The Evolution of rhPDGF-BB in Musculoskeletal Repair and its Role in Foot and Ankle Fusion Surgery

Foot and Ankle Clinics

Volumn 15, Issue 4, 2010, Pages 621-640

  DiGiovanni, Christopher W ^a   Petricek, James M ^b  

^a BROWN UNIVERSITY   (United States)

^b BioMimetic Therapeutics Inc   (United States)

Author keywords

Arthrodesis; Bone grafting; Orthopedic surgery; Platelet derived growth factor

Indexed keywords

BETA-TRICALCIUM PHOSPHATE; BIOMATERIAL; CALCIUM PHOSPHATE; PLATELET DERIVED GROWTH FACTOR; PLATELET DERIVED GROWTH FACTOR BB; PLATELET-DERIVED GROWTH FACTOR BB; RECOMBINANT PROTEIN; VASCULOTROPIN A;

ANGIOGENESIS; ANIMAL; ANKLE; ARTHRODESIS; BONE REGENERATION; CHEMOTAXIS; FOOT; HUMAN; MESENCHYMAL STEM CELL; METABOLISM; METHODOLOGY; ORTHOPEDIC SURGERY; PHYSIOLOGY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW;

ANIMALS; ANKLE; ARTHRODESIS; BIOCOMPATIBLE MATERIALS; BONE REGENERATION; CALCIUM PHOSPHATES; CHEMOTAXIS; FOOT; HUMANS; MESENCHYMAL STEM CELLS; NEOVASCULARIZATION, PHYSIOLOGIC; ORTHOPEDIC PROCEDURES; PLATELET-DERIVED GROWTH FACTOR; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECOMBINANT PROTEINS; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 78149388235     PISSN: 10837515     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.fcl.2010.07.001     Document Type: Review

References (64)

