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The Anabolic - Anti-catabolic Paradigm of Augmenting Skeletal Regeneration: A Bone Quality Perspective Preview this item
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The Anabolic - Anti-catabolic Paradigm of Augmenting Skeletal Regeneration: A Bone Quality Perspective

Author: Mathavan, Neashan
Publisher: Department of Biomedical Engineering, Lund university 2017-05-08
Edition/Format:   Downloadable archival material : English
Summary:
Successful fracture repair is a complex series of coordinated processes leading to regeneration of new bone to bridge the fracture site, remodelling of the newly formed bone and restoration of skeletal function. Disruption of these processes occurs in approximately 10% of all fractures and leads to delayed or failed healing requiring surgical interventions, increased complication rates, prolonged rehabilitation and  Read more...
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Genre/Form: thesis/doccomp
info:eu-repo/semantics/doctoralThesis
text
Document Type: Archival Material
All Authors / Contributors: Mathavan, Neashan
OCLC Number: 1048594889
Language Note: English
Notes: application/pdf

Abstract:

Successful fracture repair is a complex series of coordinated processes leading to regeneration of new bone to bridge the fracture site, remodelling of the newly formed bone and restoration of skeletal function. Disruption of these processes occurs in approximately 10% of all fractures and leads to delayed or failed healing requiring surgical interventions, increased complication rates, prolonged rehabilitation and high morbidity. In instances of fracture non-unions, the healing process could be augmented through the use of potent anabolic agents such as bone morphogenetic proteins (BMPs) or anti-catabolic agents such as the bisphosphonate Zoledronate (ZA). Use of BMP alone or synergistically combined with ZA is known to substantially increase bone formation and enhance fracture healing. Such interventions necessitate an understanding of both the mechanisms that contribute to impaired or delayed healing and the influence of the administered treatments in countering these processes. This thesis presents a multi-scale characterization of the synergistic efficacy of BMP (specifically BMP-7) and ZA using a femoral open-fracture rodent model of recalcitrant repair. The aim is to characterize the quality of the bone regenerated in response to these specific interventions that stimulate bone formation and inhibit bone resorption. Bone quality is assessed using conventional radiography, ex vivo and in vivo micro-computed tomography (μCT), three-point bending mechanical testing, histology, Fourier-transform infrared (FTIR) spectroscopy, synchrotron-based small-/wide-angle X-ray scattering (SAXS/WAXS) and positron emission tomography (PET). In the first study of this thesis, the synergistic efficacy of allograft in combination with BMP-7 and ZA is investigated. Evidence is presented for an enhanced synergistic efficacy with callus volumes and peak force measures of mechanical strength doubling relative to the gold standard of autograft treatment. Subsequently, an extensive an

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