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Cultured Bone on Biomaterial Substrates

A Tissue Engineering Approach to Treat Bone Defects
  • S. C. Mendes
  • J. D. de Bruijn
  • C. A. van Blitterswijk
Chapter
Part of the NATO Science Series book series (NAII, volume 86)

Abstract

In the present work, a tissue engineering approach to treat bone defects was investigated. Such strategy was based on the use of patient own cultured bone marrow stromal cells (BMSCs) in association with biomaterials to produce autologous living bone equivalents. When engineering such implants, three main factors had to be taken into account: (i) the cells, (ii) the culture technology and (iii) the biomaterial scaffolds. The capacity of BMSCs to proliferate, differentiate along the osteogenic lineage and form a bone like tissue was demonstrated in various in vitro assays making use of biochemical, immunological, microscopic and gene expression techniques. The ability of the cells to produce bone in vivo was established using an ectopic (extra osseous) implantation model. Results indicated that BMSC cultures were composed of a heterogeneous population containing a subpopulation of cells with high proliferative capacity and with potential to differentiate into bone forming cells. Both the growth and the differentiation pattern of these cells could be manipulated, to a certain degree, through the use of bioactive factors during culture. After implantation, the bone forming capacity of the cultures proved to be related to the amount of early osteoprogenitors and precursors cells that could be induced into starting the osteogenic differentiation process. In bone marrow aspirates, this subpopulation appeared to decrease with donor age and to be strongly dependent on the donor, indicating that the aspiration procedure plays an important role in the obtained bone marrow cell population. In order to evaluate the in vivo bone formation capacity of BMSC cultures prior to implantation, an experimental method was developed in which the amount of early osteoprogenitors and precursors cells could be quantified. With regard to the technology design, data indicated that the culture of cells on the biomaterial scaffolds prior to implantation resulted in implants with faster in vivo bone forming ability as compared to scaffolds implanted shortly after cell seeding. In addition, two biodegradable polymeric systems were proposed as scaffolds to be used in the described bone engineering approach after evaluating their ability to support bone marrow cell growth, differentiation and in vivo bone formation. In summary, although the complete knowledge of the factors controlling BMSC growth and osteogenic differentiation still needs to be further expanded, the obtained results suggest that the bone tissue engineering approach described in this work presents a great potential for the repair of bone defects and will become an advantageous alternative to the traditional autologous bone grafting.

Keywords

Bone Formation Osteogenic Differentiation Bone Marrow Stromal Cell Human Bone Marrow Bone Tissue Engineering 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Athanasiou, K.A., Zhu, C-F., Lanctot, DR, Agrawal, CM. and Wang, X. (2000) Fundamentals of biomechanics in tissue engineering of bone, Tissue Eng. 6, 361–381.CrossRefGoogle Scholar
  2. 2.
    Buckwater, JA. and Cooper, RR. (1987) Bone structure and function. Instr. Course Lect 16, 27–48.Google Scholar
  3. 3.
    Derkx, P., Nigg, A.L., Bosnian, F.T., Birkenhäger-Frenkel, D.H., Houtsmuller, A.B., Pols, HAP and van Leeuwen, J.P.T.M. (1998) Immunolocalization and quantification of noncollagenous bone matrix proteins in methylmethacrylate-embedded adult human bone in combination with histomorphometry, Bone 22, 367–373.CrossRefGoogle Scholar
  4. 4.
    Rodan, G.A. (1992) Introduction to bone biology, Bone 13, S3–S6.CrossRefGoogle Scholar
  5. 5.
    Yaszemski, M.J., Payne, R.G., Hayes, W.C., Langer, R. and Mikos, A.G. (1996) Evolution of bone transplantation: molecular, cellular and tissue strategies to engineer human bone, Biomaterials 17, 175–185.CrossRefGoogle Scholar
  6. 6.
    Aubin, J.E. and Liu, F. (1996) The steoblast lineage, in J.P. Bilezikian, L.G. Raisz and G.A. Rodan ( eds.), Principles of bone biology, Academic Press, San Diego, USA, pp. 51–67.Google Scholar
  7. 7.
    Brown, K.L. and Cruess, R.I. (1982) Bone and cartilage transplantation in orthopaedic surgery, J. Bone Joint Surg. Am. 64, 270–279.Google Scholar
  8. 8.
    de Boer, H.H. (1988) The history of bone grafts, Clin. Orthop., 226–292.Google Scholar
  9. 9.
    Damien, C.J. and Parsons, J.R. (1991) Bone graft and bone graft substitutes: A review of current technology and applications,.J. Appl. Biomaterials 2, 187–208.CrossRefGoogle Scholar
  10. 10.
    Coombes, A.G.A. and Meikle, M.C. (1994) Resorbable synthetic polymers as replacements for bone graft, Clin. Mater. 17, 35–67.CrossRefGoogle Scholar
  11. 11.
    Laurencin, CT., Attawia, M. and Borden, M.D. (1999) Advancements in tissue engineered bone substitutes, Curr. Opinion Orthop. 10, 445–451.CrossRefGoogle Scholar
  12. 12.
    Lane, J.M., Tomin, E. and Bostrom, M.P.G. (1999) Biosynthetic bone grafting, Clin. Orthop. Rel. Res. 367S, S107–S117.Google Scholar
  13. 13.
    Urist, M.R. (1965) Bone: formation by autoinduction, Science 150, 893–899.CrossRefGoogle Scholar
  14. 14.
    Cornell, C.N. and Lane, J.M. (1998) Current understanding of osteoconduction in bone regeneration, Clin. Orthop. 355, S267-73.Google Scholar
  15. 15.
    Prolo, D.J. and Rodrigo, J.J. (1985) Contempory bone graft physiology and surgery, Clin. Orthop. 200, 322–342.Google Scholar
  16. 16.
    Cowley, S.P. and Anderson, L.D. (1983) Hernias through donor sites for iliac-bone grafts, J. Bone Joint. Surg. Am. 65, 1023–1025.Google Scholar
  17. 17.
    Arrington, E.D., Smith, W.J., Chambers, H.G., Bucknell, A.L. and Davino, N.A. (1996) Compilcations of iliac crest bone graft harvesting, Clin. Orthop. 329, 300–309.CrossRefGoogle Scholar
  18. 18.
