This work refers to the area of bio-nanotechnology and concerns the selective immobilization of DNA or other bio-template on microstructured gold contacts and which then permit a coordinated cooperation of several of these nanotemplate, e.g., within a microreactor. The immobilization of such nano-objects should be realized through functional thin polymer films which provide binding groups. Thus, the main aim of this work was the development of polymeric materials for thin functional films which permit to deposit on different substrates a wide variation of functional elements or metal structures and to achieve a pattern formation using optical grid methods. In order to realize this concept it was necessary to design and develop a polymer system based on suitable photolabile units and in addition having anchoring groups which attach on specific substrates like gold. In this terpolymer concept was aimed for which consists of three components with particular functions in suitable molar ratios, which allow the tune the properties of the materials, and provide: amino photolabile protected groups for the photolithographic creation of patterned areas with free amino groups, which are available for further modifications like attachment of colloids, metallization or attachment of DNA strands; disulfide derivative anchor groups providing anchoring capacity for gold surface and spacer groups for adjusting the film quality. These multifunctional terpolymers should be synthesised by free radical polymerisation of suitable monomers. Although these techniques are successful, they are limited by their complexity, rigorous synthetic demands, as well as incompatibility with many functional termolabile and highly reactive functionalities. To overcome these difficulties a polymerisation technique based on “living” free radical polymerisation has been used in this work. A highly efficient polymer-analogous modification allows to introduce the functionalities after the polymer construction reaction. The production of suitable prepolymers [poly(styrene-r-4-propargyl-oxystyrene)] was carried out with the help of a controlled synthesis methodology “nitroxide mediate radical polymerization" followed by polymer analogous reaction using one of the most efficient click reactions, the Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition between terminal acetylenes and azides to attach further functionalities through the formation of a stable 1,4-disubstituted 1,2,3-triazol ring . The combination of nitroxide mediated radical polymerization (NMRP) and click chemistry was used to produce well-defined random copolymer. It could already be shown that also block copolymers can be prepared which give the chance to combine nanostructure formation in block copolymers with special functionality. Thus, the special properties of these functional polymers like the capability for photopatterning and anchoring onto gold substrates make them very interesting for nanotechnology applications. / Diese Arbeit bezieht sich auf das Gebiet der Bionanotechnologie und betrifft ein neuartiges Verfahren zur selektiven Immobilisierung der DNA oder anderer Biomoleküle auf mikrostrukturierten Goldkontakten, welche dann ein koordiniertes Zusammenwirken von einzelnen Nanomolekülen ermöglichen, z.B. in einem Mikroreaktor. Die Immobilisierung solcher Nanoobjekte soll durch dünne Funktionsschichten realisiert werden, die die Anbindungsgruppen liefern. Folglich war das Hauptziel dieser Arbeit die Entwicklung von Polymermaterialien für dünne Funktionsschichten, die die Aufbringung einer großen Vielzahl von Funktionselementen oder metallischen Strukturen auf verschiedenen Substraten gestatten und die Strukturierung durch den Einsatz von lithographischen Methoden ermöglichen. Um dieses Konzept zu realisieren, war es notwendig, ein Polymersystem zu gestalten und zu entwickeln, welches auf geeignete photolabile Einheiten basiert und zusätzlich Ankergruppen hat, die mit spezifischen Substraten wie Gold verbunden ist. Dieses Terpolymerkonzept wurde gezielt aus drei Komponenten mit speziellen Funktionen in entsprechenden molaren Verhältnissen gebildet, die eine Abstimmung der Materialeigenschaften ermöglicht und folgendes bereitstellt: photolabile geschützte Aminogruppen für die photolitographische Strukturerzeugung mit freien Aminogruppen, welche für weitere Modifikationen verfügbar sind wie das Anhängen von Kolloiden, die Metallisierung oder Anfügung von DNA-Strängen; disulfide Derivate für die kovalente Anbindung auf der Goldoberfläche und Spacer-Gruppe für Verbesserung der Schichtenbildung. Diese multifunktionalen Terpolymere sollen durch eine freie radikalische Polymerisation von entsprechenden Monomeren synthetisiert werden. Obwohl diese Techniken erfolgreich sind, sind sie eingeschränkt durch ihre Komplexität, den strengen synthetischen Anforderungen, sowie der Inkompatibilität mit vielen funktionalen thermolabilen und hochreaktiven Funktionalitäten. Um diese Schwierigkeiten zu überwinden wurde eine Polymerisationstechnik für diese Arbeit genutzt, die auf der „lebenden“ freien radikalischen Polymerisation basiert. Eine hoch effiziente polymeranaloge Modifizierung erlaubt die Einführung von Funktionalitäten nach der Polymeraufbaureaktion. Die Herstellung von entsprechenden Präpolymeren Poly(Styrol-r-4-Propargyl-oxystyrol) wurde mittels einer kontrollierten Synthesemethodik „Nitroxid-mediated controled radical polymerisation“ (NMRP) durchgeführt, gefolgt von der Polymeranalogreaktion, die eine der effizientesten Click-Reaktion - die Cu(I) katalysierte 1,3-dipolar Cycloaddition von terminalen Alkinen an Aziden nach Huisgen nutzt, um weiter Funktionalitäten durch die Bildung eines stabilen 1,4-disubstituierten-[1,2,3]-Triazolringes anzufügen. Die Kombination von NMRP und Click-Chemie wurde zur Herstellung eines exakt definierten Random Copolymers genutzt. Es konnte bereits gezeigt werden, dass auch Blockcopolymere geschaffen werden können, die eine Möglichkeit zur Kombination von Nanostrukturformationen in Blockcopolymeren mit speziellen Funktionaltäten bieten. Folglich sind die speziellen Eigenschaften dieser Funktionalpolymere wie die Fähigkeit zur Photostrukturierung und Verankerung auf Goldsubstraten für nanotechnologische Anwendungen sehr interessant.

