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In this thesis, non-modified POx, namely PnPrOx and PcycloPrOx, with an LCST in the physiological range between 20 and 37°C have been utilized as materials for three different biofabrication approaches. Their thermoresponsive behavior and processability were exploited to establish an easy-to-apply coating for cell sheet engineering, a novel method to create biomimetic scaffolds based on aligned fibrils via Melt Electrowriting (MEW) and the application of melt electrowritten sacrificial scaffolds for microchannel creation for hydrogels. Chapter 3 describes the establishment of a thermoresponsive coating for tissue culture plates. Here, PnPrOx was simply dissolved in water and dried in well plates and petri dishes in an oven. PnPrOx adsorbed to the surface, and the addition of warm media generated a cell culture compatible coating. It was shown that different cell types were able to attach and proliferate. After confluency, temperature reduction led to the detachment of cell sheets. Compared to standard procedures for surface coating, the thermoresponsive polymer is not bound covalently to the surface and therefore does not require specialized equipment and chemical knowledge. However, it should be noted that the detachment of the cell layer requires the dissolution of the PnPrOx-coating, leading to possible polymer contamination. Although it is only a small amount of polymer dissolved in the media, the detached cell sheets need to be washed by media exchange for further processing if required. ... / In dieser Dissertation wurden die unmodifizierten Poly(2-oxazoline) PnPrOx und PcycloProx, welche eine LCST im physiologischen Bereich zwischen 20 und 37°C aufweisen, für drei verschiedene Biofabrikationsansätze verwendet. Deren Thermoresponsivität und Prozessierbarkeit wurde genutzt, um ein simples Beschichten von Oberflächen für Cell Sheet Engineering, eine neue Methode zur Herstellung biomimetischer Gerüststrukturen basierend auf der Generierung von Fibrillenbündeln via Melt Electrowriting und die Anwendung als Opferstrukturen zur Generierung von Mikrokanälen in Hydrogelen zu etablieren.

This thesis focused on the mechanisms involved in negative thermal expansion of 2D/3D lattice structures. The effects of varying the constituent materials and geometry were explored. The lattices had geometries similar to those found in light-weight structures in many transport applications, including aerospace and spacecraft. One specific case was to determine how to reduce the coefficient of thermal expansivity (CTE) of such structures to near zero, by using two constituent materials with contrasting CTEs, without incurring penalties in terms of other elastic and failure properties, mass and manufacturability. The lattice geometries able to exhibit altered CTE were explored, and penalties in terms of other elastic properties were quantified. The results were scale-independent and so were generic to all such lattices. Analytical prediction and generic relationships between the geometries of the lattices and their performance were proposed. Experimental validation of the model predictions was undertaken using physical samples. The thermomechanical properties were simulated by commercial finite element method (FEM) codes (Ansys 11, Ansys, Inc.). Ansys parametric design language was adopted to generate large sets of solutions to be evaluated against chosen criteria. Results show small or, in some cases, no penalties to be paid in terms of stiffness and mass for implementing dual-material lattices with near-zero CTE. Such lattices may compete favourably with high-cost and high-density materials (e.g. Invar) and the manufacture of dual-material lattices can be by standard processes or alternative new process such as Additive Layer Manufacturing (ALM). An example of truss core sandwich application for aerospace application was modelled by FEM. Applications as cores in sandwich panels might be the first route by which the ALM manufacturing process is required to develop dual-material capability.

