Some International Constitutional Aspects of the Palestine Case

Cardiac tissue engineering via the use of stem cells is the future for repairing impaired heart function that results from a myocardial infarction. Developing an optimised platform to support the stem cells is vital to realising this, and through utilising new smart materials such as conductive polymers we can provide a multi-pronged approach to supporting and stimulating the stem cells via engineered surface properties, electrical, and electromechanical stimulation. Here we present a fundamental study on the viability of cardiac progenitor cells on conductive polymer surfaces, focusing on the impact of surface properties such as roughness, surface energy, and surface chemistry with variation of the polymer dopant molecules. The conductive polymer materials were shown to provide a viable support for both endothelial and cardiac progenitor cells, while the surface energy and roughness were observed to influence viability for both progenitor cell types. Characterising the interaction between the cardiac progenitor cells and the conductive polymer surface is a critical step towards optimising these materials for cardiac tissue regeneration, and this study will advance the limited knowledge on biomaterial surface interactions with cardiac cells

Electrochemical AFM : understanding the electromaterial-cellular interface

Organic conducting polymers are emerging as an exciting new class of biomaterial that can be used to enhance and control the growth of mammalian cells for tissue regeneration and engineering application

An Electroactive Oligo-EDOT Platform for Neural Tissue Engineering

The unique electrochemical properties of the conductive polymer poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) make it an attractive material for use in neural tissue engineering applications. However, inadequate mechanical properties, and difficulties in processing and lack of biodegradability have hindered progress in this field. Here, the functionality of PEDOT:PSS for neural tissue engineering is improved by incorporating 3,4-ethylenedioxythiophene (EDOT) oligomers, synthesized using a novel end-capping strategy, into block co-polymers. By exploiting end-functionalized oligoEDOT constructs as macroinitiators for the polymerization of poly(caprolactone), a block co-polymer is produced that is electroactive, processable, and bio-compatible. By combining these properties, electroactive fibrous mats are produced for neuronal culture via solution electrospinning and melt electrospinning writing. Importantly, it is also shown that neurite length and branching of neural stem cells can be enhanced on the materials under electrical stimulation, demonstrating the promise of these scaffolds for neural tissue engineering

Probing nanoscale properties of organic conducting polymer interfaces using atomic force microscopy

The development of new biomaterials for the field of bionics- the fusion of electronic devices with biological tissue- is an exciting area of research. The ability to control the interaction between the electronic and biological interface in devices, such as the cochlear implant, are crucial for enhancing and improving their biocompatibility and performance. Organic conducting polymers are widely studied for use as biomaterials to replace the conventional metallic materials currently used as electrodes and coatings in medical devices. These polymers are highly interesting due to fine level of control over material properties and the ability to incorporate biological components into the composition of the polymer itself. Thorough characterisation is needed to fully understand how these biological components influence the properties of the polymer itself and how they influence the interaction with living cells. Within this thesis I have used Atomic Force Microscopy to characterise an organic conducting polymer doped with various biological and non-biological molecules. This technique was applied so that the biomaterial could be studied on the nanoscale and on scales relevant to single cell interactions. Characterisation of the physical properties of the biomaterial demonstrated that irrespective of whether the dopant was biologically derived, the physical properties tended to group together with films having either a low roughness, low modulus and high strain, or vice versa. When compared to previous work, which investigated these polymers as potential biomaterials for supporting the growth and differentiation of skeletal muscle cells, these two groupings of the parameters correlated with the differing ability of the polymer substrates to support the cells. Using AFM surface characterisation techniques, namely phase imaging, current sensing and Kelvin force probe scanning, it was deduced that the polymer displays variable dopant distribution depending on the dopant. This dopant distribution created regions of attractive and repulsive interactions across the surface, which is dependent on the redox state and degree of dopant loading of the polymer. I developed a single protein force spectroscopy technique to measure the interfacial forces and interactions between a cell adhesion protein, fibronectin, and the biomaterial depending on dopant. This technique was able to resolve sub-molecular binding specificity between the dopants and binding domains of fibronectin. The interaction exploits a form of biological ‘charge complementarity’ to enable specificity. This specificity and the adhesion force were demonstrated to be influenced spatially by the distribution of dopant throughout the polymer using single protein force volume spectroscopy. In addition, the effect of stimulus on the organic conducting polymers – protein interface was investigated. When an electrical stimulus was applied to the biomaterial, the specific interaction was switched to a non-specific, high affinity binding state that was shown to be reversibly controlled using electrochemical processes. Both the specific and non-specific interactions are integral for controlling protein conformation and dynamics – the details of which give new molecular insight into controlling cellular interactions on these polymer surfaces. A different organic polymer was stimulated using an optical signal. The change in the surface charge was demonstrated to influence the level of adhesion of a non-specific interaction between the protein and polymer in a reversible manner

Quantifying fibronectin adhesion with nanoscale spatial resolution on glycosaminoglycan doped polypyrrole using Atomic Force Microscopy

The interaction of ECM proteins is critical in determining the performance of materials used in biomedical applications such as tissue regeneration, implantable bionics and biosensing. Methods: To improve our understanding of ECM protein–conducting polymer interactions, we have used Atomic Force Microscopy (AFM) to elucidate the interactions of fibronectin (FN) on polypyrrole (PPy) doped with different glycosaminoglycans. Results: We were able to classify four main types of FN interactions, including those related to 1) non-specific adhesion, 2) protein unfolding and subsequent unbinding from the surface, 3) desorption and 4) interactions with no adhesion. FN adhesion on PPy/hyaluronic acid showed a significantly lower density of surface adhesion with the adhesion restricted to nodule structures, as opposed to their peripheries, of the polymer morphology. In contrast, PPy/chondroitin sulfate showed a significantly higher density of surface adhesion to the point where the distribution of adhesion effectively masked the topography. Through conductive AFM imaging, we found that the conductive regions correlated with regions of FN adhesion. Conclusions: Given that the conductivity requires doping of the polymer, these findings suggest that FN adhesion is mediated by interactions with chondroitin sulfate and hyaluronic acid at the polymer surface and may be indicative of specific interactions due to contributions from electrostatic attraction between the FN and sulfate/anionic groups of the dopants. General significance: This study demonstrates the ability of AFM to resolve the protein–conducting polymer interactions at the molecular and nanoscale level, which will be important for interfacing these polymer materials with biological systems. This article is part of a Special Issue entitled Organic Bioelectronics — Novel Applications in Biomedicine