A study of pH-responsive microgel dispersions: from fluid-to-gel transitions to mechanical property restoration for load-bearing tissue

Abstract

An interesting, and potentially important, challenge for colloid scientists is to design injectable dispersions that enable repair of damaged and degenerated tissue. This work presents a study of the ability of pH-responsive microgel particles to restore the mechanical properties of loadbearing soft tissue. Microgel particles are cross-linked polymer colloid particles that are swollen with solvent. The first part of the study consists of an investigation of the pH-triggered swelling of poly(EA/MAA/BDDA) (ethylacrylate, methacrylic acid and 1,4-butanediol diacrylate) microgel particles using photon correlation spectroscopy (PCS) measurements. The concentrated dispersions exhibit a strong fluid-to-gel transition when the pH is increased to above 6.0, i.e., above this pH they form gelled microgel dispersions. The swelling data are used to aid interpretation of the pH-triggered changes in the gel modulus, as probed using dynamic rheology. The second part of the study involves an investigation of the mechanical properties of artificially degenerated, model intervertebral discs (IVDs) containing gelled microgel dispersions. High concentration microgel dispersions were injected as fluids into the interior of degenerated IVDs and the pH increased by subsequent alkaline solution injection to cause particle swelling and dispersion gelation. Uniaxial compression data measured for the IVDs containing injected microgel dispersions indicate that the pH-induced particle swelling of the microgel restores the mechanical properties of degenerated IVDs to values similar to those measured for normal, non-degenerated, IVDs.

A study of poly(butadiene/methacrylic acid) dispersions: From pH-responsive behaviour to the effects of added Ca2+

“…The method has been described in detail elsewhere [8] and is described briefly below. The microgel contained 66, 33 and 1 wt% of EA, MAA and BDDA, respectively, and is referred to here as poly-(EA/33MAA/BDDA).…”

“…These dispersions exhibit major changes in their particle size and dispersion properties (e.g., viscosity) in response to changes in the pH. They have mostly been studied in the context of microgel particles [4][5][6][7][8][9]. pH-responsive microgel particles are crosslinked polymer particles that swell as the pH approaches the pK a of the incorporated ionic co-monomer.…”

“…Previous work at Manchester has investigated the structureproperty relationships of MAA-containing microgel particles [8,9,14]. These include poly(EA/MAA/BDDA) (ethyl acrylate and butanediol diacrylate).…”

Factors Affecting Peptide Interactions with Surface-Bound Microgels

“…These microgels have previously been well characterized for various applications [22][23][24] and, importantly, the co-monomer composition can be easily varied during synthesis to alter microgel swelling properties, allowing for tunable performance of the system. 25 In the present study we employed this microgel platform in combination with the model cationic peptide poly-L-lysine (pLys, pI≈9 (10.5 for isolated lysine monomers 12 )).…”

Stimulus-Responsive Heteroaggregation of Colloidal Dispersions: Reversible Systems and Composite Materials

“…Microgels have recently been identified as promising in the design of highly functional bioactive scaffolds in regenerative medicine due to a combination of their rheological properties, drug delivery capability and synthesis from biodegradable and biocompatible polymers [40][41][42]. In tissue engineering gels are used as a supporting matrix for the delivery of cells.…”