Inducing Skeletal Repair by Mechanical Stimulation

Summary

Principal Investigator: Elise Morgan
Affiliation: Boston University
Country: USA
Abstract: Mechanical cues play a critical role in the development and maintenance of articular cartilage as well as in skeletal repair. Defining relationships between the mechanical environment and key cell and molecular events involved in cartilage formation has direct application in developing novel, regenerative approaches to articular cartilage repair that produce tissue with the requisite mechanical function. However, these relationships are not well understood. The long term goal of this research is to define the cellular, molecular and mechano-regulatory processes involved in the postnatal development of hyaline cartilage. Toward this end, we have developed an in vivo rat model of skeletal repair in which a cyclic bending motion applied daily to a mid-diaphyseal osteotomy gap results in robust cartilage formation within and surrounding the gap. Importantly, this newly generated cartilage has many characteristics of hyaline cartilage, as opposed to the fibrous cartilage typically formed during bone repair. The hypothesis of the work proposed here is that functional hyaline cartilage can be formed postnatally via mechano-regulated skeletal repair processes. Three specific aims are proposed. Aim #1 will characterize the mechanical function of the newly generated cartilage. Nanoindentation, osmotic loading, and biochemical assays will be used to compare the biphasic material properties, swelling behavior, and fixed charge density of the newly generated cartilage to those of native articular cartilage. Aim #2 will define the spatiotemporal patterns of gene expression and tissue structure induced by the mechanical stimulation using in situ hybridization, immunohistochemistry and histomorphometry. Aim #3 will define the local mechanical environment induced during the mechanical stimulation via finite element analyses that use experimentally determined tissue material properties and geometry as input. Experimental validation of the finite element results will be performed. Integration of results from Aims #2 and #3 will allow direct assessment of correspondence between local mechanical cues and cell and molecular responses. The collective findings will in turn identify candidate pathways that can be targeted in future studies of articular cartilage repair and regeneration. Taken together, these experiments represent the first steps in defining the mechano-regulated processes involved in the postnatal formation of functional hyaline cartilage.
Funding Period: 2005-09-26 - 2009-08-31
more information: NIH RePORT

Top Publications

  1. pmc Assessment of contrast-enhanced computed tomography for imaging of cartilage during fracture healing
    Lauren N M Hayward
    Department of Biomedical Engineering, Boston University, Boston, MA, USA
    J Orthop Res 31:567-73. 2013
  2. pmc MRT letter: Contrast-enhanced computed tomographic imaging of soft callus formation in fracture healing
    Lauren Nicole Miller Hayward
    Department of Mechanical Engineering, Boston University, Boston, Massachusetts
    Microsc Res Tech 75:7-14. 2012
  3. pmc Correlations between local strains and tissue phenotypes in an experimental model of skeletal healing
    Elise F Morgan
    Orthopaedic and Developmental Biomechanics Laboratory, Department of Mechanical Engineering, Boston University, Boston, MA 02215, USA
    J Biomech 43:2418-24. 2010
  4. pmc Assessment of a mechano-regulation theory of skeletal tissue differentiation in an in vivo model of mechanically induced cartilage formation
    Lauren Nicole Miller Hayward
    Department of Mechanical Engineering, Boston University, 110 Cummington Street, Boston, MA 02215, USA
    Biomech Model Mechanobiol 8:447-55. 2009
  5. pmc Use of microindentation to characterize the mechanical properties of articular cartilage: comparison of biphasic material properties across length scales
    G J Miller
    Department of Mechanical Engineering, Boston University, Boston, MA, USA
    Osteoarthritis Cartilage 18:1051-7. 2010
  6. pmc Transcriptional profiling and biochemical analysis of mechanically induced cartilaginous tissues in a rat model
    Kristy T Salisbury Palomares
    Boston University and Boston University School of Medicine, Boston, Massachusetts, USA
    Arthritis Rheum 62:1108-18. 2010
  7. pmc Mechanical stimulation alters tissue differentiation and molecular expression during bone healing
    Kristy T Salisbury Palomares
    Department of Mechanical Engineering, Boston University, Boston, Massachusetts 02215, USA
    J Orthop Res 27:1123-32. 2009
  8. pmc Micro-computed tomography assessment of fracture healing: relationships among callus structure, composition, and mechanical function
    Elise F Morgan
    Orthopaedic and Developmental Biomechanics Laboratory, Department of Mechanical Engineering, Boston University, Boston, MA 02215, USA
    Bone 44:335-44. 2009
  9. pmc Measurement of fracture callus material properties via nanoindentation
    P L Leong
    Department of Aerospace and Mechanical Engineering, Boston University, 110 Cummington Street, Boston, MA 02215, USA
    Acta Biomater 4:1569-75. 2008
  10. pmc Mechanotransduction and fracture repair
    Elise F Morgan
    Department of Aerospace and Mechanical Engineering, Boston University, 110 Cummington Street, Boston, MA 02215, USA
    J Bone Joint Surg Am 90:25-30. 2008