    Coventry, MB. and Tapper, E.M. (1972) Pelvic instability: a consequence of removing iliac bone for grafting. J. Bone Joint Surg. Am. 54, 83–101.Google Scholar
  19. 19.
    Oklund, S.A., Prolo, D.J., Gutierrez, R.V. and King, S.E. (1986) Quantitative comparisons of healing in cranial fresh autografts, frozen autografìa and processed autografts, and allografts in canine skull defects, Clin. Orthop. 205, 269–291.Google Scholar
  20. 20.
    Oikarinen, J. and Korhonen, L.K. (1979) The bone inductive capasity of various bone transplanting materials used for treatment of expermental bone defects, Clin. Orthop. 140, 208–215.Google Scholar
  21. 21.
    Anderson, M.L.C., Dhert, W.J.A., de Bruijn, J.D., Dalmeijer, A.J., Leenders, H., vanBlitterswijk, CA. and Verbout, A.J. (1999) Critical size defect in the goat’s os ilium, Clin. Orthop. Reí. Res. 364, 231–239.CrossRefGoogle Scholar
  22. 22.
    Strong, D.M., Friedlaender, G.E., Tomford, W.W., Springfield, D.S., Shives, T.C, Burchardt, H., Enneking, W.F. and Mankin, H.J. (1996) Immunologic responses in human recipients of osseous and osteochondral allografts, Clin. Orthop. 326, 107–114.CrossRefGoogle Scholar
  23. 23.
    Oreffo, R.O.C, and Triffitt, J.T. (1999) Future potentials for using osteogenic stem cells and biomaterials in orthopedics, Bone 25, 5S–9S.CrossRefGoogle Scholar
  24. 24.
    Cook, S.D., Kay, J.F., Thomas, K.A. and Jarcjo, M. (1987) Interface mechanics and histology of titanium and hydroxyla coated titanium for dental implant applications, Int. J. Oral Maxillofac. Implants 2, 15–22.Google Scholar
  25. 25.
    Cook, S.D., Thomas, K.A., Dalton, J.E., Volkman, TH., Whitecloud, T.S. and Kay, J.F. (1992) Hydroxylapatite coating of porous implants improves bone ingrowth and interface attachment strength, J. Biomed. Mater. Res. 26, 989–1001.CrossRefGoogle Scholar
  26. 26.
    Spector, M. (1992) Biomaterial failure, Orthop. Clin. North Am. 23, 211–217.Google Scholar
  27. 27.
    Klein, C.P., Patka, P. and den Hollander, W. (1989) Macroporous calcium phosphate bioceramics in dog femora: a histological study of interface and biodegradation, Biomaterials 10, 59–62.CrossRefGoogle Scholar
  28. 28.
    Lemons, J.E. (1996) Ceramics: past, present, and future, Bone 19, 121S–128S.CrossRefGoogle Scholar
  29. 29.
    Marcacci, M., Kon, E., Zaffagnini, S., Giardino, R., Rocca, M., Corsi, A., Benvenuti, A., Bianco, P., Quarto, R., Martin, I., Muraglia, A. and Cancedda, R. (1999) Reconstruction of extensive long-bone defects in sheep using porous hydroxyapatite sponges, Calcif. Tissue Int. 64, 83–90.CrossRefGoogle Scholar
  30. 30.
    Wykrota, LL, Wykrott, F.H.L and Garrido, CA (2000) Long-term bone regeneration in large human defects using calcium-phosphate paniculate, in J.E. Davies (ed.) Bone Engineering, em square incorporated, Toronto, Canada, pp. 516–565.Google Scholar
  31. 31.
    Daculsi, G. (1998) Biphasic calcium phosphate concept applied to artificial bone, implant coating and injectable bone substitute, Biomaterials 19, 1473–1478.CrossRefGoogle Scholar
  32. 32.
    van Blitterswijk, CA., Hesseling, S.C., Grote, J.J., Koerten, H.K. and de Groot, K. (1990) The biocompatibility of hydrixyapatite ceramic: a study of retrieved human middle ear implants, J. Biomed. Mater. Res. 24, 433–453.CrossRefGoogle Scholar
  33. 33.
    Furlong, R.J. and Osborn, J.F. (1991) Fixation of hip prostheses by hydroxyapatite ceramic coatings,. Bone Joint Surg. Br. 73, 741–745.Google Scholar
  34. 34.
    Salyer, K.E. and Hall, CD. (1989) Porous hydroxyapatite as an onlay bone-graft substitute for maillofacial surgery, Plast. Recensir. Surg. 84, 236–244.CrossRefGoogle Scholar
  35. 35.
    Hing, K.A., Best, S.M., Tanner, K.E., Revell, P.A. and Bonfield, W. (1998) Histomorphological and biomechanical characterization of calcium phosphates in the osseous environment, J. Eng. Medicine 212, 437–451.CrossRefGoogle Scholar
  36. 36.
    Marra, K.G., Szem, J.W., Kumta, P.N., DiMilla, P.A. and Weiss, LE. (1999) In vitro analysis of biodegradable polymer blend/hydroxyapatite composites for bone tissue engineering, J. Biomed. Mater. Res. 47, 324–335.CrossRefGoogle Scholar
  37. 37.
    Mendes, S.C., Reis, R.L, Bovell, Y.P., Cunha, A.M., van Blitterswijk, CA. and de Bruijn, J.D. (2001) Biocompatibility testing of novel starch-based materials with potential application in orthopaedic surgery: a preliminary study, Biomaterials 22, 2057–2064.CrossRefGoogle Scholar
  38. 38.
    Thomson, R.C., Yaszemski, M.J., Powers, J.M. and Mikos, A.G. (1995) Fabrication of biodegradable scaffolds to engineer trabecular bone, J. Biomater. Sci. Polym. Ed. 7, 23–38.CrossRefGoogle Scholar
  39. 39.
    Goldstein, A.R., Zhu, G., Morris, G.E., Meszlenyi, R.K. and Mikos, A.G. (1999) Effect of osteoblastic culture conditions on the structure of poly(DL-lactic-co-glycolic acid) foam scaffolds, Tissue Eng. 5, 421–433.CrossRefGoogle Scholar
  40. 40.
