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Amorphous molecule-macromolecule mixtures are ubiquitous in polymer technology and are one of the most studied routes for the development of amorphous drug formulations. For these applications it is crucial to understand how the preparation method affects the properties of the mixtures. Here, we employ differential scanning calorimetry and broadband dielectric spectroscopy to investigate dispersions of a small-molecule drug (the Nordazepam anxiolytic) in biodegradable polylactide, both in the form of solvent-cast films and electrospun microfibres. We show that the dispersion of the same small-molecule compound can have opposite (plasticizing or antiplasticizing) effects on the segmental mobility of a biopolymer depending on preparation method, temperature, and polymer enantiomerism. We compare two different chiral forms of the polymer, namely, the enantiomeric pure, semicrystalline L-polymer (PLLA), and a random, fully amorphous copolymer containing both L and D monomers (PDLLA), both of which have lower glass transition temperature (Tg) than the drug. While the drug has a weak antiplasticizing effect on the films, consistent with its higher Tg, we find that it actually acts as a plasticizer for the PLLA microfibres, reducing their Tg by as much as 14 K at 30%-weight drug loading, namely, to a value that is lower than the Tg of fully amorphous films. The structural relaxation time of the samples similarly depends on chemical composition and morphology. Most mixtures displayed a single structural relaxation, as expected for homogeneous samples. In the PLLA microfibres, the presence of crystalline domains increases the structural relaxation time of the amorphous fraction, while the presence of the drug lowers the structural relaxation time of the (partially stretched) chains in the microfibres, increasing chain mobility well above that of the fully amorphous polymer matrix. Even fully amorphous homogeneous mixtures exhibit two distinct Johari–Goldstein relaxation proc, Peer Reviewed, Postprint (author's final draft)

We present a fabrication process for the production of 3-dimensional micro-structured polymeric films. The microstructures are fabricated in a single step using thermal nanoimprint lithography as patterning technique. The micro-structured polymer films are then transformed into a 3D shape by means of a plug-assisted thermoforming process, while keeping the functionality of the micro-patterned areas. The preserved functionality is characterized by water contact angle measurements, while the deformation of the micro-structured topographies due to the thermoforming process is analyzed using confocal microscopy and Digital Image Correlation (DIC) techniques. This combined fabrication process represents a promising solution to complement in-mold decoration approaches, enabling the production of new functional surfaces. As the microstructures are fabricated by means of a mechanical modification of the surface, without the need of chemical treatments or coatings, the presented technique represents a promising, simple and green solution, suitable for the industrial fabrication of 3D nonplanar shaped functional surfaces., Peer Reviewed, Postprint (published version)

Unlike other engineered ceramic products, alumina (Al2O3) displays interesting mechanical and physical properties, which makes it an ideal candidate for a wide range of uses in different fields and in particular for catalytic applications. However, the manufacturing of ceramic components has still a major drawback in production of highly complex three-dimensional (3D) shapes, microfeatures or structures with tailored porosity. Direct Ink Writing (DIW), also known as robocasting, is a material extrusion Additive Manufacturing technology and is one of such versatile methods with unique flexibility in material and geometry. In this work, a-Al2O3 ceramic materials were designed and produced by DIW to determine the most suitable sintering treatment and ceramic ink composition to design new components for catalytic applications. Several thermal treatments varying sintering temperature and time were tested previously to the preparation of inks with different ceramic loadings, up to 75 wt%. A systematic study of the DIW specimens sintered at the optimal sintering temperature – time combination, in terms of microstructure (density and porosity) and mechanical properties (hardness and indentation fracture toughness), was performed to determine the optimize ceramic loading. Finally, finite element modeling and catalytic experiments conducted for the optimal ceramic ink showed that 3D printed parts with a rectilinear infill pattern and 40% infill density favored catalytic performance., Peer Reviewed, Postprint (author's final draft)

Poly(butylene succinate) (PBS) scaffolds with 3D microporous interconnected architecture and crystallized PBS substructures have been prepared by thermally-induced phase separation (TIPS). Curcumin (CUR) and piperine (PIP) natural drugs were incorporated into the matrices during a one-step fabrication protocol. Alterations in TIPS parameters such as solvent system (1,4 dioxane (DXN) or THF) and cooling condition (intensity and direction of thermal gradient) affected the phase separation process and the scaffold properties. Controlling the crystallization of DXN in a uniaxial direction, resulted in the formation of microtubular scaffolds with oriented porosities. Well-developed PIP crystals and matrix-integrated CUR agglomerates were uniformly distributed throughout the scaffolds. The integration of CUR to the polymer matrix was confirmed by physicochemical evaluations, attributed to a possible interaction with PBS, resulting in a slower release than PIP. The scaffolds with uniaxially-oriented porosities displayed a greater sustained release (only 50–60% after 170 h) due to the restricted drug diffusion through their dense spherulitic pore walls. Due to such structure and smoother well-arranged surfaces, the oriented scaffolds also exhibited greater biocompatibility. Our results reveal the positive influence of TIPS-derived structural orientation on properties of PBS matrices for cell/drug delivery., Peer Reviewed, Postprint (published version)

In the area of coating development, it is extremely difficult to find a substitute for bisphenol A diglycidyl ether (DGEBA), the classical petroleum-based raw material used for the formulation of epoxy thermosets. This epoxy resin offers fast curing reaction with several hardeners and the best thermal and chemical resistance properties for applications in coatings and adhesive technologies. In this work, a new biobased epoxy, derived from poly(limonene carbonate) oxide (PLCO), was combined with polyetheramine and polyamineamide curing agents, offering a spectrum of thermal and mechanical properties, superior to DGEBA-based thermosets. The best formulation was found to be a combination of PLCO and a commercial curing agent (Jeffamine) in a stoichiometric 1:1 ratio. Although PLCO is a solid due to its high molecular weight, it was possible to create a two-component partially biobased epoxy paint without the need of volatile organic compounds (i.e., solvent-free formulation), intended for use in coating technology to partially replace DGEBA-based thermosets., Peer Reviewed, Postprint (author's final draft)

Introduction: The rapid expansion of the novel SARS-CoV-2 virus has raised serious public health concerns due to the possibility of misdiagnosis in regions where arboviral diseases are endemic. We performed the first study in northern Peru to describe the detection of SARS-CoV-2 IgM antibodies in febrile patients with a suspected diagnosis of dengue and chikungunya fever. Materials and methods: A consecutive cross-sectional study was performed in febrile patients attending primary healthcare centers from April 2020 through March 2021. Patients enrolled underwent serum sample collection for the molecular and serological detection of DENV and CHIKV. Also, serological detection of IgM antibodies against SARS-CoV-2 was performed. Results: 464 patients were included during the study period, of which (40.51%) were positive for one pathogen, meanwhile (6.90%) presented co-infections between 2 or more pathogens. The majority of patients with monoinfections were positive for SARS-CoV-2 IgM with (73.40%), followed by DENV 18.09% and CHIKV (8.51%). The most frequent co-infection was DENV + SARS-CoV-2 with (65.63%), followed by DENV + CHIKV and DENV + CHIKV + SARS-CoV-2, both with (12.50%). The presence of polyarthralgias in hands (43.75%, p<0.01) and feet (31.25%, p = 0.05) were more frequently reported in patients with CHIKV monoinfection. Also, conjunctivitis was more common in patients positive for SARS-CoV-2 IgM (11.45%, p<0.01). The rest of the symptoms were similar among all the study groups. Conclusion: SARS-CoV-2 IgM antibodies were frequently detected in acute sera from febrile patients with a clinical suspicion of arboviral disease. The presence of polyarthralgias in hands and feet may be suggestive of CHIKV infection. These results reaffirm the need to consider SARS-CoV-2 infection as a main differential diagnosis of acute febrile illness in arboviruses endemic areas, as well as to consider co-infections between these pathogens., Postprint (published version)