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The increasing prevalence of diabetes and the severity of long-term complications have emphasized the need for continuous glucose monitoring. Optically-based methods are advantageous as they have potential for noninvasive or minimally invasive detection. Fluorescence-based affinity assays, in particular, can be fast, reagentless, and highly specific. Poly(ethylene glycol) (PEG) microspheres have been used to encapsulate such fluorescently labeled molecules in a hydrogel matrix for implantation into the body. The matrix is designed to retain the sensing molecules while simultaneously allowing sufficient analyte diffusion. Sensing assays which depend upon a spatial displacement of molecules, however, experience limited motility and diminished sensor response in a dense matrix. In order to overcome this, a process of hydrogel microporation has been developed to create cavities within the PEG that contain the assay components in solution, providing improved motility for large sensing elements, while limiting leaching and increasing sensor lifetime. For an implanted sensor to be successful in vivo, it should exhibit long-term stability and functionality. Even biocompatible materials that have no toxic effect on surrounding tissues elicit a host response. Over time, a fibrous capsule forms around the implant, slowing diffusion of the target analyte to the sensor and limiting optical signal propagation. To prevent this biofouling, a thermoresponsive nanocomposite hydrogel based on poly(N-isopropylacrylamide) was developed to create a self-cleaning sensor membrane. These hydrogels exist in a swollen state at temperatures below the volume phase transition temperature (VPTT) and become increasingly hydrophobic as the temperature is raised. Upon thermal cycling around the VPTT, these hydrogels exhibit significant cell release in vitro. However, the VPTT of the original formula was around 33-34 degrees C, resulting in a gel that is in a collapsed state, ultimately limiting glucose diffusion at body temperature. The hydrogel was modified by introducing a hydrophilic comonomer, N-vinylpyrrolidone (NVP), to raise the VPTT above body temperature. The new formulation was optimized with regard to diffusion, mechanical strength, and cell releasing capabilities under physiological conditions. Overall, this system is a promising method to translate a glucose-sensitive assay from the cuvette to the clinic for minimally invasive continuous glucose sensing.

This thesis presents a novel method for the preparation of quantum dot-thermoresponsive polymer nanocomposite hydrogels. The quantum dots (QD’s) were synthesized in a microwave reactor using a high temperature organometallic synthesis procedure. The initial hydrophobic surface layer on the QD’s was coated with an amphiphilic polymer to enable phase transfer from non-polar solvent to water followed by physical immobilization of the QD’s in the thermoresponsive polymer hydrogel by photopolymerization. Their temperature dependent emission properties were investigated as a function of concentration of the incorporated QD’s. The resultant temperature dependent changes in the position of the peak emission wavelength of the QD-polymer nanocomposite hydrogels were found to be due to the change in the physical environment causing increased interaction between the embedded amphiphilic polymer coated QD’s and/or due to aggregation of QD’s. This change in peak emission position was found to be reversible in the temperature range from 29 to 37 °C.

The aim of this project was to design an intelligent controlled release system based on thermoresponsive nanoparticles for cancer therapy and to evaluate the efficiencies of these systems with in vitro cell culture. Poly(Nisopropylacrylamide), an important thermoresponsive polymer, was selected for this study to prepare the responsive nanoparticles. This polymer has an lower critical solution temperature (LCST) of 32 oC, below which it is hydrophilic and above this temperature, it shows hydrophobic behavior. Controlling drug release with this property was the objective of this study. Nanoparticles were prepared by nanoprecipitation method. By using different solvent:non-solvent ratios and polymer concentrations, different samples were prepared. The particle size was decreased when solvent:non-solvent ratio was increased and polymer concentration was decreased. This was found to be related with the solution viscosity. Nanoparticles prepared from polymers prepared with different initiatoraccelarator amounts had significantly different sizes and release rates, and additionally the size of particles prepared from polymers with various crosslinker amounts were decreased with increased croslinker amount. In situ release experiments were performed both below and above polymer&amp / #8216 / s LCST degree. Uncrosslinked nanoparticles demonstrated higher release rate of Celecoxib above LCST. However, there was no significant difference with the crosslinked nanoparticles. Crosslinked and uncrosslinked nanoparticles were tested on Saos-2 cells to assess their toxicity. Both Celecoxib loaded and free crosslinked particles were found to be cytotoxic. Uncrosslinked nanoparticles showed an increased toxicity upon loading with the bioactive agent, Celecoxib. In conclusion, uncrosslinked particles would be a proper drug carrier for cancer therapy with enhanced drug loading.

