Developing physical properties of hierarchical nanostructures for biomedical applications

The present dissertation focuses on the different properties of selfaggregation processes of mixed molecular systems with the aim to design and optimize complex structures that promote the triggering of sequences leading to the deposition, nucleation and growth of hydroxyapatite crystals with the proper geometry and orientation. New strategies and novel synthetic routes were effectively developed, resulting in economically viable materials that mimic the structure and composition of the extracellular matrix, making them eligible and suitable for numerous applications in tissue regeneration and biomedical engineering

Soft Actuated Hybrid Hydrogel with Bioinspired Complexity to Control Mechanical Flexure Behavior for Tissue Engineering

Hydrogels exhibit excellent properties that enable them as nanostructured scaffolds for soft tissue engineering. However, single-component hydrogels have significant limitations due to the low versatility of the single component. To achieve this goal, we have designed and characterized different multi-component hydrogels composed of gelatin, alginate, hydroxyapatite, and a protein (BSA and fibrinogen). First, we describe the surface morphology of the samples and the main characteristics of the physiological interplay by using fourier transform infrared (FT-IR), and confocal Raman microscopy. Then, their degradation and swelling were studied and mechanical properties were determined by rheology measurements. Experimental data were carefully collected and quantitatively analyzed by developing specific approaches and different theoretical models to determining the most important parameters. Finally, we determine how the nanoscale of the system influences its macroscopic properties and characterize the extent to which degree each component maintains its own functionality, demonstrating that with the optimal components, in the right proportion, multifunctional hydrogels can be developedThe authors acknowledge Ministerio de Ciencia e Innovación (PID2019-111327GB-100) and Xunta de Galicia (ED41E2018/08)S

Reduced density matrices in molecular systems: Grand-canonical electron states

Grand-canonical like descriptions of many electron atomic and molecular open systems which are characterized by a non-integer number of electrons are presented. Their associated reduced density matrices (RDMs) are obtained by introducing the contracting mapping for this type of distributions. It is shown that there is loss of information when connecting RDMs of different order by partial contractions. The energy convexity property of these systems simplifies the description. Consequently, this formulation opens the possibility to a new look for chemical descriptors such as chemical potential and reactivity among others. Examples are presented to discuss the theoretical aspects of this work.Fil: Bochicchio, Roberto Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; ArgentinaFil: Miranda Quintana, Ramón A.. Universidad de La Habana. Facultad de Química. Laboratorio de Química Computacional y Teórica; CubaFil: Rial, Diego Fernando. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Investigaciones Matematicas

Conformational binding mechanism of lysozyme induced by interactions with penicillin antibiotic drugs

In this study we present an in-depth and detailed analysis of the binding process between two antibiotics (cloxacillin and dicloxacillin) and a blood serum protein (lysozyme). Our objectives have been several: to determine, at the atomic level, the structural and conformational changes that take place in both molecular structures once the complex is formed; to investigate the effect that the substitution of a hydrogen atom for a chlorine atom has on the bonding process; and to relate these local modifications with macromolecular parameters. Achieving these goals requires a multi-pronged approach and effective resource management. In our case, we have combined different experimental (isothermal titration calorimetry, UV–vis and fluorescence spectroscopy) and computational techniques (molecular docking and network models), in order to obtain comprehensive and contrasted information of the interaction process. Both approaches have showed an excellent correlation, confirming that there is a single binding site, that both penicillins are moderate binders and hydrogen bond and van der Waals forces are predominant. On the other hand, the small discrepancies between the two techniques highlighted the pressing need to approach the study of these systems from both atomic and macromolecular perspectivesThe authors acknowledge Ministerio de Ciencia e Innovación (PID2019-111327GB-100)S

The design and green nanofabrication of noble hydrogel systems with encapsulation of doped bioactive hydroxyapatite toward sustained drug delivery

