Bioactive Coatings on Titanium: A Review on Hydroxylation, Self-Assembled Monolayers (SAMs) and Surface Modification Strategies

Titanium (Ti) and its alloys have been demonstrated over the last decades to play an important role as inert materials in the field of orthopedic and dental implants. Nevertheless, with the widespread use of Ti, implant-associated rejection issues have arisen. To overcome these problems, antibacterial properties, fast and adequate osseointegration and long-term stability are essential features. Indeed, surface modification is currently presented as a versatile strategy for developing Ti coatings with all these challenging requirements and achieve a successful performance of the implant. Numerous approaches have been investigated to obtain stable and well-organized Ti coatings that promote the tailoring of surface chemical functionalization regardless of the geometry and shape of the implant. However, among all the approaches available in the literature to functionalize the Ti surface, a promising strategy is the combination of surface pre-activation treatments typically followed by the development of intermediate anchoring layers (self-assembled monolayers, SAMs) that serve as the supporting linkage of a final active layer. Therefore, this paper aims to review the latest approaches in the biomedical area to obtain bioactive coatings onto Ti surfaces with a special focus on (i) the most employed methods for Ti surface hydroxylation, (ii) SAMs-mediated active coatings development, and (iii) the latest advances in active agent immobilization and polymeric coatings for controlled release on Ti surfaces.This research was funding by Basque Government (ELKARTEK program, HAZITEK program–IMABI exp number ZE-2019/00012), Department of Development and Infrastructures of the Basque Country, University of the Basque Country UPV/EHU (GIU 207075), Ministry of Economy, Industry and Competitiveness (grant MAT2017-89553-P) and i+Med S. Coop

Sustained Drug Release from Biopolymer-Based Hydrogels and Hydrogel Coatings

Biopolymer based hydrogels are three-dimensional physically or chemically crosslinked polymeric networks based on natural polymers, with an intrinsic hydrophilic character due to their functional groups. They display high water content, softness, flexibility, permeability, and biocompatibility and possess a very high affinity for biological fluids. These properties resemble those of many soft living tissues, which opens up many opportunities in the biomedical field. In this regard, hydrogels provide fine systems for drug delivery and sustained release of drugs. Moreover, biopolymer based hydrogels can be applied as coatings on medical implants in order to enhance the biocompatibility of the implants and to prevent medical conditions. In this chapter we review the latest achievements concerning the use of biopolymeric physical and chemically crosslinked hydrogels as well as hydrogel coatings as sustained drug release platforms

Drug Delivery from Hyaluronic Acid-BDDE Injectable Hydrogels for Antibacterial and Anti-Inflammatory Applications

Hyaluronic acid (HA) injectable biomaterials are currently applied in numerous biomedical areas, beyond their use as dermal fillers. However, bacterial infections and painful inflammations are associated with healthcare complications that can appear after injection, restricting their applicability. Fortunately, HA injectable hydrogels can also serve as drug delivery platforms for the controlled release of bioactive agents with a critical role in the control of certain diseases. Accordingly, herein, HA hydrogels were crosslinked with 1 4-butanediol diglycidyl ether (BDDE) loaded with cefuroxime (CFX), tetracycline (TCN), and amoxicillin (AMX) antibiotics and acetylsalicylic acid (ASA) anti-inflammatory agent in order to promote antibacterial and anti-inflammatory responses. The hydrogels were thoroughly characterized and a clear correlation between the crosslinking grade and the hydrogels’ physicochemical properties was found after rheology, scanning electron microscopy (SEM), thermogravimetry (TGA), and differential scanning calorimetry (DSC) analyses. The biological safety of the hydrogels, expected due to the lack of BDDE residues observed in 1H-NMR spectroscopy, was also corroborated by an exhaustive biocompatibility test. As expected, the in vitro antibacterial and anti-inflammatory activity of the drug-loaded HA-BDDE hydrogels was confirmed against Staphylococcus aureus by significantly decreasing the pro-inflammatory cytokine levels.This research was funded by the i+Med S. Coop., Basque Government (FRONTIERS project, ELKARTEK program, HAZITEK program: IMABI exp number ZE-2019/00012), and the Department of Development and Infrastructures of the Basque Country. Jon Andrade del Olmo thanks the Basque Government for the “Program of Industrial Doctorates. Bikaintek 2018” (exp. number 01-AF-W2-2018-00002)

Effect of viral storm in patients admitted to intensive care units with severe COVID-19 in Spain: a multicentre, prospective, cohort study

