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Arquivos de Medicina

versão On-line ISSN 2183-2447

Arq Med v.19 n.4 Porto jul. 2005


Substitutos Ósseos

Conceitos Gerais e Estado Actual

Manuel Gutierres*, Maria Ascensão Lopes†‡, Nandyala Sooraj Hussain†‡, Abel Trigo Cabral*, Luís Almeida*, José Domingos Santos†‡

*Faculdade de Medicina da Universidade do Porto; † Faculdade de Engenharia da Universidade do Porto; ‡Instituto de Engenharia Biomédica, Porto



Os substitutos ósseos são actualmente objecto de intensa investigação a nível mundial, com vista a ultrapassar as limitações decorrentes da colheita de enxerto ou do recurso a bancos de osso, para preencher defeitos ósseos. Além disso, a utilização de substâncias com capacidade osteogénica abre novas perspectivas no tratamento de fracturas, pseudartroses e nas artrodeses vertebrais.

Dada a grande quantidade de informação existente sobre esta matéria, este artigo pretende não só rever conceitos gerais como também sumarizar o que de mais recente foi publicado na área da aplicação de substitutos ósseos para regeneração óssea.

Palavras-chave: Enxerto ósseo, substituto ósseo, biomaterial, hidroxiapatite, factores de crescimento



Bone Substitutes: General Concepts and "State of the Art"

Bone grafts are nowadays the subject of extensive research worldwide, aimed at overcoming limitations associated with the use of autografts or bone banks to fill bone defects. Additionally, the use of osteogenic substances opens new perspectives in the treatment of fractures, pseudarthroses and vertebral arthrodeses. Due to the large amount of information available in the area of bone grafts, this paper aims not only to revise general concepts but also to summarize what has been published recently in the area of bone substitutes for bone regeneration.

Key-words: Autografts, bone graft, biomaterial, hydroxyapatite, bone growth factors


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1 - Laurencin CT. Chapter I- Bone graft and bonegraft substitutes a brief history. In: Laurencin CT, editors. Bone graft substitute - ASTM International.2004 - ASTM International. 2004.

2 - Ratner BD. A history of Biomaterials. In: Ratner, edits. Biomaterials Science. 2nd edition. Elsevier Inc. 2004. pp.10- 9.

3 - Williams et al. Conferência de consensos sobre definições em Biomateriais. Chester 1991.

4 - Mainard. Les substituts osseox em 2001: Monographie Editée par GESTO (Association pour L‘etude des Greffes et substitutes Tissulaires en Orthopédie) sous la direction de Dr. Mainard , Edition Romillat , Paris, 2001.

5 - Banwart JC. Iliac crest bone graft harvest donor site morbidity. Spine 1995;20:1055-60.         [ Links ]

6 - Tomford WW. Bone allografts : Past, Present and future. Cell Tissue Bank 2000;1:105-9.

7 - Vaccaro AR. The Role of the Osteoconductive Scaffold in Synthetic Bone Graft. Orthopedics 2002; 25 (suppl 5): S71-8.

8 - Khan SN. Clinical applications of Bone Graft substitutes. Orthop Clin North Am 2000;31:389-98.

9 - Nishida K, Gilbertson LG, Evans CH, Kang JD. Potential applications of gene therapy to the treatment of spinal disorders. Spine 2000;25:1308-14.

10 - Proubasta J, Mur JG, Planell JA. Biocompatibilidad, materiales implantables, tipos de implante. In: Fundamentos de Biomecânica y Biomateriales, Ediciones Ergon. Madrid. 1997. pp. 271-350.

11 - Davies JE. Histodynamics of endosseous wound healing. In: Davies JE, editors. Bone engineering. Canada: EM2. 2000. pp. 1-11.

12 - Anderson. Biological responses to materials. Annu Rev Mater Res 2001;31:81-110.

13 - Bauer TW, Muschler GF. Bone Graft Materials. Clin Orthop 2000;37:10-27.

14 - Fleming JE Jr, Cornell CN, Muschler GF. Bone cells and matrices in Orthopedic Tissue Engineering. Orthop Clin North Am 2000;31:357-74.

