Skip to main content

Advertisement

SpringerLink
Log in

Surgical Fixation Hardware for Regeneration of Long Bone Segmental Defects: Translating Large Animal Model and Human Experiences

  • Fracture healing and bone regeneration
  • Published:
Clinical Reviews in Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Orthopedic fracture surgery has made significant advances in recent years, but large segmental bone defects remain a significant clinical problem. While surgical techniques have been developed or modified to address these issues, challenges remain. Further, to effectively address this issue, a suitable path from the benchtop to the clinic must be established. This is most commonly done using large animal models, which provide the opportunity to test different treatment options. This is certainly more complicated than it appears, as various anatomic and physiologic differences can produce complications not normally seen in humans. For this reason, proper species and bone selection is critically important. Here we review the current experimental methods, types of internal and external fixation, and large animal models used in segmental bone defect studies conducted in weight-bearing long bones. This review will also provide insight into the efficacy of hardware fixation strategies and the translatability of said strategies into clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Schmitz JP, Hollinger JO. The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res. 1986;205:299–308.

    PubMed  Google Scholar 

  2. Hollinger JO, Kleinschmidt JC. The critical size defect as an experimental model to test bone repair materials. J Craniofac Surg. 1990;1(1):60–8.

    Article  CAS  PubMed  Google Scholar 

  3. Reichert JC, Saifzadeh S, Wullschleger ME, Epari DR, Schutz MA, Duda GN, et al. The challenge of establishing preclinical models for segmental bone defect research. Biomaterials. 2009;30(12):2149–63.

    Article  CAS  PubMed  Google Scholar 

  4. Pearce AI, Richards RG, Milz S, Schneider E, Pearce SG. Animal models for implant biomaterial research in bone: a review. Eur Cell Mater. 2007;13:1–10.

    CAS  PubMed  Google Scholar 

  5. Lovett M, Lee K, Edwards A, Kaplan DL. Vascularization strategies for tissue engineering. Tissue Eng Part B Rev. 2009;15(3):353–70.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Horner EA, Kirkham J, Wood D, Curran S, Smith M, Thomson B, et al. Long bone defect models for tissue engineering applications: criteria for choice. Tissue Eng Part B Rev. 2010;16(2):263–71.

    Article  PubMed  Google Scholar 

  7. Apivatthakakul T, Phornphutkul C, Bunmaprasert T, Sananpanich K, Fernandez Dell’Oca A. Percutaneous cerclage wiring and minimally invasive plate osteosynthesis (MIPO): a percutaneous reduction technique in the treatment of Vancouver type B1 periprosthetic femoral shaft fractures. Arch Orthop Trauma Surg. 2012;132(6):813–22.

    Article  PubMed  Google Scholar 

  8. Gebhard F, Kregor P, Oliver C. https://www2.aofoundation.org/wps/portal/surgery/?showPage=redfix&bone=Femur&segment=Distal&classification=33-A3&treatment=&method=Provisional+treatment&implantstype=Temporary+external+fixator&redfix_url=1285238413692. Accessed 1 Sept 2015.

  9. Mills L, Noble B, Fenwick S, Simpson H. P103 assessment of a novel angiogenic factor in a small animal model of atrophic nonunion. J Bone Joint Surg. 2008;90-B(Supp 2):391.

    Google Scholar 

  10. Konrad G, Sudkamp N. Extra-articular proximal tibial fracture. Chirurg. 2007;78(2):161–71 (quiz 172–3).

    Article  CAS  PubMed  Google Scholar 

  11. Beltsios M, Savvidou O, Kovanis J, Alexandropoulos P, Papagelopoulos P. External fixation as a primary and definitive treatment for tibial diaphyseal fractures. Strateg Trauma Limb Reconstr. 2009;4(2):81–7.

    Article  Google Scholar 

  12. Krischak GD, Janousek A, Wolf S, Augat P, Kinzl L, Claes LE. Effects of one-plane and two-plane external fixation on sheep osteotomy healing and complications. Clin Biomech (Bristol, Avon). 2002;17(6):470–6.

