Delivery systems for bone growth factors - The new players in skeletal regeneration

Journal of Pharmacy and Pharmacology

Volumn 56, Issue 4, 2004, Pages 415-427

  Rose, Felicity R A J ^a   Hou, Qingpu ^a   Oreffo, Richard O C ^b  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALGINIC ACID; BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN 2; BONE MORPHOGENETIC PROTEIN 4; CALCIUM PHOSPHATE; COLLAGEN; COPOLYMER; ETHYLENE VINYL ACETATE COPOLYMER; FIBROBLAST GROWTH FACTOR; GELATIN; GROWTH FACTOR; HYDROXYAPATITE; LIPOSOME; MICROSPHERE; OSTEOGENIC PROTEIN 1; PLATELET DERIVED GROWTH FACTOR; PLATELET DERIVED GROWTH FACTOR BB; PLEIOTROPHIN; POLYLACTIDE; POLYMER; POLYSACCHARIDE; RECOMBINANT BONE MORPHOGENETIC PROTEIN 2; SOMATOMEDIN; SOMATOMEDIN B; SOMATOMEDIN C; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA2; UNINDEXED DRUG; VASCULOTROPIN; VASCULOTROPIN RECEPTOR;

AGING; BIOTECHNOLOGY; BONE GRAFT; BONE GROWTH; BONE REGENERATION; CERAMICS; CORAL; DRUG DELIVERY SYSTEM; GENE THERAPY; HEALTH CARE; HUMAN; NONHUMAN; NONVIRAL GENE DELIVERY SYSTEM; REVIEW; TISSUE ENGINEERING; TISSUE INJURY; TISSUE REGENERATION; TISSUE REPAIR; VIRAL GENE DELIVERY SYSTEM;

BONE AND BONES; BONE DISEASES; BONE MORPHOGENETIC PROTEINS; BONE REGENERATION; CARRIER PROTEINS; CYTOKINES; DRUG CARRIERS; GENE THERAPY; HUMANS; TISSUE ENGINEERING; TRANSFORMING GROWTH FACTOR BETA;

EID: 1842471976     PISSN: 00223573     EISSN: None     Source Type: Journal    
DOI: 10.1211/0022357023312     Document Type: Review

References (169)

1. Anseth, K. S., Metters, A. T., Bryant, S. J., Martens, P. J., Elisseeff, J. H., Bowman, C. N. (2002) In situ forming degradable networks and their application in tissue engineering and drug delivery. J. Control. Release 78: 199-209
2. Arm, D. M., Tencer, A. F., Bain, S. D., Celino, D. (1996) Effect of controlled release of platelet derived growth factor from a porous hydroxyapatite implant on bone ingrowth. Biomaterials 17: 703-709
3. Arnold, U., Schweitzer, S., Lindenhayn, K., Perka, C. (2003) Optimization of bone engineering by means of growth factors in a three-dimensional matrix. J. Biomed. Mater. Res. 67A: 260-269
4. Beck, L. S., Deguzman, L., Lee, W. P., Xu, Y., McFatridge, L. A., Gillett, N. A., Amento, E. P. (1991) TGF-beta 1 induces bone closure of skull defects. J. Bone Miner. Res. 6: 1257-1265
5. Bezemer, J. M., Radersma, R., Grijpma, D. W., Dijkstra, P. J., van Blitterswijk, C. A., Feijen, J. (2000) Microspheres for protein delivery prepared from amphiphilic multiblock copolymers. 1. Influence of preparation techniques on particle characteristics and protein delivery. J. Control. Release 67: 233-248
6. Bianco, P., Robey, P. G. (2001) Stem cells in tissue engineering. Nature 414: 118-121
7. Bianco, P., Riminucci, M., Gronthos, S., Robey, P. G. (2001) Bone marrow stromal stem cells: Nature, biology, and potential applications. Stem Cells 19: 180-192
8. Bikle, D. D., Sakata, T., Leary, C., Elalieh, H., Ginzinger, D., Rosen, C. J., Beamer, W., Majumdar, S., Halloran, B. P. (2002) Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone. J. Bone Miner. Res. 17: 1570-1578
9. Blom, E. J., Klein-Nulend, J., Wolke, J. G. C., Kurashina, K., van Waas, M. A. J., Burger, E. H. (2002) Transforming growth factor-beta 1 incorporation in an alpha-tricalcium phosphate/dicalcium phosphate dihydrate/tetracalcium phosphate monoxide cement: Release characteristics and physicochemical properties. Biomaterials 23: 1261-1268
10. Boden, S. D. (1999) Bioactive factors for bone tissue engineering. Clin. Orthop. 367: S84-S94
11. Boden, S. D., Schimandle, J. H., Hutton, W. C. (1995) The use of an osteoinductive growth factor for lumbar spinal fusion. 2. Study of dose, carrier, and species. Spine 20: 2633-2644
12. Bonewald, L. Transforming growth factor beta. Bilezikian, J. P., Raisz, L. G., and Rodan, G. A. (2003) Principles of bone biology. Academic Press, San Diego, pp 903-918
13. Bordem, M. D., Khan, Y., Attawia, M., Laurencin, C. T. (2001) Tissue engineered microsphere-based matrices for bone repair: Design, evaluation, and optimization. Biomaterials 23: 551-559
14. Boyne, P. J. (1996) Animal studies of the application of rhBMP-2 in maxillofacial reconstruction. Bone 19: S83-S92
15. Boyne, P. J. (2001) Application of bone morphogenetic proteins in the treatment of clinical oral and maxillofacial osseous defects. J. Bone Joint Surg. Am. 83A: S146-S150