Biocompatible hydrogels with antibacterial properties derived from ¿-polyglutamic acid (¿-PGA) were prepared from bulk and electrospun nanofibers. The antibacterial drugs loaded in these hydrogels were triclosan (TCS), chlorhexidine (CHX) and polyhexamethylene biguanide (PHMB); furthermore, bacteriophages were loaded as an alternative antibacterial agent. Continuous and regular ¿-PGA nanofibers were successfully obtained by the electrospinning of trifluoroacetic acid solutions in a narrow polymer concentration range and restricted parameter values of flow rate, voltage and needle-collector distance. Hydrogels were successfully obtained by using cystamine as a crosslinking agent following previous published procedures. A closed pore structure was characteristic of bulk hydrogels, whereas an open but structurally consistent structure was found in the electrospun hydrogels. In this case, the morphology of the electrospun nanofibers was drastically modified after the crosslinking reaction, increasing their diameter and surface roughness according to the amount of the added crosslinker. The release of TCS, CHX, PHMB and bacteriophages was evaluated for the different samples, being results dependent on the hydrophobicity of the selected medium and the percentage of the added cystamine. A high efficiency of hydrogels to load bacteriophages and preserve their bactericide activity was demonstrated too., Peer Reviewed, Postprint (published version)

The purpose of this paper is to demonstrate the easy manufacturing and quick characterization of several microtextured functional surfaces on two transparent thermoplastics of general interest for several industrial sectors. Microtextured polymeric surfaces with special optical, tribological and easy-cleaning properties were manufactured via isothermal injection-molding using laser-microtextured steel mold inserts. For that purpose, conventional injection molding of two chosen amorphous transparent polymers (polycarbonate, PC, and polymethyl methacrylate, PMMA) utilizing laser-microtextured steel inserts was carried out, and a detailed morphological and functional characterization of the injected specimens was conducted later on. We also report on the suitable process conditions for the injection molding of these specimens using design of experiment (DOE) techniques. The analysis of the degree of replication (DR%) on the injected samples shows that mold temperature and injection speed are the most relevant parameters to obtain a successful replication and confirm the viability of conventional injection molding as a processing technique to obtain microtextured functional surfaces in amorphous transparent thermoplastics. The success of the procedure is further checked by the confirmation of the obtained surface functionalities by various standard and self-developed methods., Peer Reviewed, Postprint (published version)

Different copolymers incorporating terpene oxide units (e.g., limonene oxide) have been evaluated considering thermal properties, degradability, and biocompatibility. Thus, polycarbonates and polyesters derived from aromatic, monocyclic and bicyclic anhydrides have been considered. Furthermore, ring substitution with myrcene terpene has been evaluated. All polymers were amorphous when evaluated directly from synthesis. However, spherulites could be observed after the slow evaporation of diluted chloroform solutions of polylimonene carbonate, with all isopropene units possessing an R configuration. This feature was surprising considering the reported information that suggested only the racemic polymer was able to crystallize. All polymers were thermally stable and showed a dependence of the maximum degradation rate temperature (from 242 °C to 342 °C) with the type of terpene oxide. The graduation of glass transition temperatures (from 44 °C to 172 °C) was also observed, being higher than those corresponding to the unsubstituted polymers. The chain stiffness of the studied polymers hindered both hydrolytic and enzymatic degradation while a higher rate was detected when an oxidative medium was assayed (e.g., weight losses around 12% after 21 days of exposure). All samples were biocompatible according to the adhesion and proliferation tests performed with fibroblast cells. Hydrophobic and mechanically consistent films (i.e., contact angles between 90° and 110°) were obtained after the evaporation of chloroform from the solutions, having different ratios of the studied biobased polyterpenes and poly(butylene succinate) (PBS). The blend films were comparable in tensile modulus and tensile strength with the pure PBS (e.g., values of 330 MPa and 7 MPa were determined for samples incorporating 30 wt.% of poly(PA-LO), the copolyester derived from limonene oxide and phthalic anhydride. Blends were degradable, biocompatible and appropriate to produce oriented-pore and random-po, Peer Reviewed, Postprint (published version)

Micro- and nanotexturization of surfaces can give to the parts different advanced functionalities, such as superhydrophobicity, self-cleaning, or antibacterial capabilities. These advanced properties in combination with the biocompatibility of Liquid Silicone Rubber are an interesting approach for obtaining high-performance medical devices. The industrial production of surface textures in polymeric materials is through the replication technique, and the best option to attain a high production rate is injection molding. Moreover, its low viscosity during processing can provide an accurate replication capacity by the easy filling by capillarity of the microtextures. An innovative replicating technique for Liquid Silicone Rubber is presented by studying the replication of different shaped textures within a diameter range of between 2 and 50 µm. The copying process consists in the overmolding of a textured polymeric inlay obtained by nanoimprint lithography. At the end of the process, a textured part is obtained, while the imprinted film remains in the mold. The injection molding parameters are optimized to increase the replication accuracy, and their effect on texture replicability is analyzed and discussed. Finally, it is shown that the textured surfaces improve their wettability behavior, which is a necessary and important characteristic in the development of biomedical devices., Peer Reviewed, Postprint (published version)

The preparation, characterization, and controlled release of hydroxyapatite (HAp) nanoparticles loaded with streptomycin (STR) was studied. These nanoparticles are highly appropriate for the treatment of bacterial infections and are also promising for the treatment of cancer cells. The analyses involved scanning electron microscopy, dynamic light scattering (DLS) and Z-potential measurements, as well as infrared spectroscopy and X-ray diffraction. Both amorphous (ACP) and crystalline (cHAp) hydroxyapatite nanoparticles were considered since they differ in their release behavior (faster and slower for amorphous and crystalline particles, respectively). The encapsulated nanoparticles were finally incorporated into biodegradable and biocompatible polylactide (PLA) scaffolds. The STR load was carried out following different pathways during the synthesis/precipitation of the nanoparticles (i.e., nucleation steps) and also by simple adsorption once the nanoparticles were formed. The loaded nanoparticles were biocompatible according to the study of the cytotoxicity of extracts using different cell lines. FTIR microspectroscopy was also employed to evaluate the cytotoxic effect on cancer cell lines of nanoparticles internalized by endocytosis. The results were promising when amorphous nanoparticles were employed. The nanoparticles loaded with STR increased their size and changed their superficial negative charge to positive. The nanoparticles’ crystallinity decreased, with the consequence that their crystal sizes reduced, when STR was incorporated into their structure. STR maintained its antibacterial activity, although it was reduced during the adsorption into the nanoparticles formed. The STR release was faster from the amorphous ACP nanoparticles and slower from the crystalline cHAp nanoparticles. However, in both cases, the STR release was slower when incorporated in calcium and phosphate during the synthesis. The biocompatibility of these nanoparticles was assayed by t, Peer Reviewed, Postprint (published version)

Background: At the end of 2019, a novel coronavirus denominated SARS-CoV-2 rapidly spread through the world causing the pandemic coronavirus disease known as COVID-19. The difference in the inflammatory response against SARS-CoV-2 infection among people living at different altitudes is a variable not yet studied. Methods: A descriptive cross-sectional study was performed in two Peruvian cities at different altitudes for compari- son: Lima and Huaraz. Five important proinflammatory cytokines were measured including: IL-6, IL-2, IL-10, IFN-¿ and TNF-a using ELISA assays. Results: A total of 35 COVID-19 patients and 10 healthy subjects were recruited from each study site. The mean levels of IL-6 (p < 0.03) and TNF-a (p < 0.01) were significantly different among the study groups. In the case of IL-6, patients from Lima had a mean level of 16.2 pg/ml (healthy) and 48.3 pg/ml (COVID-19), meanwhile, patients from Huaraz had levels of 67.3 pg/ml (healthy) and 97.9 pg/ml (COVID-19). Regarding TNF-a, patients from Lima had a mean level of 25.9 pg/ml (healthy) and 61.6 pg/ml (COVID-19), meanwhile, patients from Huaraz had levels of 89.0 pg/ml (healthy) and 120.6 pg/ml (COVID-19). The levels of IL-2, IL-10 and IFN-¿ were not significantly different in the study groups. Conclusion: Patients with COVID-19 residing at high-altitude tend to have higher levels of inflammatory cytokines compared to patients living at sea level, particularly IL-6 and TNF-a. A better understanding of the inflammatory response in different populations can contribute to the implementation of therapeutic and preventive approaches. Further studies evaluating more patients, a greater variety of cytokines and their clinical impact are required., Postprint (published version)

