Scaffold translation: Barriers between concept and clinic

Tissue Engineering - Part B: Reviews

Volumn 17, Issue 6, 2011, Pages 459-474

  Hollister, Scott J ^a   Murphy, William L ^b  

^a UNIVERSITY OF MICHIGAN   (United States)

^b UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BONE DEFECT; BONE TISSUE ENGINEERING; BUSINESS CHALLENGES; CLINICAL USE; LONG BONE; MANDIBULAR DEFECT; MARKET NEEDS; MODULAR SYSTEM; PRIVATE INVESTMENT; RESEARCH FUNDING; SPINE FUSION; TECHNICAL CHALLENGES; TECHNICAL SOLUTIONS;

BONE; DEFECTS; PHILOSOPHICAL ASPECTS; PHOTOMASKS; RESEARCH; TISSUE;

SCAFFOLDS (BIOLOGY);

TISSUE SCAFFOLD;

BONE DEFECT; BONE REMODELING; BONE TISSUE; ECONOMIC ASPECT; FUNDING; HUMAN; INVESTMENT; MARKETING; MEDICAL LITERATURE; MEDICAL RESEARCH; MEDICAL TECHNOLOGY; NONHUMAN; PRIORITY JOURNAL; PRODUCT DEVELOPMENT; PUBLISHING; RESEARCH PRIORITY; REVIEW; TISSUE ENGINEERING; TRANSLATIONAL RESEARCH; TREATMENT INDICATION;

ANIMALS; HUMANS; RESEARCH SUPPORT AS TOPIC; TISSUE SCAFFOLDS; TRANSLATIONAL MEDICAL RESEARCH;

EID: 81755166872     PISSN: 19373368     EISSN: 19373376     Source Type: Journal    
DOI: 10.1089/ten.teb.2011.0251     Document Type: Review

References (194)

1. Bockemuhl, M. Rembrandt (1606-1659). The Mystery of the Revealed Form. Kö ln, Germany: Taschen, 2000.
2. Ratcliffe, A. The clinical market for tissue engineered products in orthopaedics. In: Sandell, L.J., and Grodzinsky, A.J., eds. Tissue Engineering in Musculoskeletal Clinical Practice. Rosemond, IL: American Academy of Orthopaedic Surgeons, 2004, p. 17.
3. Ratcliffe, A. Industrial approaches in tissue engineering. In: Mao, J., Vunjak-Novakovic, G., Mikos, A.G., and Atala, A. eds. Translational Approaches in Tissue Engineering and Regenerative Medicine. Norwood, MA: Artech House, 2008, pp. 463-472.
4. Cahill, K.S., Chi, J.H., Day, A., and Claus, E.B. Prevalence, complications, and hospital charges associated with use of bone-morphogenetic proteins in spinal fusion procedures. JAMA 302, 58, 2009.
5. Ong, K.L., Villarraga, M.L., Lau, E., Carreon, L.Y., Kurtz, S.M., and Glassman, S.D. Off-label use of bone morphogenetic proteins in the United States using administrative data. Spine (Phila Pa 1976) 35, 1794, 2010.
6. Smucker, J.D., Rhee, J.M., Singh, K., Yoon, S.T., and Heller, J.G. Increased swelling complications associated with offlabel usage of rhBMP-2 in the anterior cervical spine. Spine 31, 2813, 2006.
7. Tumialan, L.M., and Rodts, G.E. Adverse swelling associated with use of rh-BMP-2 in anterior cervical discectomy and fusion. Spine J 7, 509, 2007.
8. Vaidya, R., Carp, J., Sethi, A., Bartol, S., Craig, J., and Les, C.M. Complications of anterior cervical discectomy and fusion using recombinant human bone morphogenetic protein-2. Eur Spine J 16, 1257, 2007.
9. Vaidya, R., Sethi, A., Bartol, S., Jacobson, M., Coe, C., and Craig, J.G. Complications in the use of rhBMP-2 in PEEK cages for interbody spinal fusions. J Spinal Disord Tech 21, 557, 2008.
10. Vaidya, R., Weir, R., Sethi, A., Meisterling, S., Hakeos, W., and Wybo, C.D. Interbody fusion with allograft and rhBMP-2 leads to consistent fusion but early subsidence. J Bone Joint Surg Br 89, 342, 2007.
11. Chen, N.F., Smith, Z.A., Stiner, E., Armin, S., Sheikh, H., and Khoo, L.T. Symptomatic ectopic bone formation after off-label use of recombinant human bone morphogenetic protein-2 in transforaminal lumbar interbody fusion. J Neurosurg Spine 12, 40, 2010.
12. Joseph, V., and Rampersaud, Y.R. Heterotopic bone formation with the use of rhBMP2 in posterior minimal access interbody fusion: a CT analysis. Spine 32, 2885, 2007.
13. Traynelis, V.C. Ectopic bone. J Neurosurg Spine 12, 39, 2010.
14. Wong, D.A., Kumar, A., Jatana, S., Ghiselli, G., and Wong, K. Neurologic impairment from ectopic bone in the lumbar canal: a potential complication of off-label PLIF/TLIF use of bone morphogenetic protein-2 (BMP-2). Spine J 8, 1011, 2008.
15. Boraiah, S., Paul, O., Hawkes, D., Wickham, M., and Lorich, D.G. Complications of recombinant human BMP-2 for treating complex tibial plateau fractures: a preliminary report. Clin Orthop Relat Res 467, 3257, 2009.
16. Carragee, E.J., Mitsunaga, K.A., Hurwitz, E.L., and Scuderi, G.J. Retrograde ejaculation after anterior lumbar Interbody fusion using rhBMP-2: a cohort controlled study. Spine J 11, 511, 2011.
17. Russolillo, S. FDA Rejects Medtronic Spine Device. The Wall Street Journal, March 10, 2011. Available at http://online.wsj.com/article/ SB10001424052748704823004576192 593075897446.html
18. Bak, M., Jacobson, A.S., Buchbinder, D., and Urken, M.L. Contemporary reconstruction of the mandible. Oral Oncol 46, 71, 2010.
19. Schliephake, H. Revascularized tissue transfer for the repair of complex midfacial defects in oncologic patients. J Oral Maxillofac Surg 58, 1212, 2000.
20. Torroni, A. Engineered bone grafts and bone flaps for maxillofacial defects: state of the art. J Oral Maxillofac Surg 67, 1121, 2009.