    Article  Google Scholar 

  13. Reichert JC, Epari DR, Wullschleger ME, Saifzadeh S, Steck R, Lienau J, et al. Establishment of a preclinical ovine model for tibial segmental bone defect repair by applying bone tissue engineering strategies. Tissue Eng Part B Rev. 2010;16(1):93–104.

    Article  PubMed  Google Scholar 

  14. Seekamp A, Lehmann U, Pizanis A, Pohlemann T. New aspects for minimally invasive interventions in orthopedic trauma surgery. Chirurg. 2003;74(4):301–9.

    Article  CAS  PubMed  Google Scholar 

  15. Apivatthakakul T, Anuraklekha S, Babikian G, Castelli F, Pace A, Phiphobmongkol V, et al. https://www2.aofoundation.org/wps/portal/surgery/?showPage=redfix&bone=Tibia&segment=Shaft&classification=42-B3&treatment=&method=CRIF+-+Closed+reduction+internal+fixation&implantstype=MIO+-+Bridge+plating&redfix_url=1285239039132. Accessed 1 Sept 2015.

  16. Sommer C, Gautier E, Muller M, Helfet DL, Wagner M. First clinical results of the Locking Compression Plate (LCP). Injury. 2003;34(Suppl 2):B43–54.

    Article  PubMed  Google Scholar 

  17. Beardi J, Hessmann M, Hansen M, Rommens PM. Operative treatment of tibial shaft fractures: a comparison of different methods of primary stabilisation. Arch Orthop Trauma Surg. 2008;128(7):709–15.

    Article  CAS  PubMed  Google Scholar 

  18. Perren SM. Evolution of the internal fixation of long bone fractures. The scientific basis of biological internal fixation: choosing a new balance between stability and biology. J Bone Joint Surg Br. 2002;84(8):1093–110.

    Article  PubMed  Google Scholar 

  19. Christou C, Oliver RA, Pelletier MH, Walsh WR. Ovine model for critical-size tibial segmental defects. Comp Med. 2014;64(5):377–85.

    PubMed Central  CAS  PubMed  Google Scholar 

  20. Krettek C, Schandelmaier P, Tscherne H. New developments in stabilization of dia- and metaphyseal fractures of long tubular bones. Orthopade. 1997;26(5):408–21.

    CAS  PubMed  Google Scholar 

  21. Gautier E, Ganz R. The biological plate osteosynthesis. Zentralbl Chir. 1994;119(8):564–72.

    CAS  PubMed  Google Scholar 

  22. Gautier E, Perren SM, Cordey J. Strain distribution in plated and unplated sheep tibia an in vivo experiment. Injury. 2000;31(Suppl 3):C37–44.

    Article  PubMed  Google Scholar 

  23. Johnson BA, Fallat LM. The effect of screw holes on bone strength. J Foot Ankle Surg. 1997;36(6):446–51.

    Article  CAS  PubMed  Google Scholar 

  24. Peirone B. https://www2.aofoundation.org/wps/portal/surgery?showPage=redfix&bone=DogFemur&segment=Shaft&classification=d32-C3&treatment=&method=Bridging%20plate%20and%20alternative%20double%20plating&implantstype=&approach=&redfix_url=1415874648616&Language=en. Accessed 1 Sept 2015.

  25. Rubel IF, Kloen P, Campbell D, Schwartz M, Liew A, Myers E, et al. Open reduction and internal fixation of humeral nonunions : a biomechanical and clinical study. J Bone Joint Surg Am. 2002;84-A(8):1315–22.

    PubMed  Google Scholar 

  26. Hahn JA, Witte TS, Arens D, Pearce A, Pearce S. Double-plating of ovine critical sized defects of the tibia: a low morbidity model enabling continuous in vivo monitoring of bone healing. BMC Musculoskelet Disord. 2011;12:214-2474-12-214.

    Article  Google Scholar 

  27. Apivatthakakul T, Anuraklekha S, Babikian G, Castelli F, Pace A, Phiphobmongkol V, et al. https://www2.aofoundation.org/wps/portal/surgery?showPage=redfix&bone=Tibia&segment=Shaft&classification=42-C2&treatment=&method=CRIF%20-%20Closed%20reduction%20internal%20fixation&implantstype=Nailing&approach=&redfix_url=1285239039726&Language=en#stepUnit-8. Accessed 1 Sept 2015.