Factors that confer predisposition and vulnerability for alcoholism and other substance abuse disorders may be described usefully within the gene-environment interplay framework. Thus, it is postulated that heritability provides a major contribution not only to alcohol but also to other substances of abuse. Studies of evoked potential amplitude reduction have provided a highly suitable and testable method for the assessment of both environmentally-determined and heritable characteristics pertaining to substance use and dependence. The different personal attributes that may co-exist with parental influence or exist in a shared, monozygotic relationship contribute to the final expression of addiction. In this connection, it appears that personality disorders are highly prevalent co-morbid conditions among addicted individuals, and, this co-morbidity is likely to be accounted for by multiple complex eti-ological relationships, not least in adolescent individuals. Co-morbidity associated with deficient executive functioning may be observed too in alcohol-related aggressiveness and crimes of violence. The successful intervention into alcohol dependence and craving brought about by baclofen in both human and animal studies elucidates glutamatergic mechanisms in alcoholism whereas the role of the dopamine transporter, in conjunction with both the noradrenergic and serotonergic transporters, are implicated in cocaine dependence and craving. The role of the cannabinoids in ontogeny through an influence upon the expression of key genes for the development of neurotransmitter systems must be considered. Finally, the particular form of behaviour/ characteristic outcome due to childhood circumstance may lie with biological, gene-based determinants, for example individual characteristics of monoamine oxidase (MAO) activity levels, thereby rendering simple predictive measures both redundant and misguiding.

The flexible and stretchable electronic market is increasing particularly in the field of biomedical electronics. Widely used printed silver conductive tracks today are only eligible for on-skin applications. However, for biomedical applications fully biocompatible, flexible and even stretchable materials for device fabrication are needed. This paper presents an additive printing approach to fabricate flexible and stretchable electronics by using a biocompatible platinum material. Usually, in order to realize electrically conducting Ptinterconnects by inkjet printing, it requires a furnace sintering at prohibitively high temperatures, which are not compatible with thermal sensitive polymeric substrates. This paper describes a high-power diode laser sintering (HPDL) and a flash lamp annealing (FLA) as promising alternative sintering methods. Both processes are eligible whereas laser sintering showed slightly better results. Bending tests and adhesive strength tests of platinum printed inks on polyimide with up to 180 000 cycles, show that printed platinum is a suitable biocompatible material for flexible electronics.

The adhesion of coatings is of high importance in the coating industry and a more thorough understanding of adhesion behavior is required. In this thesis work, seven parameters affecting adhesion of silane-modified poly(urethane urea) (PUSi) coatings on pretreated steel and aluminum substrates were studied. These parameters include substrate type, dry film thickness (20-30 and 60-70 μm), solid content (40, 60, and 70 wt%), resin ratio between two different types of PUSi (PUSi-A: PUSi-B = 70:30, 50:50, and 30:70 wt ratio), crosslinking density, additive, and curing condition. The different pretreatments of substrates include solvent wiping, sandblasting, phosphating, and galvanizing. A commercial paint product (‘yellow topcoat’) was used as a reference for the study of substrates and additives. Several formulations of clearcoat, prepared from the same PUSi resins as the commercial paint product, were mainly used in every experiment. The obtained coatings were tested for their adhesion properties using cross hatch adhesion test, bending test, and humidity resistance test. The film hardness and thermo-mechanical properties were evaluated with König pendulum hardness test and Dynamic Mechanical Analysis (DMA), respectively. Surface energies of all substrates were analyzed with Contact Angle Measurement (CAM). The PUSi-A and PUSi-B resins used in the coating formulations were characterized with Differential Scanning Calorimetry (DSC), Size-Exclusion Chromatography (SEC), and Fourier Transform Infrared Spectroscopy (FT-IR). The results showed a correlation between poor adhesion properties and the relatively low surface energies of some substrates, namely cold-rolled steel (CRS), industrial ACE aluminum, and standard Q aluminum. The use of silane-functional crosslinking agent and silane adhesion promoters in the coatings has greatly enhanced adhesion. The increase in film hardness via increased crosslinking density also did not hinder the adhesion due to the presence of silane groups in the crosslinker. Additionally, increased time and temperature during curing showed positive effects. However, the variation of resin ratio, solid content, and film thickness did not offer significant adhesion improvement in this study. / Adhesionsegenskaperna hos ytbeläggningar är av stor betydelse i färg- och lackindustrin och en djupare förståelse av vidhäftning är av stor betydelse. I detta uppsatsarbete studerades sju parametrar som påverkar vidhäftning av silanmodifierad poly(uretan-urea) (PUSi)-beläggningar på stål- och aluminiumsubstrat. Dessa parametrar inkluderar substrattyp, torr filmtjocklek (20-30 och 60-70 μm), torrhalt (40, 60 och 70 viktprocent), mängdförhållandet mellan två olika typer av PUSi (PUSi-A: PUSi-B = 70:30, 50:50 och 30:70 viktprocent), tvärbindningsdensitet, tillsatsmedel och härdningsbetingelser. Förbehandlingen av substraten inkluderar lösningsmedelsavtorkning, sandblästring, fosfatering och galvanisering. En kommersiell ytbehandlingsprodukt innehållandes gula pigment (gul topplack) användes som referens. Flera formuleringar av klarlack, framställda av samma PUSi-hartser som den kommersiella produkten, användes i det experimentella arbetet. Beläggningarna testades med avseende på deras vidhäftningsegenskaper med ’cross-hatch’-test, böjningstest och fuktbeständighetstest. Filmhårdhet och termomekaniska egenskaper utvärderades med König pendelhårdhetstest respektive Dynamisk Mekanisk Analys (DMA). Ytenergier för alla substrat analyserades med kontaktvinkelmätning (CAM). PUSi-A- och PUSi-B-hartserna som användes i ytbeläggningarna karaktäriserades med Differential Scanning Calorimetry (DSC), Size-Exclusion Chromatography (SEC) och Fourier Transform Infrared Spectroscopy (FT-IR). Resultaten visade en korrelation mellan dålig vidhäftning och låga ytenergier för vissa underlag, främst kallvalsat stål (CRS), industriellt ACE-aluminium och standard Q-aluminium. Användningen av silan-funktionell tvärbindare och en silan-baserad primer förbättrade vidhäftningen avsevärt. Ökningen i filmhårdhet genom högre tvärbindningsdensitet resulterade inte i sämre vidhäftning eftersom tvärbindaren innehåller silan-grupper vilket bidrog till att upprätthålla vidhäftningen. Längre tid och högre temperatur vid härdning gav generellt bättre vidhäftning, liksom tillsats av urea. Att variera mängden bindemedel, torrhalt eller filmtjocklek gav inte någon signifikant påverkan på vidhäftning i denna studie.