15 - Vaccaro AR, Chiba K, Heller JG, et al. Bone grafting alternatives in spinal surgery. Spine J 2002;2:206-15.

16 - Boden SD. Biology of lumbar spine fusion and use of bone graft substitutes: Present, future and next generation. Tissue Eng 2000;6:383-99.

17 - Burkus JK, Sandhu HS, Gornet MF, Longley MC. Use of rh BMP-2 in combination with structural control allografts; Clinical and radiographic outcomes in anterior lumbar spinal surgery. J Bone Joint Surg 2005;87;1205-12.

18 - Keller EE, Triplett WW. Iliac bone graft: Review of 160 consecutive cases. J Oral Maxillofac Surg 1987;45:11-4.

19 - Younger E, Chapmann M. Morbidity at bone graft-donor sites. J Orthop Trauma 1989;3:192-5.

20 - Montgomery DM, Aronson DD, Lee CL, Lamont RL. Posterior spinal fusion: Allograft versus autografts bone. J Spine Disord 1990;3:370-5.

21 - Mc Carthy RE, Peek RD, Morrisy RT, Hough AJ Jr. Allograft bone in spinal fusion for paralytic scoliosis. J Bone Joint Surg Am 1986;68: 70-5.

22 - Lane JM, Safdar NK. Bone Grafts of the 20th Century: Multiple purposes, materials and goals. Orthopedics Today. 2000.

23 - Connolly J, Guse R, Lippiello L. Development of an osteogenic bone marrow preparation. J Bone Joint Surg Am 1989;71:684-91.

24 - Peltier LF. The use of plaster of Paris to fill defects in bone. Clin Orthop 1961;21:1-31.

25 - Hogset O, Bredberg G. Plaster of Paris and hair cell morphology. A scanning electron microscopic study of an alternative implant materials for ear surgery. Acta Otolaryngol 1988;106:331-8.

26 - Peltier LF, Jones RH. Treatment of unicameral bone cysts by curetage and packing with plaster of Paris pellets. Clin Orthop 2004;422:145-7.

27 - Hench LL, Best S. Ceramic, glasses and glass ceramics. In: Ratner BD, editors. Biomaterial sciences. 2nd Edition. 2004. pp.155-70.

28 - Hench LL, Wilson J. Surface active biomaterials. Science 1984;226:630-6.

29 - Boyan BD, Nasatzky E, Keller TA, Schartz Z. Substitutos del injerto osseo. Curr Opin Orthop 1998;III:17-23.

30 - Clark AE, Hench LL, Paschall HA. The influence of surface chemistry on implant interface histology : A theorical basis for implant materials selection. J Biomed Mater Res 1976;110:161-71.

31 - Hench LL, Wilson J. Bioactive Glasses: Present and Future. Bioceramics 1998;11:31-6.

32 - Gatti AM, Zaffe D. Bioactive glasses and chemical bond. Biomaterials 1992:97-106.

33 - Hamadouche M, Sedel L. Ceramics in Orthopaedics. J Bone Joint Surg Br 2000;82:1095-9.

34 - Oonishi H, Hench LL, Wilson I. Quantitative comparison of bone growth behavior in ceramics of Bioglass ®, A-W glass ceramics and HA. J Biomed Mater Res 2000;51:37-46.

35 - Oonishi H, Kushitani S, Yasukawa E, et al. Particulate bioglass compared with hydroxyapatite as a bone graft substitute. Clin Orthop Rel Research 1997;334:316-25.

36 - Kokubo T, Ito S, Huang Z. Ca-P - Rich Layer formed on high strength bioactive glass ceramics A-W. J Biomed Mater Res 1990;24:331-43.

37 - Vogel W, Holland H, Gummel J. Development of machineable bioactive glass-ceramics for medical uses. Journal of Non-Crystaline Solids 1986;80:34-51.

38 - Holland W, Vogel W, Mortier WJ, Duvingneaud PH, Naessens G, Plumat E. A new type of crystal in machineable glass-ceramics. Glass Technology 1983;24:318-22.