Background: The contribution of the virus to the pathogenesis of severe COVID-19 is still unclear. We aimed to evaluate associations between viral RNA load in plasma and host response, complications, and deaths in critically ill patients with COVID-19. Methods: We did a prospective cohort study across 23 hospitals in Spain. We included patients aged 18 years or older with laboratory-confirmed SARS-CoV-2 infection who were admitted to an intensive care unit between March 16, 2020, and Feb 27, 2021. RNA of the SARS-CoV-2 nucleocapsid region 1 (N1) was quantified in plasma samples collected from patients in the first 48 h following admission, using digital PCR. Patients were grouped on the basis of N1 quantity: VIR-N1-Zero ([removed]2747 N1 copies per mL). The primary outcome was all-cause death within 90 days after admission. We evaluated odds ratios (ORs) for the primary outcome between groups using a logistic regression analysis. Findings: 1068 patients met the inclusion criteria, of whom 117 had insufficient plasma samples and 115 had key information missing. 836 patients were included in the analysis, of whom 403 (48%) were in the VIR-N1-Low group, 283 (34%) were in the VIR-N1-Storm group, and 150 (18%) were in the VIR-N1-Zero group. Overall, patients in the VIR-N1-Storm group had the most severe disease: 266 (94%) of 283 patients received invasive mechanical ventilation (IMV), 116 (41%) developed acute kidney injury, 180 (65%) had secondary infections, and 148 (52%) died within 90 days. Patients in the VIR-N1-Zero group had the least severe disease: 81 (54%) of 150 received IMV, 34 (23%) developed acute kidney injury, 47 (32%) had secondary infections, and 26 (17%) died within 90 days (OR for death 0·30, 95% CI 0·16–0·55; p<0·0001, compared with the VIR-N1-Storm group). 106 (26%) of 403 patients in the VIR-N1-Low group died within 90 days (OR for death 0·39, 95% CI 0·26–0·57; p[removed]11 página

The use of plants in the traditional management of diabetes in Nigeria: Pharmacological and toxicological considerations

Ethnopharmacological relevance: The prevalence of diabetes is on a steady increase worldwide and it is now identified as one of the main threats to human health in the 21st century. In Nigeria, the use of herbal medicine alone or alongside prescription drugs for its management is quite common. We hereby carry out a review of medicinal plants traditionally used for diabetes management in Nigeria. Based on the available evidence on the species׳ pharmacology and safety, we highlight ways in which their therapeutic potential can be properly harnessed for possible integration into the country׳s healthcare system. Materials and methods: Ethnobotanical information was obtained from a literature search of electronic databases such as Google Scholar, Pubmed and Scopus up to 2013 for publications on medicinal plants used in diabetes management, in which the place of use and/or sample collection was identified as Nigeria. ‘Diabetes’ and ‘Nigeria’ were used as keywords for the primary searches; and then ‘Plant name – accepted or synonyms’, ‘Constituents’, ‘Drug interaction’ and/or ‘Toxicity’ for the secondary searches. Results: The hypoglycemic effect of over a hundred out of the 115 plants reviewed in this paper is backed by preclinical experimental evidence, either in vivo or in vitro. One-third of the plants have been studied for their mechanism of action, while isolation of the bioactive constituent(s) has been accomplished for twenty three plants. Some plants showed specific organ toxicity, mostly nephrotoxic or hepatotoxic, with direct effects on the levels of some liver function enzymes. Twenty eight plants have been identified as in vitro modulators of P-glycoprotein and/or one or more of the cytochrome P450 enzymes, while eleven plants altered the levels of phase 2 metabolic enzymes, chiefly glutathione, with the potential to alter the pharmacokinetics of co-administered drugs. Conclusion: This review, therefore, provides a useful resource to enable a thorough assessment of the profile of plants used in diabetes management so as to ensure a more rational use. By anticipating potential toxicities or possible herb–drug interactions, significant risks which would otherwise represent a burden on the country׳s healthcare system can be avoided

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Elikagaien paketatze aktiborako polimeroen gainazalaren aldaketa

Nowadays biopolymers are replacing the polymers derived from petro-chemicals for the packaging industry. Poly-L-isomer of lactic acid (PLLA), blended with ZnO nanoparticles, shows good properties as food packaging material. Among these beneficial features, it should be noted the antibacterial properties. There are a large number of polymers that present antibacterial capacity, but the best capacity is that of chitosan biopolymer. In this work, therefore, surfaces of PLLA-ZnO films were modified in order to improve their antibacterial properties. For this, different modifica-tion methods will be studied, such as covalent bonding and electrostatic interactions, and the success of these modifications, as well as the final properties of the films will be analyzed.; Paketatze-industrian jatorri petrokimikoa duten polimeroak ordezka-tzeko, biopolimeroak gero eta gehiago erabiltzen dira. Poliazido laktikoaren L-isome-roak (PLLA) zink oxido (ZnO) nanopartikulekin nahastean, elikagai-industrian paketa-tzeko material moduan erabiltzeko ezaugarri onak aurkezten ditu. ZnO nanopartikulek bakterioen aurkako portaera erakusten dutela aipatzekoa da. Aktibitate antibakterianoa erakusten duten biopolimero asko daude, baina bakterioen aurkako aktibitaterik onena erakusten duena kitosanoa da. Lan honetan, beraz, PLLA-ZnO filmetan gainazalaren aldaketa gauzatuko da bakterioen aurkako ezaugarriak hobetzeko asmotan kitosanoa gainazalean txertatuz. Horretarako, lotura kobalente eta elkarrekintza elektrostatiko moduko zenbait metodo erabili dira, eta aldaketen lorpena eta garatutako filmen pro-pietateak aztertu dira