    Whang, K., Healy, K.E., Elenz, D.R., Nam, E.K., Tsai, D.C., Thomas, C.H., Nuber, G.W., Glorieux, F.H., Travers, R. and Sprague, S.M. (1999) Engineering bone regeneration with bioabsorbable scaffolds with novel microarchitecture, Tissue Eng. 5, 35–51.CrossRefGoogle Scholar
  41. 41.
    Calvert, J.W., Marra, K.G., Cook, L, Kumta, P.N., DiMilla, P.A and Weiss, LE. (2000) Characterization of osteoblast-like behavior of cultured bone marrow stromal cells on various polymer surfaces, J. Biomed. Mater. Res. 52, 279–284.CrossRefGoogle Scholar
  42. 42.
    Nichter, LS., Yadzi, M., Kosari, K., Sridjaja, R., Ebramzadeh, E. and Nimni, M.E. (1992) Demineralized bone matrix polydioxanone composite as a substitute for bone graft: a comparative study in rats, J.Craniofac. Surg. 3, 63–69.CrossRefGoogle Scholar
  43. 43.
    Peter, S.J., Lu, L, Kim, D.J. and Mikos, A.G. (2000) Marrow stromal Osteoblast function on a poly(propylene fumarate)/ß-tricalcium phosphate biodegradable orthopaedic composite, Biomaterials 21, 1207–1213.CrossRefGoogle Scholar
  44. 44.
    Martin, I., Shastri, V.P., Padera, R.F., Yang, J., Mackay, A.J., Langer, R., Vunjak-Novakovic, G. and Freed, LE. (2001) Selective differentiation of mammalian bone marrow stromal cells cultured on three-dimensional polymer foams, J. Biomed. Mater. Res. 55, 229–235.CrossRefGoogle Scholar
  45. 45.
    Saad, B., Ciardelli, G., Matter, S., Welti, M., Uhlshmid, G.K., Neuenschwander, P. and Suter, U.W. (1998) Degradable and highly porous polyesterurethane foam as biomaterial: effects and phagocytosis of degradation products in osteoblasts, J. Biomed. Mater. Res. 39, 594–602.CrossRefGoogle Scholar
  46. 46.
    Radder, A.M., Leenders, H. and van Blitterswijk, CA. (1994) Interface reactions to PEO/PBT copolymers (polyactiveR) after implantation in cortical bone, J. Biomed. Mater. Res. 28, 141–151.CrossRefGoogle Scholar
  47. 47.
    Deschamps, A.A., Claase, M.B., Sleijster, W.J., de Bruijn, J.D., Grijpma, D.W. and Feijen, J. (submmited) Design of segmental poly(ether ester) materials and structures for the tissue enginerring of bone, J. Controlled release.Google Scholar
  48. 48.
    Winter, G.D. and Simpson, B.J. (1969) Heterotopic bone formed in a synthetic sponge in the skin of young pigs, Nature 223, 88–90.CrossRefGoogle Scholar
  49. 49.
    Ripamonti, U. (1991) The morphogenesis of bone in replicas of porous hydroxyapatite obtained from conversion of calcium carbonate exoskeletons of coral, J. Bone Joint Surg. Am. 73, 692–703.Google Scholar
  50. 50.
    Yang, Z.J., Yuan, H., Zou, P., Tong, W., Qu, S. and zhang, X.D. (1997) Osteogenic response to extraskeletally implanted synthetic porous calcium phosphate ceramics: an early stage histomorphological study in dogs, 7. Mater. Sci. Mater. Med. 8, 697–701.CrossRefGoogle Scholar
  51. 51.
    Yuan, H., Yang, Z., li, Y., Zhang, X.D., de Bruijn, J.D. and de Groot, K. (1998) Osteoinduction by calcium phosphate biomaterials, J. Mater. Sci. Mater. Med. 9, 723–726.CrossRefGoogle Scholar
  52. 52.
    Li, Y., Yuan, H. and Zhang, X. (1998) Calcium phosphate biomaterials:from osteoconduction to osteoinduction, Transactions of the Society for Biomaterials 1998, San Diego, CA; p. 428.Google Scholar
  53. 53.
    Yuan, H., de Bruijn, J.D., Zhang, X., van Blitterswijk, C.A. and de Groot, K. (2001) Bone induction by porous glaas ceramic made from bioglass ® (45S5), J. Biom. Mater. Res. 58, 270–276.CrossRefGoogle Scholar
  54. 54.
    Yuan, H., de Bruijn, J.D., Li, Y., Feng, J., Yang, Z., de Groot, K. and Zhang, X. (2001) Bone formation induced by calcium phosphate ceramics in soft tissue of dogs: a comparative study between porous α-TCP and ß-TCP, J. Mater. Sci. Mater. Med. 12, 7–13.CrossRefGoogle Scholar
  55. 55.
    Yuan, H., Kurasshina, K., de Bruijn, J.D., Ii, Y., de Groot, K. and Zhang, X. (1999) A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics, Biomaterials 20, 1799–1806.CrossRefGoogle Scholar
  56. 56.
    Yang, Z., Yuan, H., Tong, W., Zou, P., Chen, W. and Zhang, X. (1996) Osteogenesis in extraskeletally implanted porous calcium phosphate ceramics: variability among different kinds of animal, Biomaterials 17, 2131–2137.CrossRefGoogle Scholar
  57. 57.
    Ripamonti, U. (1996) Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models, Biomaterials 17, 31–35.CrossRefGoogle Scholar
  58. 58.
    Langer, R. and Vacanti, J.P. (1993) Tissue engineering, Science 14, 920–926.CrossRefGoogle Scholar
  59. 59.
    Lind, M. (1996) Growth factors: possible new clinical tools, Acta Orthop. Scand. 67, 407–417.CrossRefGoogle Scholar
  60. 60.
    Urist, M.R., DeLange, R.J. and Finerman, G.A. (1983) Bone cell differentiation and growth factors, Science 220, 680–686.CrossRefGoogle Scholar
  61. 61.
    Kim, K.J., Itoh, T. and Kotake, S. (1997) Effects of recombinant human bone morphgenetic protein-2 on human bone marrow cells cultured with various biomaterials, J. Biomed. Mater. Res. 35, 279–285.CrossRefGoogle Scholar
  62. 62.