Electrospun scaffolds of the biodegradable and biocompatible poly-4-hydroxybutyrate (P4HB) polyester have been prepared using horizontal and vertical set-up configurations of electrospinning. Specifically, it has been evaluated the influence of solvent, polymer concentration, and processing parameters, such as applied voltage, flow rate, and needle tip-collector distance. Scaffolds obtained under the most favorable conditions were characterized in terms of crystallinity, lamellar supramolecular order, thermal (including calorimetric and thermogravimetric data), mechanical, and surface properties. Results pointed out significant differences with respect to commercial sutures (based in P4HB, e.g., MonoMax®) and demonstrated that electrospun scaffolds were constituted by crystalline microfibers with a tangled distribution that leads to high modulus Young modulus (4¿MPa), maximum strength (28¿MPa), and elongation (360%). Furthermore, new scaffolds had thermal stability and a rough surface that led to a hydrophobic character (105°). Scaffolds could also be successfully loaded during the electrospinning process with a peptide analog to the fibroblast growth factor (e.g., CYRSRKYSSWYVALKRC), giving rise to fully biocompatible samples with a clear acceleration in wound healing., Peer Reviewed, Postprint (author's final draft)

We examine different approaches for the controlled release of L-lactate, which is a signaling molecule that participates in tissue remodeling and regeneration, such as cardiac and muscle tissue. Robust, flexible, and self-supported 3-layers films made of two spin-coated poly(lactic acid) (PLA) layers separated by an electropolymerized poly(3,4-ethylenedioxythiophene) (PEDOT) layer, are used as loading and delivery systems. Films with outer layers prepared using homochiral PLA and with nanoperforations of diameter 146 ± 70 experience more bulk erosion, which also contributes to the release of L-lactic acid, than those obtained using heterochiral PLA and with nanoperforations of diameter 66 ± 24. Moreover, the release of L-lactic acid as degradation product is accelerated by applying biphasic electrical pulses. The four approaches used for loading extra L-lactate in the 3-layered films were: incorporation of L-lactate at the intermediate PEDOT layer as primary dopant agent using (1) organic or (2) basic water solutions as reaction media; (3) substitution at the PEDOT layer of the ClO4- dopant by L-lactate using de-doping and re-doping processes; and (4) loading of L-lactate at the outer PLA layers during the spin-coating process. Electrical stimuli were applied considering biphasic voltage pulses and constant voltages (both negative and positive). Results indicate that the approach used to load the L-lactate has a very significant influence in the release regulation process, affecting the concentration of released L-lactate up to two orders of magnitude. Among the tested approaches, the one based on the utilization of the outer layers for loading, approach (4), can be proposed for situations requiring prolonged and sustained L-lactate release over time. The biocompatibility and suitability of the engineered films for cardiac tissue engineering has also been confirmed using cardiac cells, Postprint (author's final draft)

Objective: To describe and molecularly characterize an outbreak of dengue virus (DENV) infection in Cajamarca, an Andean region in Peru. Methods: A total of 359 serum samples from patients with acute febrile illness were assessed for the presence of DENV via RT-PCR, ELISA NS1, IgM and IgG in Cajamarca, Peru from January 2017 to June 2017. The evaluation of the different diagnostic tests and their applicability was performed. Results: Dengue virus was detected in 24.7% of samples by RT- PCR. Meanwhile, serological analysis detected 30.3% positive cases via ELISA NS1 antigen, 16.7% via ELISA IgG and 9.7% via ELISA IgM. Most of the cases corresponded to DENV-3 (77.5%). The use of RT-PCR performed better in primary infections (P<0.01), while detection of ELISA IgM performed better in secondary infections (P<0.01). The combination of NS1 and IgM performed better than the other assays in detecting primary (92.5%) and secondary infections (96.6%). The most frequent symptoms associated with fever were headaches, myalgias, and arthralgias across all groups. Conclusions: We report an important outbreak of dengue infection caused by DENV-3 in Cajamarca, Peru. Our findings encourage the use of NS1 antigen and IgM co-detection. These findings demonstrate an increasing expansion of DENV-3 in Peru and highlight the importance of molecular diagnosis and serotype characterization among the clinically defined dengue cases to strengthen the Peruvian epidemiological surveillance, Postprint (published version)

Conversion of CO2 into valuable chemicals is not only a very challenging topic but also a socially demanding issue. In this work, permanently polarized hydroxyapatite obtained using a thermal stimulated polarization process is proposed as a highly selective catalyst for green production of ethanol starting from CO2 and CH4., Peer Reviewed, Postprint (author's final draft)

A new methodology for the pH-triggered degradation of polymers or for therelease of drugs under visible light irradiation based on the cyclization ofortho-hydroxy-cinnamates (oHC) to coumarins is described. The keyoHCstructural motif can be readily incorporated into the rational design of novelphotocleavable polymers via click chemistry. This main-chain moietyundergoes a fast photocleavage when irradiated with 455 nm light providedthat a suitable base is added. A series of polyethylene glycol-alt-ortho-hydroxycinnamate (polyethylene glycol (PEG)n-alt-oHC)-based polymers aresynthesized and the time-dependent visible-light initiated cleavage of thephotoactive monomer and polymer is investigated in solution by a variety ofspectroscopic and chromatographic techniques. The photo-degradationbehavior of the water-soluble poly(PEG2000-alt-oHC) is investigated within abroad pH range (pH=2.1–11.8), demonstrating fast degradation at pH 11.8,while the stability of the polymer is greatly enhanced at pH 2.1. Moreover, theneat polymer shows long-term stability under daylight conditions, thusallowing its storage without special precautions. In addition, twowater-soluble PEG-based drug-carrier molecules(mPEG2000-oHC-benzhydrol/phenol) are synthesized and used for drugdelivery studies, monitoring the process by UV–vis spectroscopy in anON/OFF intermittent manner., Peer Reviewed, Postprint (published version)

The aim of this work was to prepare and characterize polymer–ceramic composite material for dental applications, which must resist fracture and wear under extreme forces. It must also be compatible with the hostile environment of the oral cavity. The most common restorative and biocompatible copolymer, 2,2-bis(p-(2'-2-hydroxy-3'-methacryloxypropoxy)phenyl)propane and triethyleneglycol dimethacrylate, was combined with 3D-printed yttria-stabilized tetragonal zirconia scaffolds with a 50% infill. The proper scaffold deposition and morphology of samples with 50% zirconia infill were studied by means of X-ray computed microtomography and scanning electron microscopy. Samples that were infiltrated with copolymer were observed under compression stress, and the structure’s failure was recorded using an Infrared Vic 2DTM camera, in comparison with empty scaffolds. The biocompatibility of the composite material was ascertained with an MG-63 cell viability assay. The microtomography proves the homogeneous distribution of pores throughout the whole sample, whereas the presence of the biocompatible copolymer among the ceramic filaments, referred to as a polymer-infiltrated ceramic network (PICN), results in a safety “damper”, preventing crack propagation and securing the desired material flexibility, as observed by an infrared camera in real time. The study represents a challenge for future dental implant applications, demonstrating that it is possible to combine the fast robocasting of ceramic paste and covalent bonding of polymer adhesive for hybrid material stabilization., Peer Reviewed, Postprint (published version)

