Bone regeneration: Current concepts and future directions

BMC Medicine

Volumn 9, Issue , 2011, Pages

  Dimitriou, Rozalia ^a,b   Jones, Elena ^b   McGonagle, Dennis ^b   Giannoudis, Peter V ^a,b  

^a LEEDS TEACHING HOSPITALS NHS TRUST   (United Kingdom)

^b UNIVERSITY OF LEEDS   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN; GROWTH FACTOR;

BONE DEVELOPMENT; BONE GRAFT; BONE PROSTHESIS; BONE REGENERATION; FRACTURE HEALING; GENE THERAPY; HUMAN; INTRAMEDULLARY NAILING; MECHANICAL STIMULATION; MESENCHYMAL STEM CELL; NONHUMAN; PROTEIN FUNCTION; REVIEW; TIBIA FRACTURE; TISSUE ENGINEERING; BONE; BONE TRANSPLANTATION; METHODOLOGY; PHYSIOLOGY;

BONE AND BONES; BONE REGENERATION; BONE TRANSPLANTATION; FRACTURE HEALING; HUMANS;

EID: 79957652421     PISSN: None     EISSN: 17417015     Source Type: Journal    
DOI: 10.1186/1741-7015-9-66     Document Type: Review

References (88)

1. Bates P, Ramachandran M. Bone injury, healing and grafting. Basic Orthopaedic Sciences. The Stanmore Guide 2007, 123-134. London: Hodder Arnold, Ramachandran M.
2. Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop Relat Res 1998, 355(Suppl):S7-21.
3. Cho TJ, Gerstenfeld LC, Einhorn TA. Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing. J Bone Miner Res 2002, 17:513-520. 10.1359/jbmr.2002.17.3.513, 11874242.
4. Ferguson C, Alpern E, Miclau T, Helms JA. Does adult fracture repair recapitulate embryonic skeletal formation?. Mech Dev 1999, 87:57-66. 10.1016/S0925-4773(99)00142-2, 10495271.
5. Audigé L, Griffin D, Bhandari M, Kellam J, Rüedi TP. Path analysis of factors for delayed healing and nonunion in 416 operatively treated tibial shaft fractures. Clin Orthop Relat Res 2005, 438:221-232.
6. Aronson J. Limb-lengthening, skeletal reconstruction, and bone transport with the Ilizarov method. J Bone Joint Surg Am 1997, 79(8):1243-1258.
7. Green SA, Jackson JM, Wall DM, Marinow H, Ishkanian J. Management of segmental defects by the Ilizarov intercalary bone transport method. Clin Orthop Relat Re. 1992, 280:136-142.
8. Giannoudis PV, Dinopoulos H, Tsiridis E. Bone substitutes: an update. Injury 2005, 36(Suppl 3):S20-27.
9. Giannoudis PV, Einhorn TA. Bone morphogenetic proteins in musculoskeletal medicine. Injury 2009, 40(Suppl 3):S1-3.
10. Masquelet AC, Begue T. The concept of induced membrane for reconstruction of long bone defects. Orthop Clin North Am 2010, 41(1):27-37. 10.1016/j.ocl.2009.07.011, 19931050.
11. Busse JW, Bhandari M, Kulkarni AV, Tunks E. The effect of low-intensity pulsed ultrasound therapy on time to fracture healing: a meta-analysis. CMAJ 2002, 166(4):437-441. 99352, 11873920.
12. Schofer MD, Block JE, Aigner J, Schmelz A. Improved healing response in delayed unions of the tibia with low-intensity pulsed ultrasound: results of a randomized sham-controlled trial. BMC Musculoskelet Disord 2010, 11:229. 10.1186/1471-2474-11-229, 2958986, 20932272.
13. Walker NA, Denegar CR, Preische J. Low-intensity pulsed ultrasound and pulsed electromagnetic field in the treatment of tibial fractures: a systematic review. J Athl Train 2007, 42(4):530-535. 2140080, 18174942.
14. Raschke M, Oedekoven G, Ficke J, Claudi BF. The monorail method for segment bone transport. Injury 1993, 24(Suppl 2):S54-61.
15. Cole JD, Justin D, Kasparis T, DeVlught D, Knobloch C. The intramedullary skeletal kinetic distractor (ISKD): first clinical results of a new intramedullary nail for lengthening of the femur and tibia. Injury 2001, 32(Suppl 4):129-139.
16. Bauer TW, Muschler GF. Bone graft materials. An overview of the basic science. Clin Orthop Relat Res 2000, 371:10-27.
17. Pederson WC, Person DW. Long bone reconstruction with vascularized bone grafts. Orthop Clin North Am 2007, 38(1):23-35. 10.1016/j.ocl.2006.10.006, 17145292.
