Committee:
     PRESIDENT: UNGAR, GORAN
     SECRETARI: MASPOCH RULDUA, MARIA LLUÏSA
     VOCAL: MONTANÉ MONTANÉ, XAVIER
     VOCAL: SARASUA OIZ, JOSÉ RAMÓN
     VOCAL: SOLANO MINUESA, EDUARDO
Thesis abstract: Nylons, a class of linear polyamides, are well-known materials used in a huge number of different applications. Since the first production occurred during the last years of the 1940s, these polymers showed their ability to being used as technical polymers in the production of ropes, lines, nets, and injection molded pieces for the automotives industry and for household utensils. Their characteristic properties, such as the mechanical strength and the chemical and thermal resistance, are derived from their peculiar molecular conformations, characterized by the presence of strongly developed hydrogen bonds between the amidic groups of the macromolecules. The different organizations of the polymeric chains confer to nylons multiple crystalline structure. With the development of technology, nylons have been used for modern applications, such as in the 3D-printing technique, in the electronic field as triboelectric materials and in biomedicine as sutures, part of prosthetics, dental implants and catheters. In the last decades, greater attention has been devoted to the study of non-conventional nylons, based on monomers derived from bioresources or containing odd numbered carbon chains, enabling a deeper understanding of these materials and paving the way for new applications. In this sense, this doctoral thesis has been developed taking into account a new series of nylons, derived from biobased pimelic derivatives and containing monomers with a odd number of carbons. The work of the first part will be devoted to their synthesis, the crystalline characterization and the study of the thermal behavior and characterization, taking advantage of different techniques, including synchrotron light based analytical instruments. A second part of the thesis has been centered on the synthesis of poly(ester amide)s containing a bioactive triazole ring moiety. The inclusion of ester bonds in the macromolecular chains allows the introduction of a degradable group, obtaining a material that possesses the characteristic of a polyamide with the bio applicability of a polyester. The triazole ring, included in the macromolecules via a one-pot alkyne-azide click reaction, has been further studied for its bioactivity, as anti-microbial, anti-bacterial and anti-inflammatory agent. Lastly, a real application of a commercially used odd-even nylon has been tested. An injection molding machine has been used for in-situ X-ray measurement, by installing the equipment directly in a synchrotron beamline. With this configuration, the machine has been tested for direct study of the behavior of polymeric materials during the process of molding by injection.

Committee:
     PRESIDENT: SERRA ALBET, MARIA ANGELS
     SECRETARI: ALLA BEDAHNANE, ABDELILAH
     VOCAL: OH, SEJIN
Thesis abstract: Polymers have become one of the primary options in biomedical fields due to their diverse properties, functionalities, and applications. Characteristics such as mechanical strength, biocompatibility, and biodegradability have made these materials highly attractive for various medical applications. One of the most intriguing applications of these polymers is drug delivery. Biodegradable polymers and copolymers are the primary materials used for producing temporary medical and pharmaceutical devices. These polymers can be chemically synthesized or naturally produced.Biotechnological polymers, produced through biotechnological processes, have garnered significant attention due to two major advantages. First, they are derived from renewable resources; second, as they are biologically produced, they are usually biocompatible, biodegradable and bioresorbable. Therefore, modifying these polymers to tune their properties or functionalities is an effective strategy for developing biomedical materials.Poly(γ-glutamic acid) PGGAH is a biocompatible and biodegradable poly-γ-peptide with carboxylic side groups that can be substituted to modify the polymer’s properties. In this study, PGGAH was hydrophobically and cationically modified. Through hydrophobic modification and altering the hydrophilic properties, amphiphilic copolymers were produced, capable of self-assemble into nanoparticle systems for drug encapsulation and controlled release. This modification was carried out by partial esterification of carboxylate side groups with 4-phehyl-butyl bromide (4-PhBBr). Further decoration to produce stealth and targeting nanoparticles was achieved by reaction of some remaining carboxylate side groups with amino ended poly(ethylene glycol) (NH2-PEG) and NH2PEG derivatized with folic acid, respectively. Cationic modification of this biodegradable