1. Extremity reconstruction Available at:, Accessed February 24, 2010. http://www.pearldiverinc.com/.
2. Haddad S.L., Coetzee J.C., Estok R., et al. Intermediate and long-term outcomes of total ankle arthroplasty and ankle arthrodesis. A systematic review of the literature. J Bone Joint Surg Am 2007, 89(9):1899-1905.
3. Easley M.E., Trnka H.J., Schon L.C., et al. Isolated subtalar arthrodesis. J Bone Joint Surg Am 2000, 82(5):613-624.
4. Frey C., Halikus N.M., Vu-Rose T., et al. A review of ankle arthrodesis: predisposing factors to nonunion. Foot Ankle Int 1994, 15(11):581-584.
5. DeOrio J.K., Farber D.C. Morbidity associated with anterior iliac crest bone grafting in foot and ankle surgery. Foot Ankle Int 2005, 26(2):147-151.
6. Soohoo N.F., Cracchiolo A. The results of utilizing proximal tibial bone graft in reconstructive procedures of the foot and ankle. Foot Ankle Surg 2008, 14(2):62-66.
7. Raikin S.M., Brislin K. Local bone graft harvested from the distal tibia or calcaneus for surgery of the foot and ankle. Foot Ankle Int 2005, 26(6):449-453.
8. Ahlmann E., Patzakis M., Roidis N., et al. Comparison of anterior and posterior iliac crest bone grafts in terms of harvest-site morbidity and functional outcomes. J Bone Joint Surg Am 2002, 84(5):716-720.
9. Kim D.H., Rhim R., Li L., et al. Prospective study of iliac crest bone graft harvest site pain and morbidity. Spine J 2009, 9(11):886-892.
10. Robertson P.A., Wray A.C. Natural history of posterior iliac crest bone graft donation for spinal surgery: a prospective analysis of morbidity. Spine (Phila Pa 1976) 2001, 26(13):1473-1476.
11. Chou L.B., Mann R.A., Coughlin M.J., et al. Stress fracture as a complication of autogenous bone graft harvest from the distal tibia. Foot Ankle Int 2007, 28(2):199-201.
12. Banwart J.C., Asher M.A., Hassanein R.S. Iliac crest bone graft harvest donor site morbidity. A statistical evaluation. Spine (Phila Pa 1976) 1995, 20(9):1055-1060.
13. Kirmeier R., Payer M., Lorenzoni M., et al. Harvesting of cancellous bone from the proximal tibia under local anesthesia: donor site morbidity and patient experience. J Oral Maxillofac Surg 2007, 65(11):2235-2241.
14. Chen Y.C., Chen C.H., Chen P.L., et al. Donor site morbidity after harvesting of proximal tibia bone. Head Neck 2006, 28(6):496-500.
15. Schwartz C.E., Martha J.F., Kowalski P., et al. Prospective evaluation of chronic pain associated with posterior autologous iliac crest bone graft harvest and its effect on postoperative outcome. Health Qual Life Outcomes 2009, 7:49.
16. Frohberg U., Mazock J.B. A review of morbidity associated with bone harvest from the proximal tibial metaphysic. Mund Kiefer Gesichtschir 2005, 9(2):63-65.
17. Polly D.W., Ackerman S.J., Shaffrey C.I., et al. A cost analysis of bone morphogenetic protein versus autogenous iliac crest bone graft in single-level anterior lumbar fusion. Orthopedics 2003, 26(10):1027-1037.
18. Alt V., Meeder P.J., Seligson D., et al. The proximal tibia metaphysis: a reliable donor site for bone grafting?. Clin Orthop Relat Res 2003, 414:315-321.
19. Ozaki Y., Nishimura M., Sekiya K., et al. Comprehensive analysis of chemotactic factors for bone marrow mesenchymal stem cells. Stem Cells Dev 2007, 16(1):119-129.
20. Fiedler J., Etzel N., Brenner R.E. To go or not to go: migration of human mesenchymal progenitor cells stimulated by isoforms of PDGF. J Cell Biochem 2004, 93(5):990-998.
21. Alvarez R.H., Kantarjian H.M., Cortes J.E. Biology of platelet-derived growth factor and its involvement in disease. Mayo Clin Proc 2006, 81(9):1241-1257.
22. Ross R., Glomset J., Kariya B., et al. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci U S A 1974, 71(4):1207-1210.
23. Heldin C.H., Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 1999, 79(4):1283-1316.
24. Fujii H., Kitazawa R., Maeda S., et al. Expression of platelet-derived growth factor proteins and their receptor alpha and beta mRNAs during fracture healing in the normal mouse. Histochem Cell Biol 1999, 112(2):131-138.
25. Lynch S.E., Nixon J.C., Colvin R.B., et al. Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors. Proc Natl Acad Sci U S A 1987, 84(21):7696-7700.
26. Hollinger J.O., Hart C.E., Hirsch S.N., et al. Recombinant human platelet-derived growth factor: biology and clinical applications. J Bone Joint Surg Am 2008, 90(Suppl 1):48-54.
27. Bowen-Pope D.F., Malpass T.W., Foster D.M., et al. Platelet-derived growth factor in vivo: levels, activity, and rate of clearance. Blood 1984, 64(2):458-469.
28. Sun P.D., Davies D.R. The cystine-knot growth-factor superfamily. Annu Rev Biophys Biomol Struct 1995, 24:269-291.
29. Seifert R.A., Hart C.E., Phillips P.E., et al. Two different subunits associate to create isoform-specific platelet-derived growth factor receptors. J Biol Chem 1989, 264(15):8771-8778.
30. Huang Z., Nelson E.R., Smith R.L., et al. The sequential expression profiles of growth factors from osteoprogenitors to osteoblasts in vitro. Tissue Eng 2007, 13(9):2311-2320.
31. Ponte A.L., Marais E., Gallay N., et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells 2007, 25(7):1737-1745.
32. Fiedler J., Röderer G., Günther K.P., et al. BMP-2, BMP-4, and PDGF-BB stimulate chemotactic migration of primary human mesenchymal progenitor cells. J Cell Biochem 2002, 87(3):305-312.
33. Bouletreau P.J., Warren S.M., Spector J.A., et al. Factors in the fracture microenvironment induce primary osteoblast angiogenic cytokine production. Plast Reconstr Surg 2002, 110(1):139-148.
34. Bergers G., Song S. The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol 2005, 7(4):452-464.
35. Smiell J.M., Wieman T.J., Steed D.L., et al. Efficacy and safety of becaplermin (recombinant human platelet-derived growth factor-BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies. Wound Repair Regen 1999, 7(5):335-346.
