Committee:
     PRESIDENT: SAURINA CANALS, JOAN
     SECRETARI: GARRIGA SOLE, PERE
     VOCAL: MARÍN GENESCÀ, MARC
Thesis abstract: On April 29th, 2015, the EU enacted Directive 2015/720, aimed at reducing plastic consumption, promoting the use of reusable bags and encouraging the replacement of single-use plastic bags with biodegradable alternatives. This European legislation was transposed into Spanish law by Royal Decree 293/2018, dated May 18th.This legislation and its accompanying regulations have significantly impacted the transformation sector, forcing it to reinvent itself to continue its activities. This work aims to provide answers to the challenges faced by manufacturers due to this new context, as well as address the needs resulting from it. Distinctive features of this project are its practical nature and industrial scale.A primary objective is to establish the processability and quality windows for recycled post-industrial and post-consumer materials, ensuring the production of a final product with predefined quality standards. The study examines three types of polyethylene: virgin, post-industrial, and post-consumer. Each type undergoes a combined cycle simulating an industrial recycling process, with post-industrial material being processed up to twelve times and post-consumer material up to four times. This methodology of cyclic processing supports the principle of circularity in sample characterization.For each cycle, involving extrusion and recycling, the study examines micro and macroscopic changes, analyzing morphological and structural changes (using DSC, TGA, GPC, and FTIR techniques) and the evolution of mechanical properties (tensile strength, elongation at break, tear resistance, impact resistance (dart test), and colorimetric changes).At the microstructural level, two types of crystalline structures are observed, and they evolve differently through the processing cycles due to the thermo-oxidative degradation phenomena that occur along the process. The changes include a reduction in crystallinity due to the breakdown of more linear and less branched chains, and an increase in cross-linking among more branched structures. These microstructural changes affect post-industrial and post-consumer recycled polyethylene differently.Macroscopically, tear resistance is the most critical property affected during the recycling cycles, decreasing by up to 40% from the initial value and potentially becoming the main limitation for the successive reuse of these polymers.In line with the previously mentioned regulations, biodegradable polymers are another focus of interest. The study examines biodegradable compostable polymers used to manufacture single-use bags. A secondary objective is to determine how long these biodegradable polymers retain their usability properties under standard storage conditions, analyzing the samples over twelve consecutive months.Macroscopically, a progressive loss in tensile, elongation, and impact properties is the most significant phenomenon. Microscopically, two degradation mechanisms—hydrolysis and thermo-oxidation—are observed, both occurring in the amorphous phase of the material.The study concludes that the tested bags have a shelf life of over twelve months under standard storage conditions.

Committee:
     PRESIDENT: REINA DEL POZO, MANUEL
     SECRETARI: ESPAÑOL PONS, MONTSERRAT
     VOCAL: GIMÉNEZ BONAFÉ, JOSEFA
Thesis abstract: In the biomedical field, calcium phosphates have attracted attention due to their biocompatibility and bioactivity. They can be found in different individual phases (e.g., amorphous calcium phosphate, tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate and hydroxyapatite), which vary in composition, Ca/P ratio, crystalline structure, degree of substitution, and properties. Among them, carbonated-low crystallinity and highly crystalline hydroxyapatite (CHAp and HAp, respectively) have principally been used for the design of targeted drug delivery systems (DDS) and implant coatings. As the study of the CHAp and HAp nanoparticles with modified morphologies or with different ionic substituents is commonly focused on the characterization of the systems or on the general analysis of the induced biochemical response, the main objective of the thesis was to extend the knowledge of their biomolecular impact in a variety of cell lines (e.g., tumoral or osteoblastic cell lines). On the first chapter, the potential of CHAp as a carrier for doxycycline (DOX) was evaluated. The system was designed to facilitate the delivery of the antibiotic, repurposed as an antitumoral agent. Moreover, the additive effect of the constituent CHAp ions was demonstrated and the triggered changes in the proteomic and lipidomic profiles were in detail described for the first time by SR-FTIRM. The analysis of TEM micrographs helped to elucidate the morphological variations in the cells treated with CHAp or DOX- CHAp nanoparticles, providing evidence that the mineral systems induce different death mechanisms in the normal and tumoral cell lines. In order to offer a more controlled drug release and to reduce the effect of CHAp components on the normal cells, the nanoparticles were included in electrospun PLA or PLA-PEG fibers in the following chapter. Interestingly, only the PLA-PEG scaffolds allowed the release of antibiotic.In the subsequent chapter, HAp was synthesized with an urchin-like morphology. These nanoparticles were characterized and their potential role as drug carrier of gentamicin was similarly described for the first time. In addition, urchin like nanoparticles with a fluor substitution were prepared and their encapsulation efficiency compared to the values obtained with CHAp and the non-substituted urchin-like systems. The formulated carriers were originally thought as an implant coating that could help prevent the post-surgical infections that remain the principal complication of the orthopedic procedures. The newly developed systems were successfully electrodeposited on the polydopamine/collagen coated implants, followed by a final electrodeposited layer of poly-lysine.