polymer enabled the formation of nanopolyplexes with DNA. This modification was carried out by esterification of carboxylate side groups with cationic 2-bromoethyl trimethylammonium bromide (BrETABr). The obtained derivatives were used to prepare nanoparticles through emulsion solvent evaporation or nanoprecipitation dialysis techniques. Nanoparticles with an approximate size of 100 to 380 nm were obtained, demonstrating their potential as drug delivery systems capable of encapsulating the anticancer drug doxorubicin.The chemical structure of the derivatives were characterized using proton and carbon-13 nuclear magnetic resonance (NMR) spectroscopy, and the physicochemical properties by gel permeation chromatography (GPC), and thermal gravimetric analysis (TGA). Functional group analysis was conducted through Fourier-transform infrared spectroscopy (FT-IR). Hydrolytic degradation was monitored by 1H NMR, while the appearance of the nanoparticles was observed using scanning electron microscopy (SEM), and their size and surface charge were determined by dynamic light scattering (DLS) and zeta potential measurements, respectively.For the hydrophobic copolymer series, cytotoxicity assays were carried out, confirming the low toxicity of the synthesized derivatives. Drug encapsulation and release was initially evaluated under physiological conditions, revealing that the release rate was higher in acidic pH and affected by the degree of polymer modification. On the other hand, cellular uptake nanoparticle tests demonstrated that the nanoparticles successfully penetrated cancer cells. The results of this study indicate that the biotechnological polymer PGGAH is a promising material for designing and developing biodegradable drug delivery systems with potential therapeutic applications for challenging diseases in pharmacological treatment.

Committee:
     PRESIDENT: HAUPT, KARSTEN
     SECRETARI: PÉREZ MADRIGAL, MARIA DEL MAR
     VOCAL: AFONSO ROQUE, ANA CECÍLIA
     VOCAL: CANAL BARNILS, CRISTINA
     VOCAL: SIRÉS SADORNIL, IGNACIO
Thesis abstract: The cost of healthcare is an increasing concern worldwide, driven by the emergence of new diseases as well as the progression of lifestyle-related conditions. For this reason, expenditure on healthcare-related research is expected to rise over the next decade. One of the main lines of research is biosensors, which have shown great potential in improving patient care, as demonstrated by the success of sensors such as glucometers. Biosensors can aid not only in disease detection but also in the regular monitoring of a patient’s status.In this work, new materials based on conducting polymers and carbon quantum dots were developed for use as electrodes in various biosensors. The work is divided into four different parts, each focusing on a different material and application. In the first part, a thin film electrode was developed based on the carbon quantum dot doping of PEDOT, which was synthesized via electropolymerization. Doping quantity optimization and as well as chemical and morphological characterizations were performed on the films. The films were then deposited on substrate and on an organic electrochemical transistor for the electrochemical detection of dopamine. In the second part, carbon quantum dots were used in an immunosensor. The carbon quantum dots were first immobilized on the surface of a carbon electrode to enhance electroconductivity then functionalized with antibodies to obtain a highly selective sensor. Electrochemical and chemical characterizations were performed for each subsequent layer. Finally, the resulting immunosensor was tested against the D-dimer antigen via electrochemical impedance spectroscopy. The third and fourth parts focus on conducting polymer hydrogel, wherein the main hydrogel matrix was mixed with the conducting polymer, PEDOT:PSS, along with other additives. In the third part, the main hydrogel used was PVA modified with tannic acid for strength and carbon quantum dot for electroactivity enhancement; while the fourth part is a GelMA-based hydrogel modified with alginate. In both works, optimization of the additive amounts was performed and as well as the investigation of the individual and synergistic effects of the components on various characteristics such as mechanical and electrochemical properties. Finally, the PVA-based hydrogel was used as a pressure sensor, while the GelMA-based hydrogel was employed as a 3D cell culture platform for an impedance-based cell monitoring system.Overall, this PhD work demonstrated the application of various techniques and materials in the development of novel conductive biomaterials for biomedical sensors. These innovative materials could serve as a foundation for next-generation biosensors, with the potential to enhance patient care and quality of life.