36. Margolis D.J., Bartus C., Hoffstad O., et al. Effectiveness of recombinant human platelet-derived growth factor for the treatment of diabetic neuropathic foot ulcers. Wound Repair Regen 2005, 13(6):531-536.
37. Nevins M., Giannobile W.V., McGuire M.K., et al. Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial. J Periodontol 2005, 76(12):2205-2215.
38. Tissue engineering: applications in oral and maxillofacial surgery and periodontics. 2nd edition 2008, Quintessence Publishing Company, Chicago (IL). S.E. Lynch, R.E. Marx, M. Nevins (Eds.).
39. Nevins M., Camelo M., Nevins M.L., et al. Periodontal regeneration in humans using recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and allogenic bone. J Periodontol 2003, 74(9):1282-1292.
40. Camelo M., Nevins M.L., Schenk R.K., et al. Periodontal regeneration in human Class II furcations using purified recombinant human platelet-derived growth factor-BB (rhPDGF-BB) with bone allograft. Int J Periodontics Restorative Dent 2003, 23(3):213-225.
41. Nevins M., Hanratty J., Lynch S.E. Clinical results using recombinant human platelet-derived growth factor and mineralized freeze-dried bone allograft in periodontal defects. Int J Periodontics Restorative Dent 2007, 27(5):421-427.
42. McGuire M.K., Scheyer T., Nevins M., et al. Evaluation of human recession defects treated with coronally advanced flaps and either purified recombinant human platelet-derived growth factor-BB with beta tricalcium phosphate or connective tissue: a histologic and microcomputed tomographic examination. Int J Periodontics Restorative Dent 2009, 29(1):7-21.
43. Hollinger J.O., Onikepe A.O., MacKrell J., et al. Accelerated fracture healing in the geriatric, osteoporotic rat with recombinant human platelet-derived growth factor-BB and an injectable beta-tricalcium phosphate/collagen matrix. J Orthop Res 2008, 26(1):83-90.
44. Al-Zube L., Breitbart E.A., O'Connor J.P., et al. Recombinant human platelet-derived growth factor BB (rhPDGF-BB) and beta-tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model. J Orthop Res 2009, 27(8):1074-1081.
45. Moore D.C., Ehrlich M.G., McAllister S.C., et al. Recombinant human platelet-derived growth factor-BB augmentation of new-bone formation in a rat model of distraction osteogenesis. J Bone Joint Surg Am 2009, 91(8):1973-1984.
46. Coughlin M.J., Grimes J.S., Traughber P.D., et al. Comparison of radiographs and CT scans in the prospective evaluation of the fusion of hindfoot arthrodesis. Foot Ankle Int 2006, 27(10):780-787.
47. Daniels T., DiGiovanni C., Lau J.T., et al. Prospective clinical pilot trial in a single cohort of rhPDGF in foot arthrodoses. Foot Ankle Int 2010, 31(6):473-479.
48. DiGiovanni CW, Baumhauer J, Lin S, et al. A prospective, randomized, controlled, multi-center human clinical feasibility trial to evaluate the preliminary safety and efficacy of rhPDGF-BB versus autologous bone graft as a bone regeneration device in a foot and ankle fusion model. Foot Ankle Int 2010, in press.
49. DiGiovanni C.W., Lin S.S., Baumhauer J.F., et al. A prospective, randomized, controlled, multi-center pivotal human clinical trial to evaluate the safety and effectiveness of Augment Bone Graft as a substitute for autologous bone. AOFAS Specialty Day Presentation. AAOS Annual Meeting, New Orleans (LA) March 13, 2010.
50. Vaccaro A.R., Lawrence J.P., Patel T., et al. The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft in posterolateral lumbar arthrodesis: a long-term (>4 years) pivotal study. Spine (Phila Pa 1976) 2008, 33(26):2850-2862.
51. Friedlaender G.E., Perry C.R., Cole J.D., et al. Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am 2001, 83(Suppl 1[Pt 2]):S151-S158.
52. Cahill K.S., Chi J.H., Day A., et al. Prevalence, complications, and hospital charges associated with use of bone-morphogenetic proteins in spinal fusion procedures. JAMA 2009, 302(1):58-66.
53. Axelrad T.W., Einhorn T.A. Bone morphogenetic proteins in orthopaedic surgery. Cytokine Growth Factor Rev 2009, 20(5-6):481-488.
54. Boakye M., Mummaneni P.V., Garrett M., et al. Anterior cervical discectomy and fusion involving a polyetheretherketone spacer and bone morphogenetic protein. J Neurosurg Spine 2005, 2(5):521-525.
55. Boraiah S., Paul O., Hawkes D., et al. Complications of recombinant human BMP-2 for treating complex tibial plateau fractures: a preliminary report. Clin Orthop Relat Res 2009, 467(12):3257-3262.
56. Brower R.S., Vickroy N.M. A case of psoas ossification from the use of BMP-2 for posterolateral fusion at L4-L5. Spine (Phila Pa 1976) 2008, 33(18):E653-E655.
57. Deutsch H. High-dose bone morphogenetic protein-induced ectopic abdomen bone growth. Spine J 2010, 10(2):e1-e4.
58. Joseph V., Rampersaud Y.R. Heterotopic bone formation with the use of rhBMP2 in posterior minimal access interbody fusion: a CT analysis. Spine (Phila Pa 1976) 2007, 32(25):2885-2890.
59. Wong D.A., Kumar A., Jatana S., et al. 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. 2008, 8(6):1011-1018.
60. Hee C.K., Wisner-Lynch L.A., Roden C.M., et al. Rotator cuff repair in an ovine model using a combination product comprised of rhPDGF-BB and a type-I bovine collagen matrix. Orthopaedic Research Society Annual Meeting 2010, New Orleans (LA), March, 2010.
61. Hee C.K., Roden C.M., Wisner-Lynch L.A., et al. Evaluation of rhPDGF-BB in combination with a flowable collagen matrix for the treatment of acute Achilles tendon injury. Orthopaedic Research Society Annual Meeting. New Orleans (LA) 2010, March, 2010.
62. Kagel E.M., Majeska R.J., Einhorn T.A. Effects of diabetes and steroids on fracture healing. Curr Opin Orthop 1995, 6(5):7-13.
63. Gerstenfeld L.C., Wronski T.J., Hollinger J.O., et al. Application of histomorphometric methods to the study of bone repair. J Bone Miner Res 2005, 20(10):1715-1722.
64. Zhang L., Leeman E., Carnes D.C., et al. Human osteoblasts synthesize and respond to platelet-derived growth factor. Am J Physiol 1991, 261(2 Pt 1):C348-C354.