Microplastics ingestion and endocrine disrupting chemicals (EDCs) by breeding seabirds in the east tropical Atlantic: Associations with trophic and foraging proxies (δ15N and δ13C).

In this study we found that endocrine disrupting chemicals (EDCs) were omnipresent in a tropical seabird community comprising diverse ecological guilds and distinct foraging and trophic preferences. Because EDCs tend to bioaccumulate within the food web and microplastics can absorb and release harmful chemical compounds, our findings draw attention to the potential threats to wildlife. Thus, the goal of this study was to investigate the role of plastic ingestion, trophic and foraging patterns (δ15N and δ13C) of five tropical seabird species breeding in sympatry, on the exposure to EDCs, namely Polybrominated diphenyl ethers (PBDEs), methoxylated polybrominated diphenyl ethers (MeO-PBDEs) and personal care products (PCPs, e.g., musk fragrances and UV-filters). Results indicated that microplastics occurrence and EDCs detection frequency varied among species. Microplastics occurrence was higher in species with dual and coastal foraging strategies. Preen oil had higher levels of MeO-PBDEs and PCPs, while serum had higher levels of PBDEs. In brown boobies, the correlation between microplastics and ∑PBDEs levels was significant, suggesting that microplastics ingestion is a key PBDEs route. Trophic position (δ15N) plays a key role in PBDEs accumulation, particularly in Bulwer's petrel, which occupies a high trophic position and had more specialized feeding ecology than the other species. MeO-PBDEs were linked to foraging habitat (δ13C), although the link to foraging locations deserves further investigation. Overall, our findings not only fill key gaps in our understanding of seabirds' exposure to microplastics and EDCs, but also provide an essential baseline for future research and monitoring efforts. These findings have broader implications for the marine wildlife conservation and pollution management in sensitive environments, such as the tropical regions off West Africa.

Anthropogenic debris ingestion in a tropical seabird community: Insights from taxonomy and foraging distribution.

Oceans have been considered as an unlimited supply of goods and services, but resource extraction and waste disposal became ubiquitous and have been damaging the health of marine ecosystems. Finding suitable sentinel species of the human impacts on the oceans is thus imperative, since they may work as early warnings of disruptive situations. In this study, we investigated how taxonomy and foraging distribution influenced the occurrence of anthropogenic debris among five seabird species inhabiting the tropical Atlantic region. Occurrence of anthropogenic debris was assessed using faeces of breeding individuals as a proxy of ingestion. A total of 268 particles were extracted from all samples. The categories "fragments" and "fibres", as well as the colour "blue", were the most prevalent characteristics across species. There was a high diversity of polymers from cellulosic particles to synthetic plastics (Anthropogenic Cellulosic 26.9 %; Polyester 7.7 %; Varnish 5.8 %; Polypropylene 1.9 %). Species with a more coastal foraging strategy exhibited higher occurrence and number of anthropogenic debris when compared to species foraging comparably more in pelagic areas. This suggests that anthropogenic debris are more prevalent in coastal foraging areas, where human activities occur in higher number and frequency (e.g., fisheries) and sources of freshwater input from inland are at close distance. These results provide more evidence to the growing perception on the ubiquity and diversity of anthropogenic debris in the marine environment, and further support the usefulness of using seabirds as bio-indicators of anthropogenic pollution in both neritic and oceanic regions.

Dual drug delivery collagen vehicles for modulation of skin fibrosisin vitro.