Committee:
     PRESIDENT: PASHKULEVA, IVA HRISTOVA
     SECRETARI: GARRIGA SOLE, PERE
     VOCAL: VASSILEVA, ELENA
Thesis abstract: Antimicrobial resistance (AMR) is a global health concern, which leads to increased morbidity and mortality, huge economic burden to the healthcare systems and potentially untreatable infections. Due to the inappropriate use of antibiotics, the natural adaptation has been accelerated and bacteria have developed multiple ways to degrade, alter, or expel drug molecules. Besides these resistance mechanisms, bacteria can adhere to surfaces and grow as biofilms – organised assemblies of surface-bound cells, enclosed in a self-produced extracellular polymer matrix (EPM). The EPM holds the pathogens together, enables adhesion to surfaces, and enhances the tolerance to host immune responses and antibiotics compared to free-floating cells. Metal nanoparticles (NPs) have been suggested as a potential solution to fight resistant bacteria due to their strong antimicrobial activity and versatile mechanisms of action. However, inherent toxicity towards mammalian cells and large variation of physical properties are challenges that preclude the clinical application of such materials. In this thesis, metal NPs have been combined with different biomolecules for enhanced biocompatibility, increased antimicrobial efficacy, and enabling new functionalities to mitigate AMR.The first part of the thesis describes the formation of Ag NPs using bioactive macromolecules to produce multifunctional nanostructures. First, the matrix-degrading enzyme (MDE) α-amylase was used to reduce Ag(I), yielding NPs with antimicrobial and biofilm-degrading activity towards both gram-positive and gram-negative bacteria. Then, chitosan-Ag NPs were decorated with the quorum-quenching enzyme (QQE) acylase I, which combination was able to kill Pseudomonas aeruginosa, hinder biofilm formation, and inhibit bacterial quorum sensing (QS) based on acyl homoserine lactones (AHLs). Finally, adipic acid dihydrazide (ADH) was grafted on hyaluronic acid (HA) and used to form Ag NPs. The modified polymer (HA-ADH) played a crucial role in the interaction of the NPs with bacterial membranes, assessed using Langmuir isotherms, and reduced the toxicity of Ag towards human cells. In the second part of the thesis, HA-ADH and epigallocatechin gallate (EGCG) were used to produce nanostructured complexes with a scarcely studied antimicrobial Co(II). On one hand, Co(II) formed a complex with the biopolymer, which complex was transformed to antimicrobial nanogels (NGs) using an ultrasonic approach. On the other hand, incubation of EGCG with Co(II) yielded nanostructured metal-phenolic networks (MPN). These cobalt-containing NPs were active towards both gram-positive and gram-negative bacteria, and were able to inhibit biofilm formation due to the capacity of ECGC to disrupt QS. The last chapter of the thesis validates the use of the novel nanomaterials for antimicrobial functionalisation of medical devices. Coating of contact lenses with NGs hindered bacterial colonisation and unspecific absorption of proteins without affecting the optical properties and comfort of the material. Inclusion of MPN NPs in thiolated hyaluronic acid (THA) hydrogels endowed these materials with properties promoting efficient chronic wound treatment. The antibiotic-free hydrogels were able to control the main factors of wound chronicity by inhibiting the activity of deleterious wound enzymes, scavenging reactive oxidative species, and demonstrating pronounced antimicrobial activity, resulting in similar to commercial products wound management efficacy confirmed in vivo.

