Graft copolymers with a random distribution of pyrrole monomer with hydrophilic functionalities

An electroactive biomaterial was obtained from the electropolymerization of pyrrole (Py) monomer and a macromonomer called PAB53, which has pyrrole as backbone and chains of PEG2000 grafted. The copolymerization was carried out at a molar ratio of 1:1 of Py:PAB53 and at three polymerization times (300, 500 and 1000s), resulting in films with cauliflower-like structures as surface morphology in all cases. The topography, thickness and wettability increased proportionally to the polymerization time, attributed to higher concentrations of PAB53 in the resulting copolymer films. Therefore, the increase of PEG chains, which favors the formation of valleys and hills in the surface morphology, is also responsible for a higher hydrophilicity in the copolymer films. The electroactivity of the compounds were affected negatively with the incorporation on the PEG. However, the optical and conductive properties were good, showing a similar band gap than the semiconductor PPy homopolymer. It was established that the best film was the copolymer P(Py-co-PAB53) generated at 1000s, which was found to be an active surface for adsorption of BSA and Lyz proteins, the results revealed that the affinity of this copolymer is higher than the PPy homopolymer, suggesting that it is a promising polymer for bioengineering applications

Modified polymers as electroactive biomaterials

Aplicat embargament des de la data de defensa fins al 31 de desembre de 2021Premi extraordinari doctorat UPC curs 2019-2020, àmbit d’Enginyeria industrialDevelopment of polymeric biomaterials with tailored properties is essential for expanding biotechnologies and, therefore, proposing novel solutions for diagnostic and treatments in modern medicine. In order to contribute with such expansion, this research suggests different strategies to modify intrinsically conducting polymers (ICPs) and overcome their few limitations. Three main engineering approaches were used to combine ICPs advantages with others from conventional insulating polymers and biopolymers, optimizing their performance as electrochemical biomaterials on tissues engineering, biomimetic platforms, actuators and specially on the biosensing field. The first strategy evaluated in this Thesis was designed to take advantage of the “grafting-through”technique and prepare graft copolymers with ICPs backbones. The incorporation of well-known biocompatible polymers like polyethylene glycol (PEG) and polycaprolactone (PCL) into ICP backbones, increased the cell viability in presence of the synthetized copolymers. Such modifications and the ICPs electroactivity allowed to estimate the copolymers performance as electrochemical sensors of biomolecules. The second approach was planned to prepare free-standing, flexible and electroactive films for the electrochemical detection of bacterial infections. The excellent mechanical properties of isotactic polypropylene (i-PP) plastic, combined with an ICP like poly (3,4-ethylendioxythiophene) (PEDOT), enabled the obtained a novel composite with good dimensional stability to be applied as electrochemical platform for bacterial detection. This composite was able to perceive extracellular nicotinamide adenine dinucleotide (NADH), generated from the respiration reactions of bacteria, and distinguishing prokaryotic microbes from eukaryotic cells. In addition, with a small adjustment, the generated films exhibited qualities as electroactive bioplatforms for tissue engineering. Finally, the third strategy fashioned an electroactive multi-functional nanomembrane for applications of flexible biomedical implants. A layer-by-layer assembly (LbL) was used to integrate the PEDOT electroactivity to the poly(lactic acid) (PLA) biopolymer. The self-supported nanomembrane of 5 layers, showed benefits as biomimetic platforms for selective ion and ATP transport, as well as actuator/artificial muscles. Overall, the characterization studies of the electroactive and biocompatible composites presented in this Thesis, offer a comprehensive view on how modifications in ICPs optimize its abilities as biomaterials and open a wide range of possible applications in biomedicine.El desarrollo de biomateriales poliméricos con propiedades específicas, es esencial para la expansión biotecnológica y, por lo tanto, para el diseño de soluciones novedosas en el diagnóstico y tratamientos de enfermedades en la medicina moderna. Con el objetivo de contribuir con dicha expansión, esta investigación propone diferentes estrategias de modificación en polímeros conductores intrínsecos (ICPs por sus siglas en ingles), y superar con ello sus pocas limitaciones. Tres principales enfoques de ingeniería fueron utilizados para combinar las ventajas de ICPs con las de otros polímeros convencionales y biopolímeros, optimizando su rendimiento como biomateriales electroquímicos en ingeniería de tejidos, plataformas biomiméticas, actuadores y, especialmente, en el campo de la biodetección. La primera estrategia evaluada en esta Tesis, fue diseñada para aprovechar la técnica de injerto y preparar copolímeros con una cadena principal de ICP. Empleando esta técnica, la incorporación de polímeros biocompatibles, como el polietilenglicol (PEG) y la policaprolactona (PCL), en la cadena principal de un ICP, aumentó la viabilidad celular en presencia de los copolímeros formados. Dichas modificaciones y la electroactividad de los ICPs, permitieron estimar el rendimiento de los copolímeros como sensores electroquímicos de biomoléculas. El segundo enfoque fue planeado para preparar películas auto soportables, flexibles y electroactivas, que permitieran la detección electroquímica de infecciones bacterianas. Las excelentes propiedades mecánicas del polipropileno isotáctico (i-PP) en combinación con un ICP, como el poli (3,4-etilendioxitiofeno) (PEDOT), permitieron obtener un nuevo compuesto electroquímico capaz de percibir el dinucleótido adenina de nicotianamina (NADH por su siglas en ingles), generado extracelularmente durante las reacciones respiratorias de las bacterias, y distinguir los microbios procariotas de las células eucariotas. Además, con un pequeño ajuste, las películas generadas exhibieron cualidades como bioplataformas electroactivas para la ingeniería de tejidos. Finalmente, con la tercera estrategia se diseñó una nanomembrana electroactiva multifuncional, para aplicaciones de implantes biomédicos flexibles. Un ensamble de capa por capa, fue utilizado para integrar la electroactividad del PEDOT con el biopolímero ácido poli láctico (PLA por sus siglas en ingles). La nanomembrana auto soportable de 5 capas, mostró beneficios como plataforma biomimética para el transporte selectivo de iones y adenosín trifosfato; o como músculos artificiales o actuadores. En general, los estudios de caracterización de los compuestos electroactivos y biocompatibles presentados en esta Tesis, ofrecen una visión integral de cómo las modificaciones en los ICPs optimizan sus capacidades como biomateriales, y abren una amplia gama de posibles aplicaciones en biomedicina.Award-winningPostprint (published version