Tesis por compendio / [ES] Uno de los mayores retos en los que incurre la producción agrícola hoy en día reside en alimentar de forma sostenible a una población creciente a la vez que concentra sus esfuerzos en hacerlo con el menor impacto ecológico posible. El actual sistema agroalimentario no solo impacta negativamente desde la perspectiva de la emisión de gases invernadero, sino que también favorece otros ámbitos como la degradación de los productos naturales, la pérdida de la biodiversidad o los cambios en el uso del suelo. La evidencia de este proceso de deterioro a escala mundial requiere de la puesta en marcha de planes de acción basados tanto en la mitigación del cambio climático (mediante la reducción de los gases de efecto invernadero) como en la adaptación al mismo mediante buenas prácticas agrícolas que consigan reducir la vulnerabilidad de los cultivos. Los objetivos de esta tesis se enmarcan en las vías de actuación definidas como prioritarias por la Asamblea General de las Naciones Unidas "Transformar nuestro mundo: la Agenda 2030 para el Desarrollo Sostenible". Más concretamente, en la mejora de la sostenibilidad del cultivo del almendro (Prunus dulcis Miller) prestando especial atención a la respuesta del sistema radical y su capacidad para mejorar la adaptación del cultivo a los nuevos escenarios derivados del proceso de cambio climático. En esta tesis se caracterizaron química y morfométricamente tres patrones de almendro. Se observaron diferencias significativas tanto en los sistemas radiculares como vegetativos de los mismos siendo el patrón GN el más vigoroso, el GF 677 el que presentó mayor número de raíces principales y el RP-R secundarias. Además, GN destacó por presentar mayor poder antioxidante y mayor contenido en fenoles, pudiendo estas propiedades influir en los mecanismos de defensa de la planta al inducir resistencia frente a determinados estreses. Los patrones se sometieron a diferentes medios de cultivo mediante el uso de dos sustratos. Las plantas cultivadas bajo fibra de coco presentaron un aumento masivo de raíces absorbentes y un engrosamiento del tronco mientras que las plantas cultivadas en la mezcla de turba y arena presentaron mayor longitud del sistema radical. Se estudió la respuesta de los patrones frente al aporte de bioestimulantes de raíz en vistas a contribuir a un manejo más racional y sostenible del cultivo. La fertilización mediante bioestimulantes tuvo un impacto significativo en el desarrollo de las plantas tanto a nivel aéreo como radicular y consiguió acortar los plazos de vivero, logrando plantas con mejor o más rápida capacidad de adaptación al campo. A grandes rasgos los mejores resultados se obtuvieron con el bioestimulante compuesto por materia orgánica, aminoácidos y extractos de algas. Adicionalmente y en respuesta a los retos medioambientales actuales se analizaron las propiedades energéticas del almendro y el posible uso de sus residuos como fuente de energía renovable atendiendo a diferentes factores que podrían influir sus propiedades energéticas como son la variedad, el patrón o el tipo de fertilización. Observamos que las variables que más influyeron en el poder calorífico del material fueron la variedad, el patrón y la interacción entre ambos. Siendo el cultivar Marcona y el patrón GF 305 los que presentaron mejores propiedades energéticas. / [CA] Un dels majors reptes en els quals incorre la producció agrícola hui dia resideix a alimentar de manera sostenible a una població creixent alhora que concentra els seus esforços a fer-ho amb el menor impacte ecològic possible. L'actual sistema agroalimentari no sols impacta negativament des de la perspectiva de l'emissió de gasos amb efecte d'hivernacle, sinó que també afavoreix altres àmbits com la degradació dels productes naturals, la pèrdua de la biodiversitat o els canvis en l'ús del sòl. L'evidència d'aquest procés de deterioració a escala mundial requereix de la posada en marxa de plans d'acció basats tant en la mitigació del canvi climàtic (mitjançant la reducció dels gasos d'efecte d'hivernacle) com en l'adaptació al mateix mitjançant bones pràctiques agrícoles que aconseguisquen reduir la vulnerabilitat dels cultius. Els objectius d'aquesta tesi s'emmarquen en les vies d'actuació definides com a prioritàries per l'Assemblea General de les Nacions Unides "Transformar el nostre món: l'Agenda 2030 per al Desenvolupament Sostenible". Més concretament, en la millora de la sostenibilitat del cultiu de l'ametler (Prunus dulcis Miller) prestant especial atenció a la resposta del sistema radical i la seua capacitat per a millorar l'adaptació del cultiu als nous escenaris derivats del procés de canvi climàtic. En aquesta tesi es van caracteritzar química i morfométricament tres patrons d'ametler. Es van observar diferències significatives tant en els sistemes radiculars com vegetatius dels mateixos sent el patró GN el més vigorós, el GF 677 el que va presentar major nombre d'arrels principals i el RP-R secundàries. A més, GN va destacar per presentar major poder antioxidant i major contingut en fenols, podent aquestes propietats influir en els mecanismes de defensa de la planta en induir resistència enfront de determinats estressos. Els patrons es van sotmetre a diferents mitjans de cultiu mitjançant l'ús de dos substrats. Les plantes cultivades sota fibra de coco van presentar un augment massiu d'arrels absorbents i un engruiximent del tronc mentre que les plantes cultivades en la mescla de torba i arena van presentar major longitud del sistema radical. Es va estudiar la resposta dels patrons enfront de l'aportació de bioestimulants d'arrel en vistes a contribuir a un maneig més racional i sostenible del cultiu. La fertilització mitjançant bioestimulants va tindre un impacte significatiu en el desenvolupament de les plantes tant a nivell aeri com radicular i va aconseguir acurtar els terminis de viver, aconseguint plantes amb millor o més ràpida capacitat d'adaptació al camp. A grans trets els millors resultats es van obtindre amb el bioestimulant