bone morphogenetic proteins: From basic studies to clinical approaches. Bone 22: 591–603.

    Article  CAS  Google Scholar 

  37. Schilephake, H. (2002) Bone growth factors in maxillofacial skeletal reconstruction. Int. J. Oral Maxillofac Surg. 31: 469–484.

    Article  CAS  Google Scholar 

  38. Allendorph, G. P., W. W. Vale, and S. Choe (2006) Structure of the ternary signaling complex of a TGF-β superfamily member. PNAS 103: 7643–7648.

    Article  CAS  Google Scholar 

  39. Nohe, A., S. Hassel, M. Ehrlich, F. Neubauer, W. Sebald, and P. Knaus (2002) The mode of bone morphogenetic protein (BMP) receptor oligomerization determines different BMP-2 signaling pathways. J. Biol. Chem. 277: 5330–5338.

    Article  CAS  Google Scholar 

  40. Guo, X. and X. F. Wang (2009) Signaling cross-talk between TGF-beta/BMP and other pathways. Cell Res. 19: 71–88.

    Article  CAS  Google Scholar 

  41. Wu, B., Q. X. Zheng, X. D. Guo, Y. C. Wu, Y. Wang, and F. Z. Cui (2008) Preparation and ectopic osteogenesis in vivo of scaffold based on mineralized recombinant human-like collagen loaded with synthetic BMP-2-derived peptide. Biomed. Mater. 3: 44111.

    Article  Google Scholar 

  42. Niu, X. F., Q. L. Feng, M. B. Wang, X. D. Guo, and Q. X. Zheng (2009) In vitro degradation and release behavior of porous poly (lactic acid) scaffolds containing chitosan microspheres as a carrier for BMP-2-derived synthetic peptide. Polym. Degrad. Stabil. 94: 176–182.

    Article  CAS  Google Scholar 

  43. Ito, Y., J. Zheng, Y. Imanishi, K. Yonezawa, and M. Kasuga (1996) Protein-free cell culture on an artificial substrate with covalently immobilized insulin. Proc. Natl. Acad. Sci. USA. 93: 3598–3601.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopedics, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430-022, China

    Jing-Feng Li, Zhen-Yu Lin, Qi-Xin Zheng, Xiao-Dong Guo, Shu-Hua Yang, Hong-Wei Lu & Sheng-Hui Lan

Authors
  1. Jing-Feng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhen-Yu Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qi-Xin Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-Dong Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shu-Hua Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hong-Wei Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sheng-Hui Lan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qi-Xin Zheng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, JF., Lin, ZY., Zheng, QX. et al. Bone formation in ectopic and osteogenic tissue induced by a novel BMP-2-related peptide combined with rat tail collagen. Biotechnol Bioproc E 15, 725–732 (2010). https://doi.org/10.1007/s12257-009-3130-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12257-009-3130-0

Keywords

Search

Navigation