Maria Vamvakaki

Ultra-Low Shrinkage Hybrid Photosensitive Material for Two-Photon Polymerization Microfabrication

Investigations into the structuring by two-photon polymerization of a nonshrinking, photosensitive, zirconium sol-gel material are presented. This hybrid material can be photostructured even when it contains up to 30 mol % of zirconium propoxide (ZPO); by varying the materials inorganic content, it is possible to modify and tune its refractive index. The introduction of ZPO significantly increases the photosensitivity of the resulting photopolymer. The fabricated three-dimensional photonic crystal structures demonstrate high resolution and a clear band-stop in the near-IR region. In contrast to common practice, no additional effort is required to precompensate for shrinkage or to improve the structural stability of the fabricated photonic crystals; this, combined with the possibility of tuning this materials optical, mechanical, and chemical properties, makes it suitable for a variety of applications by two-photon polymerization manufacturing.

Multiresponsive polymers: nano-sized assemblies, stimuli-sensitive gels and smart surfaces

The complex function of living systems is dictated by their inherent cooperative response to multiple external stimuli which induce dynamic changes in their physicochemical properties. Advances in the areas of nano- and bio-technology demand for the development of “smart” synthetic materials that would resemble the living systems in their complex behaviour as a response to applied stimuli. This reversible response directs the formation of hierarchical self-assemblies or stimulates changes in the volume, the shape or the surface characteristics of the system. Progress in this rapidly expanding area can lead to the development of dynamically multiresponsive constructs in the form of polymers, particles, gels or surfaces, for potential use in a wide range of applications such as drug delivery, tissue engineering, self-healing materials, bioseparations, sensors and actuators. This review highlights the recent advances in polymer chemistry to design multiresponsive polymeric materials that recognize independently or synergistically more than one stimulus exhibiting collective responses. Emerging developments, challenges and future trends in this exciting field are also discussed.

Direct Laser Writing of 3D scaffolds for neural tissue engineering applications

This study reports on the production of high-resolution 3D structures of polylactide-based materials via multi-photon polymerization and explores their use as neural tissue engineering scaffolds. To achieve this, a liquid polylactide resin was synthesized in house and rendered photocurable via attaching methacrylate groups to the hydroxyl end groups of the small molecular weight prepolymer. This resin cures easily under UV irradiation, using a mercury lamp, and under femtosecond IR irradiation. The results showed that the photocurable polylactide (PLA) resin can be readily structured via direct laser write (DLW) with a femtosecond Ti:sapphire laser and submicrometer structures can be produced. The maximum resolution achieved is 800 nm. Neuroblastoma cells were grown on thin films of the cured PLA material, and cell viability and proliferation assays revealed good biocompatibility of the material. Additionally, PC12 and NG108-15 neuroblastoma growth on bespoke scaffolds was studied in more detail to assess potential applications for neuronal implants of this material.

Multiphoton polymerization of hybrid materials

Multiphoton polymerization has been developed as a direct laser writing technique for the preparation of complex 3D structures with resolution beyond the diffraction limit of light. The combination of two or more hybrid materials with different functionalities in the same system has allowed the preparation of structures with advanced properties and functions. Furthermore, the surface functionalization of the 3D structures opens new avenues for their applications in a variety of nanobiotechnological fields. This paper describes the principles of 2PP and the experimental set-up used for 3D structure fabrication. It also gives an overview of the materials that have been employed in 2PP so far and depicts the perspectives of this technique in the development of new active components.

Copolymers of amine methacrylate with poly(ethylene glycol) as vectors for gene therapy

A series of structurally related copolymers of tertiary amine methacrylate with poly(ethylene glycol) (PEG) were investigated for their potential to serve as vectors for gene therapy. The effects of copolymer structure on the complexation and transfection ability were assessed. The ability of the PEG-based copolymers and DMAEMA homopolymer to bind and condense DNA was confirmed by gel electrophoresis, ethidium bromide displacement and transmission electron microscopy. The presence of PEG in the copolymers had a beneficial effect on their ability to bind to DNA. Colloidally stable complexes were obtained for all the PEG-copolymer systems as shown by uniformly discrete spherical images from transmission electron microscopy and approximate diameters of 80-100 nm by dynamic light scattering studies. DMAEMA homopolymer, however, produced agglomerated particles, confirming the important role played by the PEG chains in producing compact stable DNA complexes. Assessment of the effect of ionic strength of the buffer on the complexation and dissociation of the complexes indicated the importance of both electrostatic and non-electrostatic interactions in the polymer-DNA complexation. In vitro transfection experiments showed that DMAEMA homopolymer gave the highest level of transfection comparable to a control poly-L-lysine (PLL) system. The PEG-based copolymers gave reduced levels of transfection, most likely due to the steric stabilization effect of a PEG corona.