    Puleo, D.A. (1997) Dependence of mesenchymal cell responses on duration of exposure to bone morphogenetic protein-2 in vitro, J. Cell. Physiol. 173, 93–101.CrossRefGoogle Scholar
  63. 63.
    Balk, M.L., Bray, J., Day, C, Epperly, M, Greenberger, J., Evans, C.H. and Biyibizi, C. (1997) Effect of rhBMP-2 on the osteogenic potential of bone marrow stromal cells from an Osteogenesis imperfecta mouse (oim), Bone 21, 7–15.CrossRefGoogle Scholar
  64. 64.
    Takiguchi, T., Kobayashi, M., Suzuki, R., Yamaguchi, A., Isatsu, K., Nishihara, T., Nagumo, M. and Hasegawa, K. (1998) Recombinant human bone morphohenetic. protein-2 stimulates Osteoblast differentiation and suppresses matrix metalloproteinase-l production in human bone cells isolated from mandibulea, J. Periodont. Res. 33, 476–485.CrossRefGoogle Scholar
  65. 65.
    Fromigué, O., Marie, P.J. and Lomri, A. (1998) Bone morphogenetic protein-2 and transforming growth factor-ß2 interact to modulate human bone marrow stromal cell proliferation and differentiation, J. Cell Biochem. 68, 411–426.CrossRefGoogle Scholar
  66. 66.
    Whang, K., Tsai, D.C., Aitken, M., Sprague, S.M., Patel, P. and Healy, K.E. (1998) Ectopie bone formation via rhBMP-2 delivery from porous bioabsorbable polymer scaffolds, J. Biomed. Mater. Res. 42, 491–499.CrossRefGoogle Scholar
  67. 67.
    Ripamonti, U., Ramoshebi, L.N., Matsaba, T., Tasker, J., Crooks, J. and Teare, J. (2001) Bone induction by BMPs/Ops and related family members in primates, J. Bone Joint. Sur. 83, S116-S127.Google Scholar
  68. 68.
    Aspenberg, P., Jeppsson, C, Wang, J.S. and Boström, M. (1996) Transforming growth factor beta and bone morphogenetic protein 2 for bone ingrowth: a comparison using bone chambers in rats, Bone 19, 499–503.CrossRefGoogle Scholar
  69. 69.
    Boden, S.D., Martin, G.J., Morone, M., Ugbo, J.L., Titus, L. and Hutton, W.C. (1999) The use of coralline hydroxyapatite with bone marrow, autogenous bone graft, or osteoinductive bone protein extract for posterolateral lumbar spine fusion, Spine 24, 320–327.CrossRefGoogle Scholar
  70. 70.
    Wikesjö, U.M.E., Sorenson, R.G. and Wozney, J.M. (2001) Augmentation of alveolar bone and dental implant osseointegration: clinical implications of studies with rhBMP-2, J. Bone Joint. Sur. 83, S136-S145.Google Scholar
  71. 71.
    Brekke, J.H. and Toth, J.M. (1998) Principles of tissue engineering applied to programmable Osteogenesis, J. Biomed. Mater. Res. 43, 380–398.CrossRefGoogle Scholar
  72. 72.
    Boyne, P.J., Marx, R.E., Nevins, M., Triplett, G., Lazaro, E., Lilly, L.C., Alder, M. and Nummikoski, P. (1997) A feasibility study evaluating rhBMP-2/absorbable collagen sponge for maxillary sinus floor augmentation, Int. J. Periondontics Restorative Dent. 17, 11–25.Google Scholar
  73. 73.
    Geesink, R.G., Hoefnagels, N.H. and Bulstra, S.K. (1999) Osteogenic activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibular defect, J. Bone Joint Surg. Br. 81, 710–718.CrossRefGoogle Scholar
  74. 74.
    King, G.N., King, N., Cruchley, A.T., Wozney, J.M. and Hughes, F.J. (1997) Recombinant human bone morphogenetic protein-2 promotes wound healing in rat periodontal fenestration defects, J. Dent. Res. 76, 1460–1470.CrossRefGoogle Scholar
  75. 75.
    Mehler, M.F., Mabie, P.C., Zhang, D. and Kessler, J.A. (1997) Bone morphogenetic proteins in the nervous system, Trends Neurosci. 20, 309–317.CrossRefGoogle Scholar
  76. 76.
    Liu, P., Oyajobi, B.O., Russell, R.G.G. and Scutt, A. (1999) Regulation of osteogenic differentiation of human bone marrow stromal cells: interaction between transforming growth factor-ß and 1,25(OH)2 vitamin D3 in vitro, Calcif. Tissue Int. 65, 173–180.CrossRefGoogle Scholar
  77. 77.
    Sumner, D.R., Turner, T.M., Purchio, A.F., Gombotz, W.R., Urban, R.M. and Galante, J.O. (1995) Enhancement of bone ingrowth by transforming growth factor-beta, J. Bone Joint Surg. Am. 77, 1135–1147.Google Scholar
  78. 78.
    Martin, L, Muraglia, A., Campanile, G., Cancedda, R. and Quarto, R. (1997) Fibroblast growth factor-2 supports ex vivo expansion and maintenance of osteogenic precursors from human bone marrow, Endocrinology 138, 4456–4462.CrossRefGoogle Scholar
  79. 79.
    Zellin, G. and Linde, A. (2000) Effects of recombinant human fibroblast growth factor-2 on osteogenic cell populations during orthopic Osteogenesis in vivo, Bone 26, 161–168.CrossRefGoogle Scholar
  80. 80.
    Nefussi, J.R., Brami, G., Modrowski, D., Oboeuf, M. and Forest, N. (1997) Sequential expression of bone matrix proteins during rat calvaría Osteoblast differentiation and bone nodule formation in vitro, J. Histochem. Cytochem. 45, 493–503.CrossRefGoogle Scholar
  81. 81.
    Wada, Y., Kataoaka, H., Yokose, S., bhizuya, T., Miyazono, K., Gao, Y.H., Shibasaki, Y. and Yamguchi, A. (1998) Changes in Osteoblast phenotype during differentiation of enzymatically isolated rat calvaría cells, Bone 22, 479–485.CrossRefGoogle Scholar
  82. 82.
    Takushima, A., Kitano, Y. and Hani, K. (1998) Osteogenic potential of cultured periosteal cells in a distrated bone gap in rabbits, J. Surg. Res. 78, 68–77.CrossRefGoogle Scholar
  83. 83.