Hybrid free-standing biomimetic materials are developed by integrating the VDAC36 ß-barrel protein into robust and flexible three-layered polymer nanomembranes. The first and third layers are prepared by spin-coating a mixture of poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVA). PVA nanofeatures are transformed into controlled nanoperforations by solvent-etching. The two nanoperforated PLA layers are separated by an electroactive layer, which is successfully electropolymerized by introducing a conducting sacrificial substrate under the first PLA nanosheet. Finally, the nanomaterial is consolidated by immobilizing the VDAC36 protein, active as an ion channel, into the nanoperforations of the upper layer. The integration of the protein causes a significant reduction of the material resistance, which decreases from 21.9 to 3.9 kO cm2. Electrochemical impedance spectroscopy studies using inorganic ions and molecular metabolites (i.e.L-lysine and ATP) not only reveal that the hybrid films behave as electrochemical supercapacitors but also indicate the most appropriate conditions to obtain selective responses against molecular ions as a function of their charge. The combination of polymers and proteins is promising for the development of new devices for engineering, biotechnological and biomedical applications.Hybrid free-standing biomimetic materials are developed by integrating the VDAC36 ß-barrel protein into robust and flexible three-layered polymer nanomembranes. The first and third layers are prepared by spin-coating a mixture of poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVA). PVA nanofeatures are transformed into controlled nanoperforations by solvent-etching. The two nanoperforated PLA layers are separated by an electroactive layer, which is successfully electropolymerized by introducing a conducting sacrificial substrate under the first PLA nanosheet. Finally, the nanomaterial is consolidated by immobilizing the VDAC36 protein, active as an ion channe, Peer Reviewed, Postprint (author's final draft)

This work aims to synthesize biocompatible composite materials loaded with recycled porcine bone powder (BP) to fabricate scaffolds for in-situ reconstruction of bone structures. Polylactic acid (PLA) and poly(e-caprolactone) (PCL) were tested as matrices in percentages from 40 wt% to 80 wt%. Chitosan (CS) was selected for its antibacterial properties, in the amount from 5 wt% to 15 wt%, and BP from 20 wt% to 50 wt% as active filler to promote osseointegration. In this preliminary investigation, samples have been produced by solvent casting to introduce the highest possible percentage of fillers. PCL has been chosen as a matrix due to its greater ability to incorporate fillers, ensuring their adequate dispersion and lower working temperatures compared to PLA. Tensile tests demonstrated strength properties (6–10 MPa) suitable for hard tissue engineering applications. Based on the different findings (integration of PLA in the composite system, improvements in CS adhesiThis work aims to synthesize biocompatible composite materials loaded with recycled porcine bone powder (BP) to fabricate scaffolds for in-situ reconstruction of bone structures. Polylactic acid (PLA) and poly(e-caprolactone) (PCL) were tested as matrices in percentages from 40 wt% to 80 wt%. Chitosan (CS) was selected for its antibacterial properties, in the amount from 5 wt% to 15 wt%, and BP from 20 wt% to 50 wt% as active filler to promote osseointegration. In this preliminary investigation, samples have been produced by solvent casting to introduce the highest possible percentage of fillers. PCL has been chosen as a matrix due to its greater ability to incorporate fillers, ensuring their adequate dispersion and lower working temperatures compared to PLA. Tensile tests demonstrated strength properties (6–10 MPa) suitable for hard tissue engineering applications. Based on the different findings (integration of PLA in the composite system, improvements in CS adhesion and mechanical properties), the aut, Peer Reviewed, Postprint (published version)

This work reports a simple and scalable strategy to prepare a series of thermoresponsive polyurethanes synthesized via copolymerization of dicyclohexyl diisocyanate with glycerol ethoxylate in a single one-pot system. These polyurethanes exhibit lower critical solution temperatures (LCST) at 57¿°C. The LCST of synthesized polyurethane was determined from Dynamic Scanning Calorimetry and UV-vis measurements. Both the LCST and Tg of synthesized polyurethane was tuned by varying the ratio between hard segment (dicyclohexyl diisocyanate) and soft segment (glycerol ethoxylate). Thus, Tg values could be tuned from -54.6¿°C to -19.9¿°C for samples with different flexibility. The swelling and deswelling studies were done at room temperature and above the LCST respectively. The results showed that the swelling ratio increases with the increase of soft segment (glycerol ethoxylate) in synthesized polyurethanes. Furthermore, the mechanical properties of the membrane were studied by universal tensile testing measurements. Specifically, stress at break values varied from 0.35±0.07 MPa to 0.91±0.15 MPa for the tested membranes, whereas elongation at break data ranged from 101.9±20.9¿% to 192.4±24.4¿%, and Young's modulus varied from 0.35±0.03 MPa to 1.85±0.19 MPa. Tensile strength of the films increased with the increase of the hard segment and elongation at break decreased., Peer Reviewed, Postprint (published version)

Melt electrospinning of polylactide (PLA) loaded with chloramphenicol (CAM) has been performed and characteristics of fibers, physical properties of scaffolds, CAM release behavior, antibacterial properties and biocompatibility have been evaluated. The interest of CAM loaded samples is nowadays enhanced for biomedical applications since this antibiotic has been demonstrated to be efficient for the treatment of cancer. Melt electrospinning has been selected as an ideal preparation process because it avoids the use of toxic solvents which are harmful to the environment and could be problematic for biomedical applications. The electrospinning process rendered fibers with a relatively large diameter (between 20 µm and 40 µm depending on the load) and minimum polymer degradation. Characteristics of melt electrospun scaffolds were also compared with those prepared by solution electrospinning. Differences consisted in a more sustained release and a higher biocompatibility for the melt processed samples. Bactericide effect was evaluated as an evidence of the maintenance of the CAM bioactivity after melt processing at high temperature and the slower release caused by the relatively high diameter of the constitutive fibers. Since pure CAM showed thermal degradation at temperatures relatively close to the PLA melting temperature, a complete analysis of the degradation process of pure CAM as well as of PLA samples loaded with CAM was performed. The Invariant Kinetic Parameters method allowed determining an initial decomposition step that followed an autoaccelatory Avrami model, and then an autocatalytic decomposition reaction took place for conversions higher than 50%. Dispersion in the PLA matrix enhances the thermal stability of the antibiotic, with an onset temperature of degradation that was higher by 16 ¿C in the meltelectrospun fibers than in the liquid state of pure CAM., Peer Reviewed, Postprint (author's final draft)

Rapid detection of bacterial presence on implantable medical devices is essential to prevent biofilm formation, which consists of densely packed bacteria colonies able to withstand antibiotic-mediated killing. In this work, a smart approach is presented to integrate electrochemical sensors for detecting bacterial infections in biomedical implants made of isotactic polypropylene (i-PP) using chemical assembly. The electrochemical detection is based on the capacity of conducting polymers (CPs) to detect extracellular nicotinamide adenine dinucleotide (NADH) released from cellular respiration of bacteria, which allows distinguishing prokaryotic from eukaryotic cells. Oxygen plasma-functionalized free-standing i-PP, coated with a layer (˜1.1 µm in thickness) of CP nanoparticles obtained by oxidative polymerization, is used as working electrode for the anodic polymerization of a second CP layer (˜8.2 µm in thickness), which provides very high electrochemical activity and stability. The resulting layered material, i-PPf/CP2, detects the electro-oxidation of NADH in physiological media with a sensitivity 417 µA cm-2 and a detection limit up to 0.14 × 10-3 m, which is below the concentration of extracellular NADH found for bacterial cultures of biofilm-positive and biofilm-negative strains., Peer Reviewed, Postprint (author's final draft)

