A poly (octanediol citrate)/gallium-containing bioglass composite for bone tissue regeneration / Ehsan Zeimaran
Bone can be affected by osteosarcomae requiring surgical excision of the tumor as part of a treatment regime. Complete removal of cancerous cells is difficult and conventionally requires the removal of a margin of safety around the tumor to offer improved patient prognosis. Gallium has been shown...
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Format: | Thesis |
Published: |
2016
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Online Access: | http://studentsrepo.um.edu.my/9878/1/Ehsan_Zeimaran.pdf http://studentsrepo.um.edu.my/9878/5/Ehsan_Zeimaran_%2D_Thesis.pdf http://studentsrepo.um.edu.my/9878/ |
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Summary: | Bone can be affected by osteosarcomae requiring surgical excision of the tumor as part
of a treatment regime. Complete removal of cancerous cells is difficult and
conventionally requires the removal of a margin of safety around the tumor to offer
improved patient prognosis. Gallium has been shown to be clinically effective, both
against bone resorption and for the treatment of cancer-related hypercalcemia. This
work considers a novel series of composite scaffolds based on poly (octanediol citrate)
(POC) impregnated with a gallium-containing bioactive glass (0.48SiO2-0.12CaO-
0.32ZnO-0.08Ga2O3, molar fraction) microparticles for possible incorporation into
bone following tumor removal. The objective of this research was to fabricate and
characterize these scaffolds and subsequently report on their mechanical, thermal,
structural and biological properties. The porous microcomposite scaffolds, with
various concentrations of bioactive glass (10, 20, 30 wt%) incorporated, were
fabricated using a salt leaching technique. The scaffolds exhibited compression moduli
in the range of 0.3-7 MPa. The addition of bioactive glass increased the mechanical
properties even though porosity increased. Furthermore, increasing the concentration
of bioactive glass had a significant influence on glass transition temperature from 2.5
°C for the pure polymer to approximately 25 °C for 30 % bioactive glass-containing
composite. The ion release study revealed that composites containing 30 % bioactive
glass had the highest ion release ratio after 28 days of soaking in phosphate buffered
saline (PBS). The interaction of the bioactive glass phase with POC led to the
formation of additional ionic crosslinks, aside from the covalent crosslinks, which
further resulted in increased stiffness and decreased weight loss. The antibacterial
activity of these scaffolds was investigated against both Gram-positive
(Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria in vitro. The
ability of the scaffolds to release ions and the subsequent ingress of these ions into hard tissue was evaluated using a bovine bone model. Scaffolds containing bioactive
glass exhibited antibacterial activity which increased with higher bioactive glass loads;
viable cells decreased to about 20 % for the composite scaffold containing 30 %
bioactive glass. The Ga3+ release rate increased as a function of time and Zn2+ was
shown to incorporate into the surrounding bone. The effect of composite scaffolds on
growth and osteogenic differentiation of human osteoblast-like cells and human bone
marrow-derived mesenchymal stem cells (hBMSCs) was investigated. The osteoblastlike
cells were well attached and growth on composites and collagen synthesis
increased particularly with the 10 % bioactive glass concentration. All the scaffolds
were able to support the growth of hBMSCs and guide their osteogenic differentiation
without osteogenic media stimulation. The expression of bone-associated genes
(collagen I, osteonectin and osteocalcin, bone morphogenetic protein 2, runt-related
transcription factor 2) was significantly increased by a culture time for of up to 2
weeks, particularly for the composite scaffolds loaded with 10 % bioactive glass. The
composite scaffolds significantly stimulated alkaline phosphatase (ALP) activity
compared to the pure POC scaffolds. Cellular mineralization of the secreted
extracellular matrix illustrated a higher calcium level on the composites than pure
POC, and increased with culture time. These results suggest that composite scaffolds
of POC and a bioactive glass doped with therapeutic elements provides favourable
conditions for osteogenic differentiation of hBMSCs and can potentially be used to
induce bone healing and regeneration.
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