    Miura, Y. and O’Driscoll, S.W. (1998) Culturing periosyeum in vitro: the influence of different sizes of expiants, Cell Transplantation 7, 453–457.CrossRefGoogle Scholar
  84. 84.
    Robey, P.G. and Termine, J.D. (1985) Human bone cells in vitro, Calcif. Tissue Int. 37, 453–460.CrossRefGoogle Scholar
  85. 85.
    Gundle, R., Joyner, C.J. and Triffitt, J.T. (1997) Interactions of human osteoprogenitors with porous ceramic following diffusion chamber implantation in a xenogenic host, J. Mater. Sci. Mater. Med. 8, 519–523.CrossRefGoogle Scholar
  86. 86.
    Druder, S.P. and Fox, B.S. (1999) Tissue engineering of bone. Cell based strategies, Clin. Orthop. 167, S68-S83.Google Scholar
  87. 87.
    Doherty, M.J., Ashton, B.A., Walsh, S., Beresford, J.N., Grant, M.E. and Canfield, A.E. (1998) Vasular pericytes express osteogenic potential in vitro and in vivo, J. Bone Miner. Res. 13, 828–838.CrossRefGoogle Scholar
  88. 88.
    Lecoeur, L. and Ouhayoun, J.P. (1997) In vitro induction of osteogenic differentiation from non-osteogenic mesenchymal cells, Biomaterials 18, 989–993.CrossRefGoogle Scholar
  89. 89.
    Friedenstein, A.J., Chailakhyan, R.K. and Gerasimov, U.V. (1987) Bone marrow osteogenic stem cells: invitro cultivation and transplantation in diffusion chambers, Cell Tissue Kinet. 20, 263–272.Google Scholar
  90. 90.
    Maniatopoulos, C, Sodek, J. and Melcher, A.H. (1988) Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats, Cell Tissue Res. 254, 317–329.CrossRefGoogle Scholar
  91. 91.
    Owen, M. (1988) Marrow stromal stem cells, J. Cell Sci. 10, 63–76.Google Scholar
  92. 92.
    Ohgushi, H. and Okumura, M. (1990) Osteogenic capacity of rat and human marrow cells in porous ceramics, Acta Orthop. Scand. 61, 431–434.CrossRefGoogle Scholar
  93. 93.
    Beresford, J.N. (1989) Osteogenic stem cells and the stromal system of bone and marrow, Clin. Orthop. 240, 270–80.Google Scholar
  94. 94.
    Muschler, G.F., Boehm, C. and Easley, K. (1997) Aspiration to obtain Osteoblast progenitor cells from human bone marrow: the influence of aspiration volume, J. Bone Joint Sur. 79, 1699–1709.Google Scholar
  95. 95.
    Krebsbach, P.H., Kuznetsov, S.A. and Robey, P.G. (1999) Bone marrow stromal cells: characterization and clinical application, Crit. Rev. Oral Biol. Med. 10, 165–181.CrossRefGoogle Scholar
  96. 96.
    Bianco, P., Riminucci, M., Gronthos, S. and Robey, P.G. (2001) Bone marrow stromal cells: nature, biology, and potential applications, Stem Cells 19, 180–192.CrossRefGoogle Scholar
  97. 97.
    Gronthos, S., Graves, S.E. and Simmons, P.J. (1998) Isolation, purification and in vitro manipulation of human bone marrow stromal precursor cells, in J.N. Beresford and M.E. Owen (eds.), Marrow stromal cell culture, Cambridge University Press, Cambridge, UK, pp. 26–42.CrossRefGoogle Scholar
  98. 98.
    Owen, M.E. (1998) The marrow stromal cell system, in J.N. Beresford and M.E. Owen (eds.), Marrow stromal cell culture, Cambridge University Press, Cambridge, UK, pp. 1–9.CrossRefGoogle Scholar
  99. 99.
    Muraglia, A., Cancedda, R. and Quarto, R. (2000) Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model, J. Cell Science 113, 1161–1166.Google Scholar
  100. 100.
    Aubin, J.E. (2000) Osteogenic cell differentiation, in J.E. Davies (ed.) Bone Engineering, em square incorporated, Toronto, Canada, pp. 19–29.Google Scholar
  101. 101.
    Dennis, J.E., Merriam, A., Awadallah, A., Yoo, J.U., Johnstone, B. and Caplan, A.I. (1999) A quadripotential mesenchymal progenitor cell isolated from the marrow of an adult mouse, J. Bone Miner. Res. 14, 700–709.CrossRefGoogle Scholar
  102. 102.
    Pittenger, M.F., Makay, A.M., Beck, S.C., Jaiswal, R.K., Douglas, R., Mosca, J.D., Moorman, M.A., Simonetti, D.W., Craig, S. and Marshak, D.R. (1999) Multilineage potential of adult human mesenchymal stem cells, Science 284, 143–146.CrossRefGoogle Scholar
  103. 103.
    Bruder, S.P., Jaiswal, N. and Haynesworth, S.E. (1997) Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation, J. CellBiochem. 64, 278–294.CrossRefGoogle Scholar
  104. 104.
    Jaiswal, N., Haynesworth, S.E., Caplan, A.I. and Bruder, S.P. (1997) Ostegenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro, J. CellBiochem. 64, 295–312.CrossRefGoogle Scholar
  105. 105.
    Pri-Chen, S., Pitara, S., Lokiec, F. and Savion, N. (1998) Basic fibroblast growth factor enhances the growth and expression of the osteogenic phenotype of dexamethasone-treated human bone marrow-derived bone-like cells in culture, Bone 23, 111–117.CrossRefGoogle Scholar
  106. 106.
    Malaval, L., Modrowski, D., Gupta, A.K. and Aubin, J.E. (1994) Cellular expression of bone-related proteins during in vitro Osteogenesis in rat bone marrow stromal cell cultures, J. Cell Physiol. 158, 555–572.CrossRefGoogle Scholar
  107. 107.
    Rickard, D.J., Kassem, M., Hefferan, T.E., Sarkar, G., Spelsberg, T.C. and Riggs, B.L. (1996) Isolatin and characterization of Osteoblast precursor cells from human bone marrow, J. Bone Miner. Res. 11, 312–324.CrossRefGoogle Scholar
  108. 108.