21. Wells, M.D. Mandibular reconstruction using vascularized bone grafts. J Oral Maxillofac Surg 54, 883, 1996.
22. Hollister, S.J. Scaffold design and manufacturing: from concept to clinic. Adv Mater 21, 3330, 2009.
23. Brekke, J.H., and Toth, J.M. Principles of tissue engineering applied to programmable osteogenesis. J Biomed Mater Res 43, 380, 1998.
24. Hutmacher, D.W. Scaffold design and fabrication technologies for engineering tissues-state of the art and future perspectives. J Biomater Sci Polym Ed 12, 107, 2001.
25. Yaszemski, M.J., Payne, R.G., Hayes, W.C., Langer, R., and Mikos, A.G. Evolution of bone transplantation: molecular, cellular and tissue strategies to engineer human bone. Biomaterials 17, 175, 1996.
26. Hollister, S.J., Liao, E.E., Moffitt, E.N., Jeong, C.G., and Williams, J.M. Defining design targets for tissue engineering scaffolds. In: Meyer, U., ed. Fundamentals of Tissue Engineering and Regenerative Medicine. Berlin: Springer-Verlag, 2009, pp. 521-537.
27. Ciarelli, M.J., Goldstein, S.A., Kuhn, J.L., Cody, D.D., and Brown, M.B. Evaluation of orthogonal mechanical properties and density of human trabecular bone from the major metaphyseal regions with materials testing and computed tomography. J Orthop Res 9, 674, 1991.
28. Goldstein, S.A. The mechanical properties of trabecular bone: dependence on anatomic location and function. J Biomech 20, 1055, 1987.
29. Goulet, R.W., Goldstein, S.A., Ciarelli, M.J., Kuhn, J.L., Brown, M.B., and Feldkamp, L.A. The relationship between the structural and orthogonal compressive properties of trabecular bone. J Biomech 27, 375, 1994.
30. Katz, J.L., and Meunier, A. The elastic anisotropy of bone. J Biomech 20, 1063, 1987.
31. Rho, J.Y., Ashman, R.B., and Turner, C.H. Young's modulus of trabecular and cortical bone material: ultrasonic and microtensile measurements. J Biomech 26, 111, 1993.
32. Cheal, E.J., Mansmann, K.A., DiGioia, A.M., 3rd, Hayes, W.C., and Perren, S.M. Role of interfragmentary strain in fracture healing: ovine model of a healing osteotomy. J Orthop Res 9, 131, 1991.
33. Loboa, E.G., Beaupre, G.S., and Carter, D.R. Mechanobiology of initial pseudarthrosis formation with oblique fractures. J Orthop Res 19, 1067, 2001.
34. Molster, A.O. Effects of rotational instability on healing of femoral osteotomies in the rat. Acta Orthop Scand 55, 632, 1984.
35. Molster, A.O., and Gjerdet, N.R. Effects of instability on fracture healing in the rat. Acta Orthop Scand 55, 342, 1984.
36. Perren, S.M. Physical and biological aspects of fracture healing with special reference to internal fixation. Clin Orthop Relat Res (138), 175, 1979.
37. Baldwin, C.Y., and Clark, K.B. Design Rules: the Power of Modularity, Vol. 1. Cambridge, MA: The MIT Press, 2000.
38. Arthur, W.B. The Nature of Technology: What It Is and How It Evolves. NY: Free Press, 2009.
39. He, J., Sun, J., Deem, M.W. Spontaneous emergence of modularity in a model of evolving individuals and in real networks. Phys Rev E Stat Nonlin Soft Matter Phys 79, 031907, 2009.
40. Newman, M.E. Modularity and community structure in networks. Proc Natl Acad Sci USA 103, 8577, 2006.
41. Sun, J., and Deem, M.W. Spontaneous emergence of modularity in a model of evolving individuals. Phys Rev Lett 99, 228107 2007.
42. Guedes, J.M., and Kikuchi, N. Preprocessing and postprocessing for materials based on the homogenization method with adaptive finite element methods. Comput Methods Appl Mech Eng 83, 143, 1990.
43. Sanchez-Palencia, E. Non-Homogeneous Media and Vibration Theory. Berlin: Springer-Verlag, 1980.
44. Hollister, S.J., Brennan, J.M., and Kikuchi, N. A homogenization sampling procedure for calculating trabecular bone effective stiffness and tissue level stress. J Biomech 27, 433, 1994.
45. Hollister, S.J., Fyhrie, D.P., Jepsen, K.J., and Goldstein S.A. Application of homogenization theory to the study of trabecular bone mechanics. J Biomech 24, 825, 1991.
46. Aoubiza, B., Crolet, J.M., and Meunier, A. On the mechanical characterization of compact bone structure using the homogenization theory. J Biomech 29, 1539, 1996.
47. Yin, L., and Elliott, D.M. A homogenization model of the annulus fibrosus. J Biomech 38, 1674, 2005.
48. Bendsoe, M.P., and Kikuchi, N. Generating optimal topologies in structural design using a homogenization method. Comput Methods Appl Mech Eng 71, 197, 1988.
49. Sigmund, O. Materials with prescribed constitutive parameters-an inverse homogenization problem. Int J Solids Struct 31, 2313, 1994.
50. Adachi, T., Osako, Y., Tanaka, M., Hojo, M., and Hollister, S.J. Framework for optimal design of porous scaffold microstructure by computational simulation of bone regeneration. Biomaterials 27, 3964, 2006.
51. Hollister, S.J., Maddox, R.D., and Taboas, J.M. Optimal design and fabrication of scaffolds to mimic tissue properties and satisfy biological constraints. Biomaterials 23, 4095, 2002.
52. Lin, C.Y., Kikuchi, N., and Hollister, S.J. A novel method for biomaterial scaffold internal architecture design to match bone elastic properties with desired porosity. J Biomech 37, 623, 2004.
53. Kang, H., Lin, C., and Hollister, S.J. Topology optimization of three dimensional tissue engineering scaffold architectures for prescribed bulk modulus and diffusivity. Struct Multidiscip Optim 42, 633, 2010.
54. Coelho, P.G., Fernandes, P.R., Rodrigues, H.C., Cardoso, J.B., and Guedes, J.M. Numerical modeling of bone tissue adaptation-a hierarchical approach for bone apparent density and trabecular structure. J Biomech 42, 830, 2009.
