Current biomedical applications are focused towards solving more challenging problems with sustainable and economic solutions. Drug delivery systems, tissue engineered scaffolds and diagnostic devices are major areas of biomedical systems which require more efficient and benign fabrication and processing. Design of above mentioned systems involves three key components; biomaterial selection, structure and nutrient supply. Various factors such as, biocompatibility, degradation, toxicity, mechanical properties, need to be considered before biomaterial selection for specific application. Polymers are most widely used for biomedical applications due to their ability to tailor properties for specific requirements. Structured patterns are mandatory in most of the biomedical systems such as core-shell structure for drug delivery, porous scaffolds for tissue engineering and microchannels for microfluidics based devices. In the end, these systems demand efficient incorporation of sensitive drug and biomolecules and controlled release. Thus, designing of biomedical systems become a complex process where structure needs to be maintained for a biomaterial throughout the design process. High pressure carbon dioxide (CO2) offers a `green’s benign and inexpensive way for fabrication and impregnation of additives in the biocompatible polymers. CO2 assisted plasticization of polymers enhances diffusion of additives in the polymer matrix. However, interactions among polymer, CO2 and additives are complex and difficult to understand. Density and diffusivity of CO2 can be controlled easily by adjusting temperature and pressure. Hence extent of plasticization of polymer can be controlled. In the present study, biocompatible polymer blends were investigated from biomedical applications perspective. Electrospinning is a versatile process to prepare fibrous scaffolds. This process was applied to different binary and ternary blends to fabricate electrospun scaffolds. There scaffolds were impregnated with additives using high pressure CO2 to study release profiles. Results show electrospun polymer blends interact differently with each process step adopted in this study. Effect of dominant impregnation and release parameters were investigated to control and predict release of additives from complex electrospun scaffolds. The work presented in this dissertation aids in understanding of additive release from electrospun polymer blends with complex behavior. Advisors/Committee Members: Tomasko, David (Advisor).

V doktorski dizertaciji smo raziskovali uporabo ogljikovega dioksida pri visokih tlakih za impregnacijo maščobo-topnih vitaminov. Za impregnacijo smo izbrali vitamina K3 in D3. Predvsem vitamin D3 je izjemno občutljiva substanca, zato zahteva izjemno pozornost. Za impregnacijo obeh vitaminov smo uporabili polisaharidne arogele. Aerogeli so porozni materiali z izjemnimi lastnostmi. Zaradi visokih poroznosti imajo velike specifične površine in nizke gostote. Če te lastnosti združimo še z biokomatibilnostjo ter biorazgradljivostjo polisaharidov, dobimo idealne materiale za farmacevtske aplikacije. Cilj doktorske dizertacije je bil impregnacija vitaminov v polisaharidne aerogele, da bi jih s tem dodatno zaščitili ter tako povišali njihovo stabilnost. Delo je razdeljeno v dva večja dela. V prvem delu smo uporabili superkritični ogljikov dioksid za impregnacijo vitamina K3 in vitamina D3. Vitamin K3 smo uporabili kot modelno substanco, naš glavni cilj pa je bil impregnacija vitamina D3. Raziskali smo termodinamske in kinetične lastnosti obeh vitaminov. Dobljene vrednosti smo razložili z uporabo že razvitih kinetičnih modelov. V prvem delu dizertacije smo določili tudi strukturne lastnosti vzorcev ter preverili sproščanje vitamina in vitro. V drugem delu doktorske dizertacije smo preiskovali impregnacijo vitamina D3 z ogljikovim dioksidom. Tokrat smo uporabili ogljikov dioksid pri različnih pogojih, od superkritičnega do tekočega ogljikovega dioksida. Preiskovali smo kinetično obnašanje pri različnih pogojih ter določili stopnjo degradacije vitamina glede na izbrane pogoje. Z različnimi karakterizacijskimi metodami smo določil vpliv tako superkritičnega kot tekočega ogljikovega dioksida na končne strukturne lastnosti aerogelov. V tem delu dizertacije smo prav tako izvedli sproščanje vitamina D3 in vitro, izvedli pa smo tudi stabilnostno študijo za potrditev povišane stabilnosti vitamina D3 ob impregnaciji v aerogele.

This doctoral dissertation examines utilization of carbon dioxide as solvent for high pressure impregnation of fat-soluble vitamins, in particular vitamin K3 and vitamin D3. Chosen vitamins, especially vitamin D3, are handling challenging since they are highly sensitive substances. Polysaccharide alginate aerogels were used as vitamins’ carriers. Aerogels are airy materials with outstanding properties such as high porosity, high specific surface area and low density. Combined with the biocompatible and biodegradable polysaccharides, they fulfil pharmaceutical demands for ideal candidates. General idea of this dissertation was to achieve protection and prolonged stability of sensitive vitamins against environments by impregnating them into polysaccharide aerogels. The work is divided in main two parts. In the first part, carbon dioxide was used in its supercritical state. The impregnation experiments were conducted with both vitamin K3 and vitamin D3. Vitamin K3 had the role of a model substance while the main focus was on vitamin D3, as an active substance. The thermodynamic and kinetic behaviour of both…

Advisors/Committee Members: Novak, Zoran.