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In this study, the improvement in SAE 10W-40 engine oil tribological performance after the addition of magnesium oxide (MgO) nanoadditive and two different phosphonium-based ionic liquids (ILs) was investigated. Besides, the rheological behaviour of MgO-based nanolubricant and IL-based hybrid nanolubricants at the temperature range from 293.15 to 363.15 K was studied. The nanoparticle characterization was performed by means of transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). The tribological properties, friction coefficients and wear parameters of the formulated oil modified with 0.01 wt% MgO and 1 wt% ILs compared with the neat 10W-40 oil were performed and analysed using a ball-on-three-pins tribometer and a 3D optical profilometer, respectively. Further analysis on the worn surface was shown by Raman spectroscopy and SEM images illustrating the formation of the protective IL and MgO tribo-films as hybrid additives. In friction tests with sliding steel-steel tribo-pairs, IL3-based hybrid nanolubricant decreased the coefficient of friction and wear volume by 7% and 59%, respectively, in comparison with the neat SAE 10W-40, hence better positive synergies were found for MgO and IL3 as hybrid additives. Interestingly, the thermophysical characterization by rheology also revealed that the nanoparticle and ionic liquids addition did not affect neither the viscosity response nor the Newtonian behaviour of the engine oil, adequately meeting the requirements for their use in internal combustion engines This research is part of the project ENE2017-86425-C2-1/2-R funded by MCIN/AEI/10.13039/501100011033 and by ERDF “A way of making Europe” and has also been supported through the GRC grant ED431C 2020/10 by the Xunta de Galicia. Dr. M.J.G.G. acknowledges a postdoctoral fellowship (ED481B-2019-015) from the Xunta de Galicia (Spain). Dr. J.M.L.dR and Dr. R.R. are grateful for financial support through the Margarita Salas programme, funded by MCIN/AEI/10.13039/501100011033 and "NextGenerationEU/PRTR". Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature SI

Three-dimensional conformational crystallographic binding-modes are of paramount importance to understand the docking mechanism of protein-ligand interactions and to identify potential "leading drugs" conformers towards rational drugs-design. Herein, we present an integrated computational-experimental study tackling the problem of multiple binding modes among the ligand 3-(2-Benzothiazolylthio)-propane sulfonic acid (BTS) and the fibrinogen receptor (E-region). Based on molecular docking simulations, we found that the free energy of binding values for nine of different BTS-docking complexes (i.e., BTS-pose_1-9) were very close. We have also identified a docking-mechanism of BTS-interaction mainly based on non-covalent hydrophobic interactions with H-bond contacts stabilizing the fibrinogen-BTS docking complexes. Interestingly, the different BTS-poses_1-9 were found to be able to block the fibrinogen binding site (E-region) by inducing local perturbations in effector and allosteric residues, reducing the degree of collectivity in its flexibility normal modes. As such, we theoretically suggest that the BTS-binding modes can significantly affect the physiological condition of the unoccupied fibrinogen protein structure by bringing global and local perturbations in the frequency domain spectra. The proposed theoretical mechanisms, the interactions involved and the conformational changes suggested, were further corroborated by different experimental techniques such as isothermal titration calorimetry (ITC), zeta potential, UV-vis, fluorescence and small angle X-ray scattering (SAXS). The combined results shall open new avenues towards the application of complex supra-molecular information in rational drugs-design.

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 happen This 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 Salas SI

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 acebutolol The authors acknowledge Ministerio de Ciencia e Innovación (PID2019-111327GB-100) SI

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 perspectives The authors acknowledge Ministerio de Ciencia e Innovación (PID2019-111327GB-100) SI

The rise in the use of biomaterials in bone regeneration in the last decade has exponentially multiplied the number of publications, methods, and approaches to improve and optimize their functionalities and applications. In particular, biomimetic strategies based on the self-assembly of molecules to design, create and characterize nanostructured materials have played a very relevant role. We address this idea on four different but related points: self-setting bone cements based on calcium phosphate, as stable tissue support and regeneration induction; metallic prosthesis coatings for cell adhesion optimization and prevention of inflammatory response exacerbation; bio-adhesive hybrid materials as multiple drug delivery localized platforms and finally bio-inks. The effect of the physical, chemical, and biological properties of the newest biomedical devices on their bone tissue regenerative capacity are summarized, described, and analyzed in detail. The roles of experimental conditions, characterization methods and synthesis routes are emphasized. Finally, the future opportunities and challenges of nanostructured biomaterials with their advantages and shortcomings are proposed in order to forecast the future directions of this field of research.

