The synthesis and development of novel, easily processable poly (n-isopropylacrylamide)-based hyrdogels.

This work describes the invention of a synthetic method which allows a fully-reacted PNIPAM/clay nanocomposite system to remain a watery liquid until it is cooled to a predetermined temperature. Beyond this temperature, the polymer/clay precursor hydrogel liquid (PCPH) spontaneously forms a cross-linked hydrogel that does not re-liquefy upon re-heating, but instead, possesses all of the highly utilisable stimuli-responsive properties typical of PNIPAM-based nanocomposite hydrogels synthesised in situ. This novel methodology simultaneously addresses issues including cytotoxicity, processability, injectability, cross-linking and mechanical stability. In addition, PCPH synthesis requires no specialist equipment, inexpensive and basic components typical of cross-linked hydrogels (water, monomer, clay and initiator), requires no purification steps and can be maintained as a fully-reacted liquid at evaluated temperatures for up to several weeks with no apparent loss of eventual functionality. The ability to create a fully polymerised hydrogel polymer with a liquid intermediate state has allowed the incorporation of biologically active dopants which can be dispersed and distributed homogeneously throughout the matrix prior to "phase transition triggered nanoparticle anchored gelation" (or PTTNAG) of the hydrogel.Human mesenchymal stem cells (MSCs), have been incorporated into the gel by i) placing them on the assembled gel surface - the cells responded by migrating and proliferating throughout the matrix of the gel, and more interestingly, ii) combining the MSCs with the PCPH in the liquid phase and allowing PTTNAG of the polymer matrix to occur around the cells. In both cases, cell viability was excellent throughout a series of 14-28 day experiments. The work was expanded by the exploration of PTTNAG temperature tailorability. This was achieved with the incorporation of the relatively polar comonomer dimethylacrylamide (DMAc), and non-polar comonomer glycedyl methacrylate (GMAc) which respectively increased and decreased the PTTNAG and lower-critical solution temperature (LCST) of the resulting gels. Crucially, it was found that the PTTNAG temperature can be tailored precisely and incorporation of DMAc did not affect cell viability. The process also opened several novel avenues for gel processing possibilities, including facile casting, extruding and electrospinning. Well defined and uniform electrospun fibres with diameters ~300nm are presented. The production of continuous, uniform flat PNIPAM/ clay sheets of 300pm -1000pm achieved using an industrial film extrusion line is detailed. This work represents an innovation in the way in which such hydrogels can be manufactured and produced safely and cleanly, with no additives, no energy input and no toxic by-products.Interactions between polymer and water are examined by monitoring the dehydration of 3 separate hydrogel formulations using ATR-FTIR. The pseudo diffusion coefficient (in this instance, the diffusion of water out of the polymer matrix) was not affected by dopant composition, but instead, the intercept of the slope was altered markedly. Cross-link type, cross-link density, initiation method and addition of dopants have a strong influence on the swelling/ deswelling behaviour of the hydrogels under study. PNIPAM/ clay gels exhibit much larger volume changes than those prepared with chemical cross-linking agent methylenebisacrylamide (BIS). Deswelling magnitude increases with decreasing cross-linker content for all gel types examined. Thermal deswelling is hindered in dopant-incorporated networks. The aqueous dilution of the nanocomposite in the liquid phase affects gel deswelling behaviour when clay concentration is low. De/reswelling of PNIPAM/ clay, PNIPAM/BIS and gelatine-doped PNIPAM/ clay gels can be induced by adjusting the alcohol volume fraction of the media. BIS cross-linked gels exert restricted swelling/deswelling behaviours compared to those cross-linked with clay. Cross-link density within systems does not have a significant impact on cononsolvency behaviour, although the incorporation of gelatine imposes some restriction on it, directly relative to gelatine concentration.X-ray diffraction (XRD) data proved the exfoliation of clay in the nanocomposite system post-PTTNAG. DMA data revealed that the viscoelasticity of the gels can be tailored with varying the nature and quantity of dopant materials. Gels doped with hyaluronic acid (HA) most closely resemble the mechanical properties of bovine NP tissue.