18. Korompilias AV, Beris AE, Lykissas MG, Kostas-Agnantis IP, Soucacos PN. Femoral head osteonecrosis: Why choose free vascularized fibula grafting. Microsurgery 2010,
19. Giannoudis PV, Tzioupis C, Green J. Surgical techniques: how I do it? The reamer/irrigator/aspirator (RIA) system. Injury 2009, 40(11):1231-1236. 10.1016/j.injury.2009.07.070, 19783249.
20. Ahlmann E, Patzakis M, Roidis N, Shepherd L, Holtom P. Comparison of anterior and posterior iliac crest bone graft in terms of harvest-site morbidity and functional outcomes. J Bone Joint Surg Am 2002, 84(5):716-720. 10.1302/0301-620X.84B5.12571, 12004011.
21. St John TA, Vaccaro AR, Sah AP, Schaefer M, Berta SC, Albert T, Hilibrand A. Physical and monetary costs associated with autogenous bone graft harvesting. Am J Orthop 2003, 32(1):18-23.
22. Younger EM, Chapman MW. Morbidity at bone graft donor sites. J Orthop Trauma 1989, 3(3):192-195. 10.1097/00005131-198909000-00002, 2809818.
23. Finkemeier CG. Bone-grafting and bone-graft substitutes. J Bone Joint Surg Am 2002, 84(3):454-464.
24. Bullens PH, Bart Schreuder HW, de Waal Malefijt MC, Verdonschot N, Buma P. Is an impacted morselized graft in a cage an alternative for reconstructing segmental diaphyseal defects?. Clin Orthop Relat Res 2009, 467(3):783-791. 10.1007/s11999-008-0686-5, 2635451, 19142693.
25. Ostermann PA, Haase N, Rübberdt A, Wich M, Ekkernkamp A. Management of a long segmental defect at the proximal meta-diaphyseal junction of the tibia using a cylindrical titanium mesh cage. J Orthop Trauma 2002, 16(8):597-601. 10.1097/00005131-200209000-00010, 12352570.
26. Urist MR, O'Connor BT, Burwell RG. Bone Graft Derivatives and Substitutes 1994, Oxford: Butterworth-Heinemann Ltd.
27. Komatsu DE, Warden SJ. The control of fracture healing and its therapeutic targeting: improving upon nature. J Cell Biochem 2010, 109(2):302-311.
28. Giannoudis PV, Einhorn TA, Marsh D. Fracture healing: the diamond concept. Injury 2007, 38(Suppl 4):S3-6.
29. Dimitriou R, Tsiridis E, Giannoudis PV. Current concepts of molecular aspects of bone healing. Injury 2005, 36(12):1392-1404. 10.1016/j.injury.2005.07.019, 16102764.
30. Food and Drug Administration Medical devices. [http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/default.htm]. Food and Drug Administration.
31. Blokhuis TJ. Formulations and delivery vehicles for bone morphogenetic proteins: latest advances and future directions. Injury 2009, 40(Suppl 3):S8-11.
32. Nauth A, Giannoudis PV, Einhorn TA, Hankenson KD, Friedlaender GE, Li R, Schemitsch EH. Growth factors: beyond bone morphogenetic proteins. J Orthop Trauma 2010, 24(9):543-546. 10.1097/BOT.0b013e3181ec4833, 20736791.
33. Simpson AH, Mills L, Noble B. The role of growth factors and related agents in accelerating fracture healing. J Bone Joint Surg Br 2006, 88(6):701-705. 10.1302/0301-620X.88B6.17524, 16720758.
34. Alsousou J, Thompson M, Hulley P, Noble A, Willett K. The biology of platelet-rich plasma and its application in trauma and orthopaedic surgery: a review of the literature. J Bone Joint Surg Br 2009, 91(8):987-996. 10.1302/0301-620X.91B8.22546, 19651823.
35. Argintar E, Edwards S, Delahay J. Bone morphogenetic proteins in orthopaedic trauma surgery. Injury 2010,
36. Chen FM, Ma ZW, Dong GY, Wu ZF. Composite glycidyl methacrylated dextran (Dex-GMA)/gelatin nanoparticles for localized protein delivery. Acta Pharmacol Sin 2009, 30(4):485-493. 10.1038/aps.2009.15, 19305420.
37. Pountos I, Georgouli T, Kontakis G, Giannoudis PV. Efficacy of minimally invasive techniques for enhancement of fracture healing: evidence today. Int Orthop 2010, 34(1):3-12. 10.1007/s00264-009-0892-0, 2899260, 19844709.