Committee:
     PRESIDENT: SANTAMARÍA RAMIRO, JESÚS MARCOS
     SECRETARI: GARCÍA TORRES, JOSÉ MANUEL
     VOCAL: ALVES FERREIRA, FREDERICO CASTELO
     VOCAL: GENTA, IDA
     VOCAL: FERREIRA MORGADO, JORGE MANUEL
Thesis abstract: This Ph.D. thesis delves into the realm of electrochemical biosensors, pivotal devices enabling the sensitive and timely detection of diverse biomolecules. Specifically, it explores the critical role of biosensors in biomedical applications, where the swift identification of biomarkers like Glucose (G), Dopamine (DA), Serotonin (SE), and Nicotinamide Adenine Dinucleotide (NADH) is imperative for diagnosing conditions such as diabetes, Parkinson's disease, Alzheimer's disease, and emerging infections, among other diseases.The thesis offers an in-depth examination of various biosensors engineered to target specific biomolecules, elucidating the methodologies and recent advancements pivotal in shaping device development. Noteworthy is the investigation into the influence of different materials, including conducting polymers (CPs), ceramic materials, carbon-based materials among others, on biosensor performance. Special attention is devoted to the design of intricate nanocomposites aimed at achieving heightened selectivity and sensitivity.Incorporating conducting polymers (CPs) like PEDOT into biosensors has proven successful, especially in detecting Nicotinamide Adenine Dinucleotide (NADH) from various bacteria. This enhances sensor conductivity and sensitivity, crucial for identifying bacterial activity. Notably, this thesis implements this approach in biomedical devices such as sutures and meshes, expanding biosensor applications to infection detection.On another front, the thesis highlights the success of engineering biosensors from 3D printed insulating thermoplastics for the detection of Dopamine (DA) among other biomolecules. Leveraging innovative strategies, these biosensors demonstrate remarkable selectivity and sensitivity in detecting DA, paving the way for enhanced diagnosis and monitoring of neurological disorders and other related conditions.Furthermore, the thesis explores the engineering of conductive devices based on biological materials such as Alginate hydrogels and peptides. These bio-inspired materials offer unique properties conducive to biosensor development, including biocompatibility and tunable conductivity. By harnessing the inherent characteristics of biological materials, novel biosensors with enhanced performance and functionality can be realized, opening new avenues for biomedical diagnostics and therapeutic interventions.Through this comprehensive exploration of diverse biosensor technologies and strategies, the thesis aims to contribute significantly to the ongoing evolution of electrochemical biosensors. By shedding light on the successful incorporation of advanced materials and innovative engineering approaches, it offers valuable insights into the potential of biosensors for transformative applications in various biomedical fields, ultimately advancing the frontiers of medical diagnosis and treatment.

Committee:
     PRESIDENT: RODRÍGUEZ FERNÁNDEZ, ISABEL
     SECRETARI: CASELLAS PADRO, DANIEL
     VOCAL: TYLKOWSKI, BARTOSZ
Thesis abstract: Nature is in continuous change and evolution in response to environmental shifts. That is because different micro- and nanotextures have emerged on some plant leaves or insect skins. These surface patterns enable them to possess advanced surface properties. Some examples include the superhydrophobic and self-cleaning leaves of the lotus plant, or the dry adhesion found on gecko feet. There has been a strong trend in recent years to transfer these surface textures to industrial applications to replace various coatings currently in use. The development of transformation technologies and the extensive knowledge of materials developed in recent decades have allowed for the extension of materials onto which these microtextures can be replicated.In the case of Liquid Silicone Rubber (LSR), studies on replication focus on laboratory-scale technologies that allow for high replication but low production throughput. However, these materials possess properties of great interest and can have many synergies with microtexturing: good biocompatibility for use in medical devices, weather resistance for self-cleaning or superhydrophobic surfaces, or good mechanical and chemical resistance that can extend the lifespan of microtextures on the surface. In order to extend studies on replication techniques of microtextures on liquid silicone surfaces, this thesis has been developed focusing on replication through injection of microtexturized inserts. There have been some previous works on replication using this technology; however, they fail to achieve good demolding or uniform textures in height due to the use of textured metallic inserts. Therefore, this thesis proposes the use of textured films to facilitate demolding due to the flexibility of the film.This thesis is divided into two main parts: The first part consists of the development of tools and technology for the replication of liquid silicone parts by injection. Firstly, optimization is carried out on the manufacture of textured films by nanoimprint lithography to withstand the injection conditions of this material. After this initial optimization and with the manufacturing of the necessary tools, a study and optimization of different part geometries for the different studied microtextures (pillars, lines, and holes ranging from 1 to 50 microns) are conducted. The second part of the thesis consists of an extensive study of different advanced surface properties due to microtexturing. This includes properties such as surface wettability or roughness studies, as well as different studies of part durability for the application of different mechanical stresses. Additionally, emphasis is placed on the study of biological properties, of interest in the medical sector. The studies focus on the variation of cellular growth and adhesion due to the presence of microtextures. Based on all the results obtained, a use case of an optogenetic implant is proposed.From the results obtained, it can be concluded that the replication method proposed and developed in this thesis is an optimal method for industrial scaling of these microtextures in liquid silicone. Not only because of its high production throughput but also because of the versatility of part geometries and microtextures it allows. This versatility of microtextures enables the acquisition of a wide range of surface properties of high interest at an industrial level. Particularly in the case of the medical sector, where a use case of a microtexturized implantable device with this technology has been demonstrated, which could be extendable to other applications.

