Calcified Tissue International

, Volume 56, Issue 6, pp 549–553 | Cite as

Recombinant bone morphogenetic protein-2 enhances bone healing, guided by osteopromotive e-PTFE membranes: An experimental study in rats

  • A. Linde
  • E. Hedner
Laboratory Investigations

Abstract

It has been shown earlier that it is possible to improve bone healing, to regenerate previously existing bone, and to create new bone by means of an osteopromotive membrane technique. The present study addresses the question of whether it is possible to combine this technique with a locally applied factor, stimulatory to osteogenesis. Circular transosseous ‘critical size’ defects in mandibles of rats were either implanted with recombinant human bone morphogenetic protein type 2 (rhBMP-2) or were left empty; half the number of implanted and half the number of empty defects were covered with an expanded polytetrafluoroethylene (e-PTFE) membrane (GORE-TEX®). Results were evaluated after 12 and 24 days of healing by a histomorphological scoring system. Implantation of rhBMP-2 alone resulted in bony bridging of the defect after only 12 days, but also in voluminous amounts of new bone outside the original defect area. When rhBMP-2 was combined with membrane, newly formed woven bone bridged the defect and the bone contour was maintained by the membrane. The combined treatment with membrane and rhBMP-2 demonstrated a significantly better bone healing than with e-PTFE membrane alone at both 12 days and 24 days of healing. It was concluded that rhBMP-2 has a strong osteoinductive potential and, in contrast to what was found earlier with other types of BMP preparations, this potential was retained when combining the rhBMP-2 with the osteopromotive membrane technique, yielding better bone healing than with the membrane alone, and at the same time maintaining the bone contour. This combination may have important therapeutic applications for osseous healing and in reconstructive surgery. The study also shows the importance of an appropriate carrier material when applying stimulatory substances to enhance bone formation in combination with a membrane.

Key words

Bone development Bone morphogenetic protein Artificial membrane Polytetrafluoroethylene Rats 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Linde A, Alberius P, Dahlin C, Bjurstam K, Sundin Y (1993) Osteopromotion. A soft-tissue exclusion principle using a membrane for bone healing and bone neogenesis. J Periodontol 64: 1116–1128Google Scholar
  2. 2.
    Tenenbaum HC (1990) Cellular origins and theories of differentiation of bone-forming cells. In: Hall BK (ed) Bone, vol 1: the osteoblast and osteocyte. Telford Press, Caldwell, NJ, pp 41–69Google Scholar
  3. 3.
    Baylink DJ, Finkelman RD, Mohan S (1993) Growth factors to stimulate bone formation. J Bone Miner Res 8:S565-S572Google Scholar
  4. 4.
    Urist MR (1965) Bone formation by autoinduction. Science 150: 893–899Google Scholar
  5. 5.
    Reddi AH, Huggins C (1972) Biochemical sequences in the transformation of normal fibroblasts in adolescent rats. Proc Natl Acad Sci USA 69:1601–1605Google Scholar
  6. 6.
    Urist MR, Strates BS (1971) Bone morphogenetic protein. J Dent Res 50:1392–1406Google Scholar
  7. 7.
    Kaban LB, Glowacki J (1981) Induced osteogenesis in the repair of experimental mandibular defects in rats. J Dent Res 60:1356–1364Google Scholar
  8. 8.
    Knutsen R, Mohan S, Wergedal J, Sampath K, Baylink DJ (1993) Osteogenic protein-1 stimulates proliferation and differentiation of human bone cells in vitro. Biochem Biophys Res Commun 194:1352–1358Google Scholar
  9. 9.
    Ripamonti U, Reddi AH (1992) Growth and morphogenetic factors in bone induction: role of osteogenin and related bone morphogenetic proteins in craniofacial and periodontal bone repair. Crit Rev Oral Biol Med 3:1–14Google Scholar
  10. 10.
    Wang EA, Rosen V, Cordes P, Hewick RM, Kriz MJ, Luxenberg DP, Sibley BS, Wozney JM (1988) Purification and characterization of other distinct bone-inducing factors. Proc Natl Acad Sci USA 85:9484–9488Google Scholar
  11. 11.
    Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA (1988) Novel regulators of bone formation: molecular clones and activities. Science 242: 1528–1534Google Scholar
  12. 12.
    Ozkaynak E, Rueger DC, Drier EA, Corbett C, Ridge RJ, Sampath TK, Oppermann H (1990) OP-1 cDNA encodes an osteogenic protein in the TGF-beta family. EMBO J 9:2085–2093Google Scholar
  13. 13.
    Toriumi DM, Kotler HS, Luxenberg DP, Holtrop ME, Wang EA (1991) Mandibular reconstruction with a recombinant bone-inducing factor. Arch Otolaryngol Head Neck Surg 117:1101–1112Google Scholar
  14. 14.
    Dahlin C, Linde A, Röckert H (1993) Stimulation of early bone formation by the combination of an osteopromotive membrane technique and hyperbaric oxygen. Scand J Plast Reconstr Hand Surg 27:103–108Google Scholar
  15. 15.
    Hedner E, Linde A (in press) Effect of bone morphogenetic protein implantation in rat mandibular defects, covered by osteopromotive membranes. Eur J Oral Sci 103Google Scholar
  16. 16.
    Dahlin C, Linde A, Gottlow J, Nyman S (1988) Healing of bone defects by guided tissue regeneration. Plast Reconstr Surg 81: 672–676Google Scholar
  17. 17.
    Heiple KG, Chase SW, Hernon CH (1963) A comparative study of the healing process following different types of bone transplantation. J Bone Joint Surg 45:1593–1616Google Scholar
  18. 18.
    Schmitz JP, Hollinger JO (1985) The critical size defects as an experimental model for craniomandibulofacial nonunions. Clin Orthop Rel Res 205:299–308Google Scholar
  19. 19.
    Sandberg E, Dahlin C, Linde A (1993) Bone regeneration by the osteopromotion technique using bioabsorbable membranes. An experimental study in rats. J Oral Maxillofac Surg 51:1106–1114Google Scholar
  20. 20.
    Zellin G, Gritli-Linde A, Linde A (in press) Healing of mandibular defects with different biodegradable and non-biodegradable membranes. An experimental study in rats. BiomaterialsGoogle Scholar
  21. 21.
    Takagi K, Urist MR (1982) The reaction of the dura to bone morphogenetic protein (BMP) in repair of skull defects. Ann Surg 196:100–109Google Scholar
  22. 22.
    Dahlin C, Lekholm U, Linde A (1991) Membrane-induced bone augmentation at titanium implants. A report of 10 fixtures followed from 1 to 3 years after loading. Int J Period Rest Dent 11:273–281Google Scholar
  23. 23.
    Dahlin C, Andersson L, Linde A (1991) Bone augmentation at fenestrated implants by an osteopromotive membrane technique. A controlled clinical study. Clin Oral Impl Res 2:159–165Google Scholar
  24. 24.
    Linde A, Thorén C, Dahlin C, Sandberg E (1993) Creation of new bone by an osteopromotive membrane technique. An experimental study in rats. J Oral Maxillofac Surg 51:892–897Google Scholar

Copyright information

© Springer-Verlag New York Inc 1995

Authors and Affiliations

  • A. Linde
    • 1
  • E. Hedner
    • 1
  1. 1.Department of Oral BiochemistryGöteborg UniversityGothenburgSweden

Personalised recommendations