Bone Regeneration Based on Tissue Engineering Conceptions-A 21st Century Perspective

Bone Research

Volumn 1, Issue , 2013, Pages 216-248

  Henkel, Jan ^a   Woodruff, Maria A ^a   Epari, Devakara R ^a   Steck, Roland ^a   Glatt, Vaida ^a   DIckinson, Ian C ^b   Choong, Peter F M ^c,d,e   Schuetz, Michael A ^a,b   Hutmacher, DIetmar W ^a,f  

^a QUEENSLAND UNIVERSITY OF TECHNOLOGY   (Australia)

^b PRINCESS ALEXANDRA HOSPITAL   (Australia)

^c UNIVERSITY OF MELBOURNE   (Australia)

^d ST VINCENT S HOSPITAL   (Australia)

^e PETER MACCALLUM CANCER CENTRE   (Australia)

^f GEORGIA INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

additve manufacturing; Bone tissue engineering; clinical translation; regenerative medicine; scaffolds

Indexed keywords

EID: 84900021043     PISSN: 20954700     EISSN: 20956231     Source Type: Journal    
DOI: 10.4248/BR201303002     Document Type: Review

References (246)

1. Mason C. Regenerative medicine 2.0. Regen Med. 2007;2:11-18.
2. Webster TJ, Ahn ES. Nanostructured biomaterials for tissue engineering bone. Adv Biochem Eng Biotechnol. 2007;103:275-308.
3. Rho JY, Kuhn-Spearing L, Zioupos P. Mechanical properties and the hierarchical structure of bone. Med Eng Phys. 1998;20:92-102.
4. Keaveny TM, Morgan EF, Niebur GL, Yeh OC. Biomechanics of trabecular bone. Annu Rev Biomed Eng. 2001;3:307-333.
5. Barrère F, Mahmood TA, de Groot K, van Blitterswijk CA. Advanced biomaterials for skeletal tissue regeneration: Instruc-tive and smart functions. Mat Sci Eng R. 2008;59:38-71.
6. Kaplan FS, Keaveny TM, Boskey A, Einhorn TA, Iannotti JP. Form and function of bone. Am Acad Orthop Surg. 1994; 127-184.
7. Cooper DM, Matyas JR, Katzenberg MA, Hallgrimsson B. Comparison of microcomputed tomographic and microradiogra-phic measurements of cortical bone porosity. Calcif Tissue Int. 2004;74:437-447.
8. Marks Jr SC. Structure and development of the skeleton. 2nd ed. Academic Press, 2002:3-15.
9. DiGirolamo DJ, Clemens TL, Kousteni S. The skeleton as an endocrine organ. Nat Rev Rheumatol. 2012;8:674-683.
10. Martin RB. Bone as a ceramic composite material. Mater Sci Forum. 1999;293:5-16.
11. Martin RB. Determinants of the mechanical properties of bones. J Biomech. 1991;24:79-88.
12. Kiebzak GM. Age-related bone changes. Exp Gerontol. 1991;26: 171-187.
13. Hench LL, Wilson J. An Introduction to Bioceramics. World Scientific, 1993.
14. Reilly DT, Burstein AH, Frankel VH. The elastic modulus for bone. J Biomech. 1974;7:271-275.
15. Choi K, Kuhn JL, Ciarelli MJ, Goldstein SA. The elastic moduli of human subchondral, trabecular, and cortical bone tissue and the size-dependency of cortical bone modulus. J Biomech. 1990;23: 1103-1113.
16. Rho JY, Tsui TY, Pharr GM. Elastic properties of human cortical and trabecular lamellar bone measured by nanoindentation. Biomaterials. 1997;18:1325-1330.
17. Jagodzinski M, Krettek C. Effect of mechanical stability on frac-ture healing-an update. Injury. 2007;38:S3-S10.
18. Pioletti DP. Biomechanics and tissue engineering. Osteoporos Int. 2011;22:2027-2031.
19. Klein-Nulend J, Bacabac RG, Mullender MG. Mechanobiology of bone tissue. Pathol Biol (Paris). 2005;53:576-580.
20. Epari DR, Taylor WR, Heller MO, Duda GN. Mechanical conditions in the initial phase of bone healing. Clin Biomech (Bristol, Avon). 2006;21:646-655.
21. Marsell R, Einhorn TA. The biology of fracture healing. Injury. 2011;42:551-555.
22. Dimitriou R, Jones E, McGonagle D, Giannoudis PV. Bone regeneration: Current concepts and future directions. BMC Med. 2011;9:66.
23. Einhorn TA. Enhancement of fracture healing. Instr Course Lect. 1996;45:401-416.
24. Calori GM, Albisetti W, Agus A, Iori S, Tagliabue L. Risk factors contributing to fracture non-unions. Injury. 2007;38:S11-S18.
25. Sanan A, Haines SJ. Repairing holes in the head: A history of cranioplasty. Neurosurgery. 1997;40:588-603.
26. Courville C B. Cranioplasty in prehistoric times. Bull Los Angel Neuro Soc. 1959;24:1-8.
27. Flati G. Chirurgia nella preistoria. Parte I. Provincia Med Aquila. 2004;2:8-11.
28. Donati D, Zolezzi C, Tomba P, Viganò A. Bone grafting: Historical and conceptual review, starting with an old manuscript by Vittorio Putti. Acta Orthop. 2007;78:19-25.
29. Haeseker B. Mr. Job van Meekeren (1611-1666) and surgery of the hand. Plast Reconstr Surg. 1988;82:539-546.
30. Meekeren JJ. Observationes Medico-Chirugicae. Amsterdam: Ex Officina Henrici & Vidnae Theodori Boom. 1682.
31. Tarsoly E. [Filling of bone cavities with egg shell-plaster mixture]. [Article in German] Acta Chir Acad Sci Hung. 1963;4:63-72.
32. Gluck T. Berl Klein Wochenschr. 1891;21:79.
33. Walter P. J Chir und Augen-Heilkunde. 1821;2:571.
34. MacEwen W. Observations concerning transplantation of bone illustrated by a case of inter-human osseous transplantation, whereby over two-thirds of the shaft of a humerus was restored. Proc Roy Soc Lond. 1881;32:232-247.