Diffusion-Assisted High-Resolution Direct Femtosecond Laser Writing

We present a new method for increasing the resolution of direct femtosecond laser writing by multiphoton polymerization, based on quencher diffusion. This method relies on the combination of a mobile quenching molecule with a slow laser scanning speed, allowing the diffusion of the quencher in the scanned area and the depletion of the multiphoton-generated radicals. The material we use is an organic-inorganic hybrid, while the quencher is a photopolymerizable amine-based monomer which is bound on the polymer backbone upon fabrication of the structures. We use this method to fabricate woodpile structures with a 400 nm intralayer period. This is comparable to the results produced by direct laser writing based on stimulated-emission-depletion microscopy, the method considered today as state-of-the-art in 3D structure fabrication. We optically characterize these woodpiles to show that they exhibit well-ordered diffraction patterns and stopgaps down to near-infrared wavelengths. Finally, we model the quencher diffusion, and we show that radical inhibition is responsible for the increased resolution.

Shrinkage of microstructures produced by two-photon polymerization of Zr-based hybrid photosensitive materials

An investigation of the shrinking behaviour of a zirconium-based sol-gel composite micro-structured by two-photon polymerization is presented and a simple, straightforward methodology allowing the evaluation of shrinkage is suggested. It is shown that volume reduction is directly related to the average laser power (irradiation dose) used for the microfabrication and becomes a critical issue near the polymerization threshold. It is demonstrated that this shrinkage can be employed beneficially to improve the structural resolution. This is demonstrated by the presence of stopbands in the photonic crystal nanostructures fabricated with controlled volume reduction. Well above the polymerization threshold, the studied material exhibits remarkably low shrinkage. Therefore, no additional effort for the pre-compensation of distortion and for the improvement of structural stability is required.

Photodegradable Polymers for Biotechnological Applications

Photodegradable polymers constitute an emerging class of materials that finds numerous applications in biotechnology, biomedicine, and nanoscience. This article highlights some of the emerging applications of photodegradable polymers in the form of homopolymers, particles and self-assembled constructs in solution, hydrogels for tissue engineering, and photolabile polymers for biopatterning applications. Novel photochemistries have been combined with controlled polymerization methods, which result in well-defined photodegradable materials that exhibit light mediated and often controlled fragmentation processes.

Three-Dimensional Metallic Photonic Crystals with Optical Bandgaps

The fabrication of fully three-dimensional photonic crystals with a bandgap at optical wavelengths is demonstrated by way of direct femtosecond laser writing of an organic-inorganic hybrid material with metal-binding moieties, and selective silver coating using electroless plating. The crystals have 600-nm intralayer periodicity and sub-100 nm features, and they exhibit well-defined diffraction patterns.

Harnessing photochemical internalization with dual degradable nanoparticles for combinatorial photo-chemotherapy

Light-controlled drug delivery systems constitute an appealing means to direct and confine drug release spatiotemporally at the site of interest with high specificity. However, the utilization of light-activatable systems is hampered by the lack of suitable drug carriers that respond sharply to visible light stimuli at clinically relevant wavelengths. Here, a new class of self-assembling, photo- and pH-degradable polymers of the polyacetal family is reported, which is combined with photochemical internalization to control the intracellular trafficking and release of anticancer compounds. The polymers are synthesized by simple and scalable chemistries and exhibit remarkably low photolysis rates at tunable wavelengths over a large range of the spectrum up to the visible and near infrared regime. The combinational pH and light mediated degradation facilitates increased therapeutic potency and specificity against model cancer cell lines in vitro. Increased cell death is achieved by the synergistic activity of nanoparticle-loaded anticancer compounds and reactive oxygen species accumulation in the cytosol by simultaneous activation of porphyrin molecules and particle photolysis.