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A Mouse Femoral Ostectomy Model to Assess Bone Graft Substitutes

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Skeletal Development and Repair

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2230))

Abstract

The shortcomings of autografts and allografts in bone defect healing have prompted researchers to develop suitable alternatives. Numerous biomaterials have been developed as bone graft substitutes each with their own advantages and disadvantages. However, in order to test if these biomaterials provide an adequate replacement of the clinical standard, a clinically representative animal model is needed to test their efficacy. In this chapter, we describe a mouse model that establishes a critical sized defect in the mid-diaphysis of the femur to evaluate the performance of bone graft substitutes. This is achieved by performing a femoral ostectomy and stabilization utilizing a femoral plate and titanium screws. The resulting defect enables the bone regenerative potential of bone graft substitutes to be investigated. Lastly, we provide instruction on assessing the torsional strength of the healed femurs to quantitatively evaluate the degree of healing as a primary outcome measure.

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References

  1. Giannoudis PV, Dinopoulos H, Tsiridis E (2005) Bone substitutes: an update. Injury 36(Suppl 3):S20–S27. https://doi.org/10.1016/j.injury.2005.07.029

    Article  PubMed  Google Scholar 

  2. Amini AR, Laurencin CT, Nukavarapu SP (2012) Bone tissue engineering: recent advances and challenges. Crit Rev Biomed Eng 40(5):363–408

    Article  Google Scholar 

  3. Laurencin CT, Khan Y (2009) Bone graft substitute materials. Expert Rev Med Devices 3(1):49–57

    Article  Google Scholar 

  4. Tan MH, Mankin HJ (1997) Blood transfusion and bone allografts. Effect on infection and outcome. Clin Orthop Relat Res 340:207–214. https://doi.org/10.1097/00003086-199707000-00027

    Article  Google Scholar 

  5. Nguyen H, Morgan DA, Forwood MR (2007) Sterilization of allograft bone: effects of gamma irradiation on allograft biology and biomechanics. Cell Tissue Bank 8(2):93–105. https://doi.org/10.1007/s10561-006-9020-1

    Article  PubMed  Google Scholar 

  6. Brigman BE, Hornicek FJ, Gebhardt MC, Mankin HJ (2004) Allografts about the knee in young patients with high-grade sarcoma. Clin Orthop Relat Res 421:232–239. https://doi.org/10.1097/01.blo.0000127132.12576.05

    Article  Google Scholar 

  7. Beuerlein MJ, McKee MD (2010) Calcium sulfates: what is the evidence? J Orthop Trauma 24(Suppl 1):S46–S51. https://doi.org/10.1097/BOT.0b013e3181cec48e

    Article  PubMed  Google Scholar 

  8. Bohner M, Galea L, Doebelin N (2012) Calcium phosphate bone graft substitutes: failures and hopes. J Eur Ceram Soc 32(11):2663–2671. https://doi.org/10.1016/j.jeurceramsoc.2012.02.028

    Article  CAS  Google Scholar 

  9. Fu Q, Saiz E, Rahaman MN, Tomsia AP (2011) Bioactive glass scaffolds for bone tissue engineering: state of the art and future perspectives. Mater Sci Eng C Mater Biol Appl 31(7):1245–1256. https://doi.org/10.1016/j.msec.2011.04.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sabir MI, Xu X, Li LI (2009) A review on biodegradable polymeric materials for bone tissue engineering applications. J Material Sci 44(21):5713–5724. https://doi.org/10.1007/s10853-009-3770-7

    Article  CAS  Google Scholar 

  11. Murugan R, Ramakrishna S (2005) Development of nanocomposites for bone grafting. Compos Sci Technol 65(15):2385–2406. https://doi.org/10.1016/j.compscitech.2005.07.022

    Article  CAS  Google Scholar 

  12. Whiteman D, Gropper PT, Wirtz P, Monk P (1993) Demineralized bone powder. Clinical applications for bone defects of the hand. J Hand Surg 18(4):487–490