55. Sturm, S., Zhou, S., Mai, Y.W., and Li, Q. On stiffness of scaffolds for bone tissue engineering-a numerical study. J Biomech 43, 1738, 2010.
56. Hollister, S.J. Porous scaffold design for tissue engineering. Nat Mater 4, 518, 2005.
57. Agrawal, C.M., McKinney, J.S., Lanctot, D., and Athanasiou, K.A. Effects of fluid flow on the in vitro degradation kinetics of biodegradable scaffolds for tissue engineering. Biomaterials 21, 2443, 2000.
58. Boudriot, U., Dersch, R., Greiner, A., and Wendorff, J.H. Electrospinning approaches toward scaffold engineering-a brief overview. Artif Organs 30, 785, 2006.
59. Moshfeghian, A., Tillman, J., and Madihally, S.V. Characterization of emulsified chitosan-PLGA matrices formed using controlled-rate freezing and lyophilization technique. J Biomed Mater Res Part A 79, 418, 2006.
60. Nam, Y.S., and Park, T.G. Biodegradable polymeric microcellular foams by modified thermally induced phase separation method. Biomaterials 20, 1783, 1999.
61. Nerurkar, N.L., Elliott, D.M., and Mauck, R.L. Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering. J Orthop Res 25, 1018, 2007.
62. Riddle, K.W., and Mooney, D.J. Role of poly(lactide-coglycolide) particle size on gas-foamed scaffolds. J Biomater Sci Polym Ed 15, 1561, 2004.
63. Rowlands, A.S., Lim, S.A., Martin, D., and Cooper-White, J.J. Polyurethane/poly(lactic-co-glycolic) acid composite scaffolds fabricated by thermally induced phase separation. Biomaterials 28, 2109, 2007.
64. Thomas, V., Jose, M.V., Chowdhury, S., Sullivan, J.F., Dean, D.R., and Vohra, Y.K. Mechano-morphological studies of aligned nanofibrous scaffolds of polycaprolactone fabricated by electrospinning. J Biomater Sci Polym Ed 17, 969, 2006.
65. Giordano, R.A., Wu, B.M., Borland, S.W., Cima, L.G., Sachs, E.M., and Cima, M.J. Mechanical properties of dense polylactic acid structures fabricated by three dimensional printing. J Biomater Sci Polym Ed 8, 63, 1996.
66. Levy, R.A., Chu, T.M., Halloran, J.W., Feinberg, S.E., and Hollister, S. CT-generated porous hydroxyapatite orbital floor prosthesis as a prototype bioimplant. AJNR 18, 1522, 1997.
67. Abbah, S.A., Lam, C.X., Hutmacher, D.W., Goh, J.C., and Wong, H.K. Biological performance of a polycaprolactonebased scaffold used as fusion cage device in a large animal model of spinal reconstructive surgery. Biomaterials 30, 5086, 2009.
68. Arcaute, K., Mann, B., and Wicker, R. Stereolithography of spatially controlled multi-material bioactive poly(ethylene glycol) scaffolds. Acta Biomater 6, 1047, 2010.
69. Cooke, M.N., Fisher, J.P., Dean, D., Rimnac, C., and Mikos, A.G. Use of stereolithography to manufacture critical-sized 3D biodegradable scaffolds for bone ingrowth. J Biomed Mater Res Part B Appl Biomater 64, 65, 2003.
70. Eshraghi, S., and Das, S. Mechanical and microstructural properties of polycaprolactone scaffolds with onedimensional, two-dimensional, and three-dimensional orthogonally oriented porous architectures produced by selective laser sintering. Acta Biomater 6, 2467, 2010.
71. Habibovic, P., Gbureck, U., Doillon, C.J., Bassett, D.C., van Blitterswijk, C.A., and Barralet, J.E. Osteoconduction and osteoinduction of low-temperature 3D printed bioceramic implants. Biomaterials 29, 944, 2008.
72. Hollister, S.J., Levy, R.A., Chu, T.M., Halloran, J.W., and Feinberg, S.E. An image-based approach for designing and manufacturing craniofacial scaffolds. Int J Oral Maxillofac Surg 29, 67, 2000.
73. Hutmacher, D.W., Schantz, T., Zein, I., Ng, K.W., Teoh, S.H., and Tan, K.C. Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling. J Biomed Mater Res 55, 203, 2001.
74. Kai, H., Wang, X., Madhukar, K.S., Qin, L., Yan, Y., Zhang, R., and Wang, X. Fabrication of a two-level tumor bone repair biomaterial based on a rapid prototyping technique. Biofabrication 1, 025003, 2009.
75. Kim, K., Yeatts, A., Dean, D., and Fisher, J.P. Stereolithographic bone scaffold design parameters: osteogenic differentiation and signal expression. Tissue Eng Part B Rev 16, 523, 2010.
76. Lam, C.X., Hutmacher, D.W., Schantz, J.T., Woodruff, M.A., and Teoh, S.H. Evaluation of polycaprolactone scaffold degradation for 6 months in vitro and in vivo. J Biomed Mater Res Part A 90, 906, 2009.
77. Lan, P.X., Lee, J.W., Seol, Y.J., and Cho, D.W. Development of 3D PPF/DEF scaffolds using micro-stereolithography and surface modification. J Mater Sci Mater Med 20, 271, 2009.
78. Lee, J.W., Lan, P.X., Kim, B., Lim, G., and Cho, D.W. Fabrication and characteristic analysis of a poly(propylene fumarate) scaffold using micro-stereolithography technology. J Biomed Mater Res Part B Appl Biomater 87, 1, 2008.
79. Lee, K.W.,Wang, S., Fox, B.C., Ritman, E.L., Yaszemski, M.J., and Lu, L. Poly(propylene fumarate) bone tissue engineering scaffold fabrication using stereolithography: effects of resin formulations and laser parameters. Biomacromolecules 8, 1077, 2007.
80. Li, J., Hsu, Y., Luo, E., Khadka, A., and Hu, J. Computeraided design and manufacturing and rapid prototyped nanoscale hydroxyapatite/polyamide (n-HA/PA) construction for condylar defect caused by mandibular angle ostectomy. Aesthetic Plast Surg 35, 636, 2011.
81. Li, J.P., de Wijn, J.R., van Blitterswijk, C.A., and de Groot, K. The effect of scaffold architecture on properties of direct 3D fiber deposition of porous Ti6Al4V for orthopedic implants. J Biomed Mater Res Part A 92, 33, 2010.