16. Boyne, P. J., Marx, R. E., Nevins, M., Triplett, G., Lazaro, E., Lilly, L. C., Alder, M., Nummikoski, P. (1997) A feasibility study evaluating rhBMP-2/absorbable collagen sponge for maxillary sinus floor augmentation. Int. J. Periodontics Restorative Dent. 17: 10-25
17. Bulpitt, P., Aeschlimann, D. (1999) New strategy for chemical modification of hyaluronic acid: Preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels. J. Biomed. Mater. Res. 47: 152-169
18. Burdick, J. A., Mason, M. N., Hinman, A. D., Thorne, K., Anseth, K. S. (2002) Delivery of osteoinductive growth factors from degradable PEG hydrogels influences osteoblast differentiation and mineralization. J. Controlled Release 83: 53-63
19. Burdick, J. A., Frankel, D., Dernell, W. S., Anseth, K. S. (2003) An initial investigation of photocurable three-dimensional lactic acid based scaffolds in a critical-sized cranial defect. Biomaterials 24: 1613-1620
20. Canalis, E., Varghese, S., McCarthy, T. L., Centrella, M. (1992) Role of platelet derived growth factor in bone cell function. Growth Regul. 2: 151-155
21. Centrella, M., McCarthy, T. L., Canalis, E. (1989) Platelet-derived growth factor enhances deoxyribonucleic acid and collagen synthesis in osteoblast-enriched cultures from fetal rat parietal bone. Endocrinology 125: 13-19
22. Chen, R. R., Mooney, D. J. (2003) Polymeric growth factor delivery strategies for tissue engineering. Pharm. Res. 20: 1103-1112
23. Clokie, C. M. L., Urist, M. R. (2000) Bone morphogenetic protein excipients: Comparative observations on poloxamer. Plast. Reconstr. Surg. 105: 628-637
24. Dallas, S. L., Rosser, J. L., Mundy, G. R., Bonewald, L. F. (2002) Proteolysis of latent transforming growth factor-beta (TGFbeta)-binding protein-1 by osteoclasts. A cellular mechanism for release of TGF-beta from bone matrix. J. Biol. Chem. 277: 21352-21360
25. Demers, C. N., Tabrizian, M., Petit, A., Hamdy, R. C., Yahia, L. (2002) Effect of experimental parameters on the in vitro release kinetics of transforming growth factor beta 1 from coral particles. J. Biomed. Mater. Res. 59: 403-410
26. Deuel, T. F., Zhang, N., Yeh, H. J., Silos-Santiago, I., Wang, Z. Y. (2002) Pleiotrophin: A cytokine with diverse functions and a novel signalling pathway. Arch. Biochem. Biophys. 397: 162-171
27. Dhoot, N. O., Wheatley, M. A. (2003) Microencapsulated liposomes in controlled drug delivery: Strategies to modulate drug release and eliminate the burst effect. J. Pharm. Sci. 92: 679-689
28. Ditizio, V., Karlgard, C., Lilge, L., Khoury, A. E., Mittelman, M. W., DiCosmo, F. (2000) Localized drug delivery using crosslinked gelatin gels containing liposomes: Factors influencing liposome stability and drug release. J. Biomed. Mater. Res. 51: 96-106
29. Ehrenfreund-Kleinman, T., Domb, A. J., Golenser, J. (2003) Polysaccharide scaffolds prepared by crosslinking of polysaccharides with chitosan or proteins for cell growth. J. Bioactive Compatible Polymers 18: 323-338
30. Ferrara, N. (2000) VEGF: An update on biological and therapeutic aspects. Curr. Opin. Biotechnol. 11: 617-624
31. Ferrara, N., Gerber, H. P., LeCouter, J. (2003) The biology of VEGF and its receptors. Nat. Med. 9: 669-676
32. Fong, G. H., Rossant, J., Gertsenstein, M., Breitman, M. L. (1995) Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376: 66-70
33. Friess, W., Uludag, H., Foskett, S., Biron, R. (1999a) Bone regeneration with recombinant human bone morphogenetic protein-2 (rhBMP-2) using absorbable collagen sponges (ACS): Influence of processing on ACS characteristics and formulation. Pharm. Dev. Technol. 4: 387-396
34. Friess, W., Uludag, H., Foskett, S., Biron, R., Sargeant, C. (1999b) Characterization of absorbable collagen sponges as rhBMP-2 carriers. Int. J. Pharm. 187: 91-99
35. Fu, K., Griebenow, K., Hsieh, L., Klibanov, A. M., Langer, R. (1999) FTIR characterization of the secondary structure of proteins encapsulated within PLGA microspheres. J. Control. Release 58: 357-366
36. Gao, T. J., Uludag, H. (2001) Effect of molecular weight of thermoreversible polymer on in vivo retention of rhBMP-2. J. Biomed. Mater. Res. 57: 92-100
37. Gao, T. J., Kousinioris, N. A., Wozney, J. M., Winn, S., Uludag, H. (2002) Synthetic thermoreversible polymers are compatible with osteoinductive activity of recombinant human bone morphogenetic protein 2. Tissue Eng. 8: 429-440
38. Gerber, H. P., Vu, T. H., Ryan, A. M., Kowalski, J., Werb, Z., Ferrara, N. (1999) VEGF couples hypertrophic cartilage remodelling, ossification and angiogenesis during endochondral bone formation. Nat. Med. 5: 623-628