  28. Gradl G, Herlyn P, Emmerich J, Friebe U, Martin H, Mittlmeier T. Fracture near press-on interlocking enhances callus mineralisation in a sheep midshaft tibia osteotomy model. Injury. 2014;45(Suppl 1):S66–70.

    Article  PubMed  Google Scholar 

  29. Chao P, Lewis DD, Kowaleski MP, Pozzi A. Biomechanical concepts applicable to minimally invasive fracture repair in small animals. Vet Clin North Am Small Anim Pract. 2012;42(5):853–72.

    Article  PubMed  Google Scholar 

  30. Giannoudis PV, Chalidis BE, Roberts CS. Internal fixation of traumatic diastasis of pubic symphysis: Is plate removal essential? Arch Orthop Trauma Surg. 2008;128(3):325–31.

    Article  PubMed  Google Scholar 

  31. Hogel F, Schlegel U, Sudkamp N, Muller C. Fracture healing after reamed and unreamed intramedullary nailing in sheep tibia. Injury. 2011;42(7):667–74.

    Article  CAS  PubMed  Google Scholar 

  32. Frolke JP, Bakker FC, Patka P, Haarman HJ. Reaming debris in osteotomized sheep tibiae. J Trauma. 2001;50(1):65–9 (discussion 69–70).

    Article  CAS  PubMed  Google Scholar 

  33. Reichert IL, McCarthy ID, Hughes SP. The acute vascular response to intramedullary reaming. Microsphere estimation of blood flow in the intact ovine tibia. J Bone Joint Surg Br. 1995;77(3):490–3.

    CAS  PubMed  Google Scholar 

  34. Mastrogiacomo M, Corsi A, Francioso E, Di Comite M, Monetti F, Scaglione S, et al. Reconstruction of extensive long bone defects in sheep using resorbable bioceramics based on silicon stabilized tricalcium phosphate. Tissue Eng. 2006;12(5):1261–73.

    Article  CAS  PubMed  Google Scholar 

  35. Mueller CA, Rahn BA. Intramedullary pressure increase and increase in cortical temperature during reaming of the femoral medullary cavity: the effect of draining the medullary contents before reaming. J Trauma. 2003;55(3):495–503 discussion 503.

    Article  CAS  PubMed  Google Scholar 

  36. Chapman MW. The effect of reamed and nonreamed intramedullary nailing on fracture healing. Clin Orthop Relat Res. 1998;355(Suppl):S230–8.

    Article  PubMed  Google Scholar 

  37. Pape HC, Giannoudis PV. Fat embolism and IM nailing. Injury. 2006;37(Suppl 4):S1–2.

    Article  PubMed  Google Scholar 

  38. Wenda K, Ritter G, Degreif J, Rudigier J. Pathogenesis of pulmonary complications following intramedullary nailing osteosyntheses. Unfallchirurg. 1988;91(9):432–5.

    CAS  PubMed  Google Scholar 

  39. Berner A, Reichert JC, Woodruff MA, Saifzadeh S, Morris AJ, Epari DR, et al. Autologous vs. allogenic mesenchymal progenitor cells for the reconstruction of critical sized segmental tibial bone defects in aged sheep. Acta Biomater. 2013;9(8):7874–84.

    Article  CAS  PubMed  Google Scholar 

  40. Augat P, Penzkofer R, Nolte A, Maier M, Panzer S, Oldenburg G, et al. Interfragmentary movement in diaphyseal tibia fractures fixed with locked intramedullary nails. J Orthop Trauma. 2008;22(1):30–6.

    Article  PubMed  Google Scholar 

  41. Kessler SB, Hallfeldt KK, Perren SM, Schweiberer L. The effects of reaming and intramedullary nailing on fracture healing. Clin Orthop Relat Res. 1986;212:18–25.

    PubMed  Google Scholar 

  42. Lam SW, Teraa M, Leenen LP, van der Heijden GJ. Systematic review shows lowered risk of nonunion after reamed nailing in patients with closed tibial shaft fractures. Injury. 2010;41(7):671–5.