39 - Burnie J. Controlled release glass (C. R. G.) - A new biomaterial. PhD Thesis. 1988.

40 - Driessens FCM, Ramselaar MMA. Chemical reactions of calcium phosphate implants after implantation in vivo. J Mater Sci 1992;3:413-7.

41 - Betz RR. Limitation of autograft and allograft new synthesis solutions. Orthopedics 2002 (suppl.5): S561-70.

42 - Cornell CN. Osteoconductive materials and their role as substitutes for autogenous bone grafts. Orthop Clin North Am 1999;30:599-8.

43 - Lascart T, Favard L, Burdin P, Traore O. Utilisation du phosphate tricalcique dans les osteotomies tibiales de valgisation par addition interne. Ann Orthopediques de L’ Ouest 1998;30:137-41.

44 - Meynet J. Osteotomie tibiale de valgisation par ouverture interne: place des substituts osseux. Ann Orthopediques de L’Ouest 1998;30:171-3.

45 - Gaasbeek R, Toonen H, Heerwaarden R, Buma P. Mechanism of bone incorporation of ß-TCP bone substitute in open wedge tibial osteotomy in patients. Biomat erials 2005;26;33:6713-9.

46 - Yamamoto T, Onga T, Marui T, Mizuno K. Use of Hydroxyapatite to fill cavities after excision of begin bone tumors: clinical results. J Bone Joint Surg 2000;82-B:1117-20.

47 - Koshino T, Murase T, Saito T. Medial opening-wedge high tibial osteotomy with use of porous hydroxyapatite to treat medial compartment osteoarthritis of the knee. J Bone Joint Surg Am 2003; 85: 78-85.

48 - Regner L, Carlsson L, Karrholm J, Herbert P. Ceramic coating improves tibial component fixation in total knee arthroplasty. J Arthroplasty 1998; 13: 882-889.

49 - Tadic D, Epple M. A thorough physicochemical characterisation of 14 calcium phosphate-based bone substitution materials in comparison to natural bone . Biomaterials 2004; 25: 987-994.

50 - Santos JD, Hastings GW, Knowles JC. Sintered hydroxyapatite compositions and method for the preparation thereof, European Patent WO 0068164. 1999.

51 - Lopes MA. Glass reinforced hydroxyapatite composites: structure, physico chemical characterization and biological performance. PhD Thesis. FEUP. 1999.

52 - Lopes MA, Santos JD, Monteiro FJ, Ohtsuki C, Osaka A , Kaneko S, Inove H. Osteocompatibility and in vivo evaluation of glass reinforced hydroxyapatite composite. Bioceramics 1999;12:421-4.

53 - Lopes MA, Monteiro FJ, Santos JD. Glass reinforced hydroxyapatite composites: secondary phase proportions and densification effects on bioactive bending strength. J Biomed Mater Res 1999;48:734-40.

54 - Santos JD, Vasconcelos M, Reis RL, Afonso A, Monteiro FJ, Hastings GH. Glass reinforced hydroxyapatite composites: physical properties and preliminary histological studies in rabbits. Bioceramics 1994;7:243-8.

55 - Afonso A, Santos JD, Vasconcelos M, Branco R, Cavalheiro J. Granules of osteoapatite and glass-reinforced hydroxya-patite implanted in rabbit tibia. J Mat Scien: Materials in Medicine 1996;7:507-10.

56 - Costa MA, Gutierres M, Almeida L, Lopes MA, Santos JD, Fernandes MH. In vitro mineralization of human bone marrow cells cultured on Bonelike® . Key Engineering Materials 2004;254-256:821-4.

57 - Ferraz MP, Fernandes MH , Cabral T, Santos JD, Monteiro, FJ. In vitro growth and differentiation of osteo-blast-like human bone marrow cells on glass reinforced hydroxyapatite plasma-sprayed coatings. J Mat Scien: Materials in Medicine 1999;10:567-76.