We present a computational analysis coupled with experimental studies, focusing on the binding-interaction between beta-adrenoreceptor blocking agents (acebutolol and propranolol) with fibrinogen protein (E-region). Herein, computational modeling on structural validation and flexibility properties of fibrinogen E-region showed that the E-region interacting residues, which form the funnel-shaped hydrophobic cavity for ligand-binding, can be efficiently modeled. The obtained free energy of binding (FEB) values for the docking complexes, namely acebutolol/fibrinogen E-region and propranolol/fibrinogen E-region, were very close and amounted to - 6.9 kcal/mol and - 6.8 kcal/mol, respectively. They were supported by a high binding-accuracy (R.M.S.D < 2 A) for the best crystallographic binding-poses in both cases. In this regard, we identify a docking-mechanism of interaction for the propranolol and acebutolol mainly based on non-covalent hydrophobic contacts with the fibrinogen E-region binding-site. Besides, the beta-adrenoreceptor blocking agents are able to induce local perturbations affecting particularly the fibrinogen E-region allosteric residues linked to significant changes in the inter-residue communication and flexibility properties of residue network. In this sense, we show that the key biophysical parameters like frequency and collectivity degree may be compromised in different ways by the interaction with acebutolol and propranolol. Isothermal titration calorimetry, zeta potential and small angle X-ray scattering (SAXS) measurements were performed to complete and corroborate computational analysis. The combined experimental results point out that acebutolol acts to a lesser extent to fibrinogen structure than propranolol.

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 directions This research was funded by MINISTERIO DE CIENCIA E INNOVACIÓN (PID2019-111327GB-100). SI

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 areas The authors acknowledge Ministerio de Ciencia e Innovacion (PID2019-111327GB-100). N. H. thanks Proyecto FONDECYT de Iniciación (11170849) and FONDAP (15130011) SI

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 developed The authors acknowledge Ministerio de Ciencia e Innovación (PID2019-111327GB-100) and Xunta de Galicia (ED41E2018/08) SI

Bioceramic nanoparticles exhibit excellent features that enable them to function as an ideal material for hard tissue engineering. However, to fully understand their behavior, it is of crucial importance to understand their behavior within the fluids of the human body. To achieve this goal, we have studied the interaction between hydroxyapatite nanorods (HA) and bovine serum albumin (BSA). First, we describe the surface morphology of the nanoparticle. Then, the main characteristics of the physiological interplay of BSA and the hydroxyapatite nanoparticle are presented by using a battery of techniques: ITC, zeta potential, UV–vis, fluorescence, and CD. Experimental data was analyzed by developing specific approaches to determining important parameters such as rates, affinities, and stochiometries of protein associated with the nanoparticles. ITC has been confirmed as a powerful technique for determining the affinity, binding, and thermodynamics of BSA–nanoparticle interactions. Careful quantitative assessment of the kinetic properties of the adsorption were revealed by UV–vis and fluorescence measurements. Finally, CD measurements highlight the important role of protein flexibility in these kinds of systems. Fil: Rial, Ramón. Universidad de Santiago de Compostela; España Fil: Tichnell, Brandon. Frostburg State University; Estados Unidos Fil: Latimer, Brendan. Frostburg State University; Estados Unidos Fil: Liu, Zhen. Frostburg State University; Estados Unidos Fil: Messina, Paula Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Ruso, Juan M.. Universidad de Santiago de Compostela; España

Protein aggregation plays important roles in life science as, for instance, those associated to neurodegenerative diseases. Although extensive efforts have been done to elucidate all the possible variables related to the aggregation process, much has yet to be done to unveil the main pathways governing protein assembling. In the current work, we induce bovine serum albumin (BSA) association, at pH 3.7, by adding sodium dodecyl sulfate (SDS) and sodium perfluorooctanoate (SPFO) surfactants to BSA solution as promoters of protein aggregation. Firstly, we combine molecular dynamic simulations (MD) to obtain a partially unfolded state of BSA's monomer at the acid pH and small angle X-ray scattering (SAXS) to validate the model. Interestingly, we found by SAXS that at pH 3.7 BSA monomers coexist with dimers in surfactant-free solution. Upon SDS and SPFO addition, the partial unfolded BSA may evolve to large aggregates depending on surfactant concentration. The threshold occurs at 30:1 and 45:1 SDS:BSA and SPFO:BSA molar ratio, respectively, according to turbidity, Thioflavin (ThT) fluorescence, synchrotron radiation circular dichroism (SRCD), SAXS and scanning electron microscopy (SEM) experiments. BSA aggregates are larger in the presence of SDS and structurally more defined upon SPFO binding. Isothermal titration calorimetry (ITC) results give support to infer that both surfactants initially bind to the BSA macromolecule forming a complex. Then, these complexes self-associate towards supramolecular aggregates. Taking into account the physicochemical characteristics of both surfactants and also MD simulations we may suggest that the higher rigidity of the fluorinated chains in respect to hydrogenated ones is crucial to induce more ordered and smaller BSA's aggregates. Our results thus evidence that the ligand structural flexibility might be of a key importance in the pathway of protein aggregation and may pave the way to better understand the early steps of neurodegenerative disorders.

