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Title: Hydrogel biocomposites for bone tissue regeneration
Author: Nkhwa, Shathani
ISNI:       0000 0004 7656 2384
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2016
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The biomedical burden of large bone defects caused by trauma, infection, tumours or inherent genetic disorders remains a clinical challenge. Autologous bone or autograft continue to be the clinical “gold standard” for most effective bone regeneration, which is limited by bone supply and donor site morbidity. Thus, current synthetic substitutes need to be improved to match the performance of autografts. Bone tissue engineering is an attractive approach for regeneration of bone especially in relation to critical sized defects and a scaffold with osteoinductive properties and adequate mechanical properties is expected to enhance bone formation. The aim of the study is to enhance bone regeneration and the concept is based on adequate design of three dimensional scaffolds that mimic the structure of bone, which by virtue of its inherent properties have the ability to localise fluids rich in osteoinductive factors. The hydrogels and composites were all synthesized with a base polymer polyvinyl alcohol (PVA), which is both robust, biocompatible and FDA approved material. Facile methods of crosslinking such as air-drying and freeze-drying which introduces a level of porosity in the materials due to the lyophilisation process, were used to render the hydrogels insoluble, and conditions optimised to yield materials with properties suitable for soft bone tissue applications. PVA hydrogels were synthesized and characterised, results indicated that water uptake, glass transition and tensile strength were influenced by varying concentration of the polymer solution. A new type of dual network (DN) hydrogel composed of PVA and alginate was developed and optimised. Characterisations by spectral and thermal analysis, confirmed incorporation of alginate within the PVA network structure. Hydration dynamics and tensile properties, indicated that DN formed from a PVA base crosslinked by two freeze thaw cycles yielded tough hydrogels with controlled swelling, making them suitable for soft tissue applications as well as the diversity of being further incorporated with ceramic fillers for the development of bone composite substitutes. Incorporation of bioglass® 45S5 within the polymeric network structure of the DN led to enhancement of the mechanical properties such as tensile strength and fracture toughness as well as imparting bioactivity within the hydrogel composites, which was demonstrated by the development of hydroxy carbonated apatite on the surface and internal structure of the composites, this result was further corroborated by the increase in tensile strength and stiffness of the composites when placed in simulated body fluid over a period of 28 days. The second group of hydrogel composites was composed of a PVA fluid phase and calcium metaphosphate (CMP) ceramic phase, crosslinked by freeze drying. This hydrogel composite was developed to have a high mineral content with properties that closely resemble the properties of bone based on its inorganic/organic nanocomposite structure. Compression and water uptake behaviour of the composite could be modulated by varying concentration of PVA and the composite system properties were found to be suitable and lie within the range values for trabecular bone. In vitro cell culture tests were used to assess biocompatibility and the selected scaffolds were seeded with human osteoblast cells (HOB) and were evaluated by MTT, and live dead staining. All the systems were found to be biocompatible and cells were able to attach and proliferate within the scaffolds. Biofunctionality was assessed on the scaffolds which all showed a peak increase in alkaline phosphatase activity (ALP) at day 14, an important bone marker indicating osteoblast differentiation.
Supervisor: Deb, Sanjukta Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available