35. Ollier LL. Traite experimental et clinique de la regeneration des os et de la production artificielle du tissu osseux. V. Masson Vol. I and Vol. II. 1867.
36. Barth A. Histologische Untersuchung über Knochen implanta-tionen. Beitr Pathol Anat Allg Pathol. 1895;17:65-142.
37. Bush LF. The use of homogenous bone grafts; a preliminary report on the bone bank. J Bone Joint Surg Am. 1947;29:620-628.
38. Chalmers J. Transplantation immunity in bone homografting. J Bone Joint Surg Br. 1959;41-B:160-179.
39. Enneking WF. Immunologic aspects of bone transplantation. South Med J. 1962;55:894-900.
40. Maatz R. [The animal bone chip in the bone bank]. [Article in German] Dtsch Med J. 1957;8:190-194.
41. Katthagen BD. Knochenregeneration mit Knochenersatzmateria-lien: Eine tierexperimentelle studie. Hefte Unfallheilk. 1986.
42. Hinsenkamp M, Muylle L, Eastlund T, Fehily D, Noël L, Strong DM. Adverse reactions and events related to musculoskeletal allografts: Reviewed by the World Health Organisation Project NOTIFY. Int Orthop. 2012;36:633-641.
43. Matti H. Ueber die freie Transplantation von Knochenspongiosa. Langenbecks Arch Clin Chir. 1932:168-236.
44. Schweiberer L. [Experimental studies on bone transplantation with unchanged and denaturated bone substance. A contribution on causal osteogenesis]. [Article in German]. Hefte Unfallheilkd. 1970;103:1-70.
45. Dinopoulos H, Dimitriou R, Giannoudis PV. Bone graft substitutes: What are the options Surgeon. 2012;10:230-239.
46. De Long WG Jr, Einhorn TA, Koval K, McKee M, Smith W, Sanders R, Watson T. Bone grafts and bone graft substitutes in orthopaedic trauma surgery. A critical analysis. J Bone Joint Surg Am. 2007;89:649-658.
47. Schieker M, Heiss C, Mutschler W. [Bone substitutes]. [Article in German]. Unfallchirurg. 2008;111:613-619; quiz 620.
48. Myeroff C, Archdeacon M. Autogenous bone graft: Donor sites and techniques. J Bone Joint Surg Am. 2011;93:2227-2236.
49. Stafford PR, Norris BL. Reamer-irrigator-aspirator bone graft and bi Masquelet technique for segmental bone defect nonunions: A review of 25 cases. Injury. 2010;41:S72-S77.
50. Weiland AJ, Phillips TW, Randolph MA. Bone grafts: A radiologic, histologic, and biomechanical model comparing autografts, allografts, and free vascularized bone grafts. Plast Reconstr Surg. 1984;74:368-379.
51. Pederson WC, Person DW. Long bone reconstruction with vascularized bone grafts. Orthop Clin North Am. 2007;38:23-35.
52. Aronson J. Limb-lengthening, skeletal reconstruction, and bone transport with the Ilizarov method. J Bone Joint Surg Am. 1997; 79:1243-1258.
53. Sailhan F. Bone lengthening (distraction osteogenesis): A literature review. Osteoporos Int. 2011;22:2011-2015.
54. Spiegelberg B, Parratt T, Dheerendra SK, Khan WS, Jennings R, Marsh DR. Ilizarov principles of deformity correction. Ann R Coll Surg Engl. 2010;92:101-105.
55. Paley D, Maar DC. Ilizarov bone transport treatment for tibial defects. J Orthop Trauma. 2000;14:76-85.
56. Dendrinos GK, Kontos S, Lyritsis E. Use of the Ilizarov technique for treatment of non-union of the tibia associated with infection. J Bone Joint Surg Am. 1995;77:835-846.
57. Smith JO, Aarvold A, Tayton ER, Dunlop DG, Oreffo RO. Skeletal tissue regeneration: Current approaches, challenges, and novel reconstructive strategies for an aging population. Tissue Eng Part B Rev. 2011;17:307-320.
58. Klaue K, Knothe U, Masquelet A. Effet biologique des mem-branes à corps etranger induites in situ sur la consolidation des greffes d'os spongieux. Rev Chir Orthop Suppl. 1995;70:109-110.
59. Giannoudis PV, Faour O, Goff T, Kanakaris N, Dimitriou R. Masquelet technique for the treatment of bone defects: Tips-tricks and future directions. Injury. 2011;42:591-598.
60. Masquelet AC, Begue T. The concept of induced membrane for reconstruction of long bone defects. Orthop Clin North Am. 2010; 41:27-37.
61. Pelissier P, Masquelet AC, Bareille R, Pelissier SM, Amedee J. Induced membranes secrete growth factors including vascular and osteoinductive factors and could stimulate bone regeneration. J Orthop Res. 2004;22:73-79.
62. Pélissier P, Lefevre Y, Delmond S, Villars F, Vilamitjana-Amedee J. [Influences of induced membranes on heterotopic bone formation within an osteo-inductive complex. Experimental study in rabbits]. [Article in French]. Ann Chir Plast Esthet. 2009;54:16-20.
63. DepuySynthes. Reamer/Irrigator/Aspirator (RIA). http://www.synthes.com/sites/NA/Products/Trauma/IntramedullaryNailingSystems/Pages/Reamer-Irrigator-Aspirator-RIA.aspx . 2013.
64. McCall TA, Brokaw DS, Jelen BA, Scheid DK, Scharfenberger AV, Maar DC, Green JM, Shipps MR, Stone MB, Musapatika D, Weber TG. Treatment of large segmental bone defects with reamer-irrigator-aspirator bone graft: Technique and case series. Orthop Clin North Am. 2010;4163-4173.
65. Husebye EE, Lyberg T, Madsen JE, Eriksen M, Røise O. The influence of a one-step reamer-irrigator-aspirator technique on the intramedullary pressure in the pig femur. Injury. 2006;37: 935-940.