We describe the assembly of layer-by-layer (LbL) ultrathin films containing bioactive hydroxyapatite (HAp) rod-shaped nanoparticles with mineralizing capacity. Monodisperse 96 nm long and 9 nm wide HAp nanorods with a surface charge of â 14 mV were produced with a microfluidic system. The negatively charged HAp nanorods were assembled with the polycation poly-L-lysine (PLL) in LbL fashion. The successful deposition of alternating layers was confirmed by quartz-crystal microbalance with dissipation monitoring. The Voigt-based viscoelastic model demonstrated steady film growth where three PLL/HAp bilayers reached a thickness of 70 nm. The bioactivity of [PLL/HAp]3 was evaluated in vitro by following the formation of a mineralized hydroxyapatite layer in simulated body fluid (SBF). X-ray diffraction, energy-dispersive X-ray spectroscopy and scanning electron microscopy (SEM) demonstrated formation of a crystalline hydroxyapatite layer and complete surface coverage within 7 days. SaOs-2 osteoblasts-like cells attached to the mineralized surfaces and developed longer filopodia extensions when compared to non-mineralized samples. Our results showed that [PLL/HAp]3 films are feasible osteoconductive coatings applicable to orthopedic implants and fixation devices., The authors acknowledge Fundación Ramón Areces, Xunta de Galicia (ED431B 2017/21, ED41E2018/08), Programa Iacobus, financial support from “Fundação para a Ciência e Tecnologia” (grant CEECIND/02842/2017 to R. R. C. and project Norte-01-0145-FEDER-022190) and the EC H2020 programme through the projects ELASTISLET (NMP-2014-646075)

Background: Understanding the physicochemical basis and the different models of nanosystems is nowadays fundamental in a great number of scientific areas and industrial processes. Results: Here, we focus on nanosystems created by self-assembly, molecular or inorganic. The organization of single units at these scales is a challenging matter in light of the inherently small dimensions involved, the sensitivity of the system to small perturbations, and the problem of scaling up such a process for widespread use and implementation. Conclusion: This review examines the different self-assembly routes used to create nanostructures in both the equilibrium and non-equilibrium/dynamic systems and discusses their limits and applications. The connection to biomedicine and pharmaceutical design has been emphasized. Fil: Messina, Paula Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Rial, Ramón. Universidad de Santiago de Compostela. Facultad de Física; España Fil: Ruso, Juan M.. Universidad de Santiago de Compostela. Facultad de Física; España

The formation of liposomes, nanoparticle micelles, and related systems by mixtures of drugs and/or surfactants is of major relevance for the design of drug delivery systems. We can design new systems using different compounds. Traditionally these systems are created by trial and error using experimental data. However, in most cases measuring all the possible combinations represents a extensive work and almost always unaffordable. In this sense, we can use theoretical concepts and develop computational models to predict different physicochemical properties of self-aggregation processes of mixed molecular systems. In a previous work, we developed a new PT-LFER model (Linear Free Energy Relationships, LFER, combined with Perturbation Theory, PT, ideas) for binary systems. The best PT-LFER model found predicted the effects of 25000 perturbations over nine different properties of binary systems. The present work has two parts. Firstly, we carry out an analysis on the new results on the applications and experimental-theoretical studies of binary selfassembled systems. In the second part, we report for the first time, a new experimental-theoretic study of the NaDC-DTAB binary system. For this purpose, we have combined experimental procedures plus physicochemical thermodynamic framework with the PT-LFER model reported in our previous work. Fil: Messina, Paula Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Besada Porto, José Miguel. Universidad de Santiago de Compostela. Facultad de Física; España Fil: Rial, Ramón. Universidad de Santiago de Compostela. Facultad de Física; España Fil: Gonzalez Díaz, Humberto. Universidad del País Vasco; España. Fundación Vasca para la Ciencia; España Fil: Ruso, Juan M.. Universidad de Santiago de Compostela. Facultad de Física; España