39. Giordano, R. A., Wu, B. M., Borland, S. W., Cima, L. G., Sachs, E. M., Cima, M. J. (1996) Mechanical properties of dense polylactic acid structures fabricated by three dimensional printing. J. Biomater. Sci. Polym. Ed. 8: 63-75
40. Gittens, S. A., Uludag, H. (2001) Growth factor delivery for bone tissue engineering. J. Drug Target. 9: 407-429
41. Gombotz, W. R., Pankey, S. C., Bouchard, L. S., Ranchalis, J., Puolakkainen, P. (1993) Controlled-release of TGF-β1 from a biodegradable matrix for bone regeneration. J. Biomater. Sci. Polym. Ed. 5: 49-63
42. 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., Wisniewski, T. (2002) 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: 2123-2134
43. Green, D. W., Leveque, I., Walsh, D., Partridge, K. A., Mann, S., Oreffo, R. O. C. (2003) Innovative biomineralised polysaccharide templates for human bone cell and gene delivery. J. Bone Miner. Res. 18: 1361
44. Han, D. K., Hubbell, J. A. (1996) Lactide-based poly(ethylene glycol) polymer networks for scaffolds in tissue engineering. Macromolecules 29: 5233-5235
45. Hinrichs, W. L. J., Lommen, E., Wildevuur, C. R. H., Freijen, J. (1992) Fabrication and characterisation of an asymmetric polyurethane membrane for use as a wound dressing. J. Appl. Biomater. 3: 287-303
46. Hollinger, J. O., Leong, K. (1996) Poly(alpha-hydroxy acids): Carriers for bone morphogenetic proteins. Biomaterials 17: 187-194
47. Hollinger, J. O., Winn, S. R. (1999) Tissue engineering of bone in the craniofacial complex. Ann. N. Y. Acad. Sci. 875: 379-385
48. Hollinger, J. O., Schmitt, J. M., Buck, D. C., Shannon, R., Joh, S. P., Zegzula, H. D., Wozney, J. (1998) Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration. J. Biomed. Mater. Res. 43: 356-364
49. Hou, Q., Grijpma, D. W., Feijen, J. (2003) Preparation of inter-connected highly porous polymeric structures by a replication and freeze-drying process. J. Biomed. Mater. Res. 67B: 732-740
50. Howard, D., Partridge, K., Yang, X. B., Clarke, N. M. P., Okubo, Y., Bessho, K., Howdle, S. M., Shakesheff, K. M., Oreffo, R. O. C. (2002) Immunoselection and adenoviral genetic modulation of human osteoprogenitors: In vivo bone formation on PLA scaffold. Biochem. Biophys. Res. Commun. 299: 208-215
51. Howdle, S. M., Watson, M. S., Whitaker, M. J., Popov, M. C., Davies, M. C., Mandel, F. S., Wang, J. D., and Shakesheff, K. M. (2001) Supercritical fluid mixing: Preparation of thermally sensitive polymer composites containing bioactive materials. Chem. Commun. 1: 109-110
52. Howell, T. H., Fiorellini, J. P., Paquette, D. W., Offenbacher, S., Giannobile, W. V., Lynch, S. E. (1997) A phase I/II clinical trial to evaluate a combination of recombinant human platelet-derived growth factor-BB and recombinant human insulin-like growth factor-I in patients with periodontal disease. J. Periodontol. 68: 1186-1193
53. Hutmacher, D. W., Schantz, T., Zein, I., Ng, K. W., Teoh, S. H. Tan, K. C. (2001) Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modelling. J. Biomed. Mater. Res. 55: 203-216
54. Hwa, V., Oh, Y., Rosenfeld, R. G. (1999) The insulin-like growth factor-binding protein (IGFBP) superfamily. Endocrinol. Rev. 20: 761-787
55. Imai, S., Kaksonen, M., Raulo, E., Kinnunen, T., Fages, C., Meng, X., Lakso, M., Rauvala, H. (1998) Osteoblast recruitment and bone formation enhanced by cell matrix-associated heparin-binding growth-associated molecule (HB-GAM). J. Cell Biol. 143: 1113-1128
56. Itoh, S., Kikuchi, M., Takakuda, K., Koyama, Y., Matsumoto, H. N., Ichinose, S., Tanaka, J., Kawauchi, T., Shinomiya, K. (2001) The biocompatibility and osteoconductive activity of a novel hydroxyapatite/collagen composite biomaterial, and its function as a carrier of rhBMP-2. J. Biomed. Mater. Res. 54: 445-453
57. Jepsson, C., Aspenberg, P. (1996) BMP-2 can inhibit bone healing-bone-chamber study in rabbits. Acta Orthop. Scand. 67: 589-592
58. Jordan, K. M., Cooper, C. (2002) Epidemiology of osteoporosis. Best Pract. Res. Clin. Rheumatol. 16: 795-806
59. Jorge-Herrero, E., Fernandez, P., Turnay, J., Olmo, N., Calero, P., Garcia, R., Freile, I., Castillo-Olivares, J. L. (1999) Influence of different chemical cross-linking treatments on the properties of bovine pericardium and collagen. Biomaterials 20: 539-545
60. Kandziora, F., Scholz, M., Pflugmacher, R., Krummrey, G., Schollmeier, G., Schmidmaier, G., Schnake, K. J., Duda, G., Raschke, M., Haas, N. P. (2002) Experimental fusion of the sheep cervical spine. Part II: Effect of growth factors and carrier systems on interbody fusion. Chirurg 73: 1025