58 - Ferraz MP, Knowles JC, Olsen I, Monteiro FJ, Santos JD. Flow cytometry analysis of the effects of pre-immersion on the biocompatibility of glass-reinforced hydroxyapatite plasma-sprayed coatings. Biomaterials 2000;21:813-20.

59 - Gutierres M, Hussain NS, Afonso A, et al. Biological behaviour of bonelike® graft implanted in the tibia of humans. Key Engineering Materials 2005;284-286:1041-4.

60 - Knnack D, Goad M, Rey C, Tofigni A, Chakravarthy P, Lee D. Resorbable calcium phosphate bone substitute. J BiomedMater Res 1998;43:399-409.

61 - Kopylou P, Jonsson K, Thorngren KG. Injectable calcium phosphate in the treatment of distal radius fractures. J Hand Surg Br 1996;21:768-71.

62 - Schreiber RE, Blease K, Ambrosio A, Amburn E, Sosnowski B, Sampath TK. Bone induction by ADBMP-2/collagen implants. J Bone Joint Surg Am 2005;87:1059-68.

63 - Muschler GF, Negami S, Hyodo A , Gaisser D, Gasley K , Kambic H. Evaluation of collagen ceramic composite graft materials in a spinal fusion model. Clin Orthop 1996;328:250- 60.

64 - Chapman MW, Bucholz R, Cornell C. Treatment of acute fractures with a collagen calcium phosphate graft material. A Randomized clinical trial. J Bone Joint Surg Am 1997;79:495-502.

65 - Hollinger JO, Brekke J, Gruskin E , Lee DL. Role of bone substitutes. Clin Orthop 1996;324:55-65.

66 - Kelly EB. New frontiers in bone grafting. Orthop Techn Review 2000;2:1-5.

67 - Mathes DW, Randolph MA, Lee WP. Strategies for tolerance induction to composite tissue allografts. Microsurgery 2000;20:448-52.

68 - Boyce T, Edwards J, Scarborough N. Allograft bone: The influence of processing on safety and performance. Orthop Clin North Am 1999;30:571-81.

69 - Peterson B, Whang PG, Iglesias R , Wang JC, Lieberman JR.Osteoinductivity of commercially available demineralized bone matrix.J Bone Joint Surg Am 2004;86:2243-50.

70 -Morone MA, Boden SD. Experimental posterolateral lumbar spinal fusion with a demineralized bone matrix cell. Spine 1998;23:159-67.

71 - Elves MW, Salama R. A study of the development of cytotoxic antibodies produced in recipients of xenografts of iliac bone. J Bone joint Surg Br 1974;56:331-9.

72 - Urist MR. Bone: formation by autoinduction. Science 1965;150:893-9.

73 - Yuan H, Zou P, Yang Z, Zhang X, De Bruijn JD, Groot KD. Bone morphogenic protein and ceramic-induced osteogenesis. J Mat Scien: Materials in Medicine 1998;9:717-21.

74 - Reddi AH, Marshall R. Urist: A renaissance scientist and orthopedic surgeon. J Bone Joint Surgery Am 2003;85:3-7.

75 - Khan SN, Bostrom MP, Lane J. Bone growth factors. Orthop Clin North Am 2000;31:375-87.

76 - Reddi AH. Bone morphogenetic proteins: From basic science to clinical applications. J Bone Joint Surg Am 2001; 83-A (suppl1) (PT1): S1-6.

77 - Sugi Y, Yamamura H, Okagawa H, Markwald RR. Bone morphogenetic protein-2 can mediate myocardial regulation atrioventricular cushion mesenchymal cell formation in mice. Dev Biol 2004; 269:505-18.

78 - Asahina I, Sampath TK, Nishimura I, Hauschka PV. Human osteogenic protein-1 induces both chondroblastic and osteoblastic differentiation of osteoprogenitor cells derived from newborn rat calvaria. J Cell Biol 1993;123:921-33.

79 - Friedlander GE, Perry CR, Cole JD, et al. Osteotomic protein-1( BMP-7) in the treatment of tibial nonunions. J Bone Joint Surg Am 2001;83-A (suppl.1) (PT2): S151-8.