    Article  CAS  Google Scholar 

  13. Johal HS, Buckley RE, Le IL, Leighton RK (2009) A prospective randomized controlled trial of a bioresorbable calcium phosphate paste (alpha-BSM) in treatment of displaced intra-articular calcaneal fractures. J Trauma 67(4):875–882. https://doi.org/10.1097/TA.0b013e3181ae2d50

    Article  CAS  PubMed  Google Scholar 

  14. Zhang J, Liu W, Schnitzler V, Tancret F, Bouler J-M (2014) Calcium phosphate cements for bone substitution: chemistry, handling and mechanical properties. Acta Biomater 10(3):1035–1049. https://doi.org/10.1016/j.actbio.2013.11.001

    Article  CAS  PubMed  Google Scholar 

  15. Urban RM, Turner TM, Hall DJ, Infanger SI, Cheema N, Lim TH, Moseley J, Carroll M, Roark M (2004) Effects of altered crystalline structure and increased initial compressive strength of calcium sulfate bone graft substitute pellets on new bone formation. Orthopedics 27(1 Suppl):s113–s118

    Article  Google Scholar 

  16. Joosten U, Joist A, Gosheger G, Liljenqvist U, Brandt B, von Eiff C (2005) Effectiveness of hydroxyapatite-vancomycin bone cement in the treatment of Staphylococcus aureus induced chronic osteomyelitis. Biomaterials 26(25):5251–5258. https://doi.org/10.1016/j.biomaterials.2005.01.001

    Article  CAS  PubMed  Google Scholar 

  17. Bohner M (2010) Design of ceramic-based cements and putties for bone graft substitution. Eur Cell Mater 20:1–12

    Article  CAS  Google Scholar 

  18. Daculsi G (1998) Biphasic calcium phosphate concept applied to artificial bone, implant coating and injectable bone substitute. Biomaterials 19(16):1473–1478

    Article  CAS  Google Scholar 

  19. Petite H, Viateau V, Bensaid W, Meunier A, de Pollak C, Bourguignon M, Oudina K, Sedel L, Guillemin G (2000) Tissue-engineered bone regeneration. Nat Biotechnol 18(9):959–963. https://doi.org/10.1038/79449

    Article  CAS  PubMed  Google Scholar 

  20. Peterson JR, Chen F, Nwankwo E, Dekker TJ, Adams SB (2019) The use of bone grafts, bone graft substitutes, and orthobiologics for osseous healing in foot and ankle. Surgery 4(3):2473011419849019. https://doi.org/10.1177/2473011419849019

    Article  Google Scholar 

  21. Carragee EJ, Hurwitz EL, Weiner BK (2011) A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J 11(6):471–491. https://doi.org/10.1016/j.spinee.2011.04.023

    Article  PubMed  Google Scholar 

  22. Street J, Bao M, deGuzman L, Bunting S, Peale FV Jr, Ferrara N, Steinmetz H, Hoeffel J, Cleland JL, Daugherty A, van Bruggen N, Redmond HP, Carano RAD, Filvaroff EH (2002) Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci U S A 99(15):9656–9661. https://doi.org/10.1073/pnas.152324099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Meinel L, Zoidis E, Zapf J, Hassa P, Hottiger MO, Auer JA, Schneider R, Gander B, Luginbuehl V, Bettschart-Wolfisberger R, Illi OE, Merkle HP, Rechenberg BV (2003) Localized insulin-like growth factor I delivery to enhance new bone formation. Bone 33(4):660–672. https://doi.org/10.1016/S8756-3282(03)00207-2

    Article  CAS  PubMed  Google Scholar 

  24. Kawaguchi H, Nakamura K, Tabata Y, Ikada Y, Aoyama I, Anzai J, Nakamura T, Hiyama Y, Tamura M (2001) Acceleration of fracture healing in nonhuman primates by fibroblast growth factor-2. J Clin Endocrinol Metab 86(2):875–880. https://doi.org/10.1210/jcem.86.2.7199

    Article  CAS  PubMed  Google Scholar 

  25. Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR (1998) Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 85(6):638–646

    Article  CAS  Google Scholar 

  26. Wildemann B, Kadow-Romacker A, Haas NP, Schmidmaier G (2007) Quantification of various growth factors in different demineralized bone matrix preparations. J Biomed Mater Res A 81(2):437–442. https://doi.org/10.1002/jbm.a.31085

