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Polypeptides have shown an excellent potential in nanomedicine thanks to their biocompatibility, biodegradability, high functionality, and responsiveness to several stimuli. Polypeptides exhibit high propensity to organize at the supramolecular level; hence, they have been extensively considered as building blocks in the layer-by-layer (LbL) assembly. The LbL technique is a highly versatile methodology, which involves the sequential assembly of building blocks, mainly driven by electrostatic interactions, onto planar or colloidal templates to fabricate sophisticated multilayer nanoarchitectures. The simplicity and the mild conditions required in the LbL approach have led to the inclusion of biopolymers and bioactive molecules for the fabrication of a wide spectrum of biodegradable, biocompatible, and precisely engineered multilayer films for biomedical applications. This review focuses on those examples in which polypeptides have been used as building blocks of multilayer nanoarchitectures for tissue engineering and drug delivery applications, highlighting the characteristics of the polypeptides and the strategies adopted to increase the stability of the multilayer film. Cross-linking is presented as a powerful strategy to enhance the stability and stiffness of the multilayer network, which is a fundamental requirement for biomedical applications. For example, in tissue engineering, a stiff multilayer coating, the presence of adhesion promoters, and/or bioactive molecules boost the adhesion, growth, and differentiation of cells. On the contrary, antimicrobial coatings should repel and inhibit the growth of bacteria. In drug delivery applications, mainly focused on particles and capsules at the micro- and nano-meter scale, the stability of the multilayer film is crucial in terms of retention and controlled release of the payload. Recent advances have shown the key role of the polypeptides in the adsorption of genetic material with high loading efficiency, and in addressing different pathways of the particles/capsules during the intracellular uptake, paving the way for applications in personalized medicine. Although there are a few studies, the responsiveness of the polypeptides to the pH changes, together with the inclusion of stimuli-responsive entities into the multilayer network, represents a further key factor for the development of smart drug delivery systems to promote a sustained release of therapeutics. The degradability of polypeptides may be an obstacle in certain scenarios for the controlled intracellular release of a drug once an external stimulus is applied. Nowadays, the highly engineered design of biodegradable LbL particles/capsules is oriented on the development of theranostics that, limited to use of polypeptides, are still in their infancy.
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Coloides , Péptidos , Ingeniería de Tejidos , Péptidos/química , Péptidos/farmacología , Humanos , Ingeniería de Tejidos/métodos , Coloides/química , Nanoestructuras/química , Sistemas de Liberación de Medicamentos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Animales , Propiedades de SuperficieRESUMEN
The prevalence of central nervous system (CNS) dysfunction as a result of disease or trauma remains a clinically unsolved problem which is raising increased awareness in our aging society. Human Dental Pulp Stem Cells (hDPSCs) are excellent candidates to be used in tissue engineering and regenerative therapies of the CNS due to their neural differentiation ability and lack of tumorigenicity. Accordingly, they have been successfully used in animal models of spinal cord injury, stroke and peripheral neuropathies. The ideal therapy in brain injury should combine strategies aiming to protect the damaged lesion and, at the same time, accelerate brain tissue regeneration, thus promoting fast recovery while minimizing side or long-term effects. The use of bioresorbable nanopatterned poly(lactide-co-É-caprolactone) (PLCL) polymeric scaffolds as hDPCSs carriers can represent an advantage for tissue regeneration. In this chapter, we describe the surgical procedures to implant functionalized bioresorbable scaffolds loaded with hDPSCs to improve the brain lesion microenvironment in an intracranial stab wound injury model severing the rostral migratory stream (RMS) that connects the brain subventricular zone (SVZ) and the olfactory bulb in nude mice. Additionally, we also describe the technical steps after animal sacrifice for histological tissue observation and characterization.