compost per matèria orgànica, aminoàcids i extractes d'algues. Addicionalment i en resposta als reptes mediambientals actuals es van analitzar les propietats energètiques de l'ametler i el possible ús dels seus residus com a font d'energia renovable atenent a diferents factors que podrien influir en les seues propietats energètiques com són la varietat, el patró o el tipus de fertilització. Observem que les variables que més van influir en el poder calorífic del material van ser la varietat, el patró i la interacció entre tots dos. Sent el cultivar Marcona i el patró GF 305 els que van presentar millors propietats energètiques. / [EN] One of the greatest challenges that agricultural production is facing today lies in sustainably feeding a growing population while concentrating on doing so with the least possible ecological impact. The current agri-food system not only has a negative impact from the perspective of greenhouse gas emissions, but also favors other areas such as the degradation of natural products, the loss of biodiversity or the changes in land use. The evidence of this process of deterioration on a global scale requires the implementation of action plans based on both climate change mitigation (by reducing greenhouse gases) and climate adaptation through good agricultural practices that manage to reduce the vulnerability of crops. The objectives of this thesis are framed in the courses of action defined as priorities by the General Assembly of the United Nations "Transforming our world: the 2030 Agenda for Sustainable Development". More specifically, in improving the sustainability of almond (Prunus dulcis Miller) cultivation, paying special attention to the response of the root system and its ability to improve the adaptation of the crop to the new scenarios derived from the process of climate change. In this thesis, three almond rootstocks were chemically and morphometrically characterized. Significant differences were observed both in their root and vegetative systems, with the GN rootstock being the most vigorous, the GF 677 the one with the highest number of main roots, and the RP-R the one showing more secondary roots. In addition, GN stood out for presenting greater antioxidant power and higher phenol content, these properties being able to influence the plant's defense mechanisms by inducing resistance to certain stresses. The rootstocks were subjected to different culture media by using two substrates. The plants grown under coconut fiber showed a massive increase in absorbent roots and a thickening of the trunk, while the plants grown in the mixture of peat and sand showed greater length of the root system. The response of rootstocks to the contribution of root biostimulants was studied to contribute to a more rational and sustainable management of the crop. Fertilization using biostimulants had a significant impact on the development of plants both at aerial and root levels and managed to shorten nursery periods, achieving plants with a better or faster capacity to adapt to the field. Broadly, the best results were obtained with the biostimulant composed of organic matter, amino acids and algae extracts. Additionally, and in response to current environmental challenges, the energy properties of the almond tree and the possible use of its residues as a source of renewable energy were analyzed considering different factors that could influence its energy properties, such as the variety, rootstock, or type of fertilization. We observed that the variables that most influenced the calorific power of the material were the variety, the rootstock and the interaction between both. The Marcona variety and the GF 305 rootstock were the ones that presented the best energy properties. / This work was funded by Project 20170734. Development of methods of quantification of riparian vegetation biomass for the management of channels of the Comunitat Valencianaect . Dirección General de Universidades. Generalitat Valenciana (Spain). / Mondragón Valero, A. (2022). Caracterización de materiales de almendro y mejora del desarrollo de planta joven [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/184486 / Compendio

Tesis por compendio / [ES] Actualmente las lesiones del sistema nervioso periférico que conllevan una pérdida de continuidad de los haces axonales suelen implicar secuelas de tipo permanente. Es cierto que en el sistema nervioso periférico existe una cierta regeneración natural de los tractos axonales dañados, pero solamente cuando el espacio entre ambos extremos de la lesión es pequeño, como máximo de 5 mm. Si el espacio es mayor que esta distancia la regeneración no sucede de forma natural y se crea un neuroma traumático. Por tanto, estas lesiones largas requieren de una intervención quirúrgica para puentear la lesión, normalmente con un nervio autógrafo del propio paciente o un nervio alógrafo de un cadáver. No obstante, su uso presenta diversos inconvenientes, como la morbilidad del sitio donante donde puede ocurrir un neuroma, la necesidad de realizar una segunda cirugía, la diferencia de tamaño entre nervio receptor y donante o la necesidad de inmunosupresión en el caso de los nervios alógrafos. Por ello, la ingeniería de tejidos trabaja en el desarrollo de los conductos de guiado nervioso que incorporan estrategias para guiar topográficamente la regeneración, así como células y moléculas bioactivas. La presente tesis doctoral presenta un nuevo conducto de guiado nervioso con una aproximación multimodular para su aplicación en la regeneración de lesiones nerviosas largas (a partir de 15 mm) que hace uso de conductos tubulares huecos modulares de ácido hialurónico (HA) que contienen en su interior una estructura tubular de microfibras de ácido poliláctico (PLA). La estructura fibrilar aporta un guiado topográfico necesario para guiar el crecimiento axonal durante la regeneración a la vez que mantiene unidos los diferentes módulos de HA. Por su parte, los conductos de HA son un hidrogel que evita adherencias con el tejido circundante. A su