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Smart multi Stimuli-responsive Supports for controlled cell growth

Final Report Summary - THREE-S (Smart multi Stimuli-responsive Supports for controlled cell growth)

Stimuli-responsive materials are characterized by dynamic switching of their properties depending on external stimuli. Responsive elements may be anisotropic deformation, non-linear stress-strain behavior, thermal and/or optical changes to the elastic modulus of the material framework. Nature is full of example of responsive materials, such as the skin of lizard or cuttlefish, which change their body patterns and colors depending on the surrounding environment. Recently, numerous synthetic examples of responsive surfaces have emerged, which rely on conformational change in the polymer network, or pattern change. Very interesting and appealing seems to be the combination of several stimuli to tune the properties of the materials in manifold ways. There are not many examples of multi-stimuli responsive thin films, because they require precise control on the coordination among surface chemistry and response.
The goal of this project is to develop a smart stimuli-responsive environment. Smartness in this context means that our material will respond to more than one stimulus at the same time. We want to combine light and humidity responsiveness to reversibly change the mechanical properties of the material to control the cell attachment and growth.
With this purpose, we functionalized the top 15 nm of a poly(hydroxyethylmethacrylate) (PHEMA) hydrogel with azobenzene. The azobenzene undergoes a reversible isomerisation upon irradiation. This process is usually accompanied with a polarity change. We developed a light-responsive hydrogel, verifying the idea that a change in polarity after the isomerization of the azobenzene group upon illumination can induce a different water uptake in the hydrogel film. Achieving a precise control over the water uptake through light irradiation will be used to induce controlled and reversible changes in the stiffness and elasticity of the hydrogel. The hydrogel swelling in water results in changes in the mechanical properties, protein adsorption capabilities and hydrophilicity of the polymer. In the swollen state, hydrogels can have the same water content as living tissues.
The hydrogels obtained within this project present fast and reversible swelling in humidity and under water immersion. The swelling of pure PHEMA hydrogel was measured to be 40% in relative humidity of 80%, while the cross-linked hydrogel gave a 14% swelling after immersion in water. The swelling rate and the amount of swelling increased after irradiation of the hydrogels with UV light from 10% to 20% depending on the amount of azobenzene incorporated. Humidity and light cycles showed that the swelling and the change in swelling after light irradiation was completely reversible.

The technique we used to develop such material is the initiated Chemical Vapor Deposition (iCVD), as a surface polymerization method, it shows a high tolerance towards functional groups. It is a free-radical polymerization. The initiator and monomer species enter the iCVD chamber as vapors. The initiator is decomposed by interaction with a relatively hot filament (150-300°C). These temperatures are enough to selectively break only labile bonds present in the initiator structure, (e.g. the O-O bond in the tert-butyl peroxide, TBPO). The monomer decomposition temperatures are > 500°C, therefore the monomer fully retain its chemical structure. In analogy to solution-phase synthesis, in the iCVD, the initiator radicals activate the chain growth polymerization of the monomer. The absence of solvents in iCVD makes of it an ideal method to develop hydrogels, which would be damaged otherwise by swelling the solvent in conventional synthetic procedures. Functional and responsive organic materials obtained by iCVD can complement the existing thin films technologies and couple the advantages related to a deposition from the vapor-phase (solventless, scalable, control over thickness, conformality) to the richness and predictability of organic synthesis by liquid-phase polymerizations.
The conceptual development on iCVD was carried out mainly in Prof. Karen K. Gleason’s group at MIT, Boston. The ambition of the proposed project was to transfer the knowledge about iCVD from MIT to Europe as new method for polymer deposition and as source of new research areas in the field of biotechnologies and regenerative medicine. Figure 1.1 shows the picture of the iCVD reactor built at the Graz University of Technology.
An important follow-up of this project will be the demonstration of the biological outcome, this part will be done in collaboration with the Institute of Molecular Biotechnology of the TUGraz. Cells will be immobilized on the surface of the smart hydrogel and the adhesion and growth will be verified. The stimuli responsiveness of the material will be used to control the cell growth. This research project is expected to have important implications also for regenerative stem-cell therapies, because it may provide important clues on how to control the differentiation, by changing the stiffness of the substrate. The development of light-responsive hydrogel on biodegradable substrates may also be used for in vivo tissue engineering by adapting the elasticity of the material to the one of the corrupted body area.
A project website is available at