Finding a bioactive hybrid material with the potential for a controlled drug release has been one of the major targets of tissue engineering in the recent years. In this line, the present work describes a new approach for producing singular hydrogel microparticles (HMPs) with different morphologies and compositions by combining experimental and computational methods. Calcium-Alginate microparticles (Ca-ALG) and core–shell Alginate-Chitosan microspheres (Ca-ALG-CHI) were synthesized with the presence of drug-doped Hydroxyapatite (HA) in their inner matrix. The methodology relies on the use of a microfluidic system to obtain crosslinked HMPs with homogeneous sizes and morphologies, integrating external and internal gelation. The impact of the water-to-oil volume ratio, as well as variations in the collecting baths, morphology, and dispersion, were considered. The drug models chosen were Propranolol hydrochloride and Cloxacillin sodium salt monohydrate. Avrami's parameters were used to study and address the adsorption kinetics of each drug onto the bioactive HA, and the Korsmeyer-Peppas model was used to analyze the posterior desorption profiles. The conception and development of this type of hydrogel microparticles with improved functionalities are essential for the creation of granular hydrogels, which are an innovative, green, sustained and highly promising solution for different therapies in regenerative medicine areasThe authors acknowledge Ministerio de Ciencia e Innovacion (PID2019-111327GB-100). N. H. thanks Proyecto FONDECYT de Iniciación (11170849) and FONDAP (15130011)S

Lysozyme allosteric interactions with β-blocker drugs

Effective and reliable prediction of allosteric molecular interactions involved in protein-ligand systems are essential to understand pharmacological modulation and toxicology processes that are driven by multiple factors covering from the atomistic to cellular level. Even though the interactions taking place within a defined biophysical environment are usually intricate and complex, having a preliminary knowledge of the structural determinant and biochemical function of target enzyme in the physiological or unbound state represent a step forward in the characterization of the forces involved these processes under interaction conditions as induced by drugs. In the present work, we tackle the study of relevant binding interactions between two well-recognized betablocker drugs and the lysozyme biological target from an experimental-computational perspective. In this way, molecular docking, machine learning and perturbation analysis combined with UV–vis and fluorescence measurements will allow us to determine the allosteric regulation and functional dynamics of lysozyme by binding propranolol and acebutololThe authors acknowledge Ministerio de Ciencia e Innovación (PID2019-111327GB-100)S

Advanced Materials Based on Nanosized Hydroxyapatite

The development of new materials based on hydroxyapatite has undergone a great evolution in recent decades due to technological advances and development of computational techniques. The focus of this review is the various attempts to improve new hydroxyapatite-based materials. First, we comment on the most used processing routes, highlighting their advantages and disadvantages. We will now focus on other routes, less common due to their specificity and/or recent development. We also include a block dedicated to the impact of computational techniques in the development of these new systems, including: QSAR, DFT, Finite Elements of Machine Learning. In the following part we focus on the most innovative applications of these materials, ranging from medicine to new disciplines such as catalysis, environment, filtration, or energy. The review concludes with an outlook for possible new research directionsThis research was funded by MINISTERIO DE CIENCIA E INNOVACIÓN (PID2019-111327GB-100).S

Tribological enhancement using Mn3O4-Graphene nanocomposites as additives for potential transmission fluids of electric vehicles

This research reports the antifriction and antiwear properties of Mn3O4-Graphene nanocomposites (Mn3O4-G) as additives of a paraffinic base oil commonly used in the formulation of electric vehicles transmission oils, G-III base oil. Four G-III base oil nanodispersions have been designed, G-III base oil + 0.025 wt% Mn3O4-G, G-III base oil + 0.050 wt% Mn3O4-G, G-III base oil + 0.075 wt% Mn3O4-G and G-III base oil + 0.100 wt% Mn3O4-G, to know the optimal concentration of nanoadditive. Tribological experiments were carried out with these nanolubricants and with neat G-III base oil at pure sliding conditions under a working load of 9.43 N. All tested nanolubricants led to similar friction coefficients in comparison to that obtained using G-III base oil. Tribological specimens tested with formulated nanolubricants revealed less wear than that obtained with G-III base oil, obtaining the greatest wear reduction using the G-III base oil + 0.075 wt% Mn3O4-G nanolubricant, with reductions of 25, 50 and 64% in wear scar diameter, maximum depth and transversal area, respectively. Moreover, by means of confocal Raman microscopy and roughness evaluation of worn tribological specimens, it was concluded that synergetic effect, tribofilm formation and rolling mechanisms happenThis research is supported by Xunta de Galicia (ED431C 2020/10), by the State Research Agency (AEI) of Spain and the European Regional Development Fund (ERDF, FEDER in Spanish) through the PID2020-112846RB-C22 project. JMLDR and RR are granted by the Program for the requalification, international mobility, and attraction of talent in the Spanish university system, modality Margarita SalasS