    Article  CAS  PubMed  Google Scholar 

  43. Augat P, Merk J, Ignatius A, Margevicius K, Bauer G, Rosenbaum D, et al. Early, full weightbearing with flexible fixation delays fracture healing. Clin Orthop Relat Res. 1996;328:194–202.

    Article  PubMed  Google Scholar 

  44. Aerssens J, Boonen S, Lowet G, Dequeker J. Interspecies differences in bone composition, density, and quality: potential implications for in vivo bone research. Endocrinology. 1998;139(2):663–70.

    CAS  PubMed  Google Scholar 

  45. Thorwarth M, Schultze-Mosgau S, Kessler P, Wiltfang J, Schlegel KA. Bone regeneration in osseous defects using a resorbable nanoparticular hydroxyapatite. J Oral Maxillofac Surg. 2005;63(11):1626–33.

    Article  PubMed  Google Scholar 

  46. Newman E, Turner AS, Wark JD. The potential of sheep for the study of osteopenia: current status and comparison with other animal models. Bone. 1995;16(4 Suppl):277S–84S.

    Article  CAS  PubMed  Google Scholar 

  47. Manolagas SC, Kronenberg HM. Reproducibility of results in preclinical studies: a perspective from the bone field. J Bone Miner Res. 2014;29(10):2131–40.

    Article  PubMed Central  PubMed  Google Scholar 

  48. Bong MR, Kummer FJ, Koval KJ, Egol KA. Intramedullary nailing of the lower extremity: biomechanics and biology. J Am Acad Orthop Surg. 2007;15(2):97–106.

    PubMed  Google Scholar 

  49. Bhandari M, Guyatt GH, Tornetta P III, Swiontkowski MF, Hanson B, Sprague S, et al. Current practice in the intramedullary nailing of tibial shaft fractures: an international survey. J Trauma. 2002;53(4):725–32.

    Article  PubMed  Google Scholar 

  50. Henley MB, Chapman JR, Agel J, Harvey EJ, Whorton AM, Swiontkowski MF. Treatment of type II, IIIA, and IIIB open fractures of the tibial shaft: a prospective comparison of unreamed interlocking intramedullary nails and half-pin external fixators. J Orthop Trauma. 1998;12(1):1–7.

    Article  CAS  PubMed  Google Scholar 

  51. Tzioupis C, Giannoudis PV. Prevalence of long-bone non-unions. Injury. 2007;38(Suppl 2):S3–9.

    Article  PubMed  Google Scholar 

  52. Field JR, McGee M, Wildenauer C, Kurmis A, Margerrison E. The utilization of a synthetic bone void filler (JAX) in the repair of a femoral segmental defect. Vet Comp Orthop Traumatol. 2009;22(2):87–95.

    CAS  PubMed  Google Scholar 

  53. Kirker-Head CA, Gerhart TN, Armstrong R, Schelling SH, Carmel LA. Healing bone using recombinant human bone morphogenetic protein 2 and copolymer. Clin Orthop Relat Res. 1998;349:205–17.

    Article  PubMed  Google Scholar 

  54. Kirker-Head CA, Gerhart TN, Schelling SH, Hennig GE, Wang E, Holtrop ME. Long-term healing of bone using recombinant human bone morphogenetic protein 2. Clin Orthop Relat Res. 1995;318:222–30.

    PubMed  Google Scholar 

  55. Gugala Z, Gogolewski S. Healing of critical-size segmental bone defects in the sheep tibiae using bioresorbable polylactide membranes. Injury. 2002;33(Suppl 2):B71–6.

    Article  PubMed  Google Scholar 

  56. Marcacci M, Kon E, Zaffagnini S, Giardino R, Rocca M, Corsi A, et al. Reconstruction of extensive long-bone defects in sheep using porous hydroxyapatite sponges. Calcif Tissue Int. 1999;64(1):83–90.

    Article  CAS  PubMed  Google Scholar 

  57. Maissen O, Eckhardt C, Gogolewski S, Glatt M, Arvinte T, Steiner A, et al. 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. 2006;24(8):1670–8.