61. Kim, H. D., Valentini, R. F. (1997) Human osteoblast response in vitro to platelet-derived growth factor and transforming growth factor-beta delivered from controlled-release polymer rods. Biomaterials 18: 1175-1184
62. Kim, H. D., Valentini, R. F. (2002) Retention and activity of BMP-2 in hyaluronic acid-based scaffolds in vitro. J. Biomed. Mater. Res. 59: 573-584
63. Kirker-Head, C. A., Gerhart, T. N., Armstrong, R., Schelling, S. H., Carmel, L. A. (1998) Healing bone using recombinant human bone morphogenetic protein 2 and copolymer. Clin. Orthop. 349: 205-217
64. Kirkpatrick, C. J., Unger, R. E., Krump-Konvalinkova, V., Peters, K., Schmidt, H., Kamp, G. (2003) Experimental approaches to study vascularization in tissue engineering and biomaterial applications. J. Mater. Sci. Mater. Med. 14: 677-681
65. Langer, R., Vacanti, J. P. (1993) Tissue engineering. Science 260: 920-926
66. Lee, S. C., Shea, M., Battle, M. A., Kozitza, K., Ron, E., Turek, T., Schaub, R. G., Hayes, W. C. (1994) Healing of large segmental defects in rat femurs is aided by Rhbmp-2 in PLGA matrix. J. Biomed. Mater. Res. 28: 1149-1156
67. Lee, D. D., Tofighi, A., Aiolova, M., Chakravarthy, P., Catalano, A., Majahad, A., Knaack, D. (1999) alpha-BSM (R): A biomimetic bone substitute and drug delivery vehicle. Clin. Orthop. 367: S396-S405
68. Lee, J. Y., Nam, S. H., Im, S. Y., Park, Y. J., Lee, Y. M., Seol, Y. J., Chung, C. P., Lee, S. J. (2002) Enhanced bone formation by controlled growth factor delivery from chitosan-based biomaterials. J. Control. Release 78: 187-197
69. Lee, K. Y., Peters, M. C., Anderson, K. W., Mooney, D. J. (2000) Controlled growth factor release from synthetic extracellular matrices. Nature 408: 998-1000
70. Li, R. H., Wozney, J. M. (2001) Delivering on the promise of bone morphogenetic proteins. Trends Biotechnol. 19: 255-265
71. Lind, M., Overgaard, S., Glerup, H., Soballe, K., Bunger, C. (2001) Transforming growth factor-beta 1 adsorbed to tricalciumphosphate coated implants increases peri-implant bone remodeling. Biomaterials 22: 189-193
72. Linkhart, T. A., Mohan, S., Baylink, D. J. (1996) Growth factors for bone growth and repair: IGF, TGF beta and BMP. Bone 19: 1S-12S
73. Lisignoli, G., Zini, N., Remiddi, G., Piacentini, A., Puggioli, A., Trimarchi, C., Fini, M., Maraldi, N. M., Facchini, A. (2001) Basic Fibroblast growth factor enhances in vitro mineralization of rat bone marrow stromal cells grown on non-woven hyaluronic acid based polymer scaffold. Biomaterials 22: 2095-2105
74. Lisignoli, G., Fini, M., Giavaresi, G., Aldini, N. N., Toneguzzi, S., Facchini, A. (2002) Osteogenesis of large segmental radius defects enhanced by basic fibroblast growth factor activated bone marrow stromal cells grown on non-woven hyaluronic acid-based polymer scaffold. Biomaterials 23: 1043-1051
75. Lu, L., Stamatas, G. N., Mikos, A. G. (2000) Controlled release of transforming growth factor beta 1 from biodegradable polymer microparticles. J. Biomed. Mater. Res. 50: 440-451
76. Lucas, P. A., Laurencin, C., Syftestad, G. T., Domb, A., Goldberg, V. M., Caplan, A. I., Langer, R. (1990) Ectopic induction of cartilage and bone by water-soluble proteins from bovine bone using a polyanhydride delivery vehicle. J. Biomed. Mater. Res. 24: 901-911
77. Ludwig, S. C., Boden, S. D. (1999) Osteoinductive bone graft substitutes for spinal fusion: A basic science summary. Orthop. Clin. North. Am. 30: 635-645
78. Lutolf, M. R., Weber, F. E., Schmoekel, H. G., Schense, J. C., Kohler, T., Muller, R., Hubbell, J. A. (2003) Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nat. Biotechnol. 21: 513-518
79. Lynch, S. E., de Castilla, G. R., Williams, R. C., Kiritsy, C. P., Howell, T. H., Reddy, M. S., Antoniades, H. N. (1991) The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing. J. Periodontol. 62: 458-467
80. Malafaya, P. B., Silva, G. A., Baran, E. T., Reis, R. L. (2002a) Drug delivery therapies I - general trends and its importance on bone tissue engineering applications. Curr. Opin. Solid. St. M. 6: 283-295
81. Malafaya, P. B., Silva, G. A., Baran, E. T., Reis, R. L. (2002b) Drug delivery therapies II - Strategies for delivering bone regenerating factors. Curr. Opin. Solid St. M. 6: 297-312
82. Marcelli, C., Yates, A. J., Mundy, G. R. (1990) In vivo effects of human recombinant transforming growth factor beta on bone turnover in normal mice. J. Bone Miner. Res. 5: 1087-1096