Injectable Hydrogels: From Laboratory to Industrialization

The transfer of some innovative technologies from the laboratory to industrial scale is many times not taken into account in the design and development of some functional materials such as hydrogels to be applied in the biomedical field. There is a lack of knowledge in the scientific field where many aspects of scaling to an industrial process are ignored, and products cannot reach the market. Injectable hydrogels are a good example that we have used in our research to show the different steps needed to follow to get a product in the market based on them. From synthesis and process validation to characterization techniques used and assays performed to ensure the safety and efficacy of the product, following regulation, several well-defined protocols must be adopted. Therefore, this paper summarized all these aspects due to the lack of knowledge that exists about the industrialization of injectable products with the great importance that it entails, and it is intended to serve as a guide on this area to non-initiated scientists. More concretely, in this work, the characteristics and requirements for the development of injectable hydrogels from the laboratory to industrial scale is presented in terms of (i) synthesis techniques employed to obtain injectable hydrogels with tunable desired properties, (ii) the most common characterization techniques to characterize hydrogels, and (iii) the necessary safety and efficacy assays and protocols to industrialize and commercialize injectable hydrogels from the regulatory point of view. Finally, this review also mentioned and explained a real example of the development of a natural hyaluronic acid hydrogel that reached the market as an injectable product

Hydrolysis of sterol esters by an esterase from Ophiostoma piceae: Application for pitch control in pulping of Eucalyptus globulus wood

1Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, E-28040 Madrid, Spain; 2Instituto de Recursos Naturales y Agrobiología, CSIC, Reina Mercedes 10, PO Box 1052, E-41080, Seville, Spain; 3Instituto de Catálisis, CSIC, Cantoblanco, E-28049 Madrid, Spain.A sterol esterase purified from cultures of the sapstain fungus Ophiostoma piceae was able to hydrolyse sterol esters and glycerides. The kinetics of sterol esters and triglyceride hydrolysis by this new esterase, estimated using a pH-stat, showed a Km app and a kcat app in the range of 0.9–1.1 mM and 70–300 s–1, respectively. Its ability to hydrolyse both pure sterol esters and natural mixtures of saponifiable lipids from eucalypt wood was compared with those of commercial sterol esterases from other microbial sources. Its specific activity on sterol esters was higher than that found with all the commercial esterases assayed, and the highest hydrolysis of eucalypt sterol esters was also attained using the O. piceae esterase. This sterol esterase could be of biotechnological interest for the hydrolysis of sterol esters that form pitch deposits in paper pulp manufacturing.This study has been supported by ENCE, the EU-Contract QLK5-99-1357, and the Spanish projects BIO2003-00621 and AGL2002-00393. AG acknowledges a ‘Ramón y Cajal’ contract of the Spanish MCYT.Peer reviewe

Antibacterial Coatings for Improving the Performance of Biomaterials

Biomedical devices have become essential in the health care. Every day, an enormous number of these devices are used or implanted in humans. In this context, the bacterial contamination that could be developed in implanted devices is critical since it is estimated that infections kill more people than other medical causes. Commonly, these infections are treated with antibiotics, but the biofilm formation on implant surfaces could significantly reduce the effectiveness of these antibiotics since bacteria inside the biofilm is protected from the drug. In some cases, a complete removal of the implant is necessary in order to overcome the infection. In this context, antibacterial coatings are considered an excellent strategy to avoid biofilm formation and, therefore, mitigate the derived complications. In this review, the main biomaterials used in biomedical devices, the mechanism of biofilm formation, and the main strategies for the development of antibacterial coatings, are reviewed. Finally, the main polymer-based strategies to develop antibacterial coatings are summarized, with the aim of these coatings being to avoid the bacteria proliferation by controlling the antibacterial mechanisms involved and enhancing long-term stability.This research was funded by Basque Government (ELKARTEK, FRONTIERS), by the Department of Development and Infrastructures of the Basque Country, and by i+Med S. Coop. J. A-O thanks Basque Government for “Program of Industrial Doctorates. Bikaintek 2018” (exp number: 01-AF-W2-2018-00002). V. S. M thanks the funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 795417