66. Belthur MV, Conway JD, Jindal G, Ranade A, Herzenberg JE. Bone graft harvest using a new intramedullary system. Clin Orthop Relat Res. 2008;466:2973-2980.
67. Newman JT, Stahel PF, Smith WR, Resende GV, Hak DJ, Morgan SJ. A new minimally invasive technique for large volume bone graft harvest for treatment of fracture nonunions. Orthopedics. 2008;31:257-261.
68. Dimitriou R, Mataliotakis GI, Angoules AG, Kanakaris NK, Giannoudis PV. Complications following autologous bone graft harvesting from the iliac crest and using the RIA: A systematic review. Injury. 2011;42:S3-S15.
69. Zalavras CG, Singh A, Patzakis MJ. Novel technique for medullary canal débridement in tibia and femur osteomyelitis. Clin Orthop Relat Res. 2007;461:31-34.
70. Porter RM, Liu F, Pilapil C, Betz OB, Vrahas MS, Harris MB, Evans CH. Osteogenic potential of reamer irrigator aspirator (RIA) aspirate collected from patients undergoing hip arthroplasty. J Orthop Res. 2009;27:42-49.
71. Kanakaris NK, Morell D, Gudipati S, Britten S, Giannoudis PV. Reaming Irrigator Aspirator system: Early experience of its multipurpose use. Injury. 2011;42:S28-S34.
72. Cox G, Jones E, McGonagle D, Giannoudis PV. Reamer-irrigator-A spirator indications and clinical results: A systematic review. Int Orthop. 2011;35:951-956.
73. Huffman LK, Harris JG, Suk M. Using the bi-masquelet technique and reamer-irrigator-aspirator for post-traumatic foot reconstruc-tion. Foot Ankle Int. 2009;30:895-899.
74. Schlickewei W, Schlickewei C. The Use of Bone Substitutes in the Treatment of Bone Defects-the Clinical View and History. Macromol Symp. 2007;253:10-23.
75. Langer R, Vacanti JP. Tissue engineering. Science. 1993;260:920-926.
76. Kolk A, Handschel J, Drescher W, Rothamel D, Kloss F, Blessmann M, Heiland M, Wolff KD, Smeets R. Current trends and future perspectives of bone substitute materials-from space holders to innovative biomaterials. J Craniomaxillofac Surg. 2012; 40:706-718.
77. Giannoudis PV, Einhorn TA, Marsh D. Fracture healing: The diamond concept. Injury. 2007;38:S3-S6.
78. Giannoudis PV, Einhorn TA, Schmidmaier G, Marsh D. The diamond concept-open questions. Injury. 2008;39:S5-S8.
79. Hutmacher DW, Schantz JT, Lam CX, Tan KC, Lim TC. State of the art and future directions of scaffold-based bone engineering from a biomaterials perspective. J Tissue Eng Regen Med. 2007;1: 245-260.
80. Woodruff MA, Lange C, Reichert J, Berner A, Chen F, Fratzl P, Schantz JT, Hutmacher DW. Bone tissue engineering: From bench to bedside. Materials Today. 2012;15:430-434.
81. Laurencin C, Khan Y, El-Amin SF. Bone graft substitutes. Expert Rev Med Devices. 2006;3:49-57.
82. Dinopoulos HT, Giannoudis PV. Safety and efficacy of use of demineralised bone matrix in orthopaedic and trauma surgery. Expert Opin Drug Saf. 2006;5:847-866.
83. Katz JM, Nataraj C, Jaw R, Deigl E, Bursac P. Demineralized bone matrix as an osteoinductive biomaterial and in vitro predictors of its biological potential. J Biomed Mater Res B Appl Biomater. 2009;89:127-134.
84. Bostrom MP, Seigerman DA. The clinical use of allografts, demineralized bone matrices, synthetic bone graft substitutes and osteoinductive growth factors: A survey study. HSS J. 2005;1:9-18.
85. 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.
86. Damien E, Revell PA. Coralline hydroxyapatite bone graft substitute: A review of experimental studies and biomedical applications. J Appl Biomater Biomech. 2004;2:65-73.
87. Ewers R. Maxilla sinus grafting with marine algae derived bone forming material: A clinical report of long-term results. J Oral Maxillofac Surg. 2005;63:1712-1723.
88. Baino F, Vitale-Brovarone C. Three-dimensional glass-derived scaffolds for bone tissue engineering: Current trends and forecasts for the future. J Biomed Mater Res A. 2011;97:514-535.
89. Hammouche S, Khan W, Drouin H, Procter H, McNicholas M. Calcium salts bone regeneration scaffolds: A review article. Curr Stem Cell Res Ther. 2012;7:336-346.
90. Liu B, Lun DX. Current application of beta-tricalcium phosphate composites in orthopaedics. Orthop Surg. 2012;4:139-144.
91. Sun F, Zhou H, Lee J. Various preparation methods of highly porous hydroxyapatite/polymer nanoscale biocomposites for bone regeneration. Acta Biomater. 2011;7:3813-3828.
92. Hutmacher DW, Cool S. Concepts of scaffold-based tissue engineering-the rationale to use solid free-form fabrication techniques. J Cell Mol Med. 2007;11: 654-669.
93. Swetha M, Sahithi K, Moorthi A, Srinivasan N, Ramasamy K, Selvamurugan N. Biocomposites containing natural polymers and hydroxyapatite for bone tissue engineering. Int J Biol Macromol. 2010;47:1-4.
94. Bose S, Tarafder S. Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: A review. Acta Biomater. 2012; 8:1401-1421.
95. Woodruff MA, Hutmacher DW. The return of a forgotten polymer-Polycaprolactone in the 21st century. Prog Polym Sci. 2010;35:1217-1256.
96. Puppi D, Chiellini F, Piras AM, Chiellini E. Polymeric materials for bone and cartilage repair. Prog Polym Sci. 2010;35:403-440.