Improving pipelining tools for pre-processing data

The last several years have seen the emergence of data mining and its transformation into a powerful tool that adds value to business and research. Data mining makes it possible to explore and find unseen connections between variables and facts observed in different domains, helping us to better understand reality. The programming methods and frameworks used to analyse data have evolved over time. Currently, the use of pipelining schemes is the most reliable way of analysing data and due to this, several important companies are currently offering this kind of services. Moreover, several frameworks compatible with different programming languages are available for the development of computational pipelines and many research studies have addressed the optimization of data processing speed. However, as this study shows, the presence of early error detection techniques and developer support mechanisms is very limited in these frameworks. In this context, this study introduces different improvements, such as the design of different types of constraints for the early detection of errors, the creation of functions to facilitate debugging of concrete tasks included in a pipeline, the invalidation of erroneous instances and/or the introduction of the burst-processing scheme. Adding these functionalities, we developed Big Data Pipelining for Java (BDP4J, https://github.com/sing-group/bdp4j), a fully functional new pipelining framework that shows the potential of these features.Agencia Estatal de Investigación | Ref. TIN2017-84658-C2-1-RXunta de Galicia | Ref. ED481D-2021/024Xunta de Galicia | Ref. ED431C2018/55-GR

Effectiveness and safety of a microcrystalline tyrosine‐adjuvanted <i>Dermatophagoides pteronyssinus</i> allergoid immunotherapy in adult patients with allergic asthma and rhinitis: A real‐life prospective observational study

Introduction: Although clinical trials have shown the efficacy and safety of allergen-specific immunotherapy (AIT) in the treatment of allergic asthma, there is a need for real-life studies. We aimed to assess the effectiveness and safety of a microcrystalline tyrosine-adjuvanted Dermatophagoides pteronyssinus allergoid (Acarovac Plus (R)) in patients with house dust mite (HDM)-induced allergic asthma in a real-life study. Methods: A subanalysis of a multicenter, prospective, observational, real-life study. Patients with rhinitis and allergic asthma caused by HDMs were assessed before AIT with Acarovac Plus (R) and at 6 and 12 months after this treatment. Assessment parameters were percentage of days with asthma symptoms, percentage of days on asthma medication, classification of asthma according to Spanish guidelines for the management of asthma, asthma-related quality of life (quality of life in adults with asthma questionnaire [QLAAQ]), perception of symptoms (visual analog scale [VAS]), and treatment satisfaction (treatment satisfaction questionnaire for medication [TSQM]). Safety was assessed by the number and severity of adverse reactions. Results: This subanalysis included 55 patients. Treatment with Acarovac Plus (R) showed significant differences in the analyzed variables when the baseline visit was compared with the 12-month visit: reduction of the mean (SD) percentage of days with asthma symptoms (23.9 [9.2] vs. 5.1 [12.8]; p = .002), of the mean [SD] percentage of days on asthma medication (67.6 [42.9] vs. 45.1 [46.8]; p = .002), and of the percentage of patients with persistent asthma (78.2% vs. 38.9%; p = .009). Acarovac Plus (R) significantly improved asthma-related quality of life, as shown by a decrease of 1.39 points in QLAAQ score at 12 months (p < .001), and in the subjective perception of symptoms on the VAS (-3.50, p < .0001). Patients showed high treatment satisfaction according to the TSQM, and it was well tolerated. No serious adverse events were reported. Conclusions: Acarovac Plus (R) was effective and safe for the treatment of patients with HDM-induced allergic asthma in a real-life study