Committee:
     PRESIDENT: SANTANA PEREZ, ORLANDO ONOFRE
     SECRETARI: GONZALEZ QUIÑONEZ, NATHALY
     VOCAL: JOVANCIC, PETAR
Thesis abstract: This doctoral thesis presents a comprehensive study on the structure-property relationships, processing behavior, and functional performance of polyhydroxyalkanoates (PHAs), with the aim of enhancing their applicability as sustainable alternatives to conventional plastics. The work focuses on various PHA-based materials and explores their modification through blending strategies and the incorporation of functional additives. A wide range of processing techniques were employed, including melt compounding, injection molding, ultrasonic molding, solvent casting, and electrospinning. These methods enabled the fabrication of various PHA-based formulations tailored for specific applications. Physicochemical characterization was carried out using nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), polarized optical microscopy (POM), tensile testing, and synchrotron-based FTIR microspectroscopy (SR-FTIR). These techniques enabled the investigation of molecular structure, crystallization kinetics, morphology, thermal stability, and mechanical properties.The results demonstrate that copolymer composition plays a critical role in defining the crystallinity, thermal behavior, and mechanical performance of PHAs. The incorporation of comonomers such as 3-hydroxyvalerate (3HV), 3-hydroxyhexanoate (3HHx), and 4-hydroxybutyrate (4HB) effectively tuned the material properties. The addition of nucleating agents, such as boron nitride (BN) and poly(3-hydroxybutyrate) (PHB), were found to significantly accelerate the crystallization rate of P3HBHHx without adversely affecting its molecular or thermal stability. Blending P3HBHHx with other biopolymers, such as poly(latic acid) (PLA), poly(butylene adipate-co-terephthalate) (PBAT), poly(butylene succinate) (PBS), and poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB), further modulated its performance, although compatibility remained a challenge in certain formulations. Biomedical applications were also explored using electrospinning and ultrasonic molding. Drug-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers exhibited tunable release kinetics and antibacterial activity, while P34HB demonstrated excellent processability and thermal resistance under ultrasonic molding conditions. Finally, SR-FTIR microspectroscopy revealed spatial orientation patterns within PHBV spherulites, offering new insights into the molecular organization of PHAs. Overall, this thesis establishes a comprehensive framework for tailoring PHA materials through formulation and processing innovations. It contributes to the scientific understanding and technological advancement of PHAs as viable sustainable material across various sectors.

Committee:
     PRESIDENT: ALEMAN LLANSO, CARLOS ENRIQUE
     SECRETARI: LANZALACO, SONIA
     VOCAL: CHAMORRO GARCIA, ALEJANDRO
     VOCAL: MATYSZEWSKA, DOROTA
     VOCAL: ESTEVEZ ALBEROLA, MARIA CARMEN
Thesis abstract: At the intersection of materials science and biomedicine, this thesis explores the development of bioinspired and biodegradable polymeric systems capable of supporting lipid bilayers and enabling functional applications in biosensing and biomedical delivery. Conducted within the Marie Skłodowska-Curie Innovative Training Network BioInspireSensing, this research reflects a collaborative effort involving Universitat Politècnica de Catalunya (UPC) in Spain, the University of Teramo in Italy and the University of Warsaw in Poland.At the heart of this thesis lies the use of polylactic acid (PLA), a biocompatible and bioresorbable polymer, to develop two distinct yet complementary material platforms: nanostructures for biosensing and microparticles for therapeutic delivery. The first part of the work focuses on the fabrication of PLA nanomembranes and thin films, functionalized with PEG-cholesterol and bioactive peptides for sensing and to facilitate the stable immobilization of lipid bilayers. These biomimetic membrane systems were subsequently integrated into electrochemical sensors capable of detecting biologically relevant molecules—such as antioxidants and cholesterol—offering enzyme-free, biocompatible detection platforms with high sensitivity and selectivity.The second part of the thesis shifts focus to the design of PLA-based microparticles as delivery vehicles. Porous PLA microparticles functionalized with PEG-cholesterol were developed for the targeted and controlled release of therapeutic agents, including the anticancer drugs curcumin and tamoxifen. These systems were evaluated through in vitro studies to evaluate drug release profiles, confirm cytocompatibility, and examine the antitumor efficacy of the microparticles in model cancer cell lines. Taken together, these two material systems highlight the remarkable versatility of PLA as a foundation for building hierarchical, multifunctional biointerfaces. By connecting advances in molecular sensing, biomimetic membrane design, and therapeutic delivery, this work pushes forward the development of next-generation biodegradable materials with real potential in areas like implantable sensors, smart drug delivery systems, and bioelectronic devices. Beyond its technical contributions, the thesis reflects the collaborative and interdisciplinary spirit of the BioInspireSensing network—bringing together insights from materials science, molecular engineering, and biomedical research.