    Fromigué, O., Marie, P.J. and Lomri, A. (1997) Differential effects of transforming growth factor ß2, dexamethasone and 1,25-dihydroxyvitamin D on human bone marrow stromal cells, Cytokine 9, 613–623.CrossRefGoogle Scholar
  109. 109.
    Cooper, L.F., Harris, CT., Brader, S.P., Kowalski, R. and Kadiyala, S. (2001) Incipient analysis of mesenchymal stem-cell-dreived Osteogenesis, J. Dent. Res. 80, 314–320.CrossRefGoogle Scholar
  110. 110.
    Komori, T., Yagi, H., Nomura, S., Yamaguchi, A., Sasaki, K., Deguchi, K., Shimizu, Y., Bronson, R.T., Gao, Y.H., Inada, M., Sato, M., Okamoto, R., Kitamura, Y., Yoshiki, S. and Kishimoto, T. (1997) Targeted disruption of cbfal results in a complete lack of bone formation owing to marurational arrest of osteoblasts, Cell 89, 755–764.CrossRefGoogle Scholar
  111. 111.
    Hayneswoth, S.E., Baber, M.A. and Caplan, A.I. (1992) Cell surface antigens on human marrow-derived mesenchymal cells are detected by monoclonal antibodies, Bone 13, 69–80.CrossRefGoogle Scholar
  112. 112.
    Joyner, C.J., Bennett, A. and Triffitt, J.T. (1997) Identification and enrichment of human osteoprogenitor cells by using differentiation stage-specific monoclonal antibodies, Bone 21, 1–6.CrossRefGoogle Scholar
  113. 113.
    Simmons, P.J. and Torok-Storb, B. (1991) Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1, Blood 78, 55–62.Google Scholar
  114. 114.
    Gronthos, S., Graves, S.E., Ohta, S. and Simmons, P.J. (1994) The STRO-1+ fraction of adult human bone marrow contains the osteogenic precursors, Blood 84, 4164–4173.Google Scholar
  115. 115.
    Gronthos, S. and Simmons, P.J. (1995) The growth factor requirements of STRO-1-positive human bone marrow stromal precursors under serum-deprived condotions in vitro, Blood 85, 929–940.Google Scholar
  116. 116.
    Oyajobi, B.O., Lomri, A., Hott, M. and Marie, P.J. (1999) Isolation and characterization of human clonogenic Osteoblast progenitors immunoselected from fetal bone marrow stroma using STRO-1 monoclonal antibody, J. Bone Miner. Res. 14, 351–361.CrossRefGoogle Scholar
  117. 117.
    Stewart, K., Walsh, S., Screen, J., Jefferiss, CM., Chainey, J., Jordan, G.R. and Beresford, J.N. (1999) Further characterization of cells expressing STRO-1 in cultures of adult human bone marrow stromal cells, J. Bone Miner. Res. 14, 1345–1356.CrossRefGoogle Scholar
  118. 118.
    Walsh, S., Jefferiss, C, Stewart, K., Jordan, G.R., Screen, J. and Beresford, J.N. (2000) Expression of the developmental markers STRO-1 and alkaline Phosphatase in cultures of human marrow stromal cells: regulation by fibroblast growth factor (FGF)-2 and relationship to the expression of FGF receptors 1-4, Bone 27, 185–195.CrossRefGoogle Scholar
  119. 119.
    Bennett, J.H., Joyner, C.J., Triffitt, J.T. and Owen, M.E. (1991) Adipocytic cells cultured from marrow have osteogenic potential, J. Cell Science 99, 131–139.Google Scholar
  120. 120.
    Galotto, M., Campanile, G., Robino, G., Cancedda, F.D., Bianco, P. and Cancedda, R. (1994) Hypertrophic chondrocytes undergo further differentiation to osteoblast-like cells and participate in the initial bone formation in developing chick embryo, J. Bone Miner. Res. 9, 1239–49.CrossRefGoogle Scholar
  121. 121.
    Yosbikawa, T., Ohgishi, H., Dohi, Y. and Davies, J.E. (1997) Viable bone formation in porous hydroxyapatite: marrow cell-derived in vitro bone on the surface of ceramics, Bio-Med. Mater. Eng. 7, 49–58.Google Scholar
  122. 122.
    Herbertson, A. and Aubin, J.E. (1995) Dexamethasone alters the subpopulation make-up of rat bone marrow stromal cell cultures, J. Bone Miner. Res. 10, 285–294.CrossRefGoogle Scholar
  123. 123.
    Hanada, K., Dennis, J.E. and Caplan, A.I. (1997) Stimulatory effects of basic fibroblast growth factor and bone morphogenetic protein-2 on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells, J. Bone Miner. Res. 12, 1606–1614.CrossRefGoogle Scholar
  124. 124.
    Vilamitjana-Amedee, J., Bareille, R., Rouais, F., Caplan, A.I. and Harmand, M.F. (1993) Human bone marrow stromal cells express an osteoblastic phenotype in culture, In Vitro Cell Dev. Biol. 29A, 699–707.CrossRefGoogle Scholar
  125. 125.
    Lennon, D.P., Haynesworth, S.E., Brader, S.P., Jaiswal, N. and Caplan, A.I. (1996) Human and animal mesenchymal progenitor cells from bone marrow: identification of serum for optimal selection and proliferation, In Vitro Cell Dev. Biol. 32, 602–611.CrossRefGoogle Scholar
  126. 126.
    Reid, LR. (1997) Glucocorticoid osteoporosis-mechanisms and management, Eur. J. Endocrin. 137, 209–217.CrossRefGoogle Scholar
  127. 127.
    Cheng, S-L., Yang, J.W., Rifas, L. and Zhang, U-F. (1994) Avioli LV, Differntiation of human bone marrow osteogenic stromal cells in vitro: induction of the Osteoblast phenotype by dexamethasone, Endocrinology 134, 277–286.CrossRefGoogle Scholar
  128. 128.
    Kim, C-H., Cheng, S-L. and Kim, G.S. (1999) Effects of dexamethasone on proliferation, activity, and cytokine secretion of normal human bone marrow stromal cells: possible mechanisms of glucocorticoid-induced bone loss, J.Endocr. 162, 371–379.CrossRefGoogle Scholar
  129. 129.
