Multi-responsive Microgels and Hydrogels

Abstract

Microgels (MGs) are swellable crosslinked polymer colloids. They can also be used as the only building block to construct nanostructured hydrogels which are denoted as doubly crosslinked microgels (DX MGs). Both MGs and DX MGs can be useful in biological application. This thesis presents a study of multi responsive MGs and DX MGs. In the beginning, new triply responsive DX MG-x-nPh comprised of interlinked MG-x- nPh of oligo(ethylene glycol)methacrylate (OEGMA), 2-(2-methoxyethoxy)ethyl methacrylate (MEO 2 MA), methacrylic acid (MAA), o-nitrobenzyl-based UV photocleavable crosslinker (nPh) and glycidyl methacrylate (GMA) are investigated. The MG-x-nPh particles swelled or collapsed in response to temperature and pH changes and also degraded when UV irradiated. The content of crosslinker (x) does not restrict the swelling of MG-x-nPh. The concentrated MGs can be formed into DX MG-x-nPh gels via free-radical polymerisation using the GMA vinyl groups. The DX MG-x-nPh gels are injectable and implanted and they are not cytotoxic to nucleus pulposus cells. DX MG- x-nPh also shows temperature and pH responsiveness additions UV-enhanced the gel modulus. The mechanical properties and swelling of the DX MG gels were strongly affected by x. The UV-C light stabilised gels have potential application as injectable gels and implants for soft tissue. Even though the photosensitive MG-x-nPh and gels is developed in this work, the applications are limited due to irreversibly of gel formation. Next, I synthesised the reversibly photo-crosslinkable 7-(2-methacryloyloxyethoxy)-4- methylcoumarin (CMA) and copolymerised it with MEO 2 MA and MAA to prepare triply responsive CMA-based MGs (denoted as MG-CMA). MG-CMA is also multi-responsive (pH, temperature and light). It was found that the photo-dimerisation degree of CMA is related to the size of as-made MGs. The photo-switching ability between a highly 28 crosslinked and de-crosslinked state was achieved using UV-irradiation. The crosslinker density was easily adjusted by switching the wavelength of UV light. Light and pH are shown to control the release of a drug from MG-CMA. The method for preparing conventional DX MGs require addition of initiator, which limits spatial and temporal control and may adversely affect cells. At the end of the project I investigated a strategy to construct multi-responsive hydrogels utilising photo-triggered covalent interlinking of concentrated MG-CMA building blocks. This method provides precise spatial control and no other material is required to prepare the gels beyond the MG-CMA particles themselves. The multi-responsive hydrogels are reversibly responsive to light, pH and temperature. The moduli value and swelling ratios of gels are also photo-tuneable. This versatile gels show light-assisted healing, re-shaping, photo- patterning, fluorescent photo-imaging and can be built up to multi-responsive cytocompatible actuators, grippers and ON/OFF circuit components. This work provides a new strategy to construct versatile multi-responsive gels.

Date of Award	31 Dec 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Brian Saunders (Supervisor) & Jonny Blaker (Supervisor)