Polydopamine–ethylene glycol dimethacrylate copolymer is a biocompatible coating with cell adhesion promotion and antibiofilm properties. This copolymer has been successfully applied on metallic implants, such as stainless steel and titanium implants, using several deposition techniques (e.g. layer-by-layer, silane activation, chemical vapor deposition, or liquid-assisted plasma polymerization). However, its application in zirconia ceramic materials, which are widely used in dentistry and medicine, has never been described. In this work, polydopamine–ethylene glycol dimethacrylate copolymer has been deposited on ultra-smooth surfaces of yttria-stabilized zirconia discs (average roughness = 2.08 ± 0.08 nm) by using liquid-assisted atmospheric-pressure plasma-induced polymerization (LA-APPiP). After the polymerization, the nanometric coating (250 nm, measured by ellipsometry) had an average roughness of 79.85 ± 13.71 nm and water contact angle of 57.8 ± 2.2 degrees, consistent with the highly hydrophilic nature of the biocompatible copolymer, if compared to the pristine zirconia (72.7 ± 2.0 degrees). The successful covalent bonding of the copolymer with the zirconia surface, thanks to the previous activation of the substrate with oxygen plasma, was proved by X-ray photoelectron spectroscopy (XPS). The polymer composition has been investigated by XPS and Raman spectroscopies. The LA-APPiP technique has been proved to be an excellent method to produce homogenous films without the need to employ solvents and further purification steps. The new copolymer film allows the uniform growth of human osteoblast-like MG-63 cells, after 7 days of cell culture, as observed by fluorescence microscopy., Postprint (published version)

Ultrasound micromolding (USM) preparation of hybrid scaffolds based on polylactide (PLA) and hydroxyapatite (HAp) particles has been evaluated. PLA was stable under the applied ultrasound source since a minimum degradation was detected. Porous materials were achieved using polyethylene glycol (PEG) and NaCl salts to the initial PLA and the subsequent leaching of the micromolded specimens. To avoid cavitation and decomposition problems during micromolding, it was necessary to use HAp free of typical synthesis impurities like carbonate and nitrate compounds. Compact PLA/HAp pieces allowed a maximum HAp load of 60 wt%, while porous specimens could be obtained with a maximum load of 38 wt%. Physical characterization of new scaffolds was performed by X-ray diffraction, spectroscopic and calorimetric techniques, stress-strain tests and contact angle measurements. Results indicated that a degree of porosity of 35% and relatively good mechanical properties could be achieved (i.e., 580 MPa, 4%, and 15.6 MPa for the Young modulus, elongation at break, and tensile strength, respectively). Scaffolds showed the positive effect of HAp and porosity on cell proliferation; this latter was 40% higher than that detected for non-porous PLA specimens., Peer Reviewed, Postprint (published version)

Porous biodegradable scaffolds provide a physical substrate for cells allowing them to attach, proliferate and guide the formation of new tissues. A variety of techniques have been developed to fabricate tissue engineering (TE) scaffolds, among them the most relevant is the thermally-induced phase separation (TIPS). This technique has been widely used in recent years to fabricate three-dimensional (3D) TE scaffolds. Low production cost, simple experimental procedure and easy processability together with the capability to produce highly porous scaffolds with controllable architecture justify the popularity of TIPS. This paper provides a general overview of the TIPS methodology applied for the preparation of 3D porous TE scaffolds. The recent advances in the fabrication of porous scaffolds through this technique, in terms of technology and material selection, have been reviewed. In addition, how properties can be effectively modified to serve as ideal substrates for specific target cells has been specifically addressed. Additionally, examples are offered with respect to changes of TIPS procedure parameters, the combination of TIPS with other techniques and innovations in polymer or filler selection., Peer Reviewed, Postprint (published version)

The fight against nosocomial infections in hospitals, has promoted the use of microencapsulated essential oils on medical wearing uniforms. These types of microcapsules can be improved with the use of antimicrobial polymers in the shell structure. Chitosan is one of the most used biopolymers and the effectiveness of the treatment can be increased with the combination of different molecular weight chains of chitosan. This modification in the composition of shell structure allows controlling the rate of hydrolysis and, therefore the amount of its cationic form. The main objective of this work is to define a methodology to get microcapsules with different shell compositions, using surfactants as stabilizers in their first step. Once they have been obtained, these microcapsules will be fixed into textile substrates with the objective to use these tissues as surgical and medical clothes to spread the antibacterial effect, in sanitary staff, as well as in the own patient. In the process of microencapsulation the molecular weight distribution of polymers, influences strongly the delivery mechanisms of the active principle, as well as the chemical characteristics of the textile substrate used in every case. In this work, several chitosan biopolymers have been checked. Structural changes in the stabilization first step and the influence of the cross-linking extension have been related with the final antibacterial effect when fixed on cotton substrates, Authors want to show their acknowledgements to the institutions and companies that helped to the development of this work. Spanish Ministry of Science and Technology. TEXBICO (RTI2018-094014-B-100) that granted the necessary funds to do the experimental work and Biomedical Chitosan (Australia) and CHIBIO (China), for kindly supply the samples used in the Shell structure of microcapsules, Postprint (published version)

The synthesis of hydroxyapatite (HAp) with different shapes and sizes has attracted increasing attention because the applicability of this ceramic material depends on structure-properties relationships (i.e., the dimensions and morphology of HAp crystals determine properties such as the bioactivity and mechanical strength). Although different synthetic routes based on the addition of surfactants, organic modifiers, or dispersants have been proposed to control the growth of HAp crystals, many efforts are being devoted to simplify the whole process using simple parameters such as pH. However, the control of the morphology is still poor and shows low reproducibility. In this work, a new additive-free synthetic route, which is based on the hydrothermal method and the utilization of nonaqueous solvents, is proposed. The influence of the synthesis parameters such as pH, concentration of starting solutions, and the solvent on relevant features such as phase purity, crystallinity, crystallite size, and morphology has been examined using spectroscopic techniques, X-ray diffraction, and scanning electron microscopy. As a consequence, this work presents an easy and robust method based only on the use of organic solvent and the control of the pH that produces pure and crystalline HAp with a controlled shape and size. This method has been used to elucidate some of the key aspects of the crystal growth mechanism and to synthesize HAp crystals with different and well-defined shapes (e.g., belts, rods, flakes needle-like, or polymorph) and sizes, in a reproducible way., Peer Reviewed, Postprint (author's final draft)

In the present study, a composite made of conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), and a biodegradable hydrogel of poly(aspartic acid) (PASP) were electrochemically interpenetrated with poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PHMeDOT) to prepare a new interpenetrated polymer network (IPN). Different cross-linker and PEDOT MPs contents, as well as different electropolymerization times, were studied to optimize the structural and electrochemical properties. The properties of the new material, being electrically conductive, biocompatible, bioactive, and biodegradable, make it suitable for possible uses in biomedical applications., Postprint (author's final draft)

Intracellular calcium (Ca2+) is a key signaling element that is involved in a great variety of fundamental biological processes. Thus, Ca2+ deregulation would be involved in the cancer cell progression and damage of mitochondrial membrane and DNA, which lead to apoptosis and necrosis. In this study, we have prepared amorphous calcium phosphate nanoparticles (ACP NPs) for studied their incorporation by endocytosis or electroporation to epithelial, endothelial and fibroblast cells (MCF-7, HUVEC and COS-1 cells, respectively). Our results showed that internalized ACP NPs have cytotoxic effects as a consequence of the increase of the intracellular calcium content. The endocytosis pathways showed a greater cytotoxic effect since calcium ions could easily be released from the nanoparticles and be accumulated in the lysosomes and mitochondria. In addition, the cytotoxic effect could be reversed when calcium ion was chelated with ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). Modification of ACP NPs by coating with different compounds based on phosphates was also evaluated. The results indicated a reduction of the cytotoxic effect, in the order polyphosphate¿<¿phosphonic acid¿<¿orthophosphate. A differential cytotoxic effect of ACP-NPs was observed in function of the cell type; the cytotoxic effect can be ordered as i.e., HUVEC¿>¿COS-1¿>¿MCF-7. The greater cytotoxic effect caused by the increase of intracellular calcium that is observed in normal cells and the greater resistance of cancer cells suggests new perspectives for cancer research., Peer Reviewed, Postprint (published version)