38. D'Ippolito G, Schiller PC, Ricordi C, Roos BA, Howard GA. Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow. J Bone Miner Res 1999, 14(7):1115-1122. 10.1359/jbmr.1999.14.7.1115, 10404011.
39. Huibregtse BA, Johnstone B, Goldberg VM, Caplan AI. Effect of age and sampling site on the chondro-osteogenic potential of rabbit marrow-derived mesenchymal progenitor cells. J Orthop Res 2000, 18(1):18-24. 10.1002/jor.1100180104, 10716274.
40. Hernigou P, Poignard A, Beaujean F, Rouard H. Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am 2005, 87(7):1430-1437. 10.2106/JBJS.D.02215, 15995108.
41. Jäger M, Herten M, Fochtmann U, Fischer J, Hernigou P, Zilkens C, Hendrich C, Krauspe R. Bridging the gap: bone marrow aspiration concentrate reduces autologous bone grafting in osseous defects. J Orthop Res 2011, 29(2):173-180. 10.1002/jor.21230, 20740672.
42. Bianchi G, Banfi A, Mastrogiacomo M, Notaro R, Luzzatto L, Cancedda R, Quarto R. Ex vivo enrichment of mesenchymal cell progenitors by fibroblast growth factor 2. Exp Cell Res 2003, 287(1):98-105. 10.1016/S0014-4827(03)00138-1, 12799186.
43. D'Ippolito G, Diabira S, Howard GA, Menei P, Roos BA, Schiller PC. Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. J Cell Sci 2004, 117(14):2971-2981. 10.1242/jcs.01103, 15173316.
44. Patterson TE, Kumagai K, Griffith L, Muschler GF. Cellular strategies for enhancement of fracture repair. J Bone Joint Surg Am 2008, 90(Suppl 1):111-119.
45. McGonagle D, English A, Jones EA. The relevance of mesenchymal stem cells in vivo for future orthopaedic strategies aimed at fracture repair. Curr Orthop 2007, 21(4):262-267.
46. Wakitani S, Okabe T, Horibe S, Mitsuoka T, Saito M, Koyama T, Nawata M, Tensho K, Kato H, Uematsu K, Kuroda R, Kurosaka M, Yoshiya S, Hattori K, Ohgushi H. Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months. J Tissue Eng Regen Med 2011, 5(2):146-150. 10.1002/term.299, 20603892.
47. Matsumoto T, Kawamoto A, Kuroda R, Ishikawa M, Mifune Y, Iwasaki H, Miwa M, Horii M, Hayashi S, Oyamada A, Nishimura H, Murasawa S, Doita M, Kurosaka M, Asahara T. Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing. Am J Pathol 2006, 169:1440-1457. 10.2353/ajpath.2006.060064, 1698844, 17003498.
48. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 2001, 7(2):211-228. 10.1089/107632701300062859, 11304456.
49. Jackson WM, Aragon AB, Djouad F, Song Y, Koehler SM, Nesti LJ, Tuan RS. Mesenchymal progenitor cells derived from traumatized human muscle. J Tissue Eng Regen Med 2009, 3(2):129-138. 10.1002/term.149, 2814161, 19170141.
50. Im GI, Shin YW, Lee KB. Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells?. Osteoarthritis Cartilage 2005, 13(10):845-853. 10.1016/j.joca.2005.05.005, 16129630.
51. Niemeyer P, Fechner K, Milz S, Richter W, Suedkamp NP, Mehlhorn AT, Pearce S, Kasten P. Comparison of mesenchymal stem cells from bone marrow and adipose tissue for bone regeneration in a critical size defect of the sheep tibia and the influence of platelet-rich plasma. Biomaterials 2010, 31(13):3572-3529. 10.1016/j.biomaterials.2010.01.085, 20153047.
52. Jones E, McGonagle D. Human bone marrow mesenchymal stem cells in vivo. Rheumatology (Oxford) 2008, 47(2):126-131.
53. Jones EA, Kinsey SE, English A, Jones RA, Straszynski L, Meredith DM, Markham AF, Jack A, Emery P, McGonagle D. Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells. Arthritis Rheum 2002, 46(12):3349-3360. 10.1002/art.10696, 12483742.