Intrinsic material skills have a deep effect on the mechanical and biological performance of bone substitutes, as well as on its associated biodegradation properties. In this work we have manipulated the preparation of collagenous derived fiber mesh frameworks to display a specific composition, morphology, open macroporosity, surface roughness and permeability characteristics. Next, the effect of the induced physicochemical attributes on the scaffold's mechanical behavior, bone bonding potential and biodegradability were evaluated. It was found that the scaffold microstructure, their inherent surface roughness, and the compression strength of the gelatin scaffolds can be modulated by the effect of the cross-linking agent and, essentially, by mimicking the nano-scale size of hydroxyapatite in natural bone. A clear effect of bioactive hydroxyapatite nano-rods on the scaffolds skills can be appreciated and it is greater than the effect of the cross-linking agent, offering a huge perspective for the upcoming progress of bone implant technology. Fil: Sartuqui, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Gravina, Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Rial, Ramón. Universidad de Santiago de Compostela. Facultad de Física; España Fil: Benedini, Luciano Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina Fil: Yahia, L'Hocine. École Polytechnique de Montréal; Canadá Fil: Ruso, Juan M.. Universidad de Santiago de Compostela. Facultad de Física; España Fil: Messina, Paula Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina

Herein, we present an integrated computational and experimental study to tackle the interactions between recognized β-lactam antibiotics (cloxacillin and dicloxacillin) with the fibrinogen blood plasma protein. For this purpose, molecular docking simulation with elastic network based on collective low-frequency normal modes and perturbation response scanning maps were proposed to evaluate the conformational binding mechanism of fibrinogen under the unbound and bound states with the cited β-lactam antibiotics. Aiming to theoretically explore the hidden biochemical mechanisms and structural attributes leading failures in therapy success with β-lactam antibiotics. The computational results pointing that despite these conformational differences, both antibiotics exhibit very similar affinity-based free energies of binding as FEB (cloxacillin/E-region) = − 8.7 kcal/mol and FEB (dicloxacillin/E-region) = −7.7 kcal/mol. We theoretically suggest that the semi-synthetic incorporation of an additional halogen CL-atom in the dicloxacillin, respect to cloxacillin molecule, and its relative docking-pose orientation in the fibrinogen E-region could significantly reduce the appearance of potential fibrinolytic off-target effects usually associated to parenterally administered β-lactam antibiotics. Besides, the performed interactions diagrams revealed that the most relevant antibiotic binding interactions with the fibrinogen E-region (pocket 1) are mainly based on hydrophobic (C···C)-backbone-side-chain non-covalent interactions, acceptor/donor interactions with critical regulatory E-region residues SER50:Q > SER50:N associated to allosteric modulation based long-distance-based perturbations (dicloxacillin > > cloxacillin) in the E-region (Q-chain > N-chain) with remarkable conformational rigidification by decreasing the intrinsic collectivity, and leading different pattern of perturbations as allosteric signal propagation in the intrinsic conformational dynamics under bound state from both β-lactam antibiotics. An experimental validation was carried out by using calorimetric (ITC and DSC) and spectroscopic (Raman and fluorescence) methods. These methods corroborated the computational results, adding quantitative information to explain the binding process. Finally, the obtained results open new perspectives for the “de novo rational drug-design” of new derivatives of β-lactam antibiotics with high pharmacodynamic selectivity/specificity to avoid side-effects toward to achieve optimal benefit/risk rates beyond the antibiotic drug resistance phenomena, favoring the implementation of rigorous criteria for a more personalized antibiotic therapy.

Bioceramic nanoparticles have many potential applications within the biomedical device industry. However, these applications demand a precise control of their sizes, shapes and morphology which play a main role in most properties. In this work, we report a new route for the synthesis of hydroxyapatite nanoparticles using a microfluidic device. The process is carried out by continuous laminar flow through the device. The obtained nanoparticles have showed same properties (composition, length, orientation, roughness) than those produced by conventional methods, however, our device can afford to fine tune the structure via simple engineering, i.e., produce nanoparticles of different size only by varying the flow velocity. In addition to the efficiency and novelty of this system, the optimization of personnel costs makes it very profitable economically.

Tissue engineering provides solutions that require medicine to restore damaged tissues or even complete organs. This discipline combines biologically active scaffolds, cells and molecules; being the addition of nanoparticles into the scaffolds, one of the techniques that is attracting more interest these days. In this work, Hydroxyapatite Nanorods (HA) were added to the network of Gelatin hydrogel (GE), and the particular properties resulting from their interaction were studied. Specifically, viscoelastic properties were characterized as a function of gel and nanoparticle concentration, varying ratios and temperatures. Oscillatory Time Sweeps (OTS) provided the necessary information about how the timeresolved material property/structure alteration. A wide variety of Continuous Flow Tests and Frequency Sweeps were used to describe the mechanical properties of the material, proving that the presence of nanoparticles led to a reinforcement of the gel network, mechanical stiffness and strength. The thixotropic nature of the gels was also evaluated and the most common theoretical models were described and commented. The attributes inferred from the data, showed a material that can allow the natural growth of bone tissue whilst withstanding properly the mechanical efforts; resulting in a material with an outstanding suitability to be used in regenerative medicine.