Employing the Biology of Successful Fracture Repair to Heal Critical Size Bone Defects

  • Jo Ann CameronEmail author
  • Derek J. Milner
  • Jung Seok Lee
  • Jianjun Cheng
  • Nicholas X. Fang
  • Iwona M. Jasiuk
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 367)


Bone has the natural ability to remodel and repair. Fractures and small noncritical size bone defects undergo regenerative healing via coordinated concurrent development of skeletal and vascular elements in a soft cartilage callus environment. Within this environment bone regeneration recapitulates many of the same cellular and molecular mechanisms that form embryonic bone. Angiogenesis is intimately involved with embryonic bone formation and with both endochondral and intramembranous bone formation in differentiated bone. During bone regeneration osteogenic cells are first associated with vascular tissue in the adjacent periosteal space or the adjacent injured marrow cavity that houses endosteal blood vessels. Critical size bone defects cannot heal without the assistance of therapeutic aids or materials designed to encourage bone regeneration. We discuss the prospects for using synthetic hydrogels in a bioengineering approach to repair critical size bone defects. Hydrogel scaffolds can be designed and fabricated to potentially trigger the same bone morphogenetic cascade that heals bone fractures and noncritical size defects naturally. Lastly, we introduce adult Xenopus laevis hind limb as a novel small animal model system for bone regeneration research. Xenopus hind limbs have been used successfully to screen promising scaffolds designed to heal critical size bone defects.


Vascular Endothelial Growth Factor Bone Regeneration Endochondral Ossification Hypertrophic Chondrocytes Fracture Repair 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Bone morphogenetic proteins


Core binding factor 1


Cartilage-derived morphogenetic protein-1


Critical size defect


Receptor for SDF-1


Extracellular matrix


Food and Drug Administration


Fibroblast growth factors


Growth/differentiation factor 5


Skeletal growth factor




1,6 Hexanediol diacrylate


Hypoxia-induced factor alpha


Insulin-like growth factor


Indian hedgehog




Macrophage colony stimulating factor




Magnetic resonance imaging


Mesenchymal stem cells




Platelet-derived growth factor


Parathyroid hormone related peptide


Receptor activator of nuclear factor kappa-B ligand


Stromal cell-derived factor-1


Sonic hedgehog


Tricalcium phosphate


Transforming growth factor beta


Tumor necrosis factor-alpha


Vascular endothelial growth factor



We gratefully acknowledge support of the National Science Foundation (IJ, NF, JC). A special thank you is due to Heidi Richter of Precision Graphics, Champaign IL, for creating the illustrations for Figs. 1 and 2.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Jo Ann Cameron
    • 1
    Email author
  • Derek J. Milner
    • 1
  • Jung Seok Lee
    • 2
  • Jianjun Cheng
    • 2
  • Nicholas X. Fang
    • 3
  • Iwona M. Jasiuk
    • 4
  1. 1.Department of Cell and Developmental BiologyInstitute for Genomic Biology, University of Illinois at Urbana-ChampaignUrbanaUSA
  2. 2.Department of Materials Science and EngineeringInstitute for Genomic Biology, University of Illinois at Urbana-ChampaignUrbanaUSA
  3. 3.Department of Mechanical EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  4. 4.Department of Mechanical Science and EngineeringInstitute for Genomic Biology, University of Illinois at Urbana-ChampaignUrbanaUSA

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