97. Hutmacher DW. Scaffolds in tissue engineering bone and cartilage. Biomaterials. 2000;21:2529-2543.
98. Tanner KE. Bioactive composites for bone tissue engineering. Proc Inst Mech Eng H. 2010;224:1359-1372.
99. Miyazaki T. Design of bone-integrating organic-inorganic compo-site suitable for bone repair. Front Biosci (Elite Ed). 2013;5:333-340.
100. Dimitriou R, Tsiridis E, Giannoudis PV. Current concepts of molecular aspects of bone healing. Injury. 2005;36:1392-1404.
101. Salgado AJ, Coutinho OP, Reis RL. Bone tissue engineering: State of the art and future trends. Macromol Biosci. 2004;4:743-765.
102. Reichert JC, Cipitria A, Epari DR, Saifzadeh S, Krishnakanth P, Berner A, Woodruff MA, Schell H, Mehta M, Schuetz MA, Duda GN, Hutmacher DW. A tissue engineering solution for segmental defect regeneration in load-bearing long bones. Sci Transl Med. 2012;4:141-93.
103. Chatterjea A, Meijer G, van Blitterswijk C, de Boer J. Clinical application of human mesenchymal stromal cells for bone tissue engineering. Stem Cells Int. 2010;2010:215-625.
104. Baksh D, Song L, Tuan RS. Adult mesenchymal stem cells: Characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med. 2004;8:301-316.
105. Hui JH, Ouyang HW, Hutmacher DW, Goh JC, Lee EH. Mesenchymal stem cells in musculoskeletal tissue engineering: A review of recent advances in National University of Singapore. Ann Acad Med Singapore. 2005;34:206-212.
106. Xiao Y, Mareddy S, Crawford R. Clonal characterization of bone marrow derived stem cells and their application for bone regeneration. Int J Oral Sci. 2010;2:127-135.
107. Kagami H, Agata H, Tojo A. Bone marrow stromal cells (bone marrow-derived multipotent mesenchymal stromal cells) for bone tissue engineering: Basic science to clinical translation. Int J Biochem Cell Biol. 2011;43:286-289.
108. Colnot C, Zhang X, Knothe Tate ML. Current insights on the regenerative potential of the periosteum: Molecular, cellular, and endogenous engineering approaches. J Orthop Res. 2012;30:1869-1878.
109. Hutmacher DW, Sittinger M. Periosteal cells in bone tissue engin-eering. Tissue Eng. 2003;9:S45-S64.
110. Jayakumar P, Di Silvio L. Osteoblasts in bone tissue engineering. Proc Inst Mech Eng H. 2010;224:1415-1440.
111. Longo UG, Loppini M, Berton A, La Verde L, Khan WS, Denaro V. Stem cells from umbilical cord and placenta for musculoskeletal tissue engineering. Curr Stem Cell Res Ther. 2012;7:272-281.
112. Mizuno H. Adipose-derived stem cells for tissue repair and regeneration: Ten years of research and a literature review. J Nippon Med Sch. 2009;76:56-66.
113. Amini AR, Laurencin CT, Nukavarapu SP. Bone tissue engineer-ing: Recent advances and challenges. Crit Rev Biomed Eng. 2012;40:363-408.
114. Szpalski C, Barbaro M, Sagebin F, Warren SM. Bone tissue engineering: Current strategies and techniques-part II: Cell types. Tissue Eng Part B Rev. 2012;18:258-269.
115. Colnot C. Cell sources for bone tissue engineering: Insights from basic science. Tissue Eng Part B Rev. 2011;17:449-457.
116. Mason C, Dunnill P. Assessing the value of autologous and allogeneic cells for regenerative medicine. Regen Med. 2009;4:835-853.
117. Nandi SK, Roy S, Mukherjee P, Kundu B, De DK, Basu D. Orthopaedic applications of bone graft & graft substitutes: A review. Indian J Med Res. 2010;132:15-30.
118. Groeneveld EH, van den Bergh JP, Holzmann P, ten Bruggenkate CM, Tuinzing DB, Burger EH. Mineralization processes in demineralized bone matrix grafts in human maxillary sinus floor elevations. J Biomed Mater Res. 1999;48:393-402.
119. Stark GB, Horch R, Tanczos E. Biological Matrices and Tissue Reconstruction. Springer, Berlin. 1998:197-206.
120. Bostman O, Hirvensalo E, Makinen J, Rokkanen P. Foreign-body reactions to fracture fixation implants of biodegradable synthetic polymers. J Bone Joint Surg Br. 1990;72:592-596.
121. Bergsma EJ, Rozema FR, Bos RR, de Bruijn WC. Foreign body reactions to resorbable poly(L-lactide) bone plates and screws used for the fixation of unstable zygomatic fractures. J Oral Maxillofac Surg. 1993;51:666-670.
122. Bergsma JE, de Bruijn WC, Rozema FR, Bos RR, Boering G. Late degradation tissue response to poly(L-lactide) bone plates and screws. Biomaterials. 1995;16:25-31.
123. Velard F, Braux J, Amedee J, Laquerriere P. Inflammatory cell response to calcium phosphate biomaterial particles: An overview. Acta Biomater. 2013;9:4956-4963.
124. Hollinger JO, Chaudhari A. Bone regeneration materials for the mandibular and craniofacial complex. Cells Mater. 1992;2:143-151.
125. Babis GC, Soucacos PN. Bone scaffolds: The role of mechanical stability and instrumentation. Injury. 2005;36 Suppl 4:S38-S44.
126. Ponche A, Bigerelle M, Anselme K. Relative influence of surface topography and surface chemistry on cell response to bone implant materials. Part 1: Physico-chemical effects. Proc Inst Mech Eng H. 2010;224:1471-1486.
127. Boyan BD, Hummert TW, Dean DD, Schwartz Z. Role of material surfaces in regulating bone and cartilage cell response. Bioma-terials. 1996;17:137-146.
128. Kaplan FS, Hayes WC, Keaveny TM, Boskey A, Einhorn TA, Iannotti JP. Formation and Function of Bone. In: Simon SR, editor. Orthopedic Basic Science. American Academy of Orthopedic Surgeons; Rosemont, Illinois: 1994:127-184.
