Ghanbar, H; (2015) Fabrication of Porous Particulate Scaffolds Using Electrohydrodynamics and Thermally Induced Phase Separation for Biomedical Engineering Applications. Doctoral thesis , UCL (University College London).

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Abstract

Abstract The availability of forming technologies able to mass produce porous polymeric microspheres with diameters ranging from 150 to 300 µm is significant for some biomedical applications where tissue augmentation is required. Moreover, appropriate assembly of microspheres into scaffold is an important challenge to enable direct usage of the scaffolds in chronic wound treatments. In this thesis, the feasibility of the electrohydrodynamic (EHD) atomization forming combined with thermally induced phase separation (TIPS) for production of such drug delivery carriers, using biodegradable polymers (poly (lactic-co-glycolic acid) and poly (ε-caprolactone)) was explored. To achieve this goal, the first part of the thesis describes comprehensive parametric mode mappings of the diameter distribution profiles of the microspheres obtained over a broad range of key processing parameters and correlating this with the material parameters of five different polymer solutions of various concentrations. Based on the mode mapping studies, combination of poly (lactic-co-glycolic acid) (PLGA) and dimethyl carbonate (DMC) was found to be ideal for generating the microspheres within the targeted diameter range (150-300 µm). Surface porosity was achieved by electrospraying the PLGA/DMC solution and collecting the required size of the polymer particles in liquid nitrogen followed by lyophilisation. The second aim of this thesis was the in vitro release studies. In order to conduct this part of the study, the single needle and co-axial needle EHD/TIPS methods were used to generate the dye loaded microspheres of the required size. Three different dyes (Erythrosin B, Pyronin B and Reichardt’s) were selected as model drugs to be encapsulated separately in the produced microspheres. The purpose of selecting three different dyes was to have a prediction on the release profile of immunosuppressants with high toxicity used for treatment of chronic wounds such as perianal fistulae. The in vitro release studies showed that the dyes were released with the high initial burst release phase in 3.5-5.5 hours followed by a long and sustained release phase (in 30-360 hours). Systematic investigations using different external stimuli such as temperature, fresh media and sonication exposure was also carried out to observe their effects on the release rate of the encapsulated materials from the produced microspheres. The results acquired from the in vitro release studies showed that the temperature variations and the sonication with different frequencies have significant effects on the release rates of the incorporated materials from the polymeric microspheres. Moreover, the results demonstrated that the products collected by the single needle EHD/TIPS method is more capable of releasing the payload in a longer period of time with more sustained manner compared to their counterparts obtained from the co-axial needle method.

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