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

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

Abstract

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.

Abbreviations

BMPs

Bone morphogenetic proteins

Cbfa1

Core binding factor 1

CDMP-1

Cartilage-derived morphogenetic protein-1

CSD

Critical size defect

CXCR-4

Receptor for SDF-1

ECM

Extracellular matrix

FDA

Food and Drug Administration

FGFs

Fibroblast growth factors

GDF-5

Growth/differentiation factor 5

GF-11

Skeletal growth factor

HA

Hydroxyapatite

HDDA

1,6 Hexanediol diacrylate

HIFα

Hypoxia-induced factor alpha

IGF

Insulin-like growth factor

IHH

Indian hedgehog

IL

Interleukin

M-CSF

Macrophage colony stimulating factor

MMP

Metalloproteinase

MRI

Magnetic resonance imaging

MSCs

Mesenchymal stem cells

OPG

Osteoprotegerin

PDGF

Platelet-derived growth factor

PTHrP

Parathyroid hormone related peptide

RANKL

Receptor activator of nuclear factor kappa-B ligand

SDF-1

Stromal cell-derived factor-1

SHH

Sonic hedgehog

TCP

Tricalcium phosphate

TGFβ

Transforming growth factor beta

TNF-α

Tumor necrosis factor-alpha

VEGF

Vascular endothelial growth factor

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Jo Ann Cameron
    • 1
  • 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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