83. Marinucci, L., Lilli, C., Baroni, T., Becchetti, E., Belcastro, S., Balducci, C., Locci, P. (2001) In vitro comparison of bioabsorbable and non-resorbable membranes in bone regeneration. J. Periodontol. 72: 753-759
84. Marinucci, L., Lilli, C., Guerra, M., Belcastro, S., Becchetti, E., Stabellini, G., Calvi, E. M., Locci, P. (2003) Biocompatibility of collagen membranes crosslinked with glutaraldehyde or diphenylphosphoryl azide: An in vitro study. J. Biomed. Mater. Res. 67A: 504-509
85. Martin, G. J., Boden, S. D., Marone, M. A., Moskovitz, P. A. (1999) Posterolateral intertransverse process spinal arthrodesis with rhBMP-2 in a nonhuman primate: Important lessons learned regarding dose, carrier, and safety. J. Spinal Disord. 12: 179-186
86. Masuda, H., Tsujimura, A., Yoshioka, M., Arai, Y., Kuboki, Y., Mukai, T., Nakamura, T., Tsuji, H., Nakagawa, M., Hashimoto-Gotoh, T. (1997) Bone mass loss due to oestrogen deficiency is compensated in transgenic mice overexpressing human osteoblast stimulating factor-1. Biochem. Biophys. Res. Commun. 238: 528-533
87. Matsuo, T., Sugita, T., Kubo, T., Yasunaga, Y., Ochi, M., Murakami, T. (2003) Injectable magnetic liposomes as a novel carrier of recombinant human BMP-2 for bone formation in a rat bone-defect model. J. Biomed. Mater. Res. 66A: 747-754
88. Meinel, L., Illi, O. E., Zapf, J., Malfanti, M., Merkle, H. P., Gander, B. (2001) Stabilizing insulin-like growth factor-I in poly(D,L.-lactide-co-glycolide) microspheres. J. Control. Release 70: 193-202
89. Midy, V., Plouet, J. (1994) Vasculotropin/vascular endothelial growth factor induces differentiation in cultured osteoblasts. Biochem. Biophys. Res. Commun. 199: 380-386
90. Midy, V., Rey, C., Bres, E., Dard, M. (1998) Basic fibroblast growth factor adsorption and release properties of calcium phosphate. J. Biomed. Mater. Res. 41: 405-411
91. Milella, E., Barra, G., Ramires, P. A., Leo, G., Aversa, P., Romito, A. (2001) Poly(L-lactide)acid/alginate composite membranes for guided tissue regeneration. J. Biomed. Mater. Res. 57: 248-257
92. Minamide, A., Kawakami, M., Hashizume, H., Sakata, R., Tamaki, T. (2001) Evaluation of carriers of bone morphogenetic protein for spinal fusion. Spine 26: 933-939
93. Miyamoto, S., Takaoka, K., Okada, T., Yoshikawa, H., Hashimoto, J., Suzuki, S., Ono, K. (1992) Evaluation of polylactic acid homopolymers as carriers for bone morphogenetic protein. Clin. Orthop. 278: 274-285
94. Miyamoto, S., Takaoka, K., Okada, T., Yoshikawa, H., Hashimoto, J., Suzuki, S., Ono, K. (1993) Polylactic acid polyethyleneglycol block-copolymer - a new biodegradable synthetic carrier for bone morphogenetic protein. Clin. Orthop. 294: 333-343
95. Mohan, S., Baylink, D. J. (1996) Insulin-like growth factor system components and the coupling of bone formation to resorption. Horm. Res. 45: 59-62
96. Molina, I., Li, S. M., Martinez, M. B., Vert, M. (2001) Protein release from physically crosslinked hydrogels of the PLA/PEO/PLA triblock copolymer-type. Biomaterials 22: 363-369
97. Montero, A., Okada, Y., Tomita, M., Ito, M., Tsurukami, H., Nakamura, T., Doetschman, T., Coffin, J. D., Hurley, M. M. (2000) Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation. J. Clin. Invest. 105: 1085-1093
98. Mooney, D. J., Baldwin, D. F., Suh, N. P., Vacanti, L. P., Langer, R. (1996) Novel approach to fabricate porous sponges of poly(D,L.-lactic-co-glycolic acid) without the use of organic solvents Biomaterials 17: 1417-1422
99. Muzzarelli, R. A. A., Biagini, G., Belmonte, M. A., Talassi, O., Gandolfi, M. G., Solmi, R., Carraro, S., Giardino, R., Fini, M., NicoliAldini, N. (1997) Osteoinduction by chitosan-complexed BMP: Morpho-structural responses in an osteoporotic model. J. Bioactive Compatible Polymers 12: 321-329
100. Nakashima, M., Reddi, A. H. (2003) The application of bone morphogenetic proteins to dental tissue engineering. Nat. Biotechnol. 21: 1025-1032
101. Nash, T. J., Howlett, C. R., Martin, C., Steele, J., Johnson, K. A., Hicklin, D. J. (1994) Effect of platelet-derived growth factor on tibial osteotomies in rabbits. Bone 15: 203-208
102. Noda, M., Camilliere, J. J. (1989) In vivo stimulation of bone formation by transforming growth factor-beta. Endocrinology 124: 2991-2994
103. Oldham, J. B., Lu, L., Zhu, X., Porter, B. D., Hefferan, T. E., Larson, D. R., Currier, B. L., Mikos, A. G., Yaszemski, M. J. (2000) Biological activity of rhBMP-2 released from PLGA microspheres. J. Biomech. Eng. 122: 289-292
104. Oonishi, H. (1991) Orthopaedic applications of hydroxyapatite. Biomaterials 12: 171-178