Single molecule drug delivery systems have failed to yield functional therapeutic outcomes, triggering investigations into multi-molecular drug delivery vehicles. In the context of skin fibrosis, although multi-drug systems have been assessed, no system has assessed molecular combinations that directly and specifically reduce cell proliferation, collagen synthesis and transforming growth factorß1 (TGFß1) expression. Herein, a core-shell collagen type I hydrogel system was developed for the dual delivery of a TGFßtrap, a soluble recombinant protein that inhibits TGFßsignalling, and Trichostatin A (TSA), a small molecule inhibitor of histone deacetylases. The antifibrotic potential of the dual delivery system was assessed in anin vitroskin fibrosis model induced by macromolecular crowding (MMC) and TGFß1. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and high performance liquid chromatography analyses revealed that ∼50% of the TGFßtrap and ∼30% of the TSA were released from the core and shell compartments, respectively, of the hydrogel system after 10 d (longest time point assessed) in culture. As a direct consequence of this slow release, the core (TGFßtrap)/shell (TSA) hydrogel system induced significantly (p< 0.05) lower than the control group (MMC and TGFß1) collagen type I deposition (assessed via SDS-PAGE and immunocytochemistry),αsmooth muscle actin (αSMA) expression (assessed via immunocytochemistry) and cellular proliferation (assessed via DNA quantification) and viability (assessed via calcein AM and ethidium homodimer-I staining) after 10 d in culture. On the other hand, direct TSA-TGFßsupplementation induced the lowest (p< 0.05) collagen type I deposition,αSMA expression and cellular proliferation and viability after 10 d in culture. Our results illustrate the potential of core-shell collagen hydrogel systems for sustained delivery of antifibrotic molecules.

Adapting the Scar-in-a-Jar to Skin Fibrosis and Screening Traditional and Contemporary Anti-Fibrotic Therapies.

Skin fibrosis still constitutes an unmet clinical need. Although pharmacological strategies are at the forefront of scientific and technological research and innovation, their clinical translation is hindered by the poor predictive capacity of the currently available in vitro fibrosis models. Indeed, customarily utilised in vitro scarring models are conducted in a low extracellular matrix milieu, which constitutes an oxymoron for the in-hand pathophysiology. Herein, we coupled macromolecular crowding (enhances and accelerates extracellular matrix deposition) with transforming growth factor ß1 (TGFß1; induces trans-differentiation of fibroblasts to myofibroblasts) in human dermal fibroblast cultures to develop a skin fibrosis in vitro model and to screen a range of anti-fibrotic families (corticosteroids, inhibitors of histone deacetylases, inhibitors of collagen crosslinking, inhibitors of TGFß1 and pleiotropic inhibitors of fibrotic activation). Data obtained demonstrated that macromolecular crowding combined with TGFß1 significantly enhanced collagen deposition and myofibroblast transformation. Among the anti-fibrotic compounds assessed, trichostatin A (inhibitors of histone deacetylases); serelaxin and pirfenidone (pleiotropic inhibitors of fibrotic activation); and soluble TGFß receptor trap (inhibitor of TGFß signalling) resulted in the highest decrease of collagen type I deposition (even higher than triamcinolone acetonide, the gold standard in clinical practice). This study further advocates the potential of macromolecular crowding in the development of in vitro pathophysiology models.

Translational Research Symposium-collaborative efforts as driving forces of healthcare innovation.

The 5th Translational Research Symposium was organised at the annual meeting of the European Society for Biomaterials 2018, Maastricht, the Netherlands, with emphasis on the future of emerging and smart technologies for healthcare in Europe. Invited speakers from academia and industry highlighted the vision and expectations of healthcare in Europe beyond 2020 and the perspectives of innovation stakeholders, such as small and medium enterprises, large companies and Universities. The aim of the present article is to summarise and explain the main statements made during the symposium, with particular attention on the need to identify unmet clinical needs and their efficient translation into healthcare solutions through active collaborations between all the participants involved in the value chain.

Current and upcoming therapies to modulate skin scarring and fibrosis.

Skin is the largest organ of the human body. Being the interface between the body and the outer environment, makes it susceptible to physical injury. To maintain life, nature has endowed skin with a fast healing response that invariably ends in the formation of scar at the wounded dermal area. In many cases, skin remodelling may be impaired, leading to local hypertrophic scars or keloids. One should also consider that the scarring process is part of the wound healing response, which always starts with inflammation. Thus, scarring can also be induced in the dermis, in the absence of an actual wound, during chronic inflammatory processes. Considering the significant portion of the population that is subject to abnormal scarring, this review critically discusses the state-of-the-art and upcoming therapies in skin scarring and fibrosis.