Committee:
     PRESIDENT: POATER TEIXIDOR, ALBERT
     SECRETARI: SASSELLI RAMOS, IVAN
     VOCAL: CREHUET SIMON, RAMON
Thesis abstract: Viruses and their infections have always affected human lives throughout history. Globalization contributed positively to the progress of human society in science and medicine which permited to deal with viruses, but the reality is that the number of infections does not decrease over the years. Globalization itself is here agin one of the main factors, as people move in more densely populated areas, which favors the spread of viruses. Another important factor is the viruses themselves, which over the years have shown a constant evolution that allowed them to adapt to new hosts. For these reasons, human-led efforts such as vaccines, antiviral treatments, sensors etc. are critical tools for human survival, and like viruses, humans must continue to innovate. This thesis focused on providing different understandings of a series of biochemical processes at molecular the level to facilitate the design of plasmonic resonance sensors, currently used for detecting diseases such as cancer, to enable a similar detection improvement in other viruses and diseases such as HIV and SARS-Cov-2.This thesis is divided into two parts, with the first focusing on the characterization related to the HIV virus. Several studies have been carried out using a combination of different molecular simulation techniques, classical dynamics, quantum mechanics and hybrid QM/MM-MD methods. These studies characterize the behavior of the antibody chosen in the design of the sensor, IgG1 , as well as its interactions with the silica surface that compounds the sensor and its orientation once functionalized on top of the surface. Additional studies were performedm focusing on the interaction between the immunoglobulin G and the glycoprotein that forms part of the HIV virus spike, and permited to identify the interactions helping the antibody to attach to the virus for the virus inhibition.In the second part, the same molecular simulation techniques have been used to study the virus which completely changed the world in 2020, SARS-CoV-2 known for the disease COVID19. As this virus was new at the time of the thesis, there was a dramatic lack of knowledge. Molecular modelling techniques were used to study the behavior of the virus spike in presence of heat or solvated in water. Similar studies to the case of HIV-IgG1 were performed between SARS-CoV-2 spike and different promising antibodies with the goal to identify the best candidate for sensor functionalization or virus inhibition. In this section, the interaction between the virus spike and the ACE2 enzyme, the target cell that SARS-CoV-2 use to infect human body, was also characterized. Finally, new antibodies were designed combining the previous ones with IgG1 and their behavior was studied in the presence of the sensor’s silica surface and the nanoparticles gold surface used in the detector

Committee:
     PRESIDENT: RAMIREZ RANGEL, ELIANA
     SECRETARI: MARTÍNEZ GOMARIZ, EDUARDO
     VOCAL: NASIR, RIZWAN
Thesis abstract: Microencapsulation process of polymers and biopolymer is the most important technique in a polymer industry to make it unique and applicable in various fields of daily life. When it comes to the accuracy of the method only Computational Fluid Dynamic (CFD) simulations or numerical solution provides the authenticity of the method. CFD analysis gives a more schematic approach instead of any other Simulation method.In this thesis detailed use of governing equations of CFD is used to predict the accuracy of the microencapsulation method. The experimentation was done in the laboratory of the department of polymers and biopolymers under the supervision of Prof Luis J. Dell Valle. By using CFD the results are more precise, clear and accurate along with the zero minimum percentage of human error. After representing a literature review for the modeling of microencapsulation process in the first chapter, the methodology about how the process began and what parameters we followed to fulfill the requirement of the project. The effect of impeller speed 5000 rpm, 7500 rpm, 1000 rpm, 12000 rpm and 15000 rpm were determined on the number density functions and particle size reduction in the microencapsulation domain.Ansys. Fluent R2 2020 was used to model the experimental data. For the purpose of modeling the particle size distribution discrete method of population balance model is used. A total of five bins were selected to perform the size distribution analyze. The reason for selecting this small diameter range is the focus and accuracy of the solver. The bins should be more than enough to cover the distribution range and small enough to save computational time. Realizable k-e, Eulerian framework and appropriate bins initial values are used to predict the multiphase behavior. Under these conditions simulation converges very well and gives good agreement with the validation and experimental data.