Aliphatic polyamides (nylons) constitute a family of polymers with outstanding properties and multiple applications. Despite the intensive research studies carried out with nylons, there are still multiple unsolved questions concerning crystallization processes, crystalline structures, polymorphic transitions, and crystalline morphologies. Constrains imposed by the strong intermolecular interactions affect the amorphous state, the rigid amorphous phase, the molecular folding, the morphology and obviously the crystalline structure. Some of these relevant points are discussed in the present work., Peer Reviewed, Postprint (published version)

Hydrolytic degradation of poly(4-hydroxybutyrate) (P4HB) films has been studied considering media of different pH values (i.e., 3, 7 and 10) and temperatures (i.e., 37 and 55 °C). Enzymatic degradation has also been evaluated at physiological conditions using two different lipases: Pseudomonas cepacia and Rhizopus oryzae. Different bulk and surface erosion mechanisms with random chain scissions and successive removal of monomer units have been supported through weight loss measurements, molecular weight determinations by GPC and NMR spectroscopy and changes on thermal properties by DSC. Thermal annealing during exposure to different media and even degradation influenced on the melting temperature and crystallinity of samples, as well as on the lamellar geometrical parameters as evaluated by SAXS. Enzymatic degradation was ideal to selectively eliminate the amorphous regions and highlight the spherulitic morphology. Presence of ringed textures were therefore evident in bright field optical micrographs in addition to SEM images, namely observations under polarized light was not necessary to distinguish the presence of banded spherulites. Rhizopus oryzae was revealed to be the most suitable enzyme to crop out the P4HB spherulites that form part of the initial smooth surfaces of solvent casting films. After determining the appropriate activity and exposure time, the presence of rings constituted by cooperative C-shaped edge-on lamellae and flat-on lamellae was highlighted., Peer Reviewed, Postprint (author's final draft)

The self-assembly behavior of chemoenzymatic high molecular weight (ca. 30 000 Da) poly-L-phenylalanine (ePLP) and the nano-morphologies thereof are investigated. Interestingly, this supramolecular ePLP changes from a non-ordered secondary structure when solubilized in water to an a-helix with the addition of only 1 vol% HFIP co-solvent, and at a relatively low concentration (0.5 mg mL-1). The results also indicate a temperature-dependent structural stabilization, wherein the self-assembly process is mainly governed by hydrogen bonding. The analyses evidence self-assembly under controlled conditions to obtain nanotubes with an average diameter of 0.21 ± 0.04 µm, and above 100 µm length. Microbeam synchrotron radiation infrared (SRIR) spectroscopy demonstrates parallel orientations of the amide moieties in the a-helical structure, which is extraordinary for this long chain ePLP. The achievement of these highly homogeneous nanotubes is relevant since previous reports only demonstrated this arrangement for end-capped F-moc-containing short oligophenylalanines. In the same way, the conductivity behaviors of the nanotubular structure remained unchanged in the range of 273–313 K demonstrating its stability from hydrogen bonds, and also, direct dielectric measurements reveal a high orientation and stabilization by intra- and intermolecular hydrogen bonds in the nanotubes. These characteristics allow drug delivery assays with tetracycline-loaded nanotubes and further applications are envisaged., Peer Reviewed, Postprint (author's final draft)

Chronic wounds represent a major health burden and drain on medical system. Efficient wound repair is only possible if the dressing materials target simultaneously multiple factors involved in wound chronicity, such as deleterious proteolytic and oxidative enzymes and high bacterial load. Here we develop multifunctional hydrogels for chronic wound management through self-assembling of thiolated hyaluronic acid (HA-SH) and bioactive silver-lignin nanoparticles (Ag@Lig NPs). Dynamic and reversible interactions between the polymer and Ag@Lig NPs yield hybrid nanocomposite hydrogels with shear thinning and self-healing properties, coupled to zero-order kinetics release of antimicrobial silver in response to infection-related hyaluronidase (HNase). The hydrogels inhibit the major enzymes myeloperoxidase (MPO) and matrix metalloproteinases (MMPs) responsible for wound chronicity in a patient’s wound exudate. Furthermore, the lignin-capped AgNPs provide the hydrogel with antioxidant properties and strong antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. The nanocomposite hydrogels are not toxic to human keratinocytes after 7 days of direct contact. Complete tissue remodeling and restoration of skin integrity is demonstrated in vivo in a diabetic mouse model. Hematological analysis reveals lack of wound inflammation due to bacterial infection or toxicity, confirming the potential of HA-SH/Ag@Lig NPs hydrogels for chronic wound management., Peer Reviewed, Postprint (author's final draft)

The enhanced catalytic activity of permanently polarized hydroxyapatite, which is achieved using a thermally stimulated polarization process, largely depends on both the experimental conditions used to prepare crystalline hydroxyapatite from its calcium and phosphate precursors and the polarization process parameters. A mineral similar to brushite, which is an apatitic phase that can evolve to hydroxyapatite, is found at the surface of highly crystalline hydroxyapatite. It appears after chemical precipitation and hydrothermal treatment performed at 150 °C for 24 h followed by a sinterization at 1000 °C and a polarization treatment by applying a voltage of 500 V at high temperature. Both the high crystallinity and the presence of brushite-like phase on the electrophotocatalyst affect the nitrogen and carbon fixation under mild reaction conditions (95 °C and 6 bar) and the synthesis of glycine and alanine from a simple gas mixture containing N2, CO2, CH4 and H2O. Thus, the Gly/Ala ratio can be customized by controlling the presence of brushite on the surface of the catalyst, enabling to develop new strategies to regulate the production of amino acids by nitrogen and carbon fixation., Peer Reviewed, Postprint (author's final draft)

The impact of respiratory coinfections in COVID-19 is still not well understood despite the growing evidence that consider coinfections greater than expected. A total of 295 patients older than 18 years of age, hospitalized with a confirmed diagnosis of moderate/severe pneumonia due to SARS-CoV-2 infection (according to definitions established by the Ministry of Health of Peru) were enrolled during the study period. A coinfection with one or more respiratory pathogens was detected in 154 (52.2%) patients at hospital admission. The most common coinfections were Mycoplasma pneumoniae (28.1%), Chlamydia pneumoniae (8.8%) and with both bacteria (11.5%); followed by Adenovirus (1.7%), Mycoplasma pneumoniae/Adenovirus (0.7%), Chlamydia pneumoniae/Adenovirus (0.7%), RSV-B/Chlamydia pneumoniae (0.3%) and Mycoplasma pneumoniae/Chlamydia pneumoniae/Adenovirus (0.3%). Expectoration was less frequent in coinfected individuals compared to non-coinfected (5.8% vs. 12.8%). Sepsis was more frequent among coinfected patients than non-coinfected individuals (33.1% vs. 20.6%) and 41% of the patients who received macrolides empirically were PCR-positive for Mycoplasma pneumoniae and Chlamydia pneumoniae. View Full-Text, Postprint (published version)

Objective:To characterize the cervicovaginal microbiota of HPV-positive and HPV-negative asymptomatic Peruvian women, by identifying the presence of 13 representative bacteria genus.Results:A total of 100 HPV-positive and 100 HPV-negative women were matched by age for comparison of micro-biota. The following bacteria were more frequently identified in HPV-positive patients compared to HPV-negative: Eubacterium (68 vs 32%), Actinobacteria (46 vs 33%), Fusobacterium (11 vs 6%) and Bacteroides (20 vs 13%). A comparison between high-risk and low-risk genotypes was performed and differences were found in the detection of Actinobacteria (50 vs 33.33%), Bifidobacterium (50 vs 20.83%) and Enterococcus (50 vs 29.17%)., Postprint (published version)