80 - Boden SD, Zdeblick TA, Sandhu HS, Heim SE. The use of Rh BMP-2 in interbody fusion cases. Definitive evidance of osteoinduction in humans: A preliminary report. Spine 2000; 25: 376-86.

81 - Matsumoto T, Okazaki M, Inove M, et al. Hydroxyapatite particles as a controlled release carrier of protein. Biomaterials 2004;25:3807-12.

82 - Janssens K, Dijke P, Janssens S, Hul WV. Transforming growth factor-beta1 to the bone. Endocr Rev 2005: 26:743- 74.

83 - Pepper MS. Transforming growth factor-beta: vasculogenesis, angiogensis and vessel wall integrity. Cytokine Growth Factor Rev 1997;8:21-43.

84 - Letterio JJ, Roberts AB. Regulation of immune responses by TGF-beta. Annu Rev Immunol 1998;16:137-61.

85 - O´Kane S , Ferguson MW. Transforming growth factor beta and wound healing. Int J Biochem Cell Biol 1997;29:63-78.

86 - Aufdemorte TB, Fox WC, Holt GR, McGuff HS, Ammann AJ, Beck LS. An intraosseous device for studies of bone-healing. The effect of transforming growth factor beta. J Bone Joint Surg Am 74:1153-61.

87 - Siegel PM, Massague J. Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer 2003;3:807-21.

88 - Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 2001;29:117-29.

89 - Hock JM, Canalis E. Platelet derived growth factor enhances bone cell replication, but not differentiate function of osteoblasts. Endocrinol 1994;134:1423-8.

90 - Nash TJ, Howlett CR, Martin C, Steel J, Johnson KA, Hicklin DJ. Effect of platelet-derived growth factors on tibial osteotomies in rabbits. Bone 1994; 5:203-8.

91 - Marx RE, Carlson ER, Eichstaedt RM. Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surg 1998;85:638-46.

92 - Trippel SB, Coutts RD, Einhorn TA, Mundy GR, Rosenfeld RG.Instructional course lectures, the American Academy of Orthopaedic Surgeons - growth factors as therapeutic agents. J Bone Joint Surg Am 1996;78:1272-86.

93 - Koskinen EV, Lindholm RV, Nieminen RA, Puranen JP, Attila U. Human growth hormone in delayed union and nonunion of fractures. Int Orthop 1978;1:317-22.

94 - Northmore-Ball MD, Wood MR. Meegitt BF. A biomechanical study of the effects of growth hormone in experimental fracture healing. J Bone Joint Surg Br 1980;62:391-6.

95 - Ryaby JT, Fitzsimmons RJ, Khin NA, et al. A growth factor dependent model for magnetic field regeneration of bone formation. Trans Orthop Res Soc 1994;19:518.

96 - Jin Gushi S, Heydmann A, Kana SK, Macey LR, Bolander ME. Acidic fibroblast growth factor (aFGF) injection stimulates cartilage enlargement and inhibits cartilage gene expression in rat fracture healing. J Orthop Res 1990;8:364- 71.

97 - Kawaguchi H, Kurokawa T, Hanada K, et al. Stimulation of fracture repair by recombinant human basic fibroblast growth factor in normal and streptozotocin - diabetic rats. Endocrinol 1994;135:774-81.

98 - Wang JS, Aspenberg P. Basic fibroblast growth factor and bone induction in rats. Acta Orthop Scandinavia 1993;64:551- 69.

99 - Ludwig SC, Boden SD. Osteoinductive bone graft substitutes for spinal fusion. Orthop Clin North Am 1999;30:635- 45.

100 - Hench LL, Wilson J, edits. An introduction to Bioceramics. Advanced series in Ceramics 1993;1.

101 - Kingery WD, Bowen HK, Uhlmann DR. Introduction to ceramics. 2nd ed. New York: John Wiley & Sons. 1976.

102 - Schneider SJ, edits. Ceramic and Glasses. Engineered Materials Handbook. ASM International 1991;4.



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