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Pulpa Dental , Modelos Animales de Enfermedad , Ratones Desnudos , Células Madre , Andamios del Tejido , Pulpa Dental/citología , Animales , Humanos , Andamios del Tejido/química , Ratones , Células Madre/citología , Trasplante de Células Madre/métodos , Heridas Punzantes/terapia , Implantes Absorbibles , Lesiones Encefálicas/terapia , Lesiones Encefálicas/patología , Ingeniería de Tejidos/métodosRESUMEN
Freshwater macroinvertebrates are a diverse group and play key ecological roles, including accelerating nutrient cycling, filtering water, controlling primary producers, and providing food for predators. Their differences in tolerances and short generation times manifest in rapid community responses to change. Macroinvertebrate community composition is an indicator of water quality. In Europe, efforts to improve water quality following environmental legislation, primarily starting in the 1980s, may have driven a recovery of macroinvertebrate communities. Towards understanding temporal and spatial variation of these organisms, we compiled the TREAM dataset (Time seRies of European freshwAter Macroinvertebrates), consisting of macroinvertebrate community time series from 1,816 river and stream sites (mean length of 19.2 years and 14.9 sampling years) of 22 European countries sampled between 1968 and 2020. In total, the data include >93 million sampled individuals of 2,648 taxa from 959 genera and 212 families. These data can be used to test questions ranging from identifying drivers of the population dynamics of specific taxa to assessing the success of legislative and management restoration efforts.
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Invertebrados , Ríos , Animales , Europa (Continente) , Agua Dulce , Dinámica Poblacional , Calidad del Agua , Biodiversidad , EcosistemaRESUMEN
Materials from biological origin composed by renewable carbon facilitate the transition from linear carbon-intensive economy to a sustainable circular economy. Accordingly, we use solution blow spinning to develop fully biobased cellulose acetate films and nanofiber mats reinforced with fungal chitin nanofibrils (ChNFs), an emerging bio-colloid with lower carbon footprint compared to crustacean-derived nanochitin. This study incorporates fungal ChNFs into spinning processes for the first time. ChNF addition reduces film surface roughness, modifies film water affinity, and tailors the nanofiber diameter of the mats. The covalently bonded ß-D-glucans of ChNFs act as a binder to improve the interfacial properties and consequently load transference to enhance the mechanical properties. Accordingly, the Young's modulus of the films increases from 200 ± 18 MPa to 359 ± 99 MPa with 1.5 wt% ChNFs, while the elongation at break increases by ~45 %. Life cycle assessment (LCA) is applied to quantify the environmental impacts of solution blow spinning for the first time, providing global warming potential values of 69.7-347.4 kg·CO2-equiv.·kg-1. Additionally, this work highlights the suitability of ChNFs as reinforcing fillers during spinning and proves the reinforcing effect of mushroom-derived chitin in bio-based films, opening alternatives for sustainable materials development beyond nanocelluloses in the near future.
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Celulosa , Quitina , Nanofibras , Quitina/química , Nanofibras/química , Celulosa/química , Celulosa/análogos & derivados , Hongos , SolucionesRESUMEN
Inland navigation in Europe is proposed to increase in the coming years, being promoted as a low-carbon form of transport. However, we currently lack knowledge on how this would impact biodiversity at large scales and interact with existing stressors. Here we addressed this knowledge gap by analysing fish and macroinvertebrate community time series across large European rivers comprising 19,592 observations from 4,049 sampling sites spanning the past 32 years. We found ship traffic to be associated with biodiversity declines, that is, loss of fish and macroinvertebrate taxonomic richness, diversity and trait richness. Ship traffic was also associated with increases in taxonomic evenness, which, in concert with richness decreases, was attributed to losses in rare taxa. Ship traffic was especially harmful for benthic taxa and those preferring slow flows. These effects often depended on local land use and riparian degradation. In fish, negative impacts of shipping were highest in urban and agricultural landscapes. Regarding navigation infrastructure, the negative impact of channelization on macroinvertebrates was evident only when riparian degradation was also high. Our results demonstrate the risk of increasing inland navigation on freshwater biodiversity. Integrative waterway management accounting for riparian habitats and landscape characteristics could help to mitigate these impacts.