Polymers and plastics modified electrodes for biosensors: a review

Polymer materials offer several advantages as supports of biosensing platforms in terms of flexibility, weight, conformability, portability, cost, disposability and scope for integration. The present study reviews the field of electrochemical biosensors fabricated on modified plastics and polymers, focusing the attention, in the first part, on modified conducting polymers to improve sensitivity, selectivity, biocompatibility and mechanical properties, whereas the second part is dedicated to modified “environmentally friendly” polymers to improve the electrical properties. These ecofriendly polymers are divided into three main classes: bioplastics made from natural sources, biodegradable plastics made from traditional petrochemicals and eco/recycled plastics, which are made from recycled plastic materials rather than from raw petrochemicals. Finally, flexible and wearable lab-on-a-chip (LOC) biosensing devices, based on plastic supports, are also discussed. This review is timely due to the significant advances achieved over the last few years in the area of electrochemical biosensors based on modified polymers and aims to direct the readers to emerging trends in this field.Peer ReviewedPostprint (published version

Assembly of Conducting Polymer and Biohydrogel for the Release and Real-Time Monitoring of Vitamin K3

In this work, we report the design and fabrication of a dual-function integrated system to monitor, in real time, the release of previously loaded 2-methyl-1,4-naphthoquinone (MeNQ), also named vitamin K3. The newly developed system consists of poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles, which were embedded into a poly-¿-glutamic acid (¿-PGA) biohydrogel during the gelling reaction between the biopolymer chains and the cross-linker, cystamine. After this, agglomerates of PEDOT nanoparticles homogeneously dispersed inside the biohydrogel were used as polymerization nuclei for the in situ anodic synthesis of poly(hydroxymethyl-3,4-ethylenedioxythiophene) in aqueous solution. After characterization of the resulting flexible electrode composites, their ability to load and release MeNQ was proven and monitored. Specifically, loaded MeNQ molecules, which organized in shells around PEDOT nanoparticles agglomerates when the drug was simply added to the initial gelling solution, were progressively released to a physiological medium. The latter process was successfully monitored using an electrode composite through differential pulse voltammetry. The fabrication of electroactive flexible biohydrogels for real-time release monitoring opens new opportunities for theranostic therapeutic approaches.Peer ReviewedPostprint (published version