    Dieudonné, S.C., Kerr, J.M., Xu, T., Sommer, B., DeRubeis, A.R., Kuznetsov, S.A., Kim, I-S., Robey, P.G. and Young, M.F. (1999) Differential display of human marrow stromal cells reveals unique mRNA expression patterns in response to dexamethasone, J. Cell Biochem. 76, 231–243.CrossRefGoogle Scholar
  130. 130.
    Oreffo, R.O.C., Kusec, V., Romberg, S. and Triffitt, J.T. (1999) Human bone marrow osteoprogenitors express estrogen receptor-alpha and bone morphogenetic proteins 2 and 4 mRNA during osteoblastic differntiation, J. Cell Biochem. 75, 382–392.CrossRefGoogle Scholar
  131. 131.
    Leboy, P.S., Beresford, J.N., Devlin, C. and Owen, M.E. (1991) Dexamethasone induction of Osteoblast mRNAs in rat marrow stromal cell cultures, J. Cell Physiol. 146, 370–378.CrossRefGoogle Scholar
  132. 132.
    Haynesworth, S.E., Goshima, J., Goldberg, V.M. and Caplan, A.L (1992) Characterization of cells with osteogenic potential from human marrow, Bone 13, 81–88.CrossRefGoogle Scholar
  133. 133.
    Ohgushi, H., Okumura, M., Tamai, S., Shors, E.C. and Caplan, A.I. (1990) Marrow cell induced Osteogenesis in porous hydroxyapatite and tricalcium phosphate: a comparitive histomorphometric study of ectopic bone formation, J. Biomed. Mater. Res. 24, 1563–1570.CrossRefGoogle Scholar
  134. 134.
    Yoshikawa, T., Ohgushi, H. and Tamai, S. (1996) Immediate bone forming capability of prefabricated osteogenic hydroxyapatite, J. Biomed. Mater. Res. 32, 481–492.CrossRefGoogle Scholar
  135. 135.
    Dennis, J.E., Konstantakos, E.K., Arm. D. and Caplan, A.L (1998) In vivo Osteogenesis assay: a rapid method for quantitative analysis, Biomaterials 19, 1323–1328.CrossRefGoogle Scholar
  136. 136.
    de Bruijn, J.D., van den Brink, I., Mendes, S.C., Dekker, R., Bovell, Y.P. and van Blitterewijk, C.A. (1999) Bone induction by implants coated with cultured osteogenic bone marrow cells, Adv. Dent. Res. 13, 74–81.CrossRefGoogle Scholar
  137. 137.
    Yoshikawa, T., Ohgishi, H., Nakajima, H., Yamada, E., Ichijima, K., Tamai, S. and Ohta, T. (2000) In vivo osteogenic durability of cultured bone in porous ceramics, Transplantation 69, 128–134.Google Scholar
  138. 138.
    Ishaug-Riley, S.L., Crane, G.M., Gurlek, A., Miller, M.J., Yasko, A.W., Yaszemski, M.J. and Mikos, A.G. (1997) Ectopie bone formation by marrow stromal Osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery, J. Biomed. Mater. Res. 36, 1–8.CrossRefGoogle Scholar
  139. 139.
    Krebsbach, P.H., Kuznetsov, S.A., Satomura, K., Emmons, R.V.B., Rowe, D.W. and Robey, P.G. (1997) Bone formation in vivo: comparison of Osteogenesis by transplanted mouse and human marrow stromal fibroblasts, Transplantation 63, 1059–1069.CrossRefGoogle Scholar
  140. 140.
    Anselme, K., Noël, B., Flautre, B., Blary, M-C, Deleœurt, C, Descamps, M. and Hardouin, P. (1999) Association of porous hydroxyapatite and bone marrow cells for bone regeneration, Bone 25.51S–54S.CrossRefGoogle Scholar
  141. 141.
    Solchaga, L.A., Dennis, J.E., Goldberg, V.M. and Caplan, A.L (1999) Hyaluronic acid-based polymers as cell carriers for tissue-engineered repair of bone and cartilage, Orthop. Res. 17, 205–213.CrossRefGoogle Scholar
  142. 142.
    Kuznetsov, S.A., Krebsbach, P.H., Satomura, K., Kerr, J., Riminucci, M., Benayahu, D. and Robey, P.G. (1997) Single-colony derived strains of human marrow stromal fibroblasts form bone after transplantation in vivo, J. Bone Miner. Res. 12, 1335–1347.CrossRefGoogle Scholar
  143. 143.
    Yoshikawa, T., Ohgushi, H., Uemura, T., Nakajima, H., Ichijima, K., Tamai, S. and Tateisi, T. (1998) Human marrow cells-derived cultured bone in porous ceramics, Bio-Med. Mater. Eng. 8, 311–320.Google Scholar
  144. 144.
    Lennon, D.P., Haynesworth, S.E., Arm, D.M., Baber, M.A. and Caplan, A.I. (2000) Dilution of human mesenchymal stem cells with dermal fibroblasts and the effects on in vitro and in vivo osteochondrogenesis, Developmental Dynamics 219, 50–62.CrossRefGoogle Scholar
  145. 145.
    Kadiyala, S., Jaiswal, N. and Bruder, S.P. (1997) Culture-expanded, bone marrow-derived mesenchymal stem cells can regenerate a critical-sized segmental bone defect, Tissue Eng. 3, 173–185.CrossRefGoogle Scholar
  146. 146.
    Bruder, S.P., Kurth, A.A., Shea, M., Hayes, W.C., Jaiswal, N. and Kadiyala, S. (1998) Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells, J. Orthop. Res. 16, 155–162.CrossRefGoogle Scholar
  147. 147.
    Brader, S.P., Kraus, K.H., Goldberg, V.M. and Kadiyala, S. (1998) The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects, J. Bone Joint Surg. 80-a, 985–996.Google Scholar
  148. 148.
    Kon, E., Muraglia, A., Corsi, A., Bianco, P., Marcacci, M., Martin, I., Boyde, A., Ruspantini, I., Chistolin, P., Rocca, M., Giardino, R., Cancedda, R. and Quarto, R. (2000) Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones, J. Biomed. Mater. Res. 49, 328–337.CrossRefGoogle Scholar
  149. 149.