54. Jones E, English A, Churchman SM, Kouroupis D, Boxall SA, Kinsey S, Giannoudis PG, Emery P, McGonagle D. Large-scale extraction and characterization of CD271+ multipotential stromal cells from trabecular bone in health and osteoarthritis: implications for bone regeneration strategies based on uncultured or minimally cultured multipotential stromal cells. Arthritis Rheum 2010, 62(7):1944-1954.
55. Akkouch A, Zhang Z, Rouabhia M. A novel collagen/hydroxyapatite/poly(lactide-co-ε-caprolactone) biodegradable and bioactive 3D porous scaffold for bone regeneration. J Biomed Mater Res A 2011, 96A:693-704.
56. Tampieri A, Landi E, Valentini F, Sandri M, D'Alessandro T, Dediu V, Marcacci M. A conceptually new type of bio-hybrid scaffold for bone regeneration. Nanotechnology 2011, 22(1):015104. 10.1088/0957-4484/22/1/015104, 21135464.
57. Laschke MW, Witt K, Pohlemann T, Menger MD. Injectable nanocrystalline hydroxyapatite paste for bone substitution: in vivo analysis of biocompatibility and vascularization. J Biomed Mater Res B Appl Biomater 2007, 82(2):494-505.
58. Salgado AJ, Coutinho OP, Reis RL. Bone tissue engineering: state of the art and future trends. Macromol Biosci 2004, 4(8):743-765. 10.1002/mabi.200400026, 15468269.
59. Rose FR, Oreffo RO. Bone tissue engineering: hope vs hype. Biochem Biophys Res Commun 2002, 292:1-7. 10.1006/bbrc.2002.6519, 11890663.
60. Jones EA, Yang XB. Mesenchymal stem cells and their future in bone repair. Int J Adv Rheumatol 2005, 3(3):15-21.
61. Chatterjea A, Meijer G, van Blitterswijk C, de Boer J. Clinical application of human mesenchymal stromal cells for bone tissue engineering. Stem Cells Int 2010, 2010:215625. 2989379, 21113294.
62. Kim SJ, Shin YW, Yang KH, Kim SB, Yoo MJ, Han SK, Im SA, Won YD, Sung YB, Jeon TS, Chang CH, Jang JD, Lee SB, Kim HC, Lee SY. A multi-center, randomized, clinical study to compare the effect and safety of autologous cultured osteoblast (Ossron) injection to treat fractures. BMC Musculoskelet Disord 2009, 10:20. 10.1186/1471-2474-10-20, 2656455, 19216734.
63. Ohgushi H, Kotobuki N, Funaoka H, Machida H, Hirose M, Tanaka Y, Takakura Y. Tissue engineered ceramic artificial joint--ex vivo osteogenic differentiation of patient mesenchymal cells on total ankle joints for treatment of osteoarthritis. Biomaterials 2005, 26(22):4654-4661. 10.1016/j.biomaterials.2004.11.055, 15722135.
64. Kokemueller H, Spalthoff S, Nolff M, Tavassol F, Essig H, Stuehmer C, Bormann KH, Rücker M, Gellrich NC. 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 2010, 39(4):379-387. 10.1016/j.ijom.2010.01.010, 20167453.
65. Tarte K, Gaillard J, Lataillade JJ, Fouillard L, Becker M, Mossafa H, Tchirkov A, Rouard H, Henry C, Splingard M, Dulong J, Monnier D, Gourmelon P, Gorin NC, Sensebé L, . Société Française de Greffe de Moelle et Thérapie Cellulaire Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation. Blood 2010, 115(8):1549-1553. 10.1182/blood-2009-05-219907, 20032501, Société Française de Greffe de Moelle et Thérapie Cellulaire.
66. Weinand C, Xu JW, Peretti GM, Bonassar LJ, Gill TJ. Conditions affecting cell seeding onto three-dimensional scaffolds for cellular-based biodegradable implants. J Biomed Mater Res B Appl Biomater 2009, 91(1):80-87.
67. Yoshioka T, Mishima H, Ohyabu Y, Sakai S, Akaogi H, Ishii T, Kojima H, Tanaka J, Ochiai N, Uemura T. Repair of large osteochondral defects with allogeneic cartilaginous aggregates formed from bone marrow-derived cells using RWV bioreactor. J Orthop Res 2007, 25(10):1291-1298. 10.1002/jor.20426, 17549704.
68. Caplan AI. Mesenchymal stem cells and gene therapy. Clin Orthop Relat Res 2000, 379(Suppl):S67-70.
69. Chen Y. Orthopaedic application of gene therapy. J Orthop Sci 2001, 6:199-207. 10.1007/s007760100072, 11484110.
70. Calori GM, Donati D, Di Bella C, Tagliabue L. Bone morphogenetic proteins and tissue engineering: future directions. Injury 2009, 40(Suppl 3):S67-76.