Free-standing, flexible nanofeatured polymeric films prepared by spin-coating and anodic polymerization as electrodes for supercapacitors

Flexible and self-standing multilayered films made of nanoperforated poly(lactic acid) (PLA) layers separated by anodically polymerized poly(3,4-ethylenedioxythiophene) (PEDOT) conducting layers have been prepared and used as electrodes for supercapacitors. The influence of the external layer has been evaluated by comparing the charge storage capacity of four- and five-layered films in which the external layer is made of PEDOT (PLA/PEDOT/PLA/PEDOT) and nanoperforated PLA (PLA/PEDOT/PLA/PEDOT/PLA), respectively. In spite of the amount of conducting polymer is the same for both four- and five-layered films, they exhibit significant differences. The electrochemical response in terms of electroactivity, areal specific capacitance, stability, and coulombic efficiency was greater for the four-layered electrodes than for the five-layered ones. Furthermore, the response in terms of leakage current and self-discharge was significantly better for the former electrodes than for the latter ones.Postprint (author's final draft

An amphiphilic, heterografted polythiophene copolymer containing biocompatible/biodegradable side chains for use as an (electro)active surface in biomedical applications

Given that the copolymers of complex topology and composition are at the forefront of multifunctional materials research, this work reports aboutan amphiphilic random, heterografted copolymer of (A-g-B)m-ran-(A-g-C)ntype, which was designed to work as an efficient and biocompatible electronic interface. The copolymer (henceforth denoted as PTh-g-(PEG-r-PCL) for simplification) was synthesized in hierarchical fashion, having ¿-conjugated polythiophene (PTh) as main chain and polarunits, polyethylene glycol (PEG) and oligo-¿-caprolactone as side chains. Theproperties of the newcopolymer,in solution and in solid state,were evaluated. The applied investigations showed that, due to its amphiphilic character and incompatibility of the side chains, PTh-g-(PEG-r-PCL) experiences microphase separation in solutionand film states. By electronicmicroscopy techniques were evidenced two types of supramolecular structures: (a) porous spherical particles and (b) rod-like structures. When deposited on carbon electrodes,the copolymerpresented a good electroactivity and electrostability.Copolymer's biocompatibility studies, performed by using Cos-1 and Vero cell lines,demonstrated an excellent adhesion when comparing with bare steel electrode while a slight decrease of proliferation was registered, more pronounced for Vero cells, in spite of cells normal growth and morphology. Thanks to its excellent capability for electrochemically interfacing with aqueous electrolytes, the voltammetric oxidation ofNADH coenzyme at PTh-g-(PEG-r-PCL) film-modified carbon electrode revealed that it can be used as selective biosensor of this biomolecule, as well.Preprin

Free-standing faradaic motors based on biocompatible nanoperforated poly(lactic acid) layers and electropolymerized poly(3,4-ethylenedioxythiophene)

The electro-chemo-mechanical response of robust and flexible free-standing films made of three nanoperforated poly(lactic acid) (pPLA) layers separated by two anodically polymerized poly(3,4-ethylenedioxythiophene) (PEDOT) layers has been demonstrated. The mechanical and electrochemical properties of these films, which are provided by pPLA and PEDOT, respectively, have been studied by nanoindentation, cyclic voltammetry, and galvanostatic charge–discharge assays. The unprecedented combination of properties obtained for this system is appropriated for its utilization as a Faradaic motor, also named artificial muscle. Application of square potential waves has shown important bending movements in the films, which can be repeated for more than 500 cycles without damaging its mechanical integrity. Furthermore, the actuator is able to push a huge amount of mass, as it has been proved by increasing the mass of the passive pPLA up to 328% while keeping the mass of electroactive PEDOT unaltered.Peer ReviewedPostprint (author's final draft

Perforated polyester nanomebranes as templates of electroactive and robust free-standing films