    Article  CAS  PubMed  Google Scholar 

  58. den Boer FC, Patka P, Bakker FC, Wippermann BW, van Lingen A, Vink GQ, et al. New segmental long bone defect model in sheep: quantitative analysis of healing with dual energy X-ray absorptiometry. J Orthop Res. 1999;17(5):654–60.

    Article  Google Scholar 

  59. den Boer FC, Wippermann BW, Blokhuis TJ, Patka P, Bakker FC, Haarman HJ. Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant human osteogenic protein-1 or autologous bone marrow. J Orthop Res. 2003;21(3):521–8.

    Article  Google Scholar 

  60. Bloemers FW, Blokhuis TJ, Patka P, Bakker FC, Wippermann BW, Haarman HJ. Autologous bone versus calcium-phosphate ceramics in treatment of experimental bone defects. J Biomed Mater Res B Appl Biomater. 2003;66(2):526–31.

    Article  PubMed  Google Scholar 

  61. Tyllianakis M, Deligianni D, Panagopoulos A, Pappas M, Sourgiadaki E, Mavrilas D, et al. Biomechanical comparison of callus over a locked intramedullary nail in various segmental bone defects in a sheep model. Med Sci Monit. 2007;13(5):BR125–30.

    PubMed  Google Scholar 

  62. Blokhuis TJ, Wippermann BW, den Boer FC, van Lingen A, Patka P, Bakker FC, et al. Resorbable calcium phosphate particles as a carrier material for bone marrow in an ovine segmental defect. J Biomed Mater Res. 2000;51(3):369–75.

    Article  CAS  PubMed  Google Scholar 

  63. Field JR, McGee M, Stanley R, Ruthenbeck G, Papadimitrakis T, Zannettino A, et al. The efficacy of allogeneic mesenchymal precursor cells for the repair of an ovine tibial segmental defect. Vet Comp Orthop Traumatol. 2011;24(2):113–21.

    Article  CAS  PubMed  Google Scholar 

  64. Regauer M, Jurgens I, Kotsianos D, Stutzle H, Mutschler W, Schieker M. New-bone formation by osteogenic protein-1 and autogenic bone marrow in a critical tibial defect model in sheep. Zentralbl Chir. 2005;130(4):338–45.

    Article  CAS  PubMed  Google Scholar 

  65. Schneiders W, Reinstorf A, Biewener A, Serra A, Grass R, Kinscher M, et al. In vivo effects of modification of hydroxyapatite/collagen composites with and without chondroitin sulphate on bone remodeling in the sheep tibia. J Orthop Res. 2009;27(1):15–21.

    Article  CAS  PubMed  Google Scholar 

  66. Lozada-Gallegos AR, Letechipia-Moreno J, Palma-Lara I, Montero AA, Rodriguez G, Castro-Munozledo F, et al. Development of a bone nonunion in a noncritical segmental tibia defect model in sheep utilizing interlocking nail as an internal fixation system. J Surg Res. 2013;183(2):620–8.

    Article  PubMed  Google Scholar 

  67. Pluhar GE, Turner AS, Pierce AR, Toth CA, Wheeler DL. A comparison of two biomaterial carriers for osteogenic protein-1 (BMP-7) in an ovine critical defect model. J Bone Joint Surg Br. 2006;88(7):960–6.

    Article  CAS  PubMed  Google Scholar 

  68. Gerber A, Gogolewski S. Reconstruction of large segmental defects in the sheep tibia using polylactide membranes. A clinical and radiographic report. Injury. 2002;33(Suppl 2):B43–57.

    Article  PubMed  Google Scholar 

  69. Gao TJ, Lindholm TS, Kommonen B, Ragni P, Paronzini A, Lindholm TC, et al. 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. 1996;32(4):505–12.

    Article  CAS  PubMed  Google Scholar 

  70. Rozen N, Bick T, Bajayo A, Shamian B, Schrift-Tzadok M, Gabet Y, et al. Transplanted blood-derived endothelial progenitor cells (EPC) enhance bridging of sheep tibia critical size defects. Bone. 2009;45(5):918–24.