Lung cancer has the highest mortality rate relative to all types of cancers, and unfortunately there still exist numerous challenges towards decreasing this rate. One of these challenges is gaining a clear understanding of why metastatic lung cancer cells attach and detach to colonize other areas of the body. Reports suggest that the attachment of cells to secondary tumor sites does not occur randomly. It is theorized that both the physical and chemical properties of the tissue are able to create a suitable environment for their adhesion. Therefore, the motivation for the work presented herein is to use dynamic thermoresponsive polymer surfaces as a tool towards unraveling this seemingly mysterious behavior of metastatic cancer cells. This type of polymer is able to swell and deswell as a function of temperature. As such, spin-cast thin films of this polymer provide for topographies that have been used to investigate how highly metastatic lung cancer cells are able to rearrange their structure, specifically the cytoskeleton. Changes in cell to surface anchorage as a function of thin film structure can also monitored. One of the most studied reversibly binding surfaces is poly(Nisopropylacrylamide) (PNIPAAm), which has been considered for the past two decades as a non-destructive method for the harvest of confluent cell sheets. As a result of this property, a series of photocrosslinkable copolymers based on PNIPAAm and methacroyloxybenzophenone (MaBP) have been developed. Coatings are created by spin-casting the polymer followed by ultraviolet (UV) radiation, which triggers the transition in the benzophenone groups. This leads to the formation of a biradicaloid triplet that abstracts a hydrogen from a neighboring aliphatic C-H group, leading to a stable C-C bond. The characteristics of the polymer film, i.e. thickness, pattern, and topography, can be tuned during the spin casting and subsequent exposure/ developing process.The ease of tunability of this polymer allows for the investigation of the aforementioned parameters and their possible effects on bioadhesion.

This thesis present a study of thermo-gelling polycaprolactone (PCL) dispersion which consist of a mixture of PCL microspheres (MSs) and thermo-responsive, graft cationic copolymer. The PCL microspheres are solid or colloidosomes (hollow). This study aims toward an injectable colloidal cell delivery system. The thermo-responsive copolymer used in this study is a new family of cationic graft copolymer. The cationic graft copolymer consisted of cationic poly(N,N-dimethylaminoethyl methacrylate) backbone and poly 2-(2-methoxyethoxy) ethyl methacrylate (PMA) side chains. A series of new cationic graft copolymers were synthesized with different PMA arm length and grafting density. A representative copolymer showed good cell viabililty. The solid PCL MSs were prepared using solvent evaporation method. The MSs were mixed with the thermo-responsive graft copolymer. At room temperature the mixture were liquid-like and gelled at body temperature (37 ˚C). This indicates that the mixture systems were injectable. The injectable route offers a minimal invasive route to fill defect void inside the body. Furthermore, a porous morphology was evident for the mixed gels at 37 ˚C and the porosity could be altered using different composition of the mixed components. The mixed system showed self-healing properties for low volume fraction of PMA. The mixed system particle gel was more ductile in electrolyte but showed similar morphology to the mixed system particle gels prepared in water. This part of the study was carried out using PCL MSs prepared by cetyltrimethylammonium bromide (CTAB) as surfactant. A brief study using polyvinyl alcohol (PVA) as the surfactant showed that the PCL MSs had similar diameter and gel morphology which suggests that the model systems studied using CTAB may be applicable to the PVA system. Microencapsulation attracts interest due to its ability to deliver and control release actives and also its application in many fields. Colloidosomes are one of the microcapsules/microspheres used for microencapsulation. In this study a two step, facile and scaleable colloidosome preparation method was introduced. The PCL colloidosome shell consisted of partially fused small nanoparticles. The PCL colloidosomes were birefringence under cross polarised light due to the stress applied during solvent evaporation. A brief study showed that the mixture system of colloidosomes and thermo-responsive graft copolymer are able to gel at 37 ˚C.