105. Oreffo, R. O., Triffitt, J. T. (1999). Future potentials for using osteogenic stem cells and biomaterials in orthopedics. Bone 25: 5S-9S
106. Oreffo, R. O., Mundy, G. R., Seyedin, S. M., Bonewald, L. F. (1989) Activation of the bone-derived latent TGF beta complex by isolated osteoclasts. Biochem. Biophys. Res. Commun. 158: 817-823
107. Park, Y. J., Lee, Y. M., Lee, J. Y., Seol, Y. J., Chung, C. P., Lee, S. J. (2000a) Controlled release of platelet-derived growth factor-BB from chondroitin sulfate-chitosan sponge for guided bone regeneration. J. Control. Release 67: 385-394
108. Park, Y. J., Lee, Y. M., Park, S. N., Sheen, S. Y., Chung, C. P., Lee, S. J. (2000b) Platelet derived growth factor releasing chitosan sponge for periodontal bone regeneration. Biomaterials 21: 153-159
109. Partridge, K. A., Oreffo, R. O. C. (2004) Gene delivery in bone tissue engineering - progress and prospects using viral and non-viral strategies. Tissue Eng. 10: In press
110. Pearson, R. G., Bhandari, R., Quirk, R. A., Shakesheff, K. M. (2002) Recent advances in tissue engineering: An invited review. J. Long Term Eff. Med. Implants 12: 1-33
111. Peter, S. J., Miller, M. J., Yasko, A. W., Yaszemski, M. J., Mikos, A. G. (1998) Polymer concepts in tissue engineering. J. Biomed. Mater. Res. 43: 422-427
112. Pfeilschifter, J., D'Souza, S. M., Mundy, G. R. (1987) Effects of transforming growth factor-beta on osteoblastic osteosarcoma cells. Endocrinology 121: 212-218
113. Pfeilschifter, J., Wolf, O., Naumann, A., Minne, H. W., Mundy, G. R., Ziegler, R. (1990a) Chemotactic response of osteoblast like cells to transforming growth factor beta. J. Bone Miner. Res. 5: 825-830
114. Pfeilschifter, J., Bonewald, L., Mundy, G. R. (1990b) Characterization of the latent transforming growth factor beta complex in bone. J. Bone Miner. Res. 5: 49-58
115. Pfeilschifter, J., Diel, I., Pilz, U., Brunotte, K., Naumann, A., Ziegler, R. (1993) Mitogenic responsiveness of human bone cells in vitro to hormones and growth factors decreases with age. J. Bone Miner. Res. 8: 707-717
116. Pitaru, S., Kotev-Emeth, S., Noff, D., Kaffuler, S., Savion, N. (1993) Effect of basic fibroblast growth factor on the growth and differentiation of adult stromal bone marrow cells: Enhanced development of mineralized bone-like tissue in culture. J. Bone Miner. Res. 8: 919-929
117. Raiche, A. T., Puleo, D. A. (2004) In vitro effects of combined and sequential delivery of two bone growth factors. Biomaterials 25: 677-685
118. Reddi, A. H. (1992) Regulation of cartilage and bone differentiation by bone morphogenetic proteins. Curr. Opin. Cell Biol. 4: 850-855
119. Renier, M. L., Kohn, D. H. (1997) Development and characterization of a biodegradable polyphosphate. J. Biomed. Mater. Res. 34: 95-104
120. Richardson, T. P., Peters, M. C., Ennett, A. B., Mooney, D. J. (2001) Polymeric system for dual growth factor delivery. Nat. Biotechnol. 19: 1029-1034
121. Ripamonti, U., Ramoshebi, L. N., Matsaba, T., Tasker, J., Crooks, J., Teare, J. (2001a) Bone induction by BMPs/OPs and related family members in primates. J. Bone Joint Surg. Am. 83-A (Suppl. 1): S116-S127
122. Ripamonti, U., Crooks, J., Petit, J. C., Rueger, D. C. (2001b) Periodontal tissue regeneration by combined applications of recombinant human osteogenic protein-1 and bone morphogenetic protein-2. A pilot study in Chacma baboons (Papio ursinus). Eur. J. Oral Sci. 109: 241-248
123. Roach, H. I., Baker, J. E., Clarke, N. M. (1998) Initiation of the bony epiphysis in long bones: Chronology of interactions between the vascular system and the chondrocytes. J. Bone Miner. Res. 13: 950-961
124. Rose, F. R. A. J., Oreffo, R. O. C. (2002) Bone tissue engineering: Hope vs hype. Biochem. Biophys. Res. Commun. 292: 1-7
125. Ruel-Gariepy, E., Chenite, A., Chaput, C., Guirguis, S., Leroux, J. C. (2000) Characterization of thermosensitive chitosan gels for the sustained delivery of drugs. Int. J. Pharm. 203: 89-98
126. Saito, N., Okada, T., Toba, S., Miyamoto, S., Takaoka, K. (1999) New synthetic absorbable polymers as BMP carriers: Plastic properties of poly-D,L-lactic acid-polyethylene glycol block copolymers. J. Biomed. Mater. Res. 47: 104-110
127. Saito, N., Okada, T., Horiuchi, H., Murakami, N., Takakashi, J., Nawata, M., Ota, H., Miyamoto, S., Nozaki, K., Takaoka, K. (2001a) Biodegradable poly-D,L-lactic acid-polyethylene glycol block copolymers as a BMP delivery system for inducing bone. J Bone Joint Surg Am 83A: S92-S98.