    Article  CAS  PubMed  Google Scholar 

  71. Teixeira CR, Rahal SC, Volpi RS, Taga R, Cestari TM, Granjeiro JM, et al. Tibial segmental bone defect treated with bone plate and cage filled with either xenogeneic composite or autologous cortical bone graft. An experimental study in sheep. Vet Comp Orthop Traumatol. 2007;20(4):269–76.

    CAS  PubMed  Google Scholar 

  72. Niemeyer P, Schonberger TS, Hahn J, Kasten P, Fellenberg J, Suedkamp N, et al. Xenogenic transplantation of human mesenchymal stem cells in a critical size defect of the sheep tibia for bone regeneration. Tissue Eng Part A. 2010;16(1):33–43.

    Article  CAS  PubMed  Google Scholar 

  73. Chistolini P, Ruspantini I, Bianco P, Corsi A, Cancedda R, Quarto R. Biomechanical evaluation of cell-loaded and cell-free hydroxyapatite implants for the reconstruction of segmental bone defects. J Mater Sci Mater Med. 1999;10(12):739–42.

    Article  CAS  PubMed  Google Scholar 

  74. Gao TJ, Lindholm TS, Kommonen B, Ragni P, Paronzini A, Lindholm TC, et al. The use of a coral composite implant containing bone morphogenetic protein to repair a segmental tibial defect in sheep. Int Orthop. 1997;21(3):194–200.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Lindsey RW, Gugala Z, Milne E, Sun M, Gannon FH, Latta LL. The efficacy of cylindrical titanium mesh cage for the reconstruction of a critical-size canine segmental femoral diaphyseal defect. J Orthop Res. 2006;24(7):1438–53.

    Article  CAS  PubMed  Google Scholar 

  76. Zabka AG, Pluhar GE, Edwards RB III, Manley PA, Hayashi K, Heiner JP, et al. Histomorphometric description of allograft bone remodeling and union in a canine segmental femoral defect model: a comparison of rhBMP-2, cancellous bone graft, and absorbable collagen sponge. J Orthop Res. 2001;19(2):318–27.

    Article  CAS  PubMed  Google Scholar 

  77. Bernarde A, Diop A, Maurel N, Viguier E. An in vitro biomechanical study of bone plate and interlocking nail in a canine diaphyseal femoral fracture model. Vet Surg. 2001;30(5):397–408.

    Article  CAS  PubMed  Google Scholar 

  78. Kraus KH, Kadiyala S, Wotton H, Kurth A, Shea M, Hannan M, et al. Critically sized osteo-periosteal femoral defects: a dog model. J Invest Surg. 1999;12(2):115–24.

    Article  CAS  PubMed  Google Scholar 

  79. Weiland AJ, Phillips TW, Randolph MA. Bone grafts: a radiologic, histologic, and biomechanical model comparing autografts, allografts, and free vascularized bone grafts. Plast Reconstr Surg. 1984;74(3):368–79.

    Article  CAS  PubMed  Google Scholar 

  80. Brodke D, Pedrozo HA, Kapur TA, Attawia M, Kraus KH, Holy CE, et al. Bone grafts prepared with selective cell retention technology heal canine segmental defects as effectively as autograft. J Orthop Res. 2006;24(5):857–66.

    Article  PubMed  Google Scholar 

  81. Arinzeh TL, Peter SJ, Archambault MP, van den Bos C, Gordon S, Kraus K, et al. Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg Am. 2003;85-A(10):1927–35.

    PubMed  Google Scholar 

  82. Bruder SP, Kraus KH, Goldberg VM, Kadiyala S. The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. J Bone Joint Surg Am. 1998;80(7):985–96.

    CAS  PubMed  Google Scholar 

  83. Akagi H, Ochi H, Kannno N, Iwata M, Ichinohe T, Harada Y, et al. Clinical efficacy of autogenous cancellous bone and fibroblast growth factor 2 combined with frozen allografts in femoral nonunion fractures. Vet Comp Orthop Traumatol. 2013;26(2):123–9.

    Article  CAS  PubMed  Google Scholar 

  84. Markel MD, Bogdanske JJ, Xiang Z, Klohnen A. Atrophic nonunion can be predicted with dual energy X-ray absorptiometry in a canine ostectomy model. J Orthop Res. 1995;13(6):869–75.