129. Webster TJ, Ergun C, Doremus RH, Siegel RW, Bizios R. Specific proteins mediate enhanced osteoblast adhesion on nanophase ceramics. J Biomed Mater Res. 2000;51:475-483.
130. Webster TJ, Schadler LS, Siegel RW, Bizios R. Mechanisms of enhanced osteoblast adhesion on nanophase alumina involve vitronectin. Tissue Eng. 2001;7:291-301.
131. Webster TJ, Siegel RW, Bizios R. Osteoblast adhesion on nano-phase ceramics. Biomaterials. 1999;20:1221-1227.
132. Puckett S, Pareta R, Webster TJ. Nano rough micron patterned titanium for directing osteoblast morphology and adhesion. Int J Nanomedicine. 2008;3:229-241.
133. Vlacic-Zischke J, Hamlet SM, Friis T, Tonetti MS, Ivanovski S. The influence of surface microroughness and hydrophilicity of titanium on the up-regulation of TGFbeta/BMP signalling in osteoblasts. Biomaterials. 2011;32:665-671.
134. Chan O, Coathup MJ, Nesbitt A, Ho CY, Hing KA, Buckland T, Campion C, Blunn GW. The effects of microporosity on osteoinduction of calcium phosphate bone graft substitute biomaterials. Acta Biomater. 2012;8:2788-2794.
135. Scott TG, Blackburn G, Ashley M, Bayer IS, Ghosh A, Biris AS, Biswas A. Advances in bionanomaterials for bone tissue engineering. J Nanosci Nanotechnol. 2013;13:1-22.
136. McMahon RE, Wang L, Skoracki R, Mathur AB. Development of nanomaterials for bone repair and regeneration. J Biomed Mater Res B Appl Biomater. 2013;101:387-397.
137. Egli RJ, Luginbuehl R. Tissue engineering-nanomaterials in the musculoskeletal system. Swiss Med Wkly. 2012;142:w13647.
138. Saiz E, Zimmermann EA, Lee JS, Wegst UG, Tomsia AP. Perspectives on the role of nanotechnology in bone tissue engineering. Dent Mater. 2013;29:103-115.
139. Yuan H, Kurashina K, de Bruijn JD, Li Y, de Groot K, Zhang X. A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics. Biomaterials. 1999;20:1799-1806.
140. Davies JE. In vitro modeling of the bone/implant interface. Anat Rec. 1996;245:426-445.
141. Albrektsson T, Johansson C. Osteoinduction, osteoconduction and osseointegration. Eur Spine J. 2001;10 Suppl 2:S96-S101.
142. Habibovic P, de Groot K. Osteoinductive biomaterials-properties and relevance in bone repair. J Tissue Eng Regen Med. 2007;1:25-32.
143. Geesink RG, de Groot K, Klein CP. Bonding of bone to apatite-coated implants. J Bone Joint Surg Br. 1993;70:17-22.
144. Kay JF. Biological profile of calcium phosphate coatings. 1993: 89-106.
145. Hanawa T, Kamiura Y, Yamamoto S, Kohgo T, Amemiya A, Ukai H, Murakami K, Asaoka K. Early bone formation around calcium-ion-implanted titanium inserted into rat tibia. J Biomed Mater Res. 1997;36:131-136.
146. Le Huec JC, Clément D, Brouillaud B, Barthe N, Dupuy B, Foliguet B, Basse-Cathalinat B. Evolution of the local calcium content around irradiated beta-tricalcium phosphate ceramic implants: In vivo study in the rabbit. Biomaterials. 1998;19:733-738.
147. LeGeros RZ. Calcium phosphate-based osteoinductive materials. Chem Rev. 2008;108:4742-4753.
148. Vaquette C, Ivanovski S, Hamlet SM, Hutmacher DW. Effect of culture conditions and calcium phosphate coating on ectopic bone formation. Biomaterials. 2013;34:5538-5551.
149. Habibovic P, Sees TM, van den Doel MA, van Blitterswijk CA, de Groot K. Osteoinduction by biomaterials-physicochemical and structural influences. J Biomed Mater Res A. 2006;77:747-762.
150. Barradas AM, Yuan H, van Blitterswijk CA, Habibovic P. Osteoinductive biomaterials: Current knowledge of properties, experimental models and biological mechanisms. Eur Cell Mater. 2011;21:407-429.
151. Yuan H, De Bruijn JD, Li Y, Feng J, Yang Z, De Groot K, Zhang X. Bone formation induced by calcium phosphate ceramics in soft tissue of dogs: A comparative study between porous alpha-TCP and beta-TCP. J Mater Sci Mater Med. 2001;12:7-13.
152. Chai YC, Carlier A, Bolander J, Roberts SJ, Geris L, Schrooten J, Van Oosterwyck H, Luyten FP. Current views on calcium phosphate osteogenicity and the translation into effective bone regeneration strategies. Acta Biomater. 2012;8:3876-3887.
153. Anselme K, Ponche A, Bigerelle M. Relative influence of surface topography and surface chemistry on cell response to bone implant materials. Part 2: Biological aspects. Proc Inst Mech Eng H. 2010;224:1487-1507.
154. Leon CLY. New perspectives in mercury porosimetry. Adv Colloid Interface Sci. 1998;76:341-372.
155. Kuboki Y, Takita H, Kobayashi D, Tsuruga E, Inoue M, Murata M, Nagai N, Dohi Y, Ohgushi H. BMP-induced osteogenesis on the surface of hydroxyapatite with geometrically feasible and nonfeasible structures: Topology of osteogenesis. J Biomed Mater Res. 1998;39:190-199.
156. Story BJ, Wagner WR, Gaisser DM, Cook SD, Rust-Dawicki AM. In vivo performance of a modified CSTi dental implant coating. Int J Oral Maxillofac Implants. 1998;13:749-757.
157. Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials. 2005;26:5474-5491.
158. Hulbert SF, Young FA, Mathews RS, Klawitter JJ, Talbert CD, Stelling FH. Potential of ceramic materials as permanently implantable skeletal prostheses. J Biomed Mater Res. 1970;4:433-456.