    Petite, H., Viateau, V., Bensaid, W., Meunier, A., de Pollak, C, Bourguignon, M., Oudina, K., Sedei, L. and Guillemin, G. (2000) Tissue-engineered bone regeneration, Nature Biotechnology 18, 959–963.CrossRefGoogle Scholar
  150. 150.
    Louisia, S., Stromboni, M., Meunier, A., Sedei, L. and Petite, H. (1999) Coral grafting supplemented with bone marrow, J. Bone Joint Surg. 81-B, 719–724.CrossRefGoogle Scholar
  151. 151.
    de Bruijn, J.D., Yuan, H., Dekker, R., Layrolle, P., de Groot, K. and van Blitterswijk, CA. (2000) Osteoinductive biomimetic calcium-phosphate coatings and their potential use as tissueengineering scaffolds, in J.E. Davies (ed.) Bone Engineering, em square incorporated, Toronto, Canada, pp. 421–431.Google Scholar
  152. 152.
    Filshie, R.J.A., Zannettino, A.C.W., Makrynikola, V., Gronthos, S., Henniker, A.J., Bendali, L.J., Gottlieb, D.J., Simmons, P.J. and Bradstock, K.F. (1998) MUC18, a member of the immunoglobulin superfamily, is expressed on bone marrow fibroblasts and a subset of hematological malignancies, Leukemia 12, 414–421.CrossRefGoogle Scholar
  153. 153.
    Cortes, F., Deschaseaux, F., Uchida, N., Labastie, M.C., Friera, A.M., He, D., Charbord, P. and Peault, B. (1999) HCA, an immunoglobulin-like adhesion molecule present on the earliest human hematopoietic precursor cells, is also expressed by stromal cells in blood-forming tissues, Blood 93, 826–837.Google Scholar
  154. 154.
    Brader, S.P., Horowitz, M.C., Mosca, J.D. and Haynesworth, S.E. (1997) Monoclonal antibodies reactive with human osteogenic cell surface antigens, Bone 21, 225–235.CrossRefGoogle Scholar
  155. 155.
    Inui, K., Oreffo, R.O.C. and Triffitt, J.T. (1997) Effects of beta mercapto ethanol on the proliferation and differentiation of human osteoprogenitor cells, Cell Biol. Int. 21, 419–421.CrossRefGoogle Scholar
  156. 156.
    Phinney, D.G., Kopen, G., Righter, W., Webster, S., Tremain, N. and Prockop, D.J. (1999) Donor variation in the growth properties and osteogenic potential of human marrow stromal cells, J. Cell Biochem. 75, 424–436.CrossRefGoogle Scholar
  157. 157.
    Muschler, G.F., Nitto, H., Boehm, C.A. and Easley, K.A. (2001) Age and gender related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors, J. Orthop. Res. 19, 117–125.CrossRefGoogle Scholar
  158. 158.
    Bab, I., Passi-Even, L., and Gazit, D. (1988) Osteogenesis in in-vivo diffusion chamber cultures of human bone marrow cells, Bone Mineral 4, 373–386.Google Scholar
  159. 159.
    Knight, S.M. and Gowen, M. (1992) The effect of age and sex on bone cell function, Calcif. Tissue Int. 50, Suppl 1 A12.Google Scholar
  160. 160.
    D’ippolito, G., Schüler, P.C., Ricordi, G, Roos, B.A. and Howard, G.A. (1999) Age-related osteogenic potential of mesenchymal stromal cells from human vertebral bone marrow, J. Bone Miner. Res. 14, 1115–112CrossRefGoogle Scholar
  161. 161.
    Evans, C.E., Galasko, C.S. and Ward, C. (1990) Effect of donor age on the growth in vitro of cells obtained from human trabecular bone, J. Orthop. Res. 8, 234–237.CrossRefGoogle Scholar
  162. 162.
    Davies, J.E., Chernecky, B., Lowenberg, B. and Shiga, A. (1991) Deposition and résorption of calcified matrix in vitro by rat marrow cells, Cells Mater. 1, 3–15.Google Scholar
  163. 163.
    de Bnuijn, J.D., Davies, J.E., Flach, J.S., de Groot, K. and van Blitterswijk, C.A. (1992), in Tissue-Inducing Biomaterials L. Cima et al. (eds.), Boston, USA, Res. Soc. Sp. Proc., vol 252, p. 63.Google Scholar
  164. 164.
    Yao, K.L., Todescan, R. and Sodek, J. (1994) Temporal changes in the matrix protein synthesis and m-RNA expression during mineralised tissue formation by adult rat bone marrow cells in culture, J. Bone Miner. Res. 9, 231–240.CrossRefGoogle Scholar
  165. 165.
    Bulstra, S.K., Geesink, R.G., Bakker, D., Bulstra, T.H., Bouwmeester, S.J. and van der Linden, A.J. (1996) Femoral canal occlusion in total hip replacement using resorbable and flexible cement restrictor, J. Bone Joint Surg. Br. 78, 892–898.CrossRefGoogle Scholar
  166. 166.
    Breitbart, A.S., Grande, D.A., Kessler, R., Ryaby, J.T., Fitzsimmons, R.J. and Grant, R.T. (1998) Tissue engineered bone repair of calvarial defects using cultured periosteal cells, Plast. Reconst. Surg. 101, 567–574.CrossRefGoogle Scholar
  167. 167.
    Perka, G, Schultz, O., Spitzer, R.S., Lindenhayn, K., Burmester, G.R. and Sittinger, M. (2000) Segmentai bone repair by tissue-engineered periosteal cell transplants with bioresorbable fleece and fibrin scaffolds in rabbits, Biomaterials 21, 1145–1153.CrossRefGoogle Scholar
  168. 168.
    Weng, Y., Cao, Y., Silva, CA., Vacanti, M.P. and Vacanti, C.A. (2001) Tissue engineered composites of bone and cartilage for mandible condylar reconstruction, J. Oral Maxillof. Surg. 59, 185–190.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2002

Authors and Affiliations

  • S. C. Mendes
    • 1
  • J. D. de Bruijn
    • 1
  • C. A. van Blitterswijk
    • 1
  1. 1.IsoTis NV Professor Bronkhorstlaan 10BilthovenThe Netherlands

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