vez, proporcionan un soporte sobre el que pueden crecer células presembradas. En concreto se ha optado por presembrar células de Schwann, las cuales son unas células gliales de soporte críticas para la regeneración del sistema nervioso periférico. Se ha observado que dichas células son capaces recubrir por completo las paredes internas de los conductos de HA formando una estructura tipo vaina, así como de recubrir las microfibras de PLA creciendo en dirección longitudinal. Los experimentos in vivo en modelo de nervio ciático de conejo han mostrado que la aproximación multimodular mejora significativamente la regeneración nerviosa gracias a proporcionar una mejor neovascularización. A su vez, gracias a las células de Schwann presembradas se ha logrado una mejora adicional de la regeneración nerviosa gracias a su efecto favorecedor del crecimiento axonal. Además, se han estudiado diferentes mejoras aplicables al conducto de guiado nervioso con el objetivo de mejorar los resultados obtenidos in vivo. Gracias a la incorporación de fibroína de seda a los conductos de HA se ha logrado mejorar sus propiedades mecánicas y biológicas. Asimismo, también se ha desarrollado un sustrato electroconductor de microfibras de PLA recubiertas con el polímero electroconductor Polipirrol gracias al cual se ha observado in vitro que es capaz de mejorar el crecimiento axonal al aplicar una estimulación eléctrica. Además, mediante un sistema de modificación génica de las células de Schwann por electrotransfección se ha logrado aumentar su secreción del factor neurotrófico derivado del cerebro (BDNF), gracias a lo cual se ha observado que se incrementa la velocidad de crecimiento axonal in vitro. / [CA] Actualment les lesions del sistema nerviós perifèric que comporten una pèrdua de continuïtat dels feixos axonals solen implicar seqüeles de tipus permanent. És cert que al sistema nerviós perifèric hi ha una certa regeneració natural dels tractes axonals danyats, però només quan l'espai entre ambdós extrems de la lesió és petit, com a màxim de 5 mm. Si l'espai és més gran que aquesta distància la regeneració no succeeix de manera natural i es crea un neuroma traumàtic. Per tant, aquestes lesions llargues requereixen una intervenció quirúrgica per pontejar la lesió, normalment amb un nervi autògraf del pacient o un nervi al·lògraf d'un cadàver. No obstant això, el seu ús presenta diversos inconvenients, com la morbilitat del lloc donant on pot ocórrer un neuroma, la necessitat de fer una segona cirurgia, la diferència de mida entre nervi receptor i donant o la necessitat d'immunosupressió en el cas dels nervis al·lògrafs . Per això, l'enginyeria de teixits treballa en el desenvolupament dels conductes de guiatge nerviós que incorporen estratègies per guiar topogràficament la regeneració, així com cèl·lules i molècules bioactives. Aquesta tesi doctoral presenta un nou conducte de guiatge nerviós amb una aproximació multimodular per a la seva aplicació en la regeneració de lesions nervioses llargues (a partir de 15 mm) que fa ús de conductes tubulars buits modulars d'àcid hialurònic (HA) que contenen al seu interior una estructura tubular de microfibres d'àcid polilàctic (PLA). L'estructura fibril·lar aporta un guiatge topogràfic necessari per guiar el creixement axonal durant la regeneració alhora que manté units els diferents mòduls d'HA. Per part seva, els conductes d'HA són un hidrogel que evita adherències amb el teixit circumdant. Alhora, proporcionen un suport sobre el qual poden créixer cèl·lules presembrades. En concret s'ha optat per presembrar cèl·lules de Schwann, les quals són unes cèl·lules glials de suport crítiques per a la regeneració del sistema nerviós perifèric. S'ha observat que aquestes cèl·lules són capaces de recobrir completament les parets internes dels conductes d'HA formant una estructura tipus beina, així com de recobrir les microfibres de PLA creixent en direcció longitudinal. Els experiments in vivo en model de nervi ciàtic de conill han mostrat que l'aproximació multimodular millora significativament la regeneració nerviosa gràcies a proporcionar una millor neovascularització. Alhora, gràcies a les cèl·lules de Schwann presembrades s'ha aconseguit una millora addicional de la regeneració nerviosa gràcies al seu efecte afavoridor del creixement axonal. A més, s'han estudiat diferents millores aplicables al conducte de guiatge nerviós per tal de millorar els resultats obtinguts in vivo. Gràcies a la incorporació de fibroïna de seda als conductes d'HA s'ha aconseguit millorar les seues propietats mecàniques i biològiques. També s'ha desenvolupat un substrat electroconductor de microfibres de PLA recobertes amb el polímer electroconductor Polipirrol gràcies al qual s'ha observat in vitro que és capaç de millorar el creixement axonal quan s'aplica una estimulació elèctrica. A més, mitjançant un sistema de modificació gènica de les cèl·lules de Schwann per electrotransfecció s'ha aconseguit augmentar la secreció del factor neurotròfic derivat del cervell (BDNF), gràcies a la qual cosa s'ha observat que s'incrementa la velocitat de creixement axonal in vitro. / [EN] Currently, lesions of the peripheral nervous system that lead to a loss of continuity of the axonal bundles usually involve permanent sequelae. It is true that in the peripheral nervous system there is some natural regeneration of damaged axonal tracts, but only when the space between the two ends of the lesion is small, at most 5 mm. If the gap is greater than this distance, regeneration does not occur naturally, and a traumatic neuroma is created. Therefore, these long injuries require surgical intervention to bridge the injury, usually with an autograph nerve from the patient or an allograph nerve from a cadaver. However, its use has various drawbacks, such as the morbidity of the donor site where a neuroma can occur, the need to perform a second surgery, the difference in size between the recipient and donor nerves, or the need for immunosuppression in the case of allograft nerves. For this reason, tissue