Tony J. Freemont

Tuning the properties of pH-responsive and redox sensitive hollow particles and gels using copolymer composition

Biodegradable pH-responsive hollow polymer particles offer excellent potential for preparing high performance biomaterials. Unfortunately, the established methods for pH-responsive hollow particle preparation are laborious and difficult to scale up. Recently, we reported that pH-responsive hollow particles could be prepared using solvent evaporation [Bird et al., Chem. Commun., 2011, 47, 1443]. Here, we greatly expand and extend that work by investigating four new pH-responsive hollow particle systems based on poly(MMA-co-MAA) (methyl methacrylate and methacrylic acid) and poly(EA-co-MAA) (EA is ethyl acrylate). The hollow polymer particles were crosslinked with cystamine after preparation to give redox sensitive, biodegradable, hollow particles. For one of the systems a remarkable particle-in-hollow particle morphology was observed. The pH-triggered swelling of the hollow particles was studied and pH-triggered release of a model solute from these new hollow particles was demonstrated. The dispersions formed physical gels in the physiological pH range. The hollow particle physical gels had elastic modulus values as high as 4000 Pa at low total polymer concentrations. The swelling properties of the particles and the mechanical properties of the gels were tuneable using copolymer composition. The particles and gels could be disassembled with glutathione. The properties of these new gel-forming dispersions imply they have good potential for future application as injectable gels for regenerative medicine.

Hollow polymer particles that are pH-responsive and redox sensitive: two simple steps to triggered particle swelling, gelation and disassembly

A new, simple, two-step method is introduced for preparing hollow particles that are both pH-responsive and redox sensitive. Hollow poly(methyl methacrylate-co-methacrylic acid) particles swell at moderate pH values, form gels in concentrated dispersions and can be disassembled by adding reducing agents.

Doubly crosslinked microgel–polyelectrolyte complexes: three simple methods to tune and improve gel mechanical properties

Doubly crosslinked microgels (DX MGs) are hydrogels composed of covalently interlinked microgels. They are injectable and have potential application in soft tissue repair. Simple methods for tuning their mechanical properties are required. Here, we investigate the effect of added polyelectrolyte (polycations or a polyanion) as well as NaCl on the mechanical properties of the gels for the first time. Addition of polycations improved ductility and decreased the storage modulus (G′) of the DX MG–polyelectrolyte complex (DX MG–PECs) gels. The best DX MG–PEC gel had a yield strain (γc) of 109%, which is the highest reported to date for any DX MG. Furthermore, our DX MG–PEC gels were robust and maintained high G′ values as well as good ductility when swollen at pH = 7.5. The DX MG–PEC gels with improved ductility contained less than 10% polycation. We also investigated the effect of addition of NaCl solution during DX MG and DX MG–PEC preparation. This caused remarkable increases in both G′ and ductility. The best gel had a G′ of 300 kPa which is the highest elasticity reported for a DX MG to date. Addition of linear polyacrylic acid during DX MG preparation also increased the G′ values. This study has provided three new simple methods for tuning the mechanical properties of DX MGs Because the MGs used here belong to a broad class of polymer colloids the results obtained in this study should be generally applicable.

A study of hydrogel composites containing pH-responsive doubly crosslinked microgels

Recently, our group established a new approach for preparing injectable hydrogels using vinyl-functionalised pH-responsive microgel particles [Liu et al., Soft Matter, 2011, 7, 4696]. pH-responsive microgels swell when the pH approaches the pKa of the particles. Liu et al. used inter-particle crosslinking of vinyl-functionalised microgel particles to prepare hydrogels composed of doubly crosslinked microgels (D-microgels). Here, we combine vinyl-functionalised microgels with added, small-molecule, crosslinkers to prepare high modulus D-microgel/hydrogel (H-X) composites for the first time. The vinyl-functionalised microgel particles used were poly(EA/MAA/BDD)/GM; where, EA MAA, BDD and GM are ethyl acrylate and methacrylic acid, 1,4-butanediol diacrylate and glycidyl methacrylate, respectively. Two added crosslinkers were used to demonstrate the versatility of our approach. They were ethyleneglycol dimethacrylate (EGD) and N,N′-methylenebisacrylamide (BA). We compare the data to control hydrogel composites prepared using non-vinyl-functionalised singly crosslinked microgels (S-microgels). All of the composites showed pH-dependent swelling behaviours and mechanical properties. The storage modulus value for the as-made D-microgel/H-EGD composite was 0.12 MPa and is the highest reported to date for a hydrogel containing pH-responsive microgels. The as-made control S-microgel/H-X composites had high ductilities. Dynamic rheology data were used to determine the effects of vinyl functionalisation on the composite mechanical properties. All of the composites exhibited pH-dependent swelling and a “breathing in” transition occurred. The swollen D-microgel/H-X composites retained their high modulus values upon swelling; although, their ductilities decreased. Because we used two different crosslinkers and pH-responsive microgels containing carboxylic acid groups, the method introduced here for preparing high modulus hydrogel composites should be widely applicable.

Variations in immunohistochemical preservation of proteins in a mummification model

Immunohistochemistry is an important tool in the investigation of ancient mummified remains because of its ability not only to detect proteins but also to isolate their location to specific tissues and thereby improve confidence that the results are genuine. A mouse model of Egyptian mummification has been used to demonstrate that the survival of proteins, judged by the retention of immunohistochemical staining, varies markedly. Some survive the process well, whereas others become barely detectable despite the morphology of the tissue being excellently preserved. The results obtained show that protein preservation is multi‐factorial, with tissue type and degradation, and the properties of the protein itself all having significant effects. Proteins forming large, multi‐subunit complexes such as collagen IV appear to be more resistant to degradation than those that do not, such as S‐100. Although modern modelling studies cannot replicate the full extent of degradative processes and taphonomic changes experienced by real mummies, the results obtained can be useful for guiding research that requires ancient tissues.

Physiology of ageing of the musculoskeletal system

This review aims to provide a summary of current concepts of ageing in relation to the musculoskeletal system, highlighting recent advances in the understanding of the mechanisms involved in the development of age-related changes in bone, skeletal muscle, chondroid and fibrous tissues. The key components of the musculoskeletal system and their functions are introduced together with a general overview of the molecular hallmarks of ageing. A brief description of the normal architecture of each of these tissue types is followed by a summary of established and developing concepts of mechanisms contributing to the age-related alterations in each. Extensive detailed description of these changes is beyond the scope of this review; instead, we aim to highlight some of the most significant processes and, where possible, the molecular changes underlying these and refer the reader to in-depth, subspecialist reviews of the individual components for further details.