Mechanically enhanced polymeric hydrojel systems

In many areas where soft materials are used, it is critical that hydrogels have good mechanical properties. Although gels obtained from natural or synthetic polymers have some advantages, they swell too much in the liquid under physiological conditions and generally turn into a very fragile structure. The aim of this thesis is to provide viscoelasticity in the entire gel by creating a mechanism that provides energy distribution in the network structure at the molecular level to obtain a hydrogel with controllable mechanical properties. This thesis is designed in two parts, in the first part, hydrogels were prepared using a natural polymer starch and in the second part, synthetic Pluronic F127 (PF127) chains were prepared, and various experiments were carried out to mechanically improve the starch and PF127-based gels available in the literature. In the first part of the thesis, starch consisting of amylose and amylopectin, two homopolymers with the same repeating units connected in linear and branched manner, respectively, was used. The starch's abundant hydroxyl groups can be easily modified to modify and improve its functionality, including the formation of hydrogels to obtain products for a variety of applications. In the case of direct cross-linking, some of the hydroxyl groups in the starch chains are susceptible to reacting with di- or polyfunctional compounds. The use of epichlorohydrin to cross-link starch is most common in polysaccharide chemistry. The epoxy and halide groups on the ECH react with the hydroxide group in the starch structure and cross-link the two polymer chains. In this thesis, viscoelastic properties of high amylose starch (Hylon VII) - epichlorohydrin (ECH) hydrogels were investigated. The effect of the concentration amounts of the reaction components, the amylose ratio and the incorporation of hyaluronic acid, a naturally occurring linear polysaccharide, on the properties of the cross-networks were investigated. The obtained materials were examined in terms of swelling, viscoelastic and also morphological properties. The mole ratio of NaOH was found to be a key parameter in crosslinking reactions, while the elastic and viscous modules increased depending on starch and ECH concentrations. During the continuous step-deformation test, the low amylose cross mesh lost approximately 92 ± 4% of its initial mechanical strength, and the HA and non-HA high amylose gels completely returned to their original state after sol-gel transitions. Time-dependent relaxation tests were performed for high amylose gels, and it was observed that the structural dynamics were somewhat suppressed by combining HA with smaller and more stable pore structures. In the second part of the thesis, Pluronics, also known as "poloxamers" and approved for human use by the FDA, were used. These molecules are structures where hydrophilic polyethylene oxide (PEO) and hydrophobic polypropylene oxide (PPO) chains combine in the form of PEO-PPO-PEO triblock. The most important feature of the Pluronics is their temperature-based micelles formation thanks to the heat-sensitive PPO units with a concentration-dependent transition temperature. At high concentrations, sol-gel transition occurs below room temperature. Therefore, when the polymer is dissolved in water at room temperature, the micelles self-assemble due to the hydrophobic nature of PPO. While Pluronic solutions are in liquid form at low temperatures, they turn into gel form when they rise above certain temperature values and become liquid again when cooled. Within the Pluronic family, the most preferred member in medical and pharmaceutical applications is Pluronic® F127 due to its high-water solubility and high hydrophobic interactions thanks to its relatively long hydrophobic units. Although Pluronic copolymers change from liquid state to gel form very quickly at a certain temperature, they cannot last for a long time in physiological conditions due to insufficient mechanical strength of the hydrogels formed. This is one of the most important disadvantages of Pluronic-based systems. To obtain gels that are both mechanically strong and injectable, temperature sensitive Pluronic F127 micelles were combined with amphiphilic copolymers bearing photosensitive coumarin and azobenzene groups as repeating units. Thus, besides increasing the mechanical strength of temperature sensitive PF127 based smart gels, it is aimed to obtain injectable structures with light sensitivity. For this purpose, a total of four monomers were synthesized and polymerized by reversible addition-dissociation chain transfer (RAFT) polymerization. Amphiphilic diblock terpolymers were obtained by using macroRAFT material based on pre-synthesized polyethylene glycol (PEG). The structures of the copolymers were characterized and the amphiphilic diblock terpolymers were combined in water as micelles. Cross-linking of chromophore groups and micelle nuclei under UV light was investigated by UV spectroscopy. The rheological properties of the gels were evaluated as a function of temperature, composition, UV exposure time, strain and frequency, and their injectability was analyzed. It has been revealed that the prepared formulations respond to both heat and light, their mechanical properties are improved compared to PF127 structures, and they are injectable. At the last stage, the first steps were taken to be used in drug delivery applications by increasing the pores by adding f-chitosan to the system.