159. Loh QL, Choong C. Three-dimensional scaffolds for tissue engineering: Role of porosity and pore size. Tissue Eng Part B Rev. 2013 May 14. [Epub ahead of print].
160. Szpalski C, Wetterau M, Barr J, Warren SM. Bone tissue engineering: Current strategies and techniques-part I: Scaffolds. Tissue Eng Part B Rev. 2012;18:246-257.
161. Bose S, Roy M, Bandyopadhyay A. Recent advances in bone tissue engineering scaffolds. Trends Biotechnol. 2012;30:546-554.
162. Peltola SM, Melchels FP, Grijpma DW, Kellomaki M. A review of rapid prototyping techniques for tissue engineering purposes. Ann Med. 2008;40:268-280.
163. Hutmacher DW, Sittinger M, Risbud MV. Scaffold-based tissue engineering: Rationale for computer-aided design and solid free-form fabrication systems. Trends Biotechnol. 2004;22:354-362.
164. Yeong WY, Chua CK, Leong KF, Chandrasekaran M. Rapid prototyping in tissue engineering: Challenges and potential. Trends Biotechnol. 2004;22:643-652.
165. Sachlos E, Czernuszka JT. Making tissue engineering scaffolds work. Review: The application of solid freeform fabrication technology to the production of tissue engineering scaffolds. Eur Cell Mater. 2003;5:29-39; discussion 39-40.
166. Melchels FPW, Domingos MAN, Klein TJ, Malda J, Bartolo PJ, Hutmacher DW. Additive manufacturing of tissues and organs. Prog Polym Sci. 2012;37:1079-1104.
167. ASTM Standard F2792-10: Standard terminology for additive manufacturing technologies. ASTM International, 2010.
168. Ballyns JJ, Bonassar LJ. Image-guided tissue engineering. J Cell Mol Med. 2009;13:1428-1436.
169. Hollister SJ. Porous scaffold design for tissue engineering. Nat Mater. 2005;4:518-524.
170. Derby B. Printing and prototyping of tissues and scaffolds. Science. 2012;338:921-926.
171. Wendel B, Rietzel D, Kühnlein F, Feulner R, Hülder G, Schmachtenberg E. Additive Processing of Polymers. Macromol Mater Eng. 2008;293:799-809.
172. Webb PA. A review of rapid prototyping (RP) techniques in the medical and biomedical sector. J Med Eng Technol. 2000;24:149-153.
173. McGurk M, Amis AA, Potamianos P, Goodger NM. Rapid prototyping techniques for anatomical modelling in medicine. Ann R Coll Surg Engl. 1997;79:169-174.
174. Potamianos P, Amis AA, Forester AJ, McGurk M, Bircher M. Rapid prototyping for orthopaedic surgery. Proc Inst Mech Eng H. 1998;212:383-393.
175. Goiato MC, Santos MR, Pesqueira AA, Moreno A, dos Santos DM, Haddad MF. Prototyping for surgical and prosthetic treatment. J Craniofac Surg. 2011;22:914-917.
176. Debarre E, Hivart P, Baranski D, Déprez P. Speedy skeletal prototype production to help diagnosis in orthopaedic and trauma surgery. Methodology and examples of clinical applica-tions. Orthop Traumatol Surg Res. 2012;98:597-602.
177. Esses SJ, Berman P, Bloom AI, Sosna J. Clinical applications of physical 3D models derived from MDCT data and created by rapid prototyping. AJR Am J Roentgenol. 2011;196:W683-W688.
178. Melchels FP, Feijen J, Grijpma DW. A review on stereolithogra-phy and its applications in biomedical engineering. Biomaterials. 2010;31:6121-6130.
179. Maruo S, Ikuta K. Submicron stereolithography for the pro-duction of freely movable mechanisms by using single-photon polymerization. Sensor Actuat A: Phys. 2002;100:70-76.
180. Chehade MJ, Bachorski A. Development of the Australian core competencies in musculoskeletal basic and clinical science project-phase 1. Med J Aust. 2008;189:162-165.
181. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10-29.
182. Lysaght MJ, Reyes J. The growth of tissue engineering. Tissue Eng. 2001;7:485-493.
183. Wang FS. Support for tissue engineering and regenerative medicine by the National Institutes of Health. Artech House Publishers. 2008:445-462.
184. Hollister SJ. Scaffold engineering: A bridge to where Biofabrication. 2009;1:012001
185. Reichert JC, Epari DR, Wullschleger ME, Saifzadeh S, Steck R, Lienau J, Sommerville S, Dickinson IC, Schütz MA, Duda GN, Hutmacher DW. Establishment of a preclinical ovine model for tibial segmental bone defect repair by applying bone tissue engineering strategies. Tissue Eng Part B Rev. 2010;16:93-104.
186. Meslin EM, Blasimme A, Cambon-Thomsen A. Mapping the translational science policy 'valley of death'. Clin Transl Med. 2013;2:14.
187. Dawson JI, Oreffo RO. Bridging the regeneration gap: Stem cells, biomaterials and clinical translation in bone tissue engineering. Arch Biochem Biophys. 2008;473:124-131.
188. Yannas IV. Emerging rules for inducing organ regeneration. Biomaterials. 2013;34:321-330.
189. Hollister SJ, Murphy WL. Scaffold translation: Barriers between concept and clinic. Tissue Eng Part B Rev. 2011;17:459-474.
190. Kneser U, Schaefer DJ, Polykandriotis E, Horch RE. Tissue engineering of bone: The reconstructive surgeon's point of view. J Cell Mol Med. 2006;10:7-19.
191. Logeart-Avramoglou D, Anagnostou F, Bizios R, Petite H. Engineering bone: Challenges and obstacles. J Cell Mol Med. 2005;9:72-84.
192. Muschler GF, Raut VP, Patterson TE, Wenke JC, Hollinger JO. The design and use of animal models for translational research in bone tissue engineering and regenerative medicine. Tissue Eng Part B Rev. 2010;16:123-145.
193. Schoonen WG, Westerink WM, Horbach GJ. High-throughput screening for analysis of in vitro toxicity. EXS. 2009;99:401-452.