Committee:
     PRESIDENT: GARCIA QUINTANA, DAVID
     SECRETARI: RAMON PORTÉS, EVA
     VOCAL: GÓMEZ TRIAS, NÉSTOR
Thesis abstract: G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in mammals and are essential for sensing external signals and regulating intracellular signaling pathways. Among GPCRs, rhodopsin plays a critical role in phototransduction in retinal rod cells, and its structural and functional integrity is vital for vision. Mutations in the opsin gene are closely associated with inherited retinal diseases such as retinitis pigmentosa (RP), characterized by progressive photoreceptor degeneration and eventual blindness. Despite limited therapeutic options for RP, emerging strategies focusing on protein stabilization and allosteric modulation offer new hope.This study systematically explored the effects of trace metal ions and small molecules on rhodopsin stability, chromophore regeneration dynamics, and signaling properties. We found that Fe³⁺ significantly enhances the thermal and chemical stability of both wild-type (WT) and G90D mutant, while Fe²⁺ exhibited no protective effects and Cu²⁺ strongly destabilized rhodopsin and impaired its regeneration. These findings highlight the critical role of metal ion homeostasis in maintaining rhodopsin function and suggest that modulating iron oxidation states could be a therapeutic strategy for retinal degenerative diseases.Analysis of RP-associated G90D and G90V mutants revealed that while both mutations caused a blue shift in the absorption maximum, G90V exhibited markedly reduced thermal stability, impaired photobleaching response, delayed retinal release, and severely disrupted chromophore regeneration, whereas G90D showed less altered structural and functional characteristics. Although Fe³⁺ provided some stabilization to G90D, it was less effective than in WT rhodopsin, likely due to mutation-induced conformational changes.Retigabine significantly enhanced the thermal stability of rhodopsin and promoted efficient chromophore regeneration, indicating its potential as a pharmacological chaperone for stabilizing rhodopsin mutants implicated in retinal degenerative diseases. Retigabine bound rhodopsin without disrupting photobleaching kinetics or G-protein activation, likely binding to an allosteric site to stabilize protein conformation while preserving normal phototransduction. These properties highlight retigabine potential as a therapeutic strategy for retinal degeneration.Moreover, the study analyzed the F88L mutation, revealing that F88L rhodopsin maintains normal spectral properties and visual function but exhibits enhanced thermal stability and accelerated MII decay. Hydroxylamine unexpectedly stabilized the MI intermediate in F88L, indicating a novel regulatory aspect of rhodopsin photocycle. These results suggest that amino acid at position 88 may be involved in rhodopsin molecular evolution and in light adaptation in nocturnal vision. In addition, the small molecule C24 was found to modulate F88L rhodopsin by enhancing chromophore regeneration and accelerating MII decay, indicating potential strategies for fine-tuning rhodopsin dynamics.Overall, these findings provide important insights into the stabilization mechanisms of rhodopsin and lay a foundation for developing novel therapies targeting retinal degenerative diseases through metal ion regulation and small-molecule modulation.