82. Li, M.G., Tian, X.Y., and Chen, X.B. A brief review of dispensing-based rapid prototyping techniques in tissue scaffold fabrication: role of modeling on scaffold properties prediction. Biofabrication 1, 032001, 2009.
83. Lin, C.Y., Schek, R.M., Mistry, A.S., Shi, X., Mikos, A.G., Krebsbach, P.H., and Hollister, S.J. Functional bone engineering using ex vivo gene therapy and topologyoptimized, biodegradable polymer composite scaffolds. Tissue Eng 11, 1589, 2005.
84. Lin, C.Y., Wirtz, T., LaMarca, F., and Hollister, S.J. Structural and mechanical evaluations of a topology optimized titanium interbody fusion cage fabricated by selective laser melting process. J Biomed Mater Res Part A 83, 272, 2007.
85. Liu, L., Xiong, Z., Yan, Y., Hu, Y., Zhang, R., and Wang, S. Porous morphology, porosity, mechanical properties of poly(alpha-hydroxy acid)-tricalcium phosphate composite scaffolds fabricated by low-temperature deposition. J Biomed Mater Res Part A 82, 618, 2007.
86. Malda, J., Woodfield, T.B., van der Vloodt, F., Wilson, C., Martens, D.E., Tramper, J., van Blitterswijk, C.A., and Riesle, J. The effect of PEGT/PBT scaffold architecture on the composition of tissue engineered cartilage. Biomaterials 26, 63, 2005.
87. Melchels, F.P., Barradas, A.M., van Blitterswijk, C.A., de Boer, J., Feijen, J., and Grijpma, D.W. Effects of the architecture of tissue engineering scaffolds on cell seeding and culturing. Acta Biomater 6, 4208, 2010.
88. Melchels, F.P., Bertoldi, K., Gabbrielli, R., Velders, A.H., Feijen, J., and Grijpma, D.W. Mathematically defined tissue engineering scaffold architectures prepared by stereolithography. Biomaterials 31, 6909, 2010.
89. Melchels, F.P., Feijen, J., and Grijpma, D.W. A poly(D,Llactide) resin for the preparation of tissue engineering scaffolds by stereolithography. Biomaterials 30, 3801, 2009.
90. Mironov, V., Trusk, T., Kasyanov, V., Little, S., Swaja, R., and Markwald, R. Biofabrication: a 21st century manufacturing paradigm. Biofabrication 1, 022001, 2009.
91. Nakamura, M., Iwanaga, S., Henmi, C., Arai, K., and Nishiyama, Y. Biomatrices and biomaterials for future developments of bioprinting and biofabrication. Biofabrication 2, 014110, 2010.
92. Peltola, S.M., Melchels, F.P., Grijpma, D.W., and Kellomaki, M. A review of rapid prototyping techniques for tissue engineering purposes. Ann Med 40, 268, 2008.
93. Schuckert, K.H., Jopp, S., and Teoh, S.H. Mandibular defect reconstruction using three-dimensional polycaprolactone scaffold in combination with platelet-rich plasma and recombinant human bone morphogenetic protein-2: de novo synthesis of bone in a single case. Tissue Eng Part A 15, 493, 2009.
94. Schumacher, M., Deisinger, U., Detsch, R., and Ziegler, G. Indirect rapid prototyping of biphasic calcium phosphate scaffolds as bone substitutes: influence of phase composition, macroporosity and pore geometry on mechanical properties. J Mater Sci Mater Med 21, 3119, 2010.
95. Seitz, H., Rieder, W., Irsen, S., Leukers, B., and Tille, C. Three-dimensional printing of porous ceramic scaffolds for bone tissue engineering. J Biomed Mater Res Part B Appl Biomater 74, 782, 2005.
96. Shor, L., Guceri, S., Chang, R., Gordon, J., Kang, Q., Hartsock, L., An, Y., and Sun, W. Precision extruding deposition (PED) fabrication of polycaprolactone (PCL) scaffolds for bone tissue engineering. Biofabrication 1, 015003, 2009.
97. Smith, M.H., Flanagan, C.L., Kemppainen, J.M., Sack, J.A., Chung, H., Das, S., Hollister, S.J., and Feinberg, S.E. Computed tomography-based tissue-engineered scaffolds in craniomaxillofacial surgery. Int J Med Robot 3, 207, 2007.
98. Sobral, J.M., Caridade, S.G., Sousa, R.A., Mano, J.F., and Reis, R.L. Three-dimensional plotted scaffolds with controlled pore size gradients: effect of scaffold geometry on mechanical performance and cell seeding efficiency. Acta Biomater 7, 1009, 2011.
99. Sudarmadji, N., Tan, J.Y., Leong, K.F., Chua, C.K., and Loh, Y.T. Investigation of the mechanical properties and porosity relationships in selective laser-sintered polyhedral for functionally graded scaffolds. Acta Biomater 7, 530, 2011.
100. Taboas, J.M., Maddox, R.D., Krebsbach, P.H., and Hollister, S.J. Indirect solid free form fabrication of local and global porous, biomimetic and composite 3D polymer-ceramic scaffolds. Biomaterials 24, 181, 2003.
101. Tan, K.H., Chua, C.K., Leong, K.F., Cheah, C.M., Gui, W.S., Tan, W.S., and Wiria, F.E. Selective laser sintering of biocompatible polymers for applications in tissue engineering. Biomed Mater Eng 15, 113, 2005.
102. Warnke, P.H., Seitz, H., Warnke, F., Becker, S.T., Sivananthan, S., Sherry, E., Liu, Q., Wiltfang, J., and Douglas, T. Ceramic scaffolds produced by computer-assisted 3D printing and sintering: characterization and biocompatibility investigations. J Biomed Mater Res Part B Appl Biomater 93, 212, 2010.
103. Williams, J.M., Adewunmi, A., Schek, R.M., Flanagan, C.L., Krebsbach, P.H., Feinberg, S.E., Hollister, S.J., and Das, S. Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. Biomaterials 26, 4817, 2005.
104. Zein, I., Hutmacher, D.W., Tan, K.C., and Teoh, S.H. Fused deposition modeling of novel scaffold architectures for tissue engineering applications. Biomaterials 23, 1169, 2002.