71. Tang Y, Tang W, Lin Y, Long J, Wang H, Liu L, Tian W. Combination of bone tissue engineering and BMP-2 gene transfection promotes bone healing in osteoporotic rats. Cell Biol Int 2008, 32(9):1150-1157. 10.1016/j.cellbi.2008.06.005, 18638562.
72. Lacroix D, Prendergast PJ. A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading. J Biomech 2002, 35(9):1163-1171. 10.1016/S0021-9290(02)00086-6, 12163306.
73. Perren SM. Physical and biological aspects of fracture healing with special reference to internal fixation. Clin Orthop Relat Res 1979, 138:175-196.
74. Jagodzinski M, Krettek C. Effect of mechanical stability on fracture healing--an update. Injury 2007, 38(Suppl1):S3-10.
75. Epari DR, Schell H, Bail HJ, Duda GN. Instability prolongs the chondral phase during bone healing in sheep. Bone 2006, 38(6):864-870. 10.1016/j.bone.2005.10.023, 16359937.
76. Schell H, Epari DR, Kassi JP, Bragulla H, Bail HJ, Duda GN. The course of bone healing is influenced by the initial shear fixation stability. J Orthop Res 2005, 23(5):1022-1028. 10.1016/j.orthres.2005.03.005, 15878254.
77. Claes L, Eckert-Hübner K, Augat P. The effect of mechanical stability on local vascularization and tissue differentiation in callus healing. J Orthop Res 2002, 20(5):1099-1105. 10.1016/S0736-0266(02)00044-X, 12382978.
78. Lienau J, Schell H, Duda GN, Seebeck P, Muchow S, Bail HJ. Initial vascularization and tissue differentiation are influenced by fixation stability. J Orthop Res 2005, 23(3):639-645. 10.1016/j.orthres.2004.09.006, 15885486.
79. Babis GC, Soucacos PN. Bone scaffolds: The role of mechanical stability and instrumentation. Injury 2005, 36(Suppl):S38-S44.
80. Tran GT, Pagkalos J, Tsiridis E, Narvani AA, Heliotis M, Mantalaris A, Tsiridis E. Growth hormone: does it have a therapeutic role in fracture healing?. Expert Opin Investig Drugs 2009, 18(7):887-911. 10.1517/13543780902893069, 19480608.
81. Rubin MR, Bilezikian JP. Parathyroid hormone as an anabolic skeletal therapy. Drugs 2005, 65(17):2481-2498. 10.2165/00003495-200565170-00005, 16296873.
82. Tzioupis CC, Giannoudis PV. The safety and efficacy of parathyroid hormone (PTH) as a biological response modifier for the enhancement of bone regeneration. Curr Drug Saf 2006, 1(2):189-203. 10.2174/157488606776930571, 18690930.
83. Verhaar HJ, Lems WF. PTH analogues and osteoporotic fractures. Expert Opin Biol Ther 2010, 10(9):1387-1394. 10.1517/14712598.2010.506870, 20629581.
84. Kanis JA, Burlet N, Cooper C, Delmas PD, Reginster JY, Borgstrom F, Rizzoli R. European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO): European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2008, 19(4):399-428. 10.1007/s00198-008-0560-z, 2613968, 18266020.
85. Charopoulos I, Orme S, Giannoudis PV. The role and efficacy of denosumab in the treatment of osteoporosis: an update. Expert Opin Drug Saf 2011,
86. Chen Y, Alman BA. Wnt pathway, an essential role in bone regeneration. J Cell Biochem 2009, 106(3):353-362. 10.1002/jcb.22020, 19127541.
87. Wagner ER, Zhu G, Zhang BQ, Luo Q, Shi Q, Huang E, Gao Y, Gao JL, Kim SH, Rastegar F, Yang K, He BC, Chen L, Zuo GW, Bi Y, Su Y, Luo J, Luo X, Huang J, Deng ZL, Reid RR, Luu HH, Haydon RC, He TC. The therapeutic potential of the Wnt signaling pathway in bone disorders. Curr Mol Pharmacol 2011, 4(1):14-25. 10.2174/1874467211104010014, 20825362.
88. Lucotte G, Houzet A, Hubans C, Lagarde JP, Lenoir G. Mutations of the noggin (NOG) and of the activin A type I receptor (ACVR1) genes in a series of twenty-seven French fibrodysplasia ossificans progressiva (FOP) patients. Genet Couns 2009, 20(1):53-62.