No abstract

The use of injectable pH-responsive doubly cross-linked microgels (DX microgels) to improve the mechanical properties of degenerated intervertebral discs is demonstrated for the first time. The microgel comprised methyl methacrylate (MMA), methacrylic acid (MAA), ethyleneglycol dimethacrylate (EGD) and glycidyl methacrylate (GM) and was poly(MMA/MAA/EGD)-GM. The GM facilitated covalent interparticle cross-linking. The DX microgels are shown to have tunable mechanical properties. Degeneration of model bovine intervertebral discs (IVDs) was induced using collagenase. When injected into degenerated IVDs the DX microgels were shown to improve the strain, modulus, toughness and resilience. The extent of mechanical property improvement was an increasing function of DX microgel concentration, suggesting tunability. Cytotoxicity studies showed that the DX microgel was biocompatible under the conditions investigated. The results of this study imply that injectable DX microgels have good potential as a future regenerative medicine strategy for restoring the mechanical properties of degenerated load-bearing soft tissue, such as IVDs.

A new family of pH-responsive microgel-colloidosomes was prepared using microgel particles as the building blocks and macro-crosslinker. Our simple and versatile method used covalent inter-linking of vinyl-functionalised microgel particles adsorbed to oil droplets to form shells of doubly crosslinked microgels (DX MGs) and was demonstrated using two different microgel types.

Nanogels are crosslinked polymer particles with a swollen size between 1 and 100 nm. They are of major interest for advanced surface coatings, drug delivery, diagnostics and biomaterials. Synthesising polyacid nanogels that show triggered swelling using a scalable approach is a key objective of polymer colloid chemistry. Inspired by the ability of polar surfaces to enhance nanoparticle stabilisation, we report the first examples of pH-responsive polyacid nanogels containing high -COOH contents prepared by a simple, scalable, aqueous method. To demonstrate their functionalisation potential, glycidyl methacrylate was reacted with the -COOH chemical handles and the nanogels were converted to macro-crosslinkers. The concentrated (functionalised) nanogel dispersions retained their pH-responsiveness, were shear-thinning and formed physical gels at pH 7.4. The nanogels were covalently interlinked via free-radical coupling at 37 °C to form transparent, ductile, hydrogels. Mixing of the functionalised nanogels with polymer dots enabled covalent assembly of fluorescent hydrogels.

pH-responsive microgels are crosslinked polymer colloid particles that swell when the pH approaches the pK a of the polybase or polyacid chains. Poly(vinylamine) (PVAM) has the highest primary amine content of all amine-containing polymers. Despite much effort the preparation of colloidally stable PVAM microgels is still elusive. Here, we introduce a simple and scalable, two-step method for preparation of pH-responsive PVAM microgels. First, non-aqueous dispersion (NAD) polymerization was used to prepare new monodisperse water-swellable poly(N-vinylformamide-co-2-(N-vinylformamido)ethyl ether microgels (PNVF-xNVEE). Here, x is the mol% of the alkali-stable crosslinker (NVEE) used. Alkali-hydrolysis of the PNVF-xNVEE microgels in water gave colloidally stable poly(vinylamine-co-bis(ethyl vinylamine)ether) (PVAM-xBEVAME) microgel dispersions. SEM images showed that both the PNVF-9NVEE and PVAM-9BEVAME microgel particles had cluster-like morphologies. The PVAM-xBEVAME particles were positively charged at pH values less than 12. The hydrodynamic diameters and electrophoretic mobilities increased strongly as the pH decreased. In order to demonstrate that primary amines could be used as chemical handles for conjugation, pyrene carboxylic acid was coupled using N-(3-dimethylaminopropyl)-N 0ethylcarbodiimide (EDC) chemistry and its presence confirmed by fluorescence microscopy. Because this new family of colloidally stable microgels has very high primary amine contents and was prepared by a scalable synthetic method there should be potential applications in a wide range of areas from surface coatings and new hybrid particles to delivery.