engineering works on the development of nerve guidance conduits that incorporate strategies to topographically guide the regeneration, as well as cells and bioactive molecules. This doctoral thesis presents a new nerve guidance conduit with a multimodular approach for its application in the regeneration of long nerve lesions (from 15 mm) that makes use of modular hollow tubular conduits of hyaluronic acid (HA) that contain in their inside a tubular structure of microfibers of polylactic acid (PLA). The fibrillar structure provides the necessary topographic guidance to guide axonal growth during regeneration while keeping the different HA modules together. For their part, the HA conduits are a hydrogel that prevents adhesions with the surrounding tissue. In turn, they provide a support on which preseeded cells can grow. Specifically, it has been decided to pre-seed Schwann cells, which are glial support cells that are critical for the regeneration of the peripheral nervous system. It has been observed that these cells are capable of completely covering the inner walls of the HA conduits, forming a sheath-like structure, as well as covering the PLA microfibers by growing in a longitudinal direction. In vivo experiments in a rabbit sciatic nerve model have shown that the multimodular approach significantly improves nerve regeneration by providing better neovascularization. In turn, thanks to the pre-seeded Schwann cells, an additional improvement in nerve regeneration has been achieved thanks to its promoting effect on axonal growth. In addition, different improvements applicable to the nerve guidance conduit have been studied with the aim of improving the results obtained in vivo. Thanks to the incorporation of silk fibroin into HA conduits, their mechanical and biological properties have been improved. Likewise, an electroconductive substrate of PLA microfibers coated with the electroconductive polymer Polypyrrole has also been developed, thanks to which it has been observed in vitro that it is capable of improving axonal growth by applying electrical stimulation. In addition, by means of a gene modification system of Schwann cells by electrotransfection, it has been possible to increase their secretion of brain-derived neurotrophic factor (BDNF), thanks to which it has been observed that the speed of axonal growth is increased in vitro. / Agradezco la ayuda de los diferentes proyectos del Ministerio de Economía y Competitividad del Gobierno de España que han hecho posible la financiación de esta tesis doctoral: MAT2015-66666-C3-1-R, DPI2015-72863-EXP, AEI RTI2018-095872-B-C21-C22/ERDF y FPU16/01833 del Ministerio de Universidades del Gobierno de España, sin la cual no hubiera podido realizar esta tesis doctoral. / Gisbert Roca, F. (2022). Strategies for Guidance and Electrical and Biological Stimulation in a Neural Regeneration Device [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/189937 / Compendio

Freshwater is a finite resource that is rapidly becoming more scrutinized in agricultural consumption. Specialty crop producers, especially ornamental crop producers, must continually improve production sustainability, with regards to water resource management, in order to continue to stay economically viable. Soilless substrates were initially developed to have increased porosity and relatively low water holding capacity to ensure container crops would not remain overhydrated after irrigations or rain events. As a result, substrates were selected that are now considered to be in efficient in regards to water resource management. Therefore, to provide growers with additional means to improve production sustainability, soilless substrate hydrology needs be innovated to provide increased water availability while continuing to provide ample air filled porosity to ensure productive and efficient water interactions. Historically, soilless substrates have been characterized using "static" physical properties (i.e. maximum water holding capacity and minimum air-filled porosity). The research herein involves integrating dynamic soilless substrate hydraulic properties to understand how substrate hydrology can be manipulated to design sustainable substrates. This task involved adapting new technologies to analyze hydrological properties of peat and pine bark substrates by employing evaporative moisture characteristic measurements, which were originally designed for mineral soils, for soilless substrate analyses. Utilizing these evaporative measurements provide more accurate measures of substrate water potentials between -10 and -800 hPa than traditional pressure plate measurements. Soilless substrates were engineered, utilizing only three common substrate components [stabilized pine bark (Pinus taedea L.), Sphagnum peatmoss, and coconut coir fiber], via particle fractionation and fibrous additions. The engineering process yielded substrates with increased unsaturated hydraulic conductivity, pore connectivity, and more uniform pore size distributions. These substrates were tested in a greenhouse with irrigation systems designed to hold substrates at (-100 to -300 hPa) or approaching (-50 to -100 hPa) water potentials associated with drought stress. Substrate-water dynamics were monitored, as were plant morphology and drought stress indicators. It was determined that increased substrate unsaturated hydraulic conductivity within the production water potentials, allowed for increased crop growth, reduction in drought stress indicators, while producing marketable plants. Furthermore, individual plants were produced using as low as 5.3 L per plant. Increased production range substrate hydraulic conductivity was able to maintain necessary levels of air-filled porosity due to reduced irrigation volumes, while providing water for plants when needed. The substrates were able to conduct water from throughout the container volume to the plant roots for uptake when roots reduced substrate water potential. Furthermore, increased substrate hydraulic conductivity allowed plants within the