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Biodiversidad , Peces , Invertebrados , Animales , Europa (Continente) , Invertebrados/fisiología , Ríos , Agua Dulce , Conservación de los Recursos Naturales , NavíosRESUMEN
Thanks to its biobased character with embedded biogenic carbon, chitin can aid in the transition to a sustainable circular economy by replacing fossil carbon from the geosphere. However, meeting current demands for material availability and environmental sustainability requires alternative methods limiting conventional chemical and energy-consuming chitin extraction from crustaceans. To assist future chitinous bioproduct development, this work analyzes the physicochemical properties and potential environmental sustainability of fungal chitin-glucan complexes. A conventional isolation procedure using sodium hydroxide, a weak acid, and short reaction times are applied to the fruiting body of 22 fungal species. Besides, the valorization of underutilized waste streams including Agaricus bisporus and Agaricus brunnescens stipes is investigated. The carbohydrate analysis renders chitin fractions in the range of 9.5-63.5 wt %, while yields vary from 4.2 to 29.9%, and the N-acetylation degree in found in between 53.0 and 98.7%. The sustainability of the process is analyzed using life cycle assessment (LCA), providing impact quantification for global warming potential, terrestrial acidification, freshwater eutrophication, and water use. With 87.5-589.3 kg·CO2-equiv per kilo, potentially lower global warming potential values in comparison to crustacean chitin are achieved. The crystallinity degree ranged from 28 to 78%, while the apparent chitin crystalline size (L020) is between 2.3 and 5.4 nm. Ten of the species yield α-chitin coexisting with semicrystalline glucans. Zwitterionic properties are observed in aqueous solutions, shifting from cationic to anionic at pH 4.5. With its renewable carbon content, fungal chitin is an environmentally sustainable alternative for high-value applications due to its balance of minimal treatment, low carbon footprint, material renewability, ease of isolation, thermal stability, zwitterionic behavior, biodegradability, and noncytotoxicity.
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The obtention of amorphous solid dispersions (ASDs) of mycophenolic acid (MPA) in poly(ε-caprolactone) (PCL) is reported in this paper. An improvement in the bioavailability of the drug is possible thanks to the favorable specific interactions occurring in this system. Differential scanning calorimetry (DSC) was used to investigate the miscibility of PCL/MPA blends, measuring glass transition temperature (Tg) and analyzing melting point depression to obtain a negative interaction parameter, which indicates the development of favorable inter-association interactions. Fourier transform infrared spectroscopy (FTIR) was used to analyze the specific interaction occurring in the blends. Drug release measurements showed that at least 70% of the drug was released by the third day in vitro in all compositions. Finally, preliminary in vitro cell culture experiments showed a decreased number of cancerous cells over the scaffolds containing MPA, presumably arising from the anti-cancer activity attributable to MPA.
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Amino acids are indispensable compounds in the body, performing several biological processes that enable proper functioning. In this work, it is demonstrated that a single amino acid, taurine, is also able to promote the ring-opening polymerization (ROP) of several cyclic monomers under industrially relevant conditions. It is shown that the unique zwitterionic structure of taurine, where the negatively charged sulfonic acid group and the protonated amine group are separated by two methylene groups, not only provides high thermal stability but also leads to a dual activation mechanism, which is corroborated by quantum mechanical calculations. This unique mechanism allows for the synthesis of polylactide of up to 50 kDa in bulk at 180 °C with good end-group fidelity using a highly abundant catalyst. Furthermore, cytotoxicity tests confirm that PLLA synthesized with taurine is non-toxic. Moreover, it is demonstrated that the presence of taurine does not have any detrimental effect on the thermal stability of polylactide, and therefore polymers can be used directly without any post-polymerization purification. It is believed that the demonstration that a simple structure composed of a single amino acid can promote polymerization can bring a paradigm shift in the preparation of polymers.
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Humans impact terrestrial, marine and freshwater ecosystems, yet many broad-scale studies have found no systematic, negative biodiversity changes (for example, decreasing abundance or taxon richness). Here we show that mixed biodiversity responses may arise because community metrics show variable responses to anthropogenic impacts across broad spatial scales. We first quantified temporal trends in anthropogenic impacts for 1,365 riverine invertebrate communities from 23 European countries, based on similarity to least-impacted reference communities. Reference comparisons provide necessary, but often missing, baselines for evaluating whether communities are negatively impacted or have improved (less or more similar, respectively). We then determined whether changing impacts were consistently reflected in metrics of community abundance, taxon richness, evenness and composition. Invertebrate communities improved, that is, became more similar to reference conditions, from 1992 until the 2010s, after which improvements plateaued. Improvements were generally reflected by higher taxon richness, providing evidence that certain community metrics can broadly indicate anthropogenic impacts. However, richness responses were highly variable among sites, and we found no consistent responses in community abundance, evenness or composition. These findings suggest that, without sufficient data and careful metric selection, many common community metrics cannot reliably reflect anthropogenic impacts, helping explain the prevalence of mixed biodiversity trends.