Fibers of poly(4-hydroxybutyrate) (P4HB) have been submitted to both hydrolytic and enzymatic degradation media in order to generate samples with different types and degrees of chain breakage. Random chain hydrolysis is clearly enhanced by varying temperatures from 37 to 55 ¿C and is slightly dependent on the pH of the medium. Enzymatic attack is a surface erosion process with significant solubilization as a consequence of a preferent stepwise degradation. Small angle X-ray diffraction studies revealed a peculiar supramolecular structure with two different types of lamellar stacks. These were caused by the distinct shear stresses that the core and the shell of the fiber suffered during the severe annealing process. External lamellae were characterized by surfaces tilted 45¿ with respect to the stretching direction and a higher thickness, while the inner lamellae were more imperfect and had their surfaces perpendicularly oriented to the fiber axis. In all cases, WAXD data indicated that the chain molecular axis was aligned with the fiber axis and molecules were arranged according to a single orthorhombic structure. A gradual change of the microstructure was observed as a function of the progress of hydrolysis while changes were not evident under an enzymatic attack. Hydrolysis mainly affected the inner lamellar stacks as revealed by the direct SAXS patterns and the analysis of correlation functions. Both lamellar crystalline and amorphous thicknesses slightly increased as well as the electronic contrast between amorphous and crystalline regions. Thermal treatments of samples exposed to the hydrolytic media revealed microstructural changes caused by degradation, with the inner lamellae being those that melted faster, Peer Reviewed, Postprint (published version)

Nanotechnology is regarded as a promising tool to advance science for a wide range of applications, ranging from nanomedicine, nanoelectronics, imaging and diagnosis. Whilst the unique surface properties of nanostructured materials improve their performance in comparison to conventional materials, little has been done to inspect the correlation between such nanofeatures and the thermomechanical response of nanomaterials. Herein, we report the influence of structural nanofeatures in the glass transition and cold crystallization temperatures (Tg and Tcc) of poly(lactic acid) (PLA) thin films using a technology that detects the microcantilever deflection as a function of temperature. Measurements were conducted on arrays of 8-cantilevers spin-coated with PLA films (thickness of ~120–200 nm and weight of 6–9 ng) displaying several patterns (compact, nanopored and/or nanoperforated). The Tg increases by 8–13 °C when nanopores and nanoperforations are present, while only the latter affect the Tcc, which increases by ~6 °C. These phenomena have been attributed (i) the stress of the PLA molecules located at the interface of the pores and perforations, and (ii) to the film-air interface effect, which is associated with the quasi-2D nature of thin films (i.e. those with an aspect ratio of size and thickness greater than 105). On the other hand, the thermomechanical response of PLA thin films loaded with curcumin (CUR) or stiripentol (STP), which formed segregated nanodomains, also differs from that displayed by unloaded PLA films. The size and abundance of CUR and STP nanodomains are directly related to the stress of the PLA chains at the interface and the free volume, which affects the interactions strength and the mobility of polymer molecules (i.e. Tg and Tcc) with respect to neat PLA. Overall, the thermal properties of thin films, which cannot be studied using conventional calorimetric methods, is modified by the presence of nanofeatures. As a consequence, their design ne, Peer Reviewed, Postprint (published version)

Transmission electron microscopy, temperature-modulated differential scanning calorimetry, and broadband dielectric spectroscopy were employed to characterize ternary nanocomposites consisting of carboxylated carbon nanotubes (CNT) dispersed in a blend of two immiscible polymers, poly(L,lactide) (PLLA) and thermoplastic polyurethane (TPU). The nanocomposite blends were obtained by melt-compounding of PLLA and TPU in the presence of 0.2 wt-% CNT, either in the presence or absence of a Joncryl® ADR chain extender for PLLA, leading to reactive and non-reactive melt mixed samples. In both cases, the binary PLLA/TPU blend is characterized by phase separation into submicron TPU droplets dispersed in the PLLA matrix, and displays two separate glass transition temperatures. The carbon nanotubes are present either inside the TPU phase (samples obtained without chain extender), or at their boundaries (reactive-melt mixed samples). The effect of the sub-micron confinement of the TPU component is to decrease the cooperativity length of the primary segmental relaxation of this polymer, which is accentuated by the presence of the CNT fillers. Depending on the type of sample, five or six distinct relaxations are observed by means of dielectric spectroscopy, which we are able to assign to different dielectric phenomena. Our dielectric data show that the CNT fillers do not contribute directly to the long-range charge transport in the nanocomposite blends, consistent with the nanocomposites morphology, but rather result in a shift of the Maxwell-Wagner-Sillars space-charge frequency associated with charge accumulation at the PLLA/TPU boundary. Such shift testifies to a selective conductivity enhancement of the TPU phase due to the filler., Peer Reviewed, Postprint (published version)

The main aim of the present work was to approach the effect of the addition of an organic acid dopant, dodecylbenzenesulfonic acid (DBSA), in the preparation of poly(4,4-diphenylether-5,5-dibenzimidazole) (OPBI) films, commonly used as proton exchange membranes (PEMs). For this purpose, DBSA was blended with OPBI polymer matrix, at different concentrations, to evaluate the effect of such molecules in the proton conductivity of OPBI membranes. A substantial improvement in the dimensional stability of OPBI film, either for the undoped or for the phosphoric acid doped membranes, with low content of DBSA (12.5 wt.%) was achieved. Moreover, the charge mobility in OPBI/DBSA films remained stable between 22 ºC and 140 ºC, for both doped and undoped states. Therefore, the utilization of OPBI/DBSA system can be envisaged for proton exchange membrane operations at moderate temperature interval., Peer Reviewed, Postprint (author's final draft)

The influence of curcumin on the thermal stability and degradation kinetics of poly(glycolic acid) (PGA), poly-e-caprolactone (PCL) and their blend has been investigated in detail using thermogravimetric analysis. A 50/50 ratio was chosen for the blend and the effect caused by the addition of different percentages of curcumin (CUR) was evaluated. The thermogravimetric analysis was carried out under an atmosphere of inert nitrogen, operating in a dynamic regime at six different heating rates between 3 and 30¿°C/min. The results obtained from the degradation on a blend of PCL and PGA concluded that CUR hardly affects to the decomposition of PCL but instead, it significantly influences the stability of PGA. To observe this effect in detail, a more complete degradation study was carried out for the system formed by PGA incorporating 5% of the drug. The activation energy could be determined accurately using Kissinger and isoconversional methods like KAS and Friedman, without previously assuming a reaction model. Coats-Redfern method and generalized master curves were adopted to determine the optimal mechanism of degradation. Results showed a F1 model as suitable mechanism able to describe the degradation process of PGA with curcumin in a range of conversions between 20 and 60 %. Incorporation of CUR did not change the degradation mechanism of PGA but had a dramatic effect on the activation energy that was significantly lowered., Peer Reviewed, Postprint (author's final draft)

Simultaneous drug release and monitoring using a single polymeric platform represents a significant advance in the utilization of biomaterials for therapeutic use. Tracking drug release by real-time electrochemical detection using the same platform is a simple way to guide the dosage of the drug, improve the desired therapeutic effect, and reduce the adverse side effects. The platform developed in this work takes advantage of the flexibility and loading capacity of hydrogels, the mechanical strength of microfibers, and the capacity of conducting polymers to detect the redox properties of drugs. The engineered platform is prepared by assembling two spin-coated layers of poly-¿-glutamic acid hydrogel, loaded with poly(3,4-ethylenedioxythiophene) (PEDOT) microparticles, and separated by a electrospun layer of poly-e-caprolactone microfibers. Loaded PEDOT microparticles are used as reaction nuclei for the polymerization of poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PHMeDOT), that semi-interpenetrate the whole three layered system while forming a dense network of electrical conduction paths. After demonstrating its properties, the platform is loaded with levofloxacin and its release monitored externally by UV–vis spectroscopy and in situ by using the PHMeDOT network. In situ real-time electrochemical monitoring of the drug release from the engineered platform holds great promise for the development of multi-functional devices for advanced biomedical applications., Postprint (author's final draft)

