Abstract
Bone lesions above a critical size become scarred rather than regenerated, leading to nonunion. We have attempted to obtain a greater degree of regeneration by using a resorbable scaffold with regeneration-competent cells to recreate an embryonic environment in injured adult tissues, and thus improve clinical outcome. We have used a combination of a coral scaffold with in vitro-expanded marrow stromal cells (MSC) to increase osteogenesis more than that obtained with the scaffold alone or the scaffold plus fresh bone marrow. The efficiency of the various combinations was assessed in a large segmental defect model in sheep. The tissue-engineered artificial bone underwent morphogenesis leading to complete recorticalization and the formation of a medullary canal with mature lamellar cortical bone in the most favorable cases. Clinical union never occurred when the defects were left empty or filled with the scaffold alone. In contrast, clinical union was obtained in three out of seven operated limbs when the defects were filled with the tissue-engineered bone.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Damien, C. & Parsons, R. Bone graft and bone graft substitutes: a review of current technology and applications. J. Appl. Biomat. 2, 187–208 (1991).
Langer, R. & Vacanti, J.P. Tissue engineering. Science 260, 920–926 (1993).
Caplan, A.I. Mesenchymal stem cells. J. Orthop. Res. 9, 641–650 (1991).
Caplan, A.I. & Bruder, S.P. Cell and molecular engineering of bone regeneration. In Principles of tissue engineering. (eds Lanza, R.P., Langer, R. & Chick, W.L.) 603–619 (Landes, Georgetown, TX; 1997).
Prockop, D.J. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276, 71–74 (1997).
Triffitt, J.T. The stem cell of the osteoblast. In Principles of bone biology. (eds Bilezikian, J.P. & Raisz, L.G.) 39–50 (Academic, San Diego, CA; 1996).
Ohgushi, H., Goldberg, V.M. & Caplan, A.I. Repair of bone defects with marrow cells and porous ceramic. Experiments in rats. Acta Orthop. Scand. 60, 334–339 (1989).
Bruder, S.P et al. Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells. J. Orthop. Res. 16, 155–162 (1998).
Bruder, S.P., Kraus, K.H., Goldberg, V.M. & Kadiyala, S. The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. J. Bone Joint Surg. Am. 80, 985–996 (1998).
Moore, D.C., Chapman, M.W. & Manske, D. The evaluation of a biphasic calcium phosphate ceramic for use in grafting long-bone diaphyseal defects. J. Orthop. Res. 5, 356–365 (1987).
Grundel, R.E., Chapman, M.W., Yee, T., and Moore, D.C. Autogeneic bone marrow and porous biphasic calcium phosphate ceramic for segmental bone defects in the canine ulna. Clin. Orthop. 266, 244–258 (1991).
Guillemin, G., Patat, J.L. & Meunier, A. Natural corals used as bone graft substitutes. Bulletin de l'institut océanographique Monaco 14, 67–77 (1995).
Piecuch, J.F., Goldberg, A.J., Shastry, C.V. & Chrzanowski, R.B. Compressive strength of implanted porous replamineform hydroxyapatite. J. Biomed. Mater. Res. 18, 39–45 (1984).
Guillemin, G., Patat, J.L., Fournié, J. & Chétail M. The use of coral as a bone graft substitute. J. Biomed. Mater. Res. 21, 557–567 (1987).
Yukna, R.A., & Yukna C.N. A 5-year follow-up of 16 patients treated with coralline calcium carbonate (Biocoral) bone replacement grafts in infrabony defects. J. Clin. Periodontol. 25, 1036–1040 (1998).
Yukna, R.A. Clinical evaluation of coralline calcium carbonate as a bone replacement graft material in human periodontal osseous defects. J. Periodontol. 65, 177–185 (1994).
Roux, F.X., Brasnu, D., Loty, B., Georges, B. & Guillemin, G. Madreporic coral: a new bone graft substitute for cranial surgery. J. Neuro. Surg. 69, 510–513 (1988).
Pouliquen, J.C., Noat, M., Verneret, C., Guillemin, G. & Patat J.L. Coral as a substitute for bone graft in posterior spine fusion in childhood. Fr. J. Orthop. Surg. 3, 272–280 (1989).
Kadiyala, S., Jaiswal, N. & Bruder, S. Culture-expanded bone marrow-derived mesenchymal stem cells can regenerate a critical-sized segmental bone defect. Tissue Engineering 3, 173–185 (1997).