105. Moroni, L., de Wijn, J.R., and van Blitterswijk, C.A. Integrating novel technologies to fabricate smart scaffolds. J Biomater Sci Polym Ed 19, 543, 2008.
106. Park, A., Wu, B., and Griffith, L.G. Integration of surface modification and 3D fabrication techniques to prepare patterned poly(L-lactide) substrates allowing regionally selective cell adhesion. J Biomater Sci Polym Ed 9, 89, 1998.
107. Zhang, H., Lin, C.Y., and Hollister, S.J. The interaction between bone marrow stromal cells and RGD-modified three-dimensional porous polycaprolactone scaffolds. Biomaterials 30, 4063, 2009.
108. Zhang, H., Migneco, F., Lin, C.Y., and Hollister, S.J. Chemically-conjugated bone morphogenetic protein-2 on three-dimensional polycaprolactone scaffolds stimulates osteogenic activity in bone marrow stromal cells. Tissue Eng Part A 16, 3441, 2010.
109. Zhou, Y., Chen, F., Ho, S.T., Woodruff, M.A., Lim, T.M., and Hutmacher, D.W. Combined marrow stromal cellsheet techniques and high-strength biodegradable composite scaffolds for engineered functional bone grafts. Biomaterials 28, 814, 2007.
110. Wagoner Johnson, A.J., and Herschler, B.A. A review of the mechanical behavior of CaP and CaP/polymer composites for applications in bone replacement and repair. Acta Biomater 7, 16, 2011.
111. Poellmann, M.J., Harrell, P.A., King, W.P., and Wagoner Johnson, A.J. Geometric microenvironment directs cell morphology on topographically patterned hydrogel substrates. Acta Biomater 6, 3514, 2010.
112. Lan Levengood, S.K., Polak, S.J., Poellmann, M.J., Hoelzle, D.J., Maki, A.J., Clark, S.G., Wheeler, M.B., and Wagoner Johnson, A.J. The effect of BMP-2 on micro-and macroscale osteointegration of biphasic calcium phosphate scaffolds with multiscale porosity. Acta Biomater 6, 3283, 2010.
113. Lan Levengood, S.K., Polak, S.J., Wheeler, M.B., Maki, A.J., Clark, S.G., Jamison, R.D., and Wagoner Johnson, A.J. Multiscale osteointegration as a new paradigm for the design of calcium phosphate scaffolds for bone regeneration. Biomaterials 31, 3552, 2010.
114. Hak, D.J. The use of osteoconductive bone graft substitutes in orthopaedic trauma. J Am Acad Orthop Surg 15, 525, 2007.
115. Hing, K.A., Wilson, L.F., and Buckland, T. Comparative performance of three ceramic bone graft substitutes. Spine J 7, 475, 2007.
116. Guehennec, L., Soueidan, A., Layrolle, P., and Amouriq, Y. Surface treatments of titanium dental implants for rapid osseointegration. Dent Mater 23, 844, 2007.
117. Yang, Z., Yuan, H., Tong, W., Zou, P., Chen, W., and Zhang, X. Osteogenesis in extraskeletally implanted porous calcium phosphate ceramics: variability among different kinds of animals. Biomaterials 17, 2131, 1996.
118. Zreiqat, H., Ramaswamy, Y., Wu, C., Paschalidis, A., Lu, Z., James, B., Birke, O., McDonald, M., Little, D., and Dunstan, C.R. The incorporation of strontium and zinc into a calcium-silicon ceramic for bone tissue engineering. Biomaterials 31, 3175, 2010.
119. Peng, S., Zhou, G., Luk, K.D., Cheung, K.M., Li, Z., Lam, W.M., Zhou, Z., and Lu, W.W. Strontium promotes osteogenic differentiation of mesenchymal stem cells through the Ras/MAPK signaling pathway. Cell Physiol Biochem 23, 165, 2009.
120. Boden, S.D., Zdeblick, T.A., Sandhu, H.S., and Heim, S.E. The use of rhBMP-2 in interbody fusion cages. Definitive evidence of osteoinduction in humans: a preliminary report. Spine 25, 376, 2000.
121. Kanayama, M., Hashimoto, T., Shigenobu, K., Yamane, S., Bauer, T.W., and Togawa, D. A prospective randomized study of posterolateral lumbar fusion using osteogenic protein-1 (OP-1) versus local autograft with ceramic bone substitute: emphasis of surgical exploration and histologic assessment. Spine 31, 1067, 2006.
122. Govender, S., Csimma, C., Genant, H.K., Valentin-Opran, A., Amit, Y., Arbel, R., Aro, H., Atar, D., Bishay, M., Borner, M.G., Chiron, P., Choong, P., Cinats, J., Courtenay, B., Feibel, R., Geulette, B., Gravel, C., Haas, N., Raschke, M., Hammacher, E., van der Velde, D., Hardy, P., Holt, M., Josten, C., Ketterl, R.L., Lindeque, B., Lob, G., Mathevon, H., McCoy, G., Marsh, D., Miller, R., Munting, E., Oevre, S., Nordsletten, L., Patel, A., Pohl, A., Rennie, W., Reynders, P., Rommens, P.M., Rondia, J., Rossouw, W.C., Daneel, P.J., Ruff, S., Ruter, A., Santavirta, S., Schildhauer, T.A., Gekle, C., Schnettler, R., Segal, D., Seiler, H., Snowdowne, R.B., Stapert, J., Taglang, G., Verdonk, R., Vogels, L., Weckbach, A., Wentzensen, A., and Wisniewski, T. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am 84-A, 2123, 2002.
123. Murphy, W.L., and Mooney, D.J. Controlled delivery of inductive proteins, plasmid DNA and cells from tissue engineering matrices. J Periodontal Res 34, 413, 1999.
124. Choi, S., and Murphy, W.L. Sustained plasmid DNA release from dissolving mineral coatings. Acta Biomater 6, 3426, 2010.
125. Jongpaiboonkit, L., Franklin-Ford, T., and Murphy, W.L. Growth of hydroxyapatite coatings on biodegradable polymer microspheres. ACS Appl Mater Interfaces 1, 1504, 2009.
126. Lee, J.S., Lu, Y., Baer, G.S., Markel, M.D., and Murphy, W.L. Controllable protein delivery from coated surgical sutures. J Mater Chem 20, 8894, 2010.
