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The development of bone regeneration materials to support new bone formation is an active field of research. This report describes the development and characterization of a novel composite scaffold made of a chitosan-alginate co-polymer hydrogel matrix and eggshell (ES) particles. Scaffolds with ES particles or with nanotextured ES (NTES) particles following treatment with phosphoric acid were compared to scaffolds without particles. The scaffolds with particles exhibited a higher porosity and a larger median pore size. Their mechanical strength remained low, but both scaffold types were more resistant to deformation following compression than the scaffolds without particles. The osteogenic potential of the scaffolds was then evaluated with human bone-marrow derived mesenchymal stem cells (MSCs) from four different donors. Results showed that the inclusion of ES or NTES particles significantly increased MSC adherence and viability, as well as alkaline phosphatase activity in the scaffolds. A change of cell morphology and a small, although not statistically significant, increase of osteogenic protein expression (RUNX2 and osteopontin) were also observed at later time points (days 14 and 21). Overall, this research highlights the potential of ES for bone regeneration applications, opening the door for a high-value repurposing of a current industrial waste product.

The number of clinical procedures performed in the USA using bone graft substitutes was estimated at 1.1 million in 2010 and is projected to reach 1.3 million in 2015. This increasing demand for bone graft substitutes is a result of an ever-ageing population coupled with recent reports in the clinical literature of concerns regarding the safety of allograft and recombinant bone morphogenetic proteins such as rh- BMP-2 and the supply of autograft, which has led to an increased clinical interest in synthetic alternatives to allograft; autograft; and recombinant growth factors. One such synthetic material is silicate-substituted hydroxyapatite (SiCaP). Mechanical testing revealed SiCaP to have similar mechanical behaviour to morcellised cancellous bone. In computated spinal and hip models the simulated stresses in SiCaP were determined to be low when in situ, indicating a stressshielding effect from the implanted metalwork and surrounding bone. We also found an inverse relationship between porosity and Young's Modulus. Our results indicated that the strut-porosity of a material substrate should be increased to maximise the potential for formation of a precursor to bone-like apatite after implantation in osseous defects and further confirmed previous reports that betatricalcium phosphate is less bioactive than hydroxyapatite. We demonstrated a direct link between the amount of strut-porosity and the osteoinductivity of SiCaP. We learned that adding a resorbable carrier phase did not impair the osteoinductive potential of SiCaP, suggesting that osteoinductivity is not necessarily determined in the first 24-48 hours post implantation. Most notably from our studies we determined that the osteoinductivity of SiCaP correlated with its performance in orthotopic defects. Our research confirmed our hypothesis that modifying the micron-scale physical structure of a hierarchical porous SiCaP based biomaterial influences its functional performance in vitro and such modifications can be applied to improve its performance outcomes in ectopic and orthotopic treatment sites in vivo.

Strong, durable terminal regions that can be easily handled by researchers and surgeons are a key factor in the successful fabrication of tissue engineered blood vessels (TEBV). The goal of this study was to fabricate and characterize electrospun cuffs made of poly-caprolactone (PCL) combined with gelatin that reinforce and strengthen each end of cell-derived vascular tissue tubes. PCL is ideal for vascular tissue engineering applications due to its mechanical properties; however, PCL alone does not support cell attachment. Therefore, we introduced gelatin, a natural matrix-derived protein, into the electrospun material to promote cell adhesion. This work compared the effects of two different methods for introducing gelatin into the PCL materials: gelatin coating and gelatin co-electrospinning. Porosity, pore size, fiber diameter, and mechanical properties of the electrospun materials were measured in order to compare the features of gelatin PCL composites that have the greatest impact on cellular infiltration. Porosity was quantified by liquid intrusion, fiber diameter and pore size were measured using scanning electron microscopy, and tensile mechanical testing was used to evaluate strength, elastic modulus, and extensibility. Attachment and outgrowth of smooth muscle cells onto cuff materials was measured to evaluate differences in cellular interactions between materials by using a metabolic attachment assay and a cellular outgrowth assay. Finally, cuffs were fused with totally cell-derived TEBV and the integration of cuffs with tissue was evaluated by longitudinal pull to failure testing and histological analysis. Overall, these cuffs were shown to be able to add length and increase strength to the ends of TEBV for tube cannulation and manipulation during in vitro culture. In particular, PCL:gelatin cospun cuffs were shown to improve cellular attachment and cuff fusion compared to pure PCL cuffs, while still increasing the strength of the TEBV terminal ends.