Gross, U., Müller-Mai, C. and Voigt, C. Comparative morphology of the bone interface with glass ceramics, hydroxyapatite and natural coral. In The bone–biomaterial interface. (ed. Davies, J.E.). 308–320 (University of Toronto Press, Toronto, ON; 1991).
Goshima, J., Goldberg, V.M. & Caplan, A.I. Osteogenic potential of culture-expanded rat marrow cells as assayed in vivo with porous calcium phosphate ceramic. Biomaterials 12, 253–258 (1991).
Ostrum, R.F. et al. Bone injury, regeneration and repair. In Orthopaedic basic science. (ed. Simon, S.R.) 277–323 (American Academy of Orthopaedic Surgeons, Rosemont, IL; 1994).
Marks, S.C., & Hermey, D.C. The structure and development of bone. In Principles of bone biology. (eds Bilezikian, J.P. & Raisz, L.G.) 3–14 (Academic Press, San Diego, CA; 1996).
Hulbert, S.F et al. Potential of ceramic materials as permanently implantable skeletal prostheses. J. Biomed. Mater. Res. 4, 433–456 (1970).
Guillemin, G. et al. Comparison of coral resorption and bone apposition with two natural corals of different porosities. J. Biomed. Mater. Res. 23, 765–779 (1989).
Gay, C.V. & Mueller, W.J. Carbonic anhydrase and osteoclasts: localization by labeled inhibitor autoradiography. Science 183, 432–434 (1974).
Guillemin, G., Hunter, S.J. & Gay, C.V. Resorption of natural calcium carbonate by avian osteoclasts in vitro. Cells and Material s5, 157–165 (1995).
Shors, E.C. Coralline bone graft substitutes. Orthop. Clin. North Am. 30, 599–613 (1999).
Daculsi, G., Bouler, J.M. & LeGeros, R.Z. Adaptative crystal formation in normal and pathological calcifications in synthetic calcium phosphate and related biomaterials. Int. Rev. Cytol. 172, 129–191 (1997).
Pachence, J.M. & Kohn, J. Biodegradable polymers for tissue engineering. In Principles of tissue engineering. (eds Lanza, R.P., Langer, R. & Chick, W.L.) 274–193 (R.G. Landes, Georgetown, TX 1997).
Zawicki, D.F., Jain, R.K., Schmid-Schoenbein, G.W. & Chien, S. Dynamics of neovascularization in normal tissue. Microvasc. Res. 21, 27–47 (1981).
Irigaray, J.L. et al. Effet de la température sur la structure cristalline d'un Biocoral. J. Thermal Analysis 39, 3–14 (1993).
Petite, H., Kacem, K. & Triffitt, J.T. Adhesion, growth and differentiation of human bone marrow cells on non porous calcium carbonate and pastic substrata: effects of dexamethasone and 1,25 dihydroxyvitamin d3. Mater. Med. 7, 665–671 (1996).
Herbertson, A. & Aubin, J.E. Dexamethasone alters the subpopulation make-up of rat bone marrow stromal cell cultures. J. Bone Miner. Res. 10, 285–294 (1995).
Gamou, S., Shimizy, Y. & Shimizu, N. In Animal cell culture. (ed. Pollard, J. & Walker, J.) 197–207 (Humana, Clifton, NJ; 1990).
Louisia, S., Stromboni, M., Meunier, A., Sedel, L. & Petite, H. Coral grafting supplemented with bone marrow. J. Bone Joint Surg. Br. 81, 719–724 (1999).
Acknowledgements
We thank Inoteb (France) for donating the coral implants (Biocoral), Mrs M. Vallot for animal care and the Fondation pour l'Avenir ET8-263, Assistance Publique des Hopitaux de Paris AP-HP 97-002, CNRS and INSERM for financial support.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Petite, H., Viateau, V., Bensaïd, W. et al. Tissue-engineered bone regeneration. Nat Biotechnol 18, 959–963 (2000). https://doi.org/10.1038/79449
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/79449
This article is cited by
-
History of dental biomaterials: biocompatibility, durability and still open challenges
Heritage Science (2023)
-
Oral cavity-derived stem cells and preclinical models of jaw-bone defects for bone tissue engineering
Stem Cell Research & Therapy (2023)
-
Mesenchymal stem cells in fibrotic diseases—the two sides of the same coin
Acta Pharmacologica Sinica (2023)
-
Fucoxanthin diminishes oxidative stress damage in human placenta-derived mesenchymal stem cells through the PI3K/Akt/Nrf-2 pathway
Scientific Reports (2023)
-
Hierarchical helical carbon nanotube fibre as a bone-integrating anterior cruciate ligament replacement
Nature Nanotechnology (2023)