194. Colas P. High-throughput screening assays to discover small-molecule inhibitors of protein interactions. Curr Drug Discov Technol. 2008;5:190-199.
195. Horner EA, Kirkham J, Wood D, Curran S, Smith M, Thomson B, Yang XB. Long bone defect models for tissue engineering applica-tions: Criteria for choice. Tissue Eng Part B Rev. 2010;16:263-271.
196. Mooney MP, Siegel MI. Animal models for bone tissue engineer-ing. In: Wnek, G. and Bowlin, G. (Eds.). Encyclopedia of Biomaterials and Biomedical Engineering. Marcel Dekker, New York, 2005:1-19.
197. Buma P, Schreurs W, Verdonschot N. Skeletal tissue engineering-from in vitro studies to large animal models. Biomaterials. 2004;25: 1487-1495.
198. Einhorn TA. Clinically applied models of bone regeneration in tissue engineering research. Clin Orthop Relat Res. 1999;367: S59-S67.
199. O'Loughlin PF, Morr S, Bogunovic L, Kim AD, Park B, Lane JM. Selection and development of preclinical models in fracture-healing research. J Bone Joint Surg Am. 2008;90:79-84.
200. Woodruff MA, Hutmacher DW. The return of a forgotten polymer: Polycaprolactone in the 21st century. Prog Polym Sci. 2010;35:1217-1256.
201. Zein I, Hutmacher DW, Tan KC, Teoh SH. Fused deposition modeling of novel scaffold architectures for tissue engineering applications. Biomaterials. 2002;23:1169-1185.
202. Sawyer AA, Song SJ, Susanto E, Chuan P, Lam CX, Woodruff MA, Hutmacher DW, Cool SM. The stimulation of healing within a rat calvarial defect by mPCL-TCP/collagen scaffolds loaded with rhBMP-2. Biomaterials. 2009;30:2479-2488.
203. Lam CX, Teoh SH, Hutmacher DW. Comparison of the degradation of polycaprolactone and polycaprolactone-(tricalcium phosphate) scaffolds in alkaline medium. Polym Int. 2007;56:718-728.
204. Lam CX, Hutmacher DW, Schantz JT, Woodruff MA, Teoh SH. Evaluation of polycaprolactone scaffold degradation for 6 months in vitro and in vivo. J Biomed Mater Res A. 2009;90:906-919.
205. Lam CX, Savalani MM, Teoh SH, Hutmacher DW. Dynamics of in vitro polymer degradation of polycaprolactone-based scaffolds: Accelerated versus simulated physiological conditions. Biomed Mater. 2008;3:034108.
206. Ekaputra AK, Zhou Y, Cool SM, Hutmacher DW. Composite electrospun scaffolds for engineering tubular bone grafts. Tissue Eng Part A. 2009;15:3779-3788.
207. Berner A, Boerckel JD, Saifzadeh S, Steck R, Ren J, Vaquette C, Zhang JQ, Nerlich M, Guldberg RE, Hutmacher DW, Woodruff MA. Biomimetic tubular nanofiber mesh and platelet rich plasma-mediated delivery of BMP-7 for large bone defect regeneration. Cell Tissue Res. 2012;347:603-612.
208. Rai B, Lin JL, Lim ZX, Guldberg RE, Hutmacher DW, Cool SM. Differences between in vitro viability and differentiation and in vivo bone-forming efficacy of human mesenchymal stem cells cultured on PCL-TCP scaffolds. Biomaterials. 2010;31:7960-7970.
209. Zhou Y, Chen F, Ho ST, Woodruff MA, Lim TM, Hutmacher DW.Combined marrow stromal cell-sheet techniques and high-strength biodegradable composite scaffolds for engineered functional bone grafts. Biomaterials. 2007;28:814-824.
210. Berner A, Reichert JC, Müller MB, Zellner J, Pfeifer C, Dienstknecht T, Nerlich M, Sommerville S, Dickinson IC, Schütz MA, Füchtmeier B. Treatment of long bone defects and non-unions: From research to clinical practice. Cell Tissue Res. 2012;347:501-519.
211. Reichert JC, Saifzadeh S, Wullschleger ME, Epari DR, Schütz MA, Duda GN, Schell H, van Griensven M, Redl H, Hutmacher DW. The challenge of establishing preclinical models for segmental bone defect research. Biomaterials. 2009;30:2149-2163.
212. Reichert JC, Wullschleger ME, Cipitria A, Lienau J, Cheng TK, Schütz MA, Duda GN, Nth U, Eulert J, Hutmacher DW. Custom-made composite scaffolds for segmental defect repair in long bones. Int Orthop. 2011;35:1229-1236.
213. Reichert JC, Cipitria A, Epari DR, Saifzadeh S, Krishnakanth P, Berner A, Woodruff MA, Schell H, Mehta M, Schuetz MA, Duda GN, Hutmacher DW. A Tissue Engineering Solution for Segmental Defect Regeneration in Long Bones. Sci Transl Med. 2012;4:141-93.
214. Reichert JC, Epari DR, Wullschleger ME, Saifzadeh S, Steck R, Lienau J, Sommerville S, Dickinson IC, Schütz MA, Duda GN, Hutmacher DW. Establishment of a preclinical ovine model for tibial segmental bone defect repair by applying bone tissue engineering strategies. Tissue Eng Part B Rev. 2010;16:93-104.
215. Berner A, Reichert JC, Woodruff MA, Saifzadeh S, Morris AJ, Epari DR, Nerlich M, Schuetz MA, Hutmacher DW. Autologous vs. allogenic mesenchymal progenitor cells for the reconstruction of critical sized segmental tibial bone defects in aged sheep. Acta Biomater. 2013;9:7874-7884.
216. Tzioupis C, Giannoudis PV. Prevalence of long-bone non-unions. Injury. 2007;38:S3-S9.
217. Court-Brown CM, Caesar B. Epidemiology of adult fractures: A review. Injury. 2006;37:691-697.
218. Audigé L, Griffin D, Bhandari M, Kellam J, Ruëdi TP. Path analysis of factors for delayed healing and nonunion in 416 operatively treated tibial shaft fractures. Clin Orthop Relat Res. 2005;438:221-232.