    Article  CAS  PubMed  Google Scholar 

  27. Freymiller EG (2004) Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg 62(8):1046. Author reply 1047-1048

    Article  Google Scholar 

  28. Ishaug SL, Crane GM, Miller MJ, Yasko AW, Yaszemski MJ, Mikos AG (1997) Bone formation by three-dimensional stromal osteoblast culture in biodegradable polymer scaffolds. J Biomed Mater Res 36(1):17–28. https://doi.org/10.1002/(sici)1097-4636(199707)36:1<17::Aid-jbm3>3.0.Co;2-o

    Article  CAS  PubMed  Google Scholar 

  29. Wei X, Liu B, Liu G, Yang F, Cao F, Dou X, Yu W, Wang B, Zheng G, Cheng L, Ma Z, Zhang Y, Yang J, Wang Z, Li J, Cui D, Wang W, Xie H, Li L, Zhang F, Lineaweaver WC, Zhao D (2019) Mesenchymal stem cell-loaded porous tantalum integrated with biomimetic 3D collagen-based scaffold to repair large osteochondral defects in goats. Stem Cell Res Ther 10(1):72. https://doi.org/10.1186/s13287-019-1176-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Schliephake H, Knebel JW, Aufderheide M, Tauscher M (2001) Use of cultivated osteoprogenitor cells to increase bone formation in segmental mandibular defects: an experimental pilot study in sheep. Int J Oral Maxillofac Surg 30(6):531–537. https://doi.org/10.1054/ijom.2001.0164

    Article  CAS  PubMed  Google Scholar 

  31. Long T, Zhu Z, Awad HA, Schwarz EM, Hilton MJ, Dong Y (2014) The effect of mesenchymal stem cell sheets on structural allograft healing of critical sized femoral defects in mice. Biomaterials 35(9):2752–2759. https://doi.org/10.1016/j.biomaterials.2013.12.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhang X, Xie C, Lin AS, Ito H, Awad H, Lieberman JR, Rubery PT, Schwarz EM, O'Keefe RJ, Guldberg RE (2005) Periosteal progenitor cell fate in segmental cortical bone graft transplantations: implications for functional tissue engineering. J Bone Miner Res 20(12):2124–2137. https://doi.org/10.1359/JBMR.050806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Schemitsch EH (2017) Size matters: defining critical in bone defect size! J Orthop Trauma 31:S20–S22. https://doi.org/10.1097/bot.0000000000000978

    Article  PubMed  Google Scholar 

  34. Claes LE, Heigele CA, Neidlinger-Wilke C, Kaspar D, Seidl W, Margevicius KJ, Augat P (1998) Effects of mechanical factors on the fracture healing process. Clin Orthop Relat Res (355 Suppl):S132–S147. https://doi.org/10.1097/00003086-199810001-00015

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Acknowledgments

This work was supported by the NIAMS/NIH grants P30AR069655 and P50AR072000, and the AOTrauma Clinical Priority Program.

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Authors and Affiliations

  1. Orthopedic Trauma Department, US Army Institute for Surgical Research, San Antonio, TX, USA

    Ryan P. Trombetta

  2. Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA

    Emma K. Knapp & Hani A. Awad

  3. Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA

    Hani A. Awad

Authors
  1. Ryan P. Trombetta
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  2. Emma K. Knapp
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  3. Hani A. Awad
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Corresponding author

Correspondence to Hani A. Awad .

Editor information

Editors and Affiliations

  1. Department of Orthopaedic Surgery and Cell Biology, Duke Cellular, Developmental, and Genome Laboratories, Duke University School of Medicine, Durham, USA

    Matthew J. Hilton

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Trombetta, R.P., Knapp, E.K., Awad, H.A. (2021). A Mouse Femoral Ostectomy Model to Assess Bone Graft Substitutes. In: Hilton, M.J. (eds) Skeletal Development and Repair. Methods in Molecular Biology, vol 2230. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1028-2_5

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  • DOI: https://doi.org/10.1007/978-1-0716-1028-2_5

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1027-5

  • Online ISBN: 978-1-0716-1028-2

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