Poly(L-lactide) (PLLA) is a well-recognised bioresorbable polymer known to degrade after 1.5 to 5 years by hydrolysis. For certain medical device or drug delivery applications, it would be desirable to reduce this degradation time as strategies for tailoring degradation and drug release rates remain limited. This work aimed to examine a consistent series of polymers based on a large block of PLLA and small quantities of hydrophilic poly(ethylene glycol) (PEG) initiator. The polymers had PLLA number average molecular weight (Mn) values ranging between about 60 kDa and 200 kDa and PEG Mns ranging between 550 Da and 5000 Da giving very low PEG wt% values ranging between 0.1 and 1.5 wt%. There are currently no studies which consider high molecular weight PLLA polymers with small quantities of PEG for potential use in structural implants. Furthermore, reports in the literature do not consider the individual effects of PEG addition and PEG and PLLA lengths. The focus of this project was on the impact of processing, hydrolytic degradation and drug release on the morphological aspects of the materials. The materials were thoroughly characterised in their as-synthesised and processed forms. The assynthesised polymers were semi-crystalline and retained the unit cell of PLLA. The glass transition temperature (Tg) was significantly reduced by PEG functionalisation. After injection moulding, nuclear magnetic resonance (NMR) indicated that the PEG component was still present. The Mn of the PEG functionalised samples decreased by approximately two-fold compared with the as-synthesised materials while the PLLA control polymers, processed beyond 200 °C, were more affected as the processing temperature was increased. The degradation properties of the materials were considered. The processed materials were submerged in phosphate buffered saline (PBS) (pH = 7.4) at 37 °C over an 8-month degradation study. During hydrolytic degradation, PEG functionalisation resulted in an increased water uptake. Mass loss began in all polymers when the Mn fell below a threshold of about 20 kDa. In the PEG functionalised samples, the degree of crystallinity increased with time, facilitated by plasticisation from PEG and the increased water content. The molecular degradation rate, k for the PEG-functionalised polymers was dependent on the presence of PEG functionalisation but was little affected by PEG length or PLLA length in the ranges studied. The time taken to reach the critical Mn, and hence the time for mass loss to begin, therefore depended on both the initial Mn and the presence or absence of PEG functionalisation. In the presence of PEG, k, was dramatically enhanced: k for PEG-functionalised polymers fell in the range of 6 x $10^{-4}$ $h^{-1}$ to 1 x $10^{-3}$ $h^{-1}$, as compared with that of the PLLA control of 2.9 x $10^{-5}$ $h^{-1}$. The mechanism of drug release from an analogous series of polymers was investigated. Propranolol. HCl was selected as a model drug for the drug release studies due to its thermal stability and solubility in PBS. Drug loading of propranolol.HCl was achieved by mixing the polymer and drug then injection moulding. A second method of drug incorporation using supercritical CO2 to load propranolol into as-synthesised polymer granules before injection moulding was examined for comparison. The materials processed through injection moulding showed that while drug crystals were present at the surface and in the polymer matrix, a level of drug solubility was also achieved in the PEG-functionalised polymers whereas the PLLA control showed no signs of polymer-drug interaction and only a distribution of drug crystals confined to the surface. The presence of drug crystals on the surface of the PLLA control resulted in the instant dissolution of propranolol.HCl and gave a burst release compared with an initial burst release in the PEG-functionalised polymers followed by a gradual release of the drug. This initial burst release was eliminated from the profile of the samples processed via supercritical CO2. The amorphous dispersion of the drug in the matrix gave a slow, sustained release throughout the duration of the drug release study. The results in this thesis have elucidated the intricate mechanisms of degradation and drug release from PEG-functionalised PLLA polymers. The overall outcome shows new ways of controlling the degradation and drug release rates of already medically established poly(-hydroxy acid) polymers extending their potential for use within temporary structural implants.

A method for synthesis of polyol from soybean oils has been developed using a two-step continuous route. The method involved epoxidation of soy oils and subsequent hydroxylation to produce polyols. The epoxidation was carried out using biphasic catalytic system (Na2WO4 / H2WO4) with 50 % hydrogen peroxide. The major advantages of this approach are that; the use of biphasic system allows easy separation of the products, does not require any chlorinated solvent (more environment-friendly), can be conducted at room temperature and requires relatively lower catalyst load. The functional groups of soy-polyol were identified using FTIR and NMR spectroscopy. This confirmed complete disappearance of the signature of the C=C double bonds, formation of the epoxy linkage following the epoxidation process, its further disappearance and incorporation of hydroxyl groups after the hydroxylation process. The hydroxyl number, hydroxyl functionality, acid value, iodine value and viscosity of the synthesized polyols were also determined.