Advancements and Challenges in Multidomain Multicargo Delivery Vehicles.

Reparative and regenerative processes are well-orchestrated temporal and spatial events that are governed by multiple cells, molecules, signaling pathways, and interactions thereof. Yet again, currently available implantable devices fail largely to recapitulate nature's complexity and sophistication in this regard. Herein, success stories and challenges in the field of layer-by-layer, composite, self-assembly, and core-shell technologies are discussed for the development of multidomain/multicargo delivery vehicles.

An experimental toolbox for characterization of mammalian collagen type I in biological specimens.

Collagen type I is the most abundant extracellular matrix protein, and collagen type I supramolecular assemblies (e.g., tissue grafts, biomaterials and cell-assembled systems) are used extensively in tissue engineering and regenerative medicine. Many studies, for convenience or economic reasons, do not accurately determine collagen type I purity, concentration, solubility and extent of cross-linking in biological specimens, frequently resulting in erroneous conclusions. In this protocol, we describe solubility; normal, reduced and delayed (interrupted) SDS-PAGE; hydroxyproline; Sircol collagen and Pierce BCA protein; denaturation temperature; ninhydrin/trinitrobenzene sulfonic acid; and collagenase assays and assess them in a diverse range of biological samples (e.g., tissue samples; purified solutions or lyophilized materials; 3D scaffolds, such as sponges and hydrogels; and cell media and layers). Collectively, the described protocols provide a comprehensive, yet fast and readily implemented, toolbox for collagen type I characterization in any biological specimen.

Collagen Quantification in Tissue Specimens.

Collagen is the major extracellular protein in mammals. Accurate quantification of collagen is essential in the biomaterials (e.g., reproducible collagen scaffold fabrication), drug discovery (e.g., assessment of collagen in pathophysiologies, such as fibrosis), and tissue engineering (e.g., quantification of cell-synthesized collagen) fields. Although measuring hydroxyproline content is the most widely used method to quantify collagen in biological specimens, the process is very laborious. To this end, the Sircol™ Collagen Assay is widely used due to its inherent simplicity and convenience. However, this method leads to overestimation of collagen content due to the interaction of Sirius red with basic amino acids of non-collagenous proteins. Herein, we describe the addition of an ultrafiltration purification step in the process to accurately determine collagen content in tissues.

Myelin Lipids Inhibit Axon Regeneration Following Spinal Cord Injury: a Novel Perspective for Therapy.

Lack of axon regeneration following spinal cord injury has been mainly ascribed to the inhibitory environment of the injury site, i.e., to chondroitin sulfate proteoglycans (CSPGs) and myelin-associated inhibitors (MAIs). Here, we used shiverer (shi) mice to assess axon regeneration following spinal cord injury in the presence of MAIs and CSPG but in the absence of compact myelin. Although in vitro shi neurons displayed a similar intrinsic neurite outgrowth to wild-type neurons, in vivo, shi fibers had increased regenerative capacity, suggesting that the wild-type spinal cord contains additional inhibitors besides MAIs and CSPG. Our data show that besides myelin protein, myelin lipids are highly inhibitory for neurite outgrowth and suggest that this inhibitory effect is released in the shi spinal cord given its decreased lipid content. Specifically, we identified cholesterol and sphingomyelin as novel myelin-associated inhibitors that operate through a Rho-dependent mechanism and have inhibitory activity in multiple neuron types. We further demonstrated the inhibitory action of myelin lipids in vivo, by showing that delivery of 2-hydroxypropyl-ß-cyclodextrin, a drug that reduces the levels of lipids specifically in the injury site, leads to increased axon regeneration of wild-type (WT) dorsal column axons following spinal cord injury. In summary, our work shows that myelin lipids are important modulators of axon regeneration that should be considered together with protein MAIs as critical targets in strategies aiming at improving axonal growth following injury.