High resolution characterization of responsive hydrogels for biomedical application

Abstract

Hydrogels are 3D polymer network that, differing from conventional solids, can eliminate or absorb water and as a consequence undergo changes in volume, mechanical properties. Various properties of the hydrogels can be altered as a consequence of their response to external stimuli. Thus, hydrogels are considered important materials for a variety of applications in medical technology.

Here it will introduce the application of interferometric readout platform for determination of swelling properties of stimuli responsive hydrogels. These include hydrogel materials suitable for (bio) specific recognition and signal transducing matrices. Application of the interferometric readout platform for determination of hydrogel swelling is realized by depositing the responsive hydrogels on the tip of optical fibre with semi-spherical shape with size of tens αm. The other end of optical fibre is connected with the interferometer. Previous experiments have already proved its potential as (bio) sensors in determining the swelling property of responsive hydrogels with high resolution of 2nm and sampling frequency of 1Hz. The following are the extension strategies of interferometric technique for investigating the general swelling response of other designed responsive hydrogels upon specific biological analytes related to application of responsive hydrogels or soft materials characterization within medical diagnostics, drug delivery and tissue engineering.

Firstly, in the strategy of developing the optimized DNA sensitive hydrogels as signal transducing materials with potential applications in biomedical diagnosis, hydrogel-based label-free nucleic acids sensing materials were prepared and characterized with respect to molecular parameters in the design of hydrogel network. DNA-polymer hybrid hydrogels comprised of sensing (S) and blocking (B) oligonucleotide pairs copolymerized within the network forming reversible physical crosslinks in addition to stable covalent ones. The crosslinks would be destabilized by the presence of probes (P) with complementary nucleotide base pairs to S with longer complementary regions (toe-holds) compared to B. The destabilization of physical crosslinks resulted in hydrogel swelling. The influence of blocking sequence lengths, toe-hold lengths, covalent crosslink density and experimental temperature on the hydrogel swelling kinetics was determined experimentally. The observed finding of a correlation between toehold length and hydrogel swelling rates was interpreted in terms of effects on the kinetics of the strand displacement reaction within the complementary sequences and concomitant effects on the dsDNA supported physical crosslinks.

Another facet concerning the nucleic acids sensing material improving swelling kinetics of DNA hybrid hydrogel by introducing the polyethylene glycol (PEG) as a pore forming agent. Experimental data indicated that the presence of porogen could improve the swelling dynamics of DNA hybrid hydrogels upon specific ssDNA probe recognition but not influence the kinetics of osmotic pressure driven AMPSA-co-AAM hydrogels swelling at various ionic strengths.

Fine details of the helix-coil equilibrium of dsDNA crosslinks far below the helix-coil melting temperature comprised the third facets affecting the swelling of DNA hybrid hydrogel investigated in this work. The swelling responses of DNA-grafted acrylamide hydrogels due to temperature and NaCl concentration changes in the range 23-50 °C and 0.125-1.0 M, respectively, were determined. The relative abundance within the distribution of higher order structures of the DNA crosslinks due to these changes were calculated, and used as a basis for assessing the observed swelling changes. The analysis indicates that the small changes observed in the swelling volumes can be qualitatively accounted for in minute changes in the helix-coil equilibrium of the DNA supported crosslinks.

The second main research is the high resolution monitoring of the dimensional changes of hydrogel materials as models for drug delivery. A specific hydrogel comprised of copolymerized AAM, bis and weakly anionic AMPSA was characterized by interferometer to investigate its swelling properties in the presence of oppositely charged surfactants and subsequent exposure to cyclodextrins. The influence of hydrogel charge density and crosslink degree, surfactant tail length and type of cyclodextrin on the hydrogels equilibrium swelling ratio and swelling/ deswelling kinetics were determined.

Cholesterol-bearing pullulan (CHP) responsive hydrogel, fabricated by the polymerization of methacryloyl substituted CHP nanogels was additionally investigated. The destabilization of cholesteryl hydrophobic association domains in CHP hydrogel by the presence of cyclodextrins yielded an increase of the hydrogel swelling. The data reveal that the equilibrium swelling ratio of the CHP hydrogels depend on their composition, cyclodextrins types and CHP concentration. The cholesterol-bearing pullalan material is suggested to be applied as materials for controlled release, e.g. due to increased capacity to hold hydrophobic drugs. The present finding of swelling response of the CHP hydrogels depending on the type of cyclodextrins may aid in developing application of CHP for drug controlled release.

The last strategy aims for nano-mechanical characterization of reinforced hydrogels to develop the barrier controlled soft materials for tissue engineering. An anionic AMPSA-AAM hydrogel core was impregnated with oppositely charged polymers (polyallylamine or chitosan) to identify the roles of molecular parameters in the swelling properties of resulting soft materials by the interferometric technique. The results revealed that tuning molecular parameters could be used to control transport properties of polycations into polyanionic hydrogels and accomplished the transformation from polyelectrolyte hydrogel to polyampholyte hydrogel.

Subsequently, the ionic strength dependent equilibrium swelling ratio of the anionic hydrogel with deposited polymer film was modelled using a finite element approach. Adding the polymer multilayer/shell at an ionic hydrogel surface revealed that constraining the ionic strength-dependent swelling became more pronounced with the thicker film and higher crosslink density of deposited polymer film. It was targeted to be a method for determination of the mechanical properties of deposited polymer thin layer on the surface of an ionic hydrogel, similar to that in some polymer matrices for tissue engineering.

Finally, the work was implemented to study the swelling properties of polyampholyte and mixed polyelectrolyte-zwitterionic polymer hydrogels with charge balanced, anionic offset or cationic offset. Anionic-cationic monomers mixed polyampholyte hydrogels could enhance the anti-electrolyte property but not affect their swelling kinetics. The results could help us to further understand the swelling properties of polyampholytic hydrogels.