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

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New Perspectives in Regeneration

Part of the book series: Current Topics in Microbiology and Immunology ((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.

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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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Acknowledgments

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.

Author information

Authors and Affiliations

  1. Department of Cell and Developmental Biology, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Jo Ann Cameron & Derek J. Milner

  2. Department of Materials Science and Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Jung Seok Lee & Jianjun Cheng

  3. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139-4307, USA

    Nicholas X. Fang

  4. Department of Mechanical Science and Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Iwona M. Jasiuk

Authors
  1. Jo Ann Cameron
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  2. Derek J. Milner
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  3. Jung Seok Lee
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  4. Jianjun Cheng
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  5. Nicholas X. Fang
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  6. Iwona M. Jasiuk
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Corresponding author

Correspondence to Jo Ann Cameron .

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Editors and Affiliations

  1. Wistar Institute, Spruce Street 3601, Philadelphia, 19104, Pennsylvania, USA

    Ellen Heber-Katz

  2. Center for Regenerative Biology and, Medicine, Indiana University, North Blackford Street 402, Indianapolis, 46202, Indiana, USA

    David L. Stocum

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Cameron, J.A., Milner, D.J., Lee, J.S., Cheng, J., Fang, N.X., Jasiuk, I.M. (2012). Employing the Biology of Successful Fracture Repair to Heal Critical Size Bone Defects. In: Heber-Katz, E., Stocum, D. (eds) New Perspectives in Regeneration. Current Topics in Microbiology and Immunology, vol 367. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2012_291

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