    Article  CAS  PubMed  Google Scholar 

  85. Kuzyk PRT, Schemitsch EH, Davies JE. A biodegradable scaffold for the treatment of a diaphyseal bone defect of the tibia. J Orthop Res. 2010;28(4):474–80.

    CAS  PubMed  Google Scholar 

  86. Boyce AS, Reveal G, Scheid DK, Kaehr DM, Maar D, Watts M, et al. Canine investigation of rhBMP-2, autogenous bone graft, and rhBMP-2 with autogenous bone graft for the healing of a large segmental tibial defect. J Orthop Trauma. 2009;23(10):685–92.

    Article  PubMed  Google Scholar 

  87. Xu XL, Tang T, Dai K, Zhu Z, Guo XE, Yu C, et al. Immune response and effect of adenovirus-mediated human BMP-2 gene transfer on the repair of segmental tibial bone defects in goats. Acta Orthop. 2005;76(5):637–46.

    Article  PubMed  Google Scholar 

  88. Liu G, Zhao L, Zhang W, Cui L, Liu W, Cao Y. Repair of goat tibial defects with bone marrow stromal cells and beta-tricalcium phosphate. J Mater Sci Mater Med. 2008;19(6):2367–76.

    Article  CAS  PubMed  Google Scholar 

  89. Pek YS, Gao S, Arshad MS, Leck KJ, Ying JY. Porous collagen-apatite nanocomposite foams as bone regeneration scaffolds. Biomaterials. 2008;29(32):4300–5.

    Article  CAS  PubMed  Google Scholar 

  90. Raschke M, Kolbeck S, Bail H, Schmidmaier G, Flyvbjerg A, Lindner T, et al. Homologous growth hormone accelerates healing of segmental bone defects. Bone. 2001;29(4):368–73.

    Article  CAS  PubMed  Google Scholar 

  91. Fan H, Zeng X, Wang X, Zhu R, Pei G. Efficacy of prevascularization for segmental bone defect repair using beta-tricalcium phosphate scaffold in rhesus monkey. Biomaterials. 2014;35(26):7407–15.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Medical Student Affairs Summer Research Program in Academic Medicine, Indiana University School of Medicine, funded in part by NIH NIAMS T32AR065971 (JR) and the Department of Orthopaedic Surgery, Indiana University School of Medicine (MAK, TOM, JOA, KDS). In addition, research reported in this publication was supported in part by the following Grants: NIH NIAMS R01 AR060863 (MAK), USAMRMC OR120080 (MAK, T-MGC, JOA), an Indiana University Health Values Grant (KDS, MAK), Indiana Clinical and Translational Sciences Institute Grants partially supported by NIH UL1TR001108 (MAK, T-MGC, TOM, JOA), and an Indiana University Collaborative Research Grant (MAK, T-MGC). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Indiana University School of Medicine, 1130 W. Michigan St., FH 115, Indianapolis, IN, 46202, USA

    Emily Jewell, Jeff Rytlewski, Jeffrey O. Anglen, Todd O. McKinley, Karl D. Shively & Melissa A. Kacena

  2. Department of Restorative Dentistry, Indiana University School of Dentistry, Indianapolis, IN, USA

    Tien-Min G. Chu

Authors
  1. Emily Jewell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeff Rytlewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeffrey O. Anglen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Todd O. McKinley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karl D. Shively
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tien-Min G. Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Melissa A. Kacena
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Melissa A. Kacena.

Ethics declarations

Conflicts of interest

Emily Jewell, Jeff Rytlewski, Tien-Min G. Chu, Jeffrey O. Anglen, Karl D. Shively, and Melissa A. Kacena declare they have no conflict of interest. Todd O. McKinley is a consultant for Bioventus.

Animal/Human Studies

This article does not include any studies with human or animal subjects performed by the author.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jewell, E., Rytlewski, J., Anglen, J.O. et al. Surgical Fixation Hardware for Regeneration of Long Bone Segmental Defects: Translating Large Animal Model and Human Experiences. Clinic Rev Bone Miner Metab 13, 222–231 (2015). https://doi.org/10.1007/s12018-015-9195-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12018-015-9195-8

Keywords

Search

Navigation