127. Lu, Y., Lee, J.S., Nemke, B., Baer, G., Graf, B., Murphy, W.L., and Markel, M.D. Histologic evaluation of suture material loaded with basic fibroblast growth factor on acute rotator cuff repair in an ovine model. Curr Orthop Pract 22, 425, 2011.
128. Lu, Y., Markel, M.D., Nemke, B., Lee, J.S., Graf, B.K., and Murphy, W.L. Influence of hydroxyapatite-coated and growth factor-releasing interference screws on tendon-bone healing in an ovine model. Arthroscopy 25, 1427, 2009.
129. Lee, J.S., and Murphy, W.L. Modular peptides promote human mesenchymal stem cell differentiation on biomaterial surfaces. Acta Biomater 6, 21, 2010.
130. Lee, J.S., Wagoner Johnson, A.J., and Murphy, W.L. A modular, hydroxyapatite-binding version of vascular endothelial growth factor. Adv Mater 22, 5494, 2010.
131. Lee, J.S., Wagoner-Johnson, A., and Murphy, W.L. Modular peptide growth factors for substrate-mediated stem cell differentiation. Angew Chem Int Ed Engl 48, 6266, 2009.
132. Shields, L.B., Raque, G.H., Glassman, S.D., Campbell, M., Vitaz, T., Harpring, J., and Shields, C.B. Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion. Spine 31, 542, 2006.
133. FDA panel pack. AMPLIFYTM rhBMP-2 Matrix, June 2010. Available at www.fda.gov/downloads/Advisory Committees/CommitteesMeetingMaterials/ MedicalDevices/MedicalDevicesAdvisoryCommittee/OrthopaedicandRehab ilitationDevicesPanel/UCM220741.pdf
134. Haidar, Z.S., Hamdy, R.C., and Tabrizian, M. Delivery of recombinant bone morphogenetic proteins for bone regeneration and repair. Part A: current challenges in BMP delivery. Biotechnol Lett 31, 1817, 2009.
135. Alaoui-Ismaili, M.H., and Falb, D. Design of second generation therapeutic recombinant bone morphogenetic proteins. Cytokine Growth Factor Rev 20, 501, 2009.
136. Rosen, V. BMP and BMP inhibitors in bone. Ann NY Acad Sci 1068, 19, 2006.
137. Rundle, C.H., Wang, H., Yu, H., Chadwick, R.B., Davis, E.I., Wergedal, J.E., Lau, K.H., Mohan, S., Ryaby, J.T., and Baylink, D.J. Microarray analysis of gene expression during the inflammation and endochondral bone formation stages of rat femur fracture repair. Bone 38, 521, 2006.
138. Bone Anchoring System Guidance Document. Available at www.fda.gov/downloads/MedicalDevices/DeviceRegu lationandGuidance/ GuidanceDocuments/ucm080264.pdf
139. Bone Void Filler Guidance Document. Available at www .fda.gov/ohrms/ dockets/ac/03/briefing/3955b1-CALCIUM %20SALT.pdf
140. Dental Bone Void Filler Guidance Document. Available at www.fda.gov/downloads/MedicalDevices/DeviceRegula tionandGuidance/ GuidanceDocuments/ucm071857.pdf
141. Interbody Spinal Fusion Guidance Document. Available at www.fda.gov/downloads/MedicalDevices/DeviceRegula tionandGuidance/ GuidanceDocuments/ucm071410.pdf
142. Hollister, S.J. Scaffold engineering: a bridge to where? Biofabrication 1, 012001, 2009.
143. Stokes, D.E. Pasteur's Quadrant: Basic Science and Technological Innovation. Washington, DC: Brookings Institution Press, 1997.
144. Larsson, T.F., Martin Martinez, J.M., and Valles, J.L. Biomaterials for Healthcare: A Decade of EU Funded Research. European Commission. Luxembourg: Office for Official Publications of the European Communities. Available at ftp.cordis.europa.eu/pub/nmp/docs/biomaterials-web.pdf, 2007.
145. Abukawa, H., Zhang, W., Young, C.S., Asrican, R., Vacanti, J.P., Kaban, L.B., Troulis, M.J., and Yelick, P.C. Reconstructing mandibular defects using autologous tissueengineered tooth and bone constructs. J Oral Maxillofac Surg 67, 335, 2009.
146. Boyne, P.J., Salina, S., Nakamura, A., Audia, F., and Shabahang, S. Bone regeneration using rhBMP-2 induction in hemimandibulectomy type defects of elderly sub-human primates. Cell Tissue Bank 7, 1, 2006.
147. Fennis, J.P., Stoelinga, P.J., Merkx, M.A., and Jansen, J.A. Reconstruction of the mandible with a poly(D,L-lactide) scaffold, autogenous corticocancellous bone graft, and autogenous platelet-rich plasma: an animal experiment. Tissue Eng 11, 1045, 2005.
148. Fennis, J.P.M., Stoelinga, P.J.W., and Jansen, J.A. Mandibular reconstruction: a clinical and radiographic animal study on the use of autogenous scaffolds and platelet-rich plasma. Int J Oral Maxillofac Surg 31, 281, 2002.
149. Fritz, M.E., Jeffcoat, M.K., Reddy, M., Koth, D., Braswell, L.D., Malmquist, J., and Lemons, J. Guided bone regeneration of large mandibular defects in a primate model. J Periodontol 71, 1484, 2000.
150. He, Y., Zhang, Z.Y., Zhu, H.G., Qiu, W., Jiang, X., and Guo, W. Experimental study on reconstruction of segmental mandible defects using tissue engineered bone combined bone marrow stromal cells with three-dimensional tricalcium phosphate. J Craniofac Surg 18, 800, 2007.
151. Jegoux, F., Goyenvalle, E., Cognet, R., Malard, O., Moreau, F., Daculsi, G., and Aguado, E. Mandibular segmental defect regenerated with macroporous biphasic calcium phosphate, collagen membrane, and bone marrow graft in dogs. Arch Otolaryngol Head Neck Surg 136, 971, 2010.
152. Kokemueller, H., Spalthoff, S., Nolff, M., Tavassol, F., Essig, H., Stuehmer, C., Bormann, K.H., Rucker, M., and Gellrich, N.C. Prefabrication of vascularized bioartificial bone grafts in vivo for segmental mandibular reconstruction: experimental pilot study in sheep and first clinical application. Int J Oral Maxillofac Surg 39, 379, 2010.