Robust and flexible free-standing films made of spin-coated poly(lactic acid) (PLA) and poly(3,4-ethylenedioxythiophene) (PEDOT) nanolayers have been prepared. A steel sheet coated with a sacrificial layer of PEDOT:poly(styrenesulfonate) (PSS) and a spin-coated nanolayer of PLA was used as working electrode for the anodic polymerization of 3,4-ethylenedioxythiophene monomer. The latter was only successfully accomplished when rounded-shape nanoperforations of average diameter 49¿±¿14¿nm were introduced into PLA layers, which was achieved by combining the phase segregation processes undergone by immiscible PLA:poly(vinyl alcohol) (PVA) mixtures with selective solvent etching to remove PVA domains. Nanoperforations allowed the utilization of the semiconducting PEDOT:PSS sacrificial layer to immobilize the electropolymerized PEDOT chains. Morphological and topographical studies show the templating effect of PEDOT layers. In addition of flexibility and mechanical strength, free-standing 5-layered films present good electrochemical activity, evidencing their potential ability to reversibly exchange ions with the medium. These properties offer important advantages with respect to those of neat PLA and supported PEDOT films, as has been illustrated by cell culture and protein adsorption assays. Cell cultures evidenced the superior behavior of 5-layered films as bioactive platforms for fibroblast and epithelial cells proliferation, while adsorption assays reflected their potential as selective bioadhesive surfaces for protein separationPeer ReviewedPostprint (author's final draft

Self-standing, conducting and capacitive biomimetic hybrid nanomembranes for selective molecular ion separation

Hybrid free-standing biomimetic materials are developed by integrating the VDAC36 ß-barrel protein into robust and flexible three-layered polymer nanomembranes. The first and third layers are prepared by spin-coating a mixture of poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVA). PVA nanofeatures are transformed into controlled nanoperforations by solvent-etching. The two nanoperforated PLA layers are separated by an electroactive layer, which is successfully electropolymerized by introducing a conducting sacrificial substrate under the first PLA nanosheet. Finally, the nanomaterial is consolidated by immobilizing the VDAC36 protein, active as an ion channel, into the nanoperforations of the upper layer. The integration of the protein causes a significant reduction of the material resistance, which decreases from 21.9 to 3.9 kO cm2. Electrochemical impedance spectroscopy studies using inorganic ions and molecular metabolites (i.e.L-lysine and ATP) not only reveal that the hybrid films behave as electrochemical supercapacitors but also indicate the most appropriate conditions to obtain selective responses against molecular ions as a function of their charge. The combination of polymers and proteins is promising for the development of new devices for engineering, biotechnological and biomedical applications.Hybrid free-standing biomimetic materials are developed by integrating the VDAC36 ß-barrel protein into robust and flexible three-layered polymer nanomembranes. The first and third layers are prepared by spin-coating a mixture of poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVA). PVA nanofeatures are transformed into controlled nanoperforations by solvent-etching. The two nanoperforated PLA layers are separated by an electroactive layer, which is successfully electropolymerized by introducing a conducting sacrificial substrate under the first PLA nanosheet. Finally, the nanomaterial is consolidated by immobilizing the VDAC36 protein, active as an ion channel, into the nanoperforations of the upper layer. The integration of the protein causes a significant reduction of the material resistance, which decreases from 21.9 to 3.9 kO cm2. Electrochemical impedance spectroscopy studies using inorganic ions and molecular metabolites (i.e.L-lysine and ATP) not only reveal that the hybrid films behave as electrochemical supercapacitors but also indicate the most appropriate conditions to obtain selective responses against molecular ions as a function of their charge. The combination of polymers and proteins is promising for the development of new devices for engineering, biotechnological and biomedical applications.Peer ReviewedPostprint (author's final draft

Graft copolymers with a random distribution of pyrrole monomer with hydrophilic functionalities

An electroactive biomaterial was obtained from the electropolymerization of pyrrole (Py) monomer and a macromonomer called PAB53, which has pyrrole as backbone and chains of PEG2000 grafted. The copolymerization was carried out at a molar ratio of 1:1 of Py:PAB53 and at three polymerization times (300, 500 and 1000s), resulting in films with cauliflower-like structures as surface morphology in all cases. The topography, thickness and wettability increased proportionally to the polymerization time, attributed to higher concentrations of PAB53 in the resulting copolymer films. Therefore, the increase of PEG chains, which favors the formation of valleys and hills in the surface morphology, is also responsible for a higher hydrophilicity in the copolymer films. The electroactivity of the compounds were affected negatively with the incorporation on the PEG. However, the optical and conductive properties were good, showing a similar band gap than the semiconductor PPy homopolymer. It was established that the best film was the copolymer P(Py-co-PAB53) generated at 1000s, which was found to be an active surface for adsorption of BSA and Lyz proteins, the results revealed that the affinity of this copolymer is higher than the PPy homopolymer, suggesting that it is a promising polymer for bioengineering applications