128. Saito, N., Okada, T., Horiuchi, H., Murakami, N., Takahashi, J., Nawata, M., Ota, H., Nozaki, K., Takaoka, K. (2001b) A biodegradable polymer as a cytokine delivery system for inducing bone formation. Nat. Biotechnol. 19: 332-335
129. Saito, N., Okada, T., Horiuchi, H., Ota, H., Takahashi, J., Murakami, N., Nawata, M., Kojima, S., Nozaki, K., Takaoka, K. (2003) Local bone formation by injection of recombinant human bone morphogenetic protein-2 contained in polymer carriers. Bone 32: 381-386
130. Saltzman, W. M., Olbricht, W. L. (2002) Building drug delivery into tissue engineering. Nat. Rev. Drug Discov. 1: 177-186
131. Santos, E. M., Radin, S., Ducheyne, P. (1999) Sol-gel derived carrier for the controlled release of proteins. Biomaterials 20: 1695-1700
132. Schmidmaier, G., Wildemann, B., Cromme, F., Kandziora, F., Haas, N. P., Raschke, M. (2002) Bone morphogenetic protein-2 coating of titanium implants increases biomechanical strength and accelerates bone remodelling in fracture treatment: A biomechanical and histological study in rats. Bone 30: 816-822
133. Singh, M., Shirley, B., Bajwa, K., Samara, E., Hora, M., O'Hagan, D. (2001) Controlled release of recombinant insulin-like growth factor from a novel formulation of polylactide-co-glycolide microparticles. J. Control. Release 70: 21-28
134. Sittinger, M., Bujia, J., Rotter, N., Reitzel, D., Minuth, W. W., Burmester, G. R. (1996) Tissue engineering and autologous transplant formation: Practical approaches with resorbable biomaterials and new cell culture techniques. Biomaterials 17: 237-242
135. Suzuki, Y., Tanihara, M., Suzuki, K., Saitou, A., Sufan, W., Nishimura, Y. (2000) Alginate hydrogel linked with synthetic oligopeptide derived from BMP-2 allows ectopic osteoinduction in vivo. J. Biomed. Mater. Res. 50: 405-409
136. Tabata, Y., Yamamoto, M., Ikada, Y. (1998) Comparison of release profiles of various growth factors from biodegradable carriers. In: Biomaterials regulating cell function and tissue development. Materials Research Society, Warrendale, pp 13-18
137. Takaoka, K., Koezuka, M., Nakahara, H. (1991) Telopeptide-depleted bovine skin collagen as a carrier for bone morphogenetic protein. J. Orthop. Res. 9: 902-907
138. Tare, R. S., Oreffo, R. O., Clarke, N. M., Roach, H. I. (2002a) Pleiotrophin/osteoblast-stimulating factor 1: Dissecting its diverse functions in bone formation. J. Bone Miner. Res. 17: 2009-2020
139. Tare, R. S., Oreffo, R. O., Sato, K., Rauvala, H., Clarke, N. M., Roach, H. I. (2002b) Effects of targeted overexpression of pleiotrophin on postnatal bone development. Biochem. Biophys. Res. Commun. 298: 324-332
140. Thompson, R. C., Yaszemski, M. J., Powers, J. M., Mikos, A. G. (1995) Fabrication of biodegradable polymer scaffolds to engineer trabecular bone. J. Biomater. Sci. Polym. Ed. 7: 23-38
141. Ueda, H., Hong, L., Yamamoto, M., Shigeno, K., Inoue, M., Toba, T., Yoshitani, M., Nakamura, T., Tabata, Y., Shimizu, Y. (2002) Use of collagen sponge incorporating transforming growth factor-beta 1 to promote bone repair in skull defects in rabbits. Biomaterials 23: 1003-1010
142. Uludag, H., D'Augusta, D., Palmer, R., Timony, G., Wozney, J. (1999a) Characterization of rhBMP-2 pharmacokinetics implanted with biomaterial carriers in the rat ectopic model. J. Biomed. Mater. Res. 46: 193-202
143. Uludag, H., Friess, W., Williams, D., Porter, T., Timony, G., D'Augusta, D., Blake, C., Palmer, R., Biron, B., Wozney, J. (1999b) rhBMP-collagen sponges as osteoinductive devices: Effects of in vitro sponge characteristics and protein pI on in vivo rhBMP pharmacokinetics. Ann. N. Y. Acad. Sci. 875: 369-378
144. Uludag, H., D'Augusta, D., Golden, J., Li, J., Timony, G., Riedel, R., Wozney, J. M. (2000) Implantation of recombinant human bone morphogenetic proteins with biomaterial carriers: A correlation between protein pharmacokinetics and osteoinduction in the rat ectopic model. J. Biomed. Mater. Res. 50: 227-238
145. Uludag, H., Gao, T. J., Porter, T. J., Friess, W., Wozney, J. M. (2001) Delivery systems for BMPs: Factors contributing to protein retention at an application site. J. Bone Joint Surg. Am. 83A: S128-S135
146. Vacanti, C. A., Bonassar, L. J., Vacanti, J. P. (2000) Structural tissue engineering. In: Lanza, R. P., Langer, R., Vacanti, J. P. (eds) Principles of tissue engineering. Academic Press, New York
147. Vehof, J. W. M., Fisher, J. P., Dean, D., van der Waerden, J., Spauwen, P. H. M., Mikos, A. G., Jansen, J. A. (2002) Bone formation in transforming growth factor beta-1-coated porous poly(propylene fumarate) scaffolds. J. Biomed. Mater. Res. 60: 241-251
148. Wang, D. S., Miura, M., Demura, H., Sato, K. (1997) Anabolic effects of 1,25-dihydroxyvitamin D3 on osteoblasts are enhanced by vascular endothelial growth factor produced by osteoblasts and by growth factors produced by endothelial cells. Endocrinology 138: 2953-2962