219. Sandhu HS, Khan SN. Animal models for preclinical assessment of bone morphogenetic proteins in the spine. Spine (Phila Pa 1976). 2002;27:S32-S38.
220. Drespe, I. H., Polzhofer, G. K., Turner, A. S. & Grauer, J. N. Animal models for spinal fusion. Spine J. 2005;5:209S-216S.
221. Hecht BP, Fischgrund JS, Herkowitz HN, Penman L, Toth JM, Shirkhoda A. The use of recombinant human bone morphogenetic protein 2 (rhBMP-2) to promote spinal fusion in a nonhuman primate anterior interbody fusion model. Spine (Phila Pa 1976). 1999;24:629-636.
222. Cunningham BW, Kanayama M, Parker LM, Weis JC, Sefter JC, Fedder IL, McAfee PC. Osteogenic protein versus autologous interbody arthrodesis in the sheep thoracic spine. A comparative endoscopic study using the Bagby and Kuslich interbody fusion device. Spine (Phila Pa 1976). 1999;24:509-518.
223. Oehme D, Goldschlager T, Rosenfeld J, Danks A, Ghosh P, Gibbon A, Jenkin G.Lateral surgical approach to lumbar intervertebral discs in an ovine model. Sci World J. 2012;2012:873726.
224. Dubousset J. Scoliosis and its pathophysiology: Do we understand it Spine (Phila Pa 1976). 2001;26:1001.
225. Danielsson AJ, Nachemson AL. Back pain and function 22 years after brace treatment for adolescent idiopathic scoliosis: A case-control study-part I. Spine (Phila Pa 1976). 2003;28:2078-2085; discu-ssion 2086.
226. Reid JJ, Johnson JS, Wang JC. Challenges to bone formation in spinal fusion. J Biomech. 2011;44:213-220.
227. Whang PG, Wang JC. Bone graft substitutes for spinal fusion. Spine J. 2003;3:155-165.
228. Miyazaki M, Tsumura H, Wang JC, Alanay A. An update on bone substitutes for spinal fusion. Eur Spine J. 2009;18:783-799.
229. Mroz TE, Suen PW, Shamie AN, Whang PG, Wang JC. Bone graft substitutes in spinal surgery. Oper Tech Orthop. 2003;13:146-151.
230. Khan SN, Lane JM. Spinal fusion surgery: Animal models for tissue-engineered bone constructs. Biomaterials. 2004;25:1475-1485.
231. Subach BR, Haid RW, Rodts GE, Kaiser MG. Bone morphogenetic protein in spinal fusion: Overview and clinical update. Neurosurg Focus. 2001;10:E3.
232. Carlisle E, Fischgrund JS. Bone morphogenetic proteins for spinal fusion. Spine J. 2005;5:240S-249S.
233. Yong MR, Saifzadeh S, Askin GN, Labrom RD, Hutmacher DW, Adam CJ. Establishment and characterization of an open mini-thoracotomy surgical approach to an ovine thoracic spine fusion model. Tissue Eng Part C Methods. 2013 Jul 10. [Epub ahead of print].
234. Schantz JT, Lim TC, Ning C, Teoh SH, Tan KC, Wang SC, Hutmacher DW. Cranioplasty after trephination using a novel bio-degradable burr hole cover: Technical case report. Neurosurgery. 2006;58:ONS-E176; discussion ONS-E176.
235. Ast MP, Nam D, Haas SB. Patient-specific instrumentation for total knee arthroplasty: A review. Orthop Clin North Am. 2012;43:e17-e22.
236. Krishnan SP, Dawood A, Richards R, Henckel J, Hart AJ.A review of rapid prototyped surgical guides for patient-specific total knee replacement. J Bone Joint Surg Br. 2012;94:1457-1461.
237. Schweizer, A. New technologies in planning and performance of osteotonics: Example cases in hand surgery. Praxis (Bern 1994). 2013;102:579-584.
238. Benum P, Aamodt A. Uncemented custom femoral components in hip arthroplasty. Acta Orthop. 2010;81:427-435.
239. Eufinger H, Saylor B. Computer-assisted prefabrication of indivi-dual craniofacial implants. AORN J. 2001;74:648-654; quiz 655-656, 658-662.
240. Fuster-Torres MA, Albalat-Estela S, Alcañiz-Raya M, Penãrrocha-Diago M. CAD/CAM dental systems in implant dentistry: Update. Med Oral Patol Oral Cir Bucal. 2009;14:E141-E145.
241. Muirhead-Allwood S, Sandiford NA, Skinner JA, Hua J, Muirhead W, Kabir C, Walker PS. Uncemented computer-assisted design-computer-assisted manufacture femoral components in revision total hip replacement: A minimum follow-up of ten years. J Bone Joint Surg Br. 2010;92:1370-1375.
242. Muirhead-Allwood SK, Sandiford N, Skinner JA, Hua J, Kabir C, Walker PS. Uncemented custom computer-assisted design and manufacture of hydroxyapatite-coated femoral components: Sur-vival at 10 to 17 years. J Bone Joint Surg Br. 2010;92:1079-1084.
243. Brune JC, Hesselbarth U, Seifert P, Nowack D, von Versen R, Smith MD, Seifert D. CT lesion model-based structural allografts: Custom fabrication and clinical experience. Transfus Med Hemother. 2012; 39:395-404.
244. Lantada AD, Morgado PL. Rapid prototyping for biomedical engineering: Current capabilities and challenges. Annu Rev Biomed Eng. 2012;14:73-96.
245. Probst FA, Hutmacher DW, Müller DF, Machens HG, Schantz JT. Calvarial reconstruction by customized bioactive implant. Hand-chir Mikrochir Plast Chir. 2010;42:369-373.
246. Holzapfel BM, Chhaya MP, Melchels FP, Holzapfel NP, Prodinger PM, von Eisenhart-Rothe R, van Griensven M, Schantz JT, Rudert M, Hutmacher DW. Can bone tissue engineering contribute to therapy concepts after resection of musculoskeletal sarcoma Sar-coma. 2013;2013:153640.