The influence of stereochemistry on the self-assembly of phenylalanine (Phe) dipeptides bearing aromatic fluorenyl groups at both the N- and C-termini (Fmoc, OFm) has been investigated. For this purpose, Fmoc–d-Phe–l-Phe–OFm and Fmoc–l-Phe–l-Phe–OFm have been examined considering a wide variety of solvents, which differ in dielectric constant and volatility. Results reveal that replacement of l-Phe by d-Phe has a major impact on the self-assembly propensities, restricting drastically the structural diversity and polymorphism shown by the homochiral dipeptide. Thus, the analogous heterochiral dipeptide shows a great propensity to form micro/nanofibers, independently of the environmental conditions. Theoretical calculations revealed that the stability of antiparallel disposition is much higher (a factor of ca. 15) for Fmoc–d-Phe–l-Phe–OFm than that for Fmoc–l-Phe–l-Phe–OFm, which has been attributed to the hydrophobic core formed in the former. Overall, results suggest that control of the backbone chirality is a potent and versatile strategy to drive and finely tune the self-assembly propensities of highly aromatic peptides., Peer Reviewed, Postprint (author's final draft)

The electrophotocatalytic synthesis of Glycine and Alanine from a simple gas mixture containing N2, CO2, CH4 and H2O under mild reaction conditions (95 °C and 6 bar) was recently developed using a catalyst formed by permanently polarized hydroxyapatite, which is achieved using a thermally stimulated polarization process, coated with two layers of aminotris(methylenephosphonic acid) (ATMP) separated by an intermediate layer of zirconyl chloride (ZC). This work reports the optimization of the ATMP- and ZC-coating content by examining the influence of their concentration of each component in each layer on the structural and electrochemical properties of the catalyst. After exhaustive analyses, such properties have been related with the efficiency of the catalysts prepared using different ATMP- and ZC-concentrations to yield Gly and Ala amino acids by fixing nitrogen from N2 and carbon from CO2 and CH4. Results show that, although the concentrations of ATMP and ZC in the first and the intermediate layers are important, the third layer plays a predominant role as is responsible of the apparition of supramolecular structures on the surface and the capacitive behavior of the coating., Peer Reviewed, Postprint (author's final draft)

A nanocomposite based on an antibiotic-loaded hydrogel into a nano-electrospun fibre with antimicrobial and antioxidant capacities is investigated. The material is composed of nanofibres of enzymatic PCL grafted with poly(gallic acid) (PGAL), a recently developed enzyme-mediated hydrophilic polymer that features a multiradical and polyanionic nature in a helicoidal secondary structure. An extensive experimental–theoretical study on the molecular structure and morphological characterizations for this nanocomposite are discussed. The hydrogel network is formed by sodium carboxymethylcellulose (CMC) loaded with the broad-spectrum antibiotic clindamycin. This nano electrospun biomaterial inhibits a strain of Staphylococcus aureus, which is the main cause of nosocomial infections. The SPTT assay demonstrates that PGAL side chains also improve the release rates for this bactericide owing to the crosslinking to the CMC hydrogel matrix. The absence of hemolytic activity and the viability of epithelial cells demonstrates that this nanocomposite has no cytotoxicity., Postprint (published version)

Incorporation of aliphatic units to poly(butylene terephthalate) (PBT) gives rise to biodegradable copolymers with tunable properties (e.g., degradability), depending on the selected comonomer and the specific composition. Specifically, a low molecular weight poly(butylene sebacate-co-terephthalate) (PBSeT) with a high ratio of aliphatic sebacate units (i.e., 70 mol-% with respect to the total dicarboxylate content) has been employed in this work to get new electrospun biodegradable scaffolds. Appropriate electrospinning conditions have been found despite the limited copolymer molecular weight. In addition, PBSeT has been employed to improve biocompatibility and biodegradability of scaffolds based on the PBT homopolymer. Scaffolds with different properties have been prepared following two strategies: Electrospinning of single solutions of PBT and PBSeT mixtures and co-electrospinning of independent PBT and PBSeT solutions. Characterization involved spectroscopic (FTIR, NMR), calorimetric (DSC, TGA) and surface hydrophobicity analyses. Hydrolytic and enzymatic degradation studies demonstrated the success of the approach due to the susceptibility of the PBSeT component towards the enzymatic attack with lipases from Pseudomonas cepacia and even towards high temperature hydrolysis., Peer Reviewed, Postprint (author's final draft)

Herein, a versatile bilayersystem, composed by a polypropylene(PP)mesh and a covalently bonded poly(N-isopropylacrylamide) (PNIPAAm) hydrogel, is reported. The cell adhesion mechanism was successfully modulated by controlling the architecture of the hydrogel in terms of duration of PNIPAAm graftingtime, crosslinker content, and temperature of material exposure in PBS solutions (belowandabove the LCST of PNIPAAm). The best in vitroresults with fibroblast (COS-1) and epithelial (MCF-7) cells was obtained with a mesh modified with porous iPP-g-PNIPAAm bilayer system, prepared via PNIPAAm grafting for 2 h at the lowest N,N'-methylene bis(acrylamide) (MBA)concentration (1 mM). Under these conditions, the detachment of the fibroblast-like cells was 50% lower than that of the control, after 7 days of cell incubation, which represents a high de-adhesionof cellsin a short period. Moreover, the whole system showed an excellent stability in dry or wet media, proving that the thermosensitive hydrogel was well adhered to the polymer surface, after PP fibreactivation by cold plasma. This study opens new insights on the development of anti-adherent meshes for abdominal hernia repairs., Peer Reviewed, Published version

Poly(L-lactide)s (PLLAs) with different chain structures were prepared by reactive melt processing and using Joncryl ADR as chain extender. Results of gel permeation chromatography (GPC) revealed that chain extended PLLAs had high molecular weights and two differentiated molecular weight distributions. Linear rheology was sensitive to the obtained molecular structures and revealed as the increase on the amount of chain extender gradually led to a decrease of the loss factor in the whole frequency region and to an increase of melt viscosity and both storage and loss moduli. In addition, the entanglement density increased significantly with addition of chain extender and had a significant influence on crystallization kinetics. Correlation of molecular weight, viscosity and entanglements changed the crystallinity and crystallization kinetics of chain extended PLLAs in both isothermal and non-isothermal crystallizations. Specifically, samples prepared from 1 wt-% of Joncryl (PLLA1R) revealed the highest nucleation and the fastest crystallization rate., Postprint (author's final draft)

Conducting polymers have been increasingly used as biologically interfacing electrodes for biomedical applications due to their excellent and fast electrochemical response, reversible doping–dedoping characteristics, high stability, easy processability, and biocompatibility. These advantageous properties can be used for the rapid detection and eradication of infections associated to bacterial growth since these are a tremendous burden for individual patients as well as the global healthcare system. Herein, a smart nanotheranostic electroresponsive platform, which consists of chloramphenicol (CAM)-loaded in poly(3,4-ethylendioxythiophene) nanoparticles (PEDOT/CAM NPs) for concurrent release of the antibiotic and real-time monitoring of bacterial growth is presented. PEDOT/CAM NPs, with an antibiotic loading content of 11.9 ± 1.3% w/w, are proved to inhibit the growth of Escherichia coli and Streptococcus sanguinis due to the antibiotic release by cyclic voltammetry. Furthermore, in situ monitoring of bacterial activity is achieved through the electrochemical detection of ß-nicotinamide adenine dinucleotide, a redox active specie produced by the microbial metabolism that diffuse to the extracellular medium. According to these results, the proposed nanotheranostic platform has great potential for real-time monitoring of the response of bacteria to the released antibiotic, contributing to the evolution of the personalized medicine., Peer Reviewed, Postprint (author's final draft)