149. Weber, F. E., Eyrich, G., Gratz, K. W., Maly, F. E., Sailer, H. F. (2002) Slow and continuous application of human recombinant bone morphogenetic protein via biodegradable poly(lactide-co-glycolide) foamspheres. Int. J. Oral Maxillofac. Surg. 31: 60-65
150. Whang, K., Tsai, D. C., Nam, E. K., Aitken, M., Sprague, S. M., Patel, P. K., Healy, K. E. (1998) Ectopic bone formation via rhBMP-2 delivery from porous bioabsorbable polymer scaffolds. J. Biomed. Mater. Res. 42: 491-499
151. Wheeler, D. I., Chamberland, D. I., Schmitt, J. M., Buck, D. C., Brekke, J. H., Hollinger, J. O., Joh, S. P., Suh, K. W. (1998) Radiomorphometry and biomechanical assessment of recombinant human bone morphogenetic protein 2 and polymer in rabbit radius ostectomy model. J. Biomed. Mater. Res. 43: 365-373
152. Whitaker, M. J., Quirk, R. A., Howdle, S. M., Shakesheff, K. M. (2001) Growth factor release from tissue engineering scaffolds. J. Pharm. Pharmacol. 53: 1427-1437
153. Winn, S. R., Uludag, H., Hollinger, J. O. (1998) Sustained release emphasizing recombinant human bone morphogenetic protein-2. Adv. Drug. Deliv. Rev. 31: 303-318
154. Winn, S. R., Schmitt, J. M., Buck, D., Hu, Y. H., Grainger, D., Hollinger, J. O. (1999) Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats. J. Biomed. Mater. Res. 45: 414-421
155. Woo, B. H., Fink, B. F., Page, R., Schrier, J. A., Jo, Y. W., Jiang, G., DeLuca, M., Vasconez, H. C., DeLuca, P. P. (2001) Enhancement of bone growth by sustained delivery of recombinant human bone morphogenetic protein-2 in a polymeric matrix. Pharm. Res. 18: 1747-1753
156. Wozney, J. M., Rosen, V. (1998) Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clin. Orthop. 346: 26-37
157. Wozney, J. M., Rosen, V., Celeste, A. J., Mitsock, L. M., Whitters, M. J., Kriz, R. W., Hewick, R. M., Wang, E. A. (1988) Novel regulators of bone formation: Molecular clones and activities. Science 242: 1528-1534
158. Xiong, Z., Yan, Y. N., Zhang, R. J., Sun, L. (2001)
159. Yamamoto, M., Tabata, Y., Ikada, Y. (1998) Ectopic bone formation induced by biodegradable hydrogels incorporating bone morphogenetic protein. J. Biomater. Sci. Polym. Ed. 9: 439-458
160. Yamamoto, M., Tabata, Y., Hong, L., Miyamoto, S., Hashimoto, N., Ikada, Y. (2000) Bone regeneration by transforming growth factor beta 1 released from a biodegradable hydrogel. J. Control. Release 64: 133-142
161. Yamamoto, M., Takahashi, Y., Tabata, Y. (2003) Controlled release by biodegradable hydrogels enhances the ectopic bone formation of bone morphogenetic protein. Biomaterials 24: 4375-4383
162. Yang, X., Tare, R. S., Partridge, K. A., Roach, H. I., Clarke, N. M., Howdle, S. M., Shakesheff, K. M., Oreffo, R. O. (2003a) Induction of human osteoprogenitor chemotaxis, proliferation, differentiation, and bone formation by osteoblast stimulating factor-1/pleiotrophin: Osteoconductive biomimetic scaffolds for tissue engineering. J. Bone Miner. Res. 18: 47-57
163. Yang, X. B., Whitaker, M. J., Clarke, N. M. P., Sebald, W., Howdle, S. M., Shakesheff, K. M., Oreffo, R. O. C. (2003b) In vivo human bone and cartilage formation using porous polymer scaffolds encapsulated with bone morphogenetic protein-2. J. Bone Miner. Res. 18: 1366
164. Yang, X. B., Green, D. W., Roach, H. I., Clarke, N. M. P., Anderson, H. C., Howdle, S. M., Shakesheff, K. M., Oreffo, R. O. C. (2003c) Novel osteoinductive biomimetic scaffolds stimulate human osteoprogenitor activity - implications for skeletal repair. Connect. Tissue Res. 44: 312-317
165. Yasko, A. W., Lane, J. M., Fellinger, E. J., Rosen, V., Wozney, J. M., Wang, E. A. (1992) The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical study in rats. J. Bone Joint Surg. Am. 74: 659-670
166. Zellin, G. (1998) Growth factors and bone regeneration. Implications of barrier membranes. Swed. Dent. J. 129: 7-65
167. Zellin, G., Linde, A. (1997) Treatment of segmental defects in long bones using osteopromotive membranes and recombinant human bone morphogenetic protein-2. An experimental study in rabbits. Scand. J. Plast. Reconst. Surg. Hand Surg. 31: 97-104
168. Zhao, G., Monier-Faugere, M. C., Langub, M. C., Geng, Z., Nakayama, T., Pike, J. W., Chernausek, S. D., Rosen, C. J., Donahue, L. R., Malluche, H. H., Fagin, J. A., Clemens, T. L. (2000) Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: Increased trabecular bone volume without increased osteoblast proliferation. Endocrinology 141: 2674-2682
169. Ziegler, J., Mayr-Wohlfart, U., Kessler, S., Breitig, D., Gunther, K. P. (2002) Adsorption and release properties of growth factors from biodegradable implants. J. Biomed. Mater. Res. 59: 422-428