Microgel particles stabilised high internal phase emulsions for applications in tissue engineering

Abstract

Tissue engineering using polymeric scaffolds to support cell growth and tissue regeneration is currently under development as a promising solution to tissue loss or organ failure. This thesis focuses on fabricating multifunctional scaffolds for tissue engineering using emulsion templating. Poly(N-isopropylacrylamide-co-acrylic acid) [poly(NIPAAm-co-AA)] microgel particles were found capable of stabilising both w/o and o/w high internal phase emulsions (HIPEs), depending on the temperature, pH and salt concentration. PolyHIPEs were prepared by photo-polymerisation of both HIPEs containing monomers in the continuous phase and exhibited pore structures with sizes of a few hundred micrometers. For oil-soluble monomers, e.g., divinylbenzene (DVB), microgel particles stabilised w/o HIPEs were obtained at 40 °C using a microgel suspension (0.4 wt %) in 1 mM KCl solution at pH 4. For water-soluble monomers, e.g., potassium acrylate (KAA), the crosslinker content was found crucial to the formation of an open porous structure in poly(KAA) HIPEs. It was shown by cryo-scanning electron microscopy that the interconnections were not generated upon polymerisation but during solvent extraction. Highly interconnected poly(KAA) HIPEs prepared using 80 vol % internal phase possessed a low density of ca. 0.03 g/cm3 and a porosity up to 97~98%. By using active ingredient (A.I.) loaded microgel particles as emulsifiers, polyHIPEs with delivery functionality were developed. The emulsifying ability of A.I. loaded microgels was found to be dependent on A.I.-microgel interactions. Paracetamol drug loaded microgel particles resulted in stable o/w HIPEs at either low (400 rpm) or high stirring speed (1000 rpm) and hence polyHIPEs with tunable morphologies after polymerisation. Microgel particles stabilised o/w HIPEs were also used to fabricate macroporous dextran and dextran-co-polyNIPAAm. The pH of the aqueous phase was found crucial to HIPE stability and pH 6.8 resulted in stable HIPEs without coalescence and macropores with narrow pore size distribution after freeze-drying. By thermostating HIPEs prior to freezing or by varying dextran concentration, the morphology of macroporous dextran was tunable. Macroporous dextran-co-polyNIPAAm could potentially be used as a multiply responsive scaffold. Besides the stimuli-responsiveness of microgel particles, polyNIPAAm segments of the copolymers enabled scaffold integrity in water at physiological temperature. Microgel particles stabilised HIPEs were established as a truly versatile template to fabricate macroporous polymers for potential applications as tissue engineering scaffolds.