153. Malard, O., Guicheux, J., Bouler, J.M., Gauthier, O., de Montreuil, C.B., Aguado, E., Pilet, P., LeGeros, R., and Daculsi, G. Calcium phosphate scaffold and bone marrow for bone reconstruction in irradiated area: a dog study. Bone 36, 323, 2005.
154. Nolff,M.C., Gellrich, N.C., Hauschild, G., Fehr,M., Bormann, K.H., Rohn, K., Spalthoff, S., Rucker, M., and Kokemuller, H. Comparison of two beta-tricalcium phosphate composite grafts used for reconstruction of mandibular critical size bone defects. Vet Comp Orthop Traumatol 22, 96, 2009.
155. Okafuji, N., Shimizu, T., Watanabe, T., Kimura, A., Kurihara, S., Furusawa, K., Hasegawa, H., and Kawakami, T. Tissue reaction to poly (lactic-co-glycolic acid) copolymer membrane in rhBMP used rabbit experimental mandibular reconstruction. Eur J Med Res 11, 394, 2006.
156. von Wilmowsky, C., Schwarz, S., Kerl, J.M., Srour, S., Lell, M., Felszeghy, E., and Schlegel, K.A. Reconstruction of a mandibular defect with autogenous, autoclaved bone grafts and tissue engineering: an in vivo pilot study. J Biomed Mater Res Part A 93, 1510, 2010.
157. Wu, W., Chen, X., Mao, T., Chen, F., and Feng, X. Bone marrow-derived osteoblasts seeded into porous betatricalcium phosphate to repair segmental defect in canine's mandibula. Ulus Travma Acil Cerrahi Derg 12, 268, 2006.
158. Yuan, J., Cui, L., Zhang, W.J., Liu, W., and Cao, Y. Repair of canine mandibular bone defects with bone marrow stromal cells and porous beta-tricalcium phosphate. Biomaterials 28, 1005, 2007.
159. Yuan, J., Zhang, W.J., Liu, G., Wei, M., Qi, Z.L., Liu, W., Cui, L., and Cao, Y.L. Repair of canine mandibular bone defects with bone marrow stromal cells and coral. Tissue Eng Part A 16, 1385, 2010.
160. Zhou, M., Peng, X., Mao, C., Xu, F., Hu, M., and Yu, G.Y. Primate mandibular reconstruction with prefabricated, vascularized tissue-engineered bone flaps and recombinant human bone morphogenetic protein-2 implanted in situ. Biomaterials 31, 4935, 2010.
161. Bloemers, F.W., Blokhuis, T.J., Patka, P., Bakker, F.C., Wippermann, B.W., and Haarman, H.J. Autologous bone versus calcium-phosphate ceramics in treatment of experimental bone defects. J Biomed Mater Res Part B Appl Biomater 66, 526, 2003.
162. Cancedda, R., Giannoni, P., and Mastrogiacomo, M. A tissue engineering approach to bone repair in large animal models and in clinical practice. Biomaterials 28, 4240, 2007.
163. Chen, B., Pei, G.X., Wang, K., and Tang, G.H. Long-term observation of large weight-bearing bone defect in goats repaired with tissue engineering technique. Nan Fang Yi Ke Da Xue Xue Bao 26, 770, 2006.
164. Gao, T.J., Lindholm, T.S., Kommonen, B., Ragni, P., Paronzini, A., Lindholm, T.C., Jamsa, T., and Jalovaara, P. Enhanced healing of segmental tibial defects in sheep by a composite bone substitute composed of tricalcium phosphate cylinder, bone morphogenetic protein, and type IV collagen. J Biomed Mater Res 32, 505, 1996.
165. Liu, G., Zhao, L., Zhang, W., Cui, L., Liu, W., and Cao, Y. Repair of goat tibial defects with bone marrow stromal cells and beta-tricalcium phosphate. J Mater Sci Mater Med 19, 2367, 2008.
166. Maissen, O., Eckhardt, C., Gogolewski, S., Glatt, M., Arvinte, T., Steiner, A., Rahn, B., and Schlegel, U. Mechanical and radiological assessment of the influence of rhTGFbeta-3 on bone regeneration in a segmental defect in the ovine tibia: pilot study. J Orthop Res 24, 1670, 2006.
167. Mastrogiacomo, M., Corsi, A., Francioso, E., Di Comite, M., Monetti, F., Scaglione, S., Favia, A., Crovace, A., Bianco, P., and Cancedda, R. Reconstruction of extensive long bone defects in sheep using resorbable bioceramics based on silicon stabilized tricalcium phosphate. Tissue Eng 12, 1261, 2006.
168. Meinel, L., Zoidis, E., Zapf, J., Hassa, P., Hottiger, M.O., Auer, J.A., Schneider, R., Gander, B., Luginbuehl, V., Bettschart-Wolfisberger, R., Illi, O.E., Merkle, H.P., and von Rechenberg, B. Localized insulin-like growth factor I delivery to enhance new bone formation. Bone 33, 660, 2003.
169. Monjo, M., Rubert, M., Wohlfahrt, J.C., Rønold, H.J., Ellingsen, J.E., and Lyngstadaas, S.P. In vivo performance of absorbable collagen sponges with rosuvastatin in criticalsize cortical bone defects. Acta Biomater 6, 1405, 2010.
170. Reichert, J.C., Epari, D.R., Wullschleger, M.E., Saifzadeh, S., Steck, R., Lienau, J., Sommerville, S., Dickinson, I.C., Schutz, M.A., Duda, G.N., and Hutmacher, D.W. Establishment of a preclinical ovine model for tibial segmental bone defect repair by applying bone tissue engineering strategies. Tissue Eng Part B Rev 16, 93, 2010.
171. Sarkar, M.R., Augat, P., Shefelbine, S.J., Schorlemmer, S., Huber-Lang, M., Claes, L., Kinzl, L., and Ignatius, A. Bone formation in a long bone defect model using a platelet-rich plasma-loaded collagen scaffold. Biomaterials 27, 1817, 2006.
172. van der Pol, U., Mathieu, L., Zeiter, S., Bourban, P.E., Zambelli, P.Y., Pearce, S.G., Boure, L.P., and Pioletti, D.P. Augmentation of bone defect healing using a new biocomposite scaffold: an in vivo study in sheep. Acta Biomater 6, 3755, 2010.