substrate to continue absorbing water at much lower water potentials than those in unaltered (control) pine bark. Finally, HYDRUS models were utilized to simulate water flux through containerized substrates. These models allowed for better understanding of how individual hydraulic properties influence substrate water flux, and provided insight towards proportions of inaccessible pores, which do not maintain sufficient levels of available water. With the models, researchers will be able to simulate new substrates, and utilize model predictions to provide insight toward new substrates prior to implementing production tests. It has been determined, that increasing substrate hydraulic conductivity, which can be done with just commonly used components, water requirements for production can be reduced, to produce crops with minimal wasted water resources. Concluding, that re-engineering substrate hydrology can ameliorate production sustainability and decrease environmental impact. / Ph. D. / The world is rapidly approaching a time when water will become a limited resource, not only for agriculture, but all daily uses. As a result specialty crop production must continue to increase sustainability in order to continue to thrive. One area where growers and researchers believe environmental stewardship can be increased is through designing more resource efficient soilless substrates. Soilless substrates (potting media) are utilized world-wide by container crop producers as a rooting medium for specialty crops. These substrates were developed to be very forgiving for growers. By that, growers could apply excess water through irrigation or precipitations and these substrates were designed to readily drain excess water. This provides an opportunity to create more water efficient substrates to help reduce water consumption by container nurseries. The processes involving water-air-substrate interactions within the container are not well understood. As a result, my research involves measuring, manipulating, maintaining, and modeling substrate hydrology in an effort to design substrates that will conserve water in container production. I incorporated new technology used in Soil Science to measure hydraulic properties of soilless substrates through the evaporative method. I then understood how growers and allied suppliers can easily modify these substrate hydraulic properties. Next, I researched how these manipulated hydraulic properties would influence plant growth and vitality, by maintaining drought level irrigation levels over multiple crops. Finally, I modeled substrate hydraulic properties to better understand water movement through a container. Through the research herein, I was able to determine that substrate hydrology can be easily modified to provide container crops with more easily accessed water, while still keeping sufficient air-space for plant growth. Increasing unsaturated hydraulic conductivity in soilless substrates, allows ornamental crops to be held at lower water regimes moisture levels traditionally considered to be drought levels. Utilizing the HYDRUS model, I was able to determine how to develop future substrate models that will accurately simulate real-world outcomes, providing researchers with another tool to quickly predict impacts of newly developed (or still in development) soilless substrates on water status in container production.

Der zerstörungsfreien Charakterisierung und Analyse von lebenden humanen Zellen über längere Zeiträume kommt zukünftig in Medizin und Biotechnologie eine zentrale Rolle zu. Für eine therapeutische Nutzung müssen die Zellen nach der Analyse unverändert und vital vorliegen. Ein Ansatz beruht auf der Analyse von nanoskopischen Zellrückständen, die von Zellen während der Migration hinterlassen werden, den Zellspuren. Diese spiegeln in repräsentativer Weise die Merkmale der Erzeugerzelle wider. Für die technische Nutzung muss der Entstehungsprozess reproduzierbar kontrolliert werden können. Im Zusammenhang wurde ein Versuchsaufbau zur Beobachtung der dynamischen Prozesse Adhäsion, Migration und substratnahe Organisation des Zytoskeletts von lebenden Zellen entwicklet, der hochauflösende Langzeitbeobachtungen mittels Totaler Interner Reflexions Fluoreszenz (TIRF-) Mikroskopie ermöglicht. Zur Auswertung wurde eine auf Falschfarben beruhende Darstellungsweise der dynamischen Prozesse entwickelt. Es konnte eine Korrelation der Eigenschaften der Zellspuren mit dem Adhäsions- und Migrationsverhalten, sowie dem Aufbau der substratnahen Bereiche des Zytoskeletts der Erzeugerzellen nachgewiesen werden. Ebenso wurde der Einfluss der oberflächenspezifischen Substrateigenschaften (Beschichtung oder topografische Strukturierung) auf die Zellspurablage gezeigt. / Nondestructive characterisation and analysis of human living cells over a long period will be an important issue for medicin and biotechnology in the near future. In order to use the cells after analysis for therapeutical applications, the cells have to be unmodified and still alive after the analytical procedure. The analysis of nanoscopic cell residues, called cell traces, which are left behind during cell migration represent an appropriate approach. Attributes of the donor cell are shown by the cell trace characteristically. In order to use cell traces for biotechnological applications the formation and deposition of cell traces has to be repeatable. Thus, an experimental set up using Total Internal Fluorescence Microscopy (TIRF) has been established to observe the dynamic processes of cell adhesion, cell migration and the organisation of the cytoskeleton used therein. Using miscolours a new embodiment has been developed to evaluate dynamic processes. Cell adhesion, cell migration and the organisation of the actin cytoskeleton of the donor cells have been found to influence the attributes of cell traces. Further specific modified surfaces have been used to influence the deposition of cell traces. Effects have been shown for coated surfaces or surfaces with a topographic structure.