Scientific Experts

Detail Information

Publications11

  1. pmc Assessment of contrast-enhanced computed tomography for imaging of cartilage during fracture healing
    Lauren N M Hayward
    Department of Biomedical Engineering, Boston University, Boston, MA, USA
    J Orthop Res 31:567-73. 2013
    ..The non-destructive nature of this method would allow subsequent analyses, such as mechanical testing, to be performed on the callus, thus enabling higher-throughput, comprehensive investigations of bone healing...
  2. pmc MRT letter: Contrast-enhanced computed tomographic imaging of soft callus formation in fracture healing
    Lauren Nicole Miller Hayward
    Department of Mechanical Engineering, Boston University, Boston, Massachusetts
    Microsc Res Tech 75:7-14. 2012
    ....
  3. pmc Correlations between local strains and tissue phenotypes in an experimental model of skeletal healing
    Elise F Morgan
    Orthopaedic and Developmental Biomechanics Laboratory, Department of Mechanical Engineering, Boston University, Boston, MA 02215, USA
    J Biomech 43:2418-24. 2010
    ..These results indicate that shear strain may be an important regulator of tissue fate during skeletal healing...
  4. pmc Assessment of a mechano-regulation theory of skeletal tissue differentiation in an in vivo model of mechanically induced cartilage formation
    Lauren Nicole Miller Hayward
    Department of Mechanical Engineering, Boston University, 110 Cummington Street, Boston, MA 02215, USA
    Biomech Model Mechanobiol 8:447-55. 2009
    ..The results support the concept that interstitial fluid velocity and tissue shear strain are key mechanical stimuli for the differentiation of skeletal tissues...
  5. pmc Use of microindentation to characterize the mechanical properties of articular cartilage: comparison of biphasic material properties across length scales
    G J Miller
    Department of Mechanical Engineering, Boston University, Boston, MA, USA
    Osteoarthritis Cartilage 18:1051-7. 2010
    ..Direct comparisons of the biphasic properties (E, k and nu) determined using microindentation were made to those determined on the same specimens using standard macroscale testing techniques...
  6. pmc Transcriptional profiling and biochemical analysis of mechanically induced cartilaginous tissues in a rat model
    Kristy T Salisbury Palomares
    Boston University and Boston University School of Medicine, Boston, Massachusetts, USA
    Arthritis Rheum 62:1108-18. 2010
    ..To characterize patterns of molecular expression that lead to cartilage formation in vivo in a postnatal setting, by profiling messenger RNA expression across the time course of mechanically induced chondrogenesis...
  7. pmc Mechanical stimulation alters tissue differentiation and molecular expression during bone healing
    Kristy T Salisbury Palomares
    Department of Mechanical Engineering, Boston University, Boston, Massachusetts 02215, USA
    J Orthop Res 27:1123-32. 2009
    ..These findings illustrate that mechanical cues can selectively modulate osteogenesis and chondrogenesis in vivo, and suggest a potential basis for treatment regimens for injured or diseased cartilaginous tissues...
  8. pmc Micro-computed tomography assessment of fracture healing: relationships among callus structure, composition, and mechanical function
    Elise F Morgan
    Orthopaedic and Developmental Biomechanics Laboratory, Department of Mechanical Engineering, Boston University, Boston, MA 02215, USA
    Bone 44:335-44. 2009
    ..These findings form the basis for developing non-invasive assessments of fracture healing and for identifying biological and biomechanical mechanisms that lead to impaired or enhanced healing...
  9. pmc Measurement of fracture callus material properties via nanoindentation
    P L Leong
    Department of Aerospace and Mechanical Engineering, Boston University, 110 Cummington Street, Boston, MA 02215, USA
    Acta Biomater 4:1569-75. 2008
    ..004). These results demonstrate the usefulness of nanoindentation in characterizing the elastic properties of the heterogeneous mixture of tissues present in bone fracture callus...
  10. pmc Mechanotransduction and fracture repair
    Elise F Morgan
    Department of Aerospace and Mechanical Engineering, Boston University, 110 Cummington Street, Boston, MA 02215, USA
    J Bone Joint Surg Am 90:25-30. 2008
    ..A better understanding of the effect of mechanical factors on bone-healing will also benefit the study of healing, regeneration, and engineering of other skeletal tissues...