173. Viateau, V., Guillemin, G., Bousson, V., Oudina, K., Hannouche, D., Sedel, L., Logeart-Avramoglou, D., and Petite, H. Long-bone critical-size defects treated with tissueengineered grafts: a study on sheep. J Orthop Res 25, 741, 2007.
174. Xie, H., Yang, F., Deng, L., Luo, J., Qin, T., Li, X., Zhou, G., and Yang, Z. The performance of a bone-derived scaffold material in the repair of critical bone defects in a rhesus monkey model. Biomaterials 28, 3314, 2007.
175. Chang, S.C., Chung, H.Y., Tai, C.L., Chen, P.K., Lin, T.M., and Jeng, L.B. Repair of large cranial defects by hBMP-2 expressing bone marrow stromal cells: comparison between alginate and collagen type I systems. J Biomed Mater Res Part A 94, 433, 2010.
176. Chang, S.C., Lin, T.M., Chung, H.Y., Chen, P.K., Lin, F.H., Lou, J., and Jeng, L.B. Large-scale bicortical skull bone regeneration using ex vivo replication-defective adenoviralmediated bone morphogenetic protein-2 gene-transferred bone marrow stromal cells and composite biomaterials. Neurosurgery 65, 75, 2009.
177. Docherty-Skogh, A.C., Bergman, K., Waern, M.J., Ekman, S., Hultenby, K., Ossipov, D., Hilborn, J., Bowden, T., and Engstrand, T. Bone morphogenetic protein-2 delivered by hyaluronan-based hydrogel induces massive bone formation and healing of cranial defects in minipigs. Plast Reconstr Surg 125, 1383, 2010.
178. Lemperle, S.M., Calhoun, C.J., Curran, R.W., and Holmes, R.E. Bony healing of large cranial and mandibular defects protected from soft-tissue interposition: a comparative study of spontaneous bone regeneration, osteoconduction, and cancellous autografting in dogs. Plast Reconstr Surg 101, 660, 1998.
179. Mankani, M.H., Kuznetsov, S.A., Shannon, B., Nalla, R.K., Ritchie, R.O., Qin, Y., and Robey, P.G. Canine cranial reconstruction using autologous bone marrow stromal cells. Am J Pathol 168, 542, 2006.
180. Shang, Q., Wang, Z., Liu, W., Shi, Y., Cui, L., and Cao, Y. Tissue-engineered bone repair of sheep cranial defects with autologous bone marrow stromal cells. J Craniofac Surg 12, 586, 2001.
181. Yu, D., Li, Q., Mu, X., Chang, T., and Xiong, Z. Bone regeneration of critical calvarial defect in goat model by PLGA/TCP/rhBMP-2 scaffolds prepared by low-temperature rapid-prototyping technology. Int J Oral Maxillofac Surg 37, 929, 2008.
182. Abbah, S.A., Lam, C.X., Ramruttun, K.A., Hutmacher, D.W., Goh, J.C., and Wong, H.K. Autogenous bone marrow stromal cell sheets loaded mPCL/TCP scaffolds induced osteogenesis in a porcine model of spinal interbody fusion. Tissue Eng Part A 17, 809, 2011.
183. Cunningham, B.W., Sefter, J.C., Hu, N., and McAfee, P.C. Autologous growth factors versus autogenous graft for anterior cervical interbody fusion: an in vivo caprine model. J Neurosurg Spine 13, 216, 2010.
184. Ding, M., Cheng, L., Bollen, P., Schwarz, P., and Overgaard, S. Glucocorticoid induced osteopenia in cancellous bone of sheep: validation of large animal model for spine fusion and biomaterial research. Spine 35, 363, 2010.
185. Hojo, Y., Kotani, Y., Ito, M., Abumi, K., Kadosawa, T., Shikinami, Y., and Minami, A. A biomechanical and histological evaluation of a bioresorbable lumbar interbody fusion cage. Biomaterials 26, 2643, 2005.
186. Krijnen, M.R., Mullender, M.G., Smit, T.H., Everts, V., and Wuisman, P.I. Radiographic, histologic, and chemical evaluation of bioresorbable 70/30 poly-L-lactide-CO-D, Llactide interbody fusion cages in a goat model. Spine 31, 1559, 2006.
187. Kruyt, M.C., Wilson, C.E., de Bruijn, J.D., van Blitterswijk, C.A., Oner, C.F., Verbout, A.J., and Dhert, W.J. The effect of cell-based bone tissue engineering in a goat transverse process model. Biomaterials 27, 5099, 2006.
188. Lazennec, J.Y., Madi, A., Rousseau, M.A., Roger, B., and Saillant, G. Evaluation of the 96/4 PLDLLA polymer resorbable lumbar interbody cage in a long term animal model. Eur Spine J 15, 1545, 2006.
189. Mullender, M.G., Krijnen, M.R., Helder, M.N., Smit, T.H., Everts, V., and Wuisman, P.I. Lumbar body fusion with a bioresorbable cage in a goat model is delayed by the use of a carboxymethylcellulose-stabilized collagenous rhOP-1 device. J Orthop Res 25, 132, 2007.
190. Putzier, M., Strube, P., Funk, J., Gross, C., and Perka, C. Periosteal cells compared with autologous cancellous bone in lumbar segmental fusion. J Neurosurg Spine 8, 536, 2008.
191. Suh, D.Y., Boden, S.D., Louis-Ugbo, J., Mayr, M., Murakami, H., Kim, H.S., Minamide, A., and Hutton, W.C. Delivery of recombinant human bone morphogenetic protein-2 using a compression-resistant matrix in posterolateral spine fusion in the rabbit and in the non-human primate. Spine 27, 353, 2002.
192. van Gaalen, S.M., Dhert, W.J., Kruyt, M.C., Yuan, H., Oner, F.C., van Blitterswijk, C.A., Verbout, A.J., and de Bruijn, J.D. Goat bone tissue engineering: comparing an intramuscular with a posterolateral lumbar spine location. Tissue Eng Part A 16, 685, 2010.
193. Wheeler, D.L., Jenis, L.G., Kovach, M.E., Marini, J., and Turner, A.S. Efficacy of silicated calcium phosphate graft in posterolateral lumbar fusion in sheep. Spine J 7, 308, 2007.
194. Wuisman, P.I., van Dijk, M., and Smit, T.H. Resorbable cages for spinal fusion: an experimental goat model. J Neurosurg 97, 433, 2002.