Perowskite und Perowskit-artige Materialien sind von großem Interesse, da sie eine Vielzahl von strukturellen und physikalischen Eigenschaften haben, welche die Möglichkeit bieten, sie für unterschiedliche Anwendungen einzusetzen. Die Methode der Liquid-Delivery Metal Organic Chemical Vapour Deposition (LD-MOCVD) wurde gewählt, da sie eine gute Kontrolle über die Zusammensetzung ternärer Oxide und eine hohe Homogenität der Filme ermöglicht. Darüber hinaus können mit dieser Methode Filme hergestellt werden, die aus Elementen bestehen, für welche nur feste Precursor oder welche mit niedrigem Dampfdruck zur Verfügung stehen. Ziel dieser Arbeit war es, mit Hilfe der LD-MOCVD Filme aus SrRuO3, Bi4Ti3O12 und (Na,Bi)4Ti3O12 abzuscheiden und den Einfluss der Wachstumsbedingungen auf die Eigenschaften der Filme zu untersuchen. Zusätzlich wurde die Wirkung der Verspannung, die durch die Gitterfehlanpassung zwischen Substrat und Film entsteht, auf die physikalischen Eigenschaften der Schichten untersucht. SrRuO3 Filme wurden auf gestuften SrTiO3(001), NdGaO3(110) und DyScO3(110) Substraten gewachsen, deren Oberflächenterminierung durch oberflächensensitive Proton-induzierte Auger-Elektronen-Spektroskopie (AES) bestimmt wurde. Die Substrate wurden unter verschiedenen Bedingungen durch Änderung der Temperdauer und -atmosphäre präpariert. Die systematische Untersuchung der Beziehung zwischen Verspannung und Curie-Temperatur von dünnen SrRuO3(100) Filmen erfolgte unter Verwendung von Substraten mit unterschiedlichen Gitterkonstanten. Die beobachtete Curie-Temperatur sank mit erhöhter kompressiver Verspannung und nahm mit erhöhter tensiler Verspannung zu. Um stöchiometrische und epitaktische Bi4Ti3O12(001) Filme zu wachsen, war aufgrund der Flüchtigkeit des Bismuts ein Bi Überschuss in der Precursor-Lösung notwendig. Die Substitution von Bi durch Na in Bi4Ti3O12 wurde zum ersten Mal in LD-MOCVD-Filmen erreicht. / Perovskites and perovskite-like materials are actually of great interest since they offer a wide range of structural and physical properties giving the opportunity to employ these materials for different applications. Liquid-Delivery Metal Organic Chemical Vapour deposition (LD-MOCVD) was chosen due to the easy composition control for ternary oxides, high uniformity and good conformal step coverage. Additionally, it allows growing the films, containing elements, for which only solid or low vapour pressure precursors, having mainly thermal stability problems over long heating periods, are available. The purpose of this work was to grow SrRuO3, Bi4Ti3O12 and (Na, Bi)4Ti3O12 films by LD-MOCVD and to investigate the influence of the deposition conditions on the properties of the films. Additionally, the effect of the strain due to the lattice mismatch between substrates and films on the physical properties of the films was also investigated. SrRuO3 films were grown on stepped SrTiO3(001), NdGaO3(110) and DyScO3(110) substrates, which were prepared under different conditions by changing the annealing time and atmosphere. The termination of the substrates was measured by surface sensitive proton-induced Auger Electron Spectroscopy (p-AES) technique. Another systematic study of the relation between epitaxial strain and Curie temperature of thin SrRuO3(100) films was performed by using substrates with different lattice constants. The observed Curie temperature decreased with compressive and increased with tensile strain. Thin films of Bi4Ti3O12 as well as (Na, Bi)4Ti3O12 were successfully deposited. In order to grow stoichiometric and epitaxial Bi4Ti3O12(001) films, Bi excess in the precursor solution was necessary, due to the volatility of Bi. Substitution of Bi with Na in Bi4Ti3O12 was achieved for the first time for the films deposited by LD-MOCVD.

Les applications présentées dans cette thèse valorisent de diverses manières le principe d'ablation laser, c'est à dire l'arrachement de la matière d'une surface solide suite à l'irradiation avec un faisceau laser. Le plasma généré par irradiation laser impulsionnel a été utilisé pour le dépôt de couches minces ou de nanoparticules et pour l'analyse compositionnelle des couches d'épaisseur nanométrique. Nous avons synthétisé par dépôt laser combinatoire des librairies compositionnelles d'un oxyde mixte transparent d'In et Zn. En utilisant le plasma d'ablation pour le diagnostic compositionnel, nous avons déterminé les concentrations d'indium et de zinc dans les couches minces par spectroscopie laser. Des couches minces de bioverre ont été synthétisées par dépôt laser impulsionnel sur des substrats de titane. En contact avec des cellules ostéoblastes, les bioverres ont stimulé la prolifération et ont augmenté la viabilité. La prolifération des ostéoblastes cultivés sur les couches de bioverre a été 30% supérieure a l'échantillon de contrôle. On a déposé par PLD des couches minces ou nanoparticules adhérentes de ZnO sur des substrats textiles hydrophiles dans un flux d'oxygène ou sous vide pour obtenir des structures avec différentes mouillabilités. En augmentant le nombre d'impulsions laser de 10 à 100 nous avons observé la transition du recouvrement par des nanoparticules isolées vers des couches minces. En fonction de l'atmosphère environnant lors du dépôt, les couches minces et les nanoparticules ont changé leur mouillabilité, passant d'hydrophile en flux d'oxygène à un comportement superhydrophobe (angle de contact de 157°) en cas de dépôt sous vide. / The applications presented in this thesis exploit in different modes the principle of laser ablation, i.e. the material removal from a solid surface following irradiation with a pulsed laser beam. The plasma generated by laser ablation was used for thin films or nanoparticles deposition and for the compositional analysis of nanometric thin films. We synthesized by combinatorial pulsed laser deposition, thin film libraries of a complex oxide of In and Zn. Using the ablation plasma for compositional diagnostic, we determined the In and Zn concentrations in films by Laser Induced Breakdown Spectroscopy using a procedure based on the spectral luminance calculation of a plasma in local thermodynamic equilibrium. Thin films of bioactive glass were synthesized by pulsed laser deposition, magnetron sputtering and MAPLE on Ti substrates and tested the transfer accuracy by physico-chemical tests and their functionality in vitro. In contact with human osteoblast cells, the bioactive glasses stimulated their proliferation and enhanced their viability. The proliferation of osteoblasts cultivated on bioactive films was 30% superior to the control sample. ZnO thin films or nanoparticles were deposited on hydrophilic textile substrates in oxygen flux or in vacuum in order to obtain structures with different wetting behavior. Increasing the number of laser pulses from 10 to 100, we observed a coating transition from isolated nanoparticles to thin films fully coating the textile fibers. Function of the ambient atmosphere during experiments, the structures changed their wetting behavior, passing from hydrophilic in oxygen flux to superhydrophobic (157°) in case of deposition in vacuum.