Influence of the mechanical environment upon the healing of segmental bone defects in the rat femur
Glatt, Vaida (2009) Influence of the mechanical environment upon the healing of segmental bone defects in the rat femur. PhD thesis, University of Warwick.
Official URL: http://webcat.warwick.ac.uk/record=b2487946~S15
Loss of large segments of bone creates critical size defects (CSDs). These fail to heal
spontaneously and present major clinical challenges to orthopaedic surgeons. The
research described in this thesis is based upon the hypothesis that the healing of
CSDs is responsive to the ambient mechanical environment, and can be accelerated
by mechanical modulation. This hypothesis was tested in rat, femoral CSDs treated
with recombinant, human, bone morphogenetic protein-2.
For this study I designed novel external fixators allowing experimental control over
the local mechanical environment. These were characterised by extensive
mechanical testing prior to evaluation in the rat model.
Low stiffness fixators induced callus formation 9 days after surgery, whereas rigid
fixation delayed it until 2 weeks. All defects were radiologically bridged after 3
weeks. Rats were euthanised after 8 weeks and the defects evaluated by a battery of
imaging, mechanical and histological tests. All confirmed the superiority of the
lowest stiffness fixators.
Based upon these data, I hypothesised that healing would be improved by imposing
low stiffness for the first two weeks of healing, followed by high stiffness for the
remaining six weeks. The experimental data confirm that this regimen dramatically
accelerated callus formation and maturation, and induced faster remodelling of
endosteal and periosteal callus. This was associated with higher failure strength,
fewer trabeculae, decreased callus size and thicker and more uniform distribution of
new cortical bone. Histologically it was not possible to detect cartilage within the
defects prior to the appearance of bone, suggesting that healing either does not occur
through endochondral ossification, or that this process is very rapid.
These data confirm that the healing of CSDs is highly responsive to the ambient
mechanical environment, allowing the rate and quality of healing to be manipulated.
This information will help develop more efficient ways to heal CSD clinically.
|Item Type:||Thesis or Dissertation (PhD)|
|Subjects:||Q Science > QL Zoology|
|Library of Congress Subject Headings (LCSH):||Bone regeneration, Rats, External skeletal fixation (Surgery)|
|Official Date:||August 2009|
|Institution:||University of Warwick|
|Theses Department:||Warwick Medical School|
|Supervisor(s)/Advisor:||Evans, Christopher H. (Christopher Howard), 1950- ; Griffin, Damian R.|
|Sponsors:||AO foundation (S-08-42G)|
|Extent:||175 leaves : ill., charts|
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