Tetraethyl orthosilicate (TEOS)-based hydrogels, with shear stress response and drug releasing properties, can be formulated simply by TEOS hydrolysis followed by volume corrections with aqueous ...solvents and pH adjustments. Such basic thixotropic hydrogels (thixogels) form via the colloidal aggregation of nanoparticulate silica. Herein, we investigated the effects of the nanoparticulate building blocks on the drug release properties of these materials. Our data indicate that the age of the hydrolyzed TEOS used for the formulation impacts the nanoparticulate structure and stiffness of thixogels. Moreover, the mechanism of formation or the disturbance of the nanoparticulate network significantly affects the release profiles of the incorporated drug. Collectively, our results underline the versatility of these basic, TEOS-only hydrogels for drug delivery applications.
Otitis externa, also known as outer ear infection, is a frequent affliction in both humans and animals. The most prevalent treatment for otitis externa is ear drops, but it is difficult to adhere ...properly to this treatment, causing poor patient compliance and the potential for complications. As a result, we have developed a tetraethyl orthosilicate-based hydrogel for use as single application treatment for otitis externa to increase ease of use and improve patient outcomes. Herein, we investigated the manufacturability of the hydrogel, focusing on several key aspects: formulation repeatability and reproducibility, material source and tolerances, release of a variety of model drugs, and impact of application-specific physiological factors, specifically local pH and enzymatic activity on drug release. Overall, our results indicate that these hydrogels are well suited for production and scalability, as they have a robust manufacturing process, have a wide tolerance for pH level, release a variety of model drugs, and are not impacted by outer ear canal-specific physiological factors.
Understanding the factors that influence the success of ecologically and economically damaging biological invasions is of prime importance. Recent studies have shown that invasive populations ...typically exhibit minimal, if any, reductions in genetic diversity, suggesting that large founding populations and/or multiple introductions are required for the success of biological invasions, consistent with predictions of the propagule pressure hypothesis. Through population genetic analysis of neutral microsatellite markers and a gene experiencing balancing selection, we demonstrate that the solitary bee Lasioglossum leucozonium experienced a single and severe bottleneck during its introduction from Europe. Paradoxically, the success of L. leucozonium in its introduced range occurred despite the severe genetic load caused by single-locus complementary sex-determination that still turns 30% of female-destined eggs into sterile diploid males, thereby substantially limiting the growth potential of the introduced population. Using stochastic modeling, we show that L. leucozonium invaded North America through the introduction of a very small number of propagules, most likely a singly-mated female. Our results suggest that chance events and ecological traits of invaders are more important than propagule pressure in determining invasion success, and that the vigilance required to prevent invasions may be considerably greater than has been previously considered.
This work investigates the fatigue response of a class of ductile closed‐cell aluminium alloy foams, known by their commercial name Alulight M8. In order to determine the yield stress of the used ...foams, preliminary experimental tests were performed, at room temperature, in monotonic compression on cylindrical specimens of 25 mm diameter and 25 mm height, with a loading speed of 10 mm/min. Fatigue tests were performed in uniaxial compression on cylindrical specimens (25 mm × 25 mm) with a stress ratio of R = 0.1, at a frequency of 10 Hz. The peak stress was varied from 110 to 135% of the yield stress in compression. Tested specimens were cut from the same cylindrical bar, and the density of the investigated material was 500 kg/m3 ± 10%, or a total of 18 specimens being investigated. With the gathered experimental data, S–N curve was generated, and the effect of cellular structure (e.g. structure irregularity–the number and the size of cells) being investigated and discussed.
Circulating endothelial microparticles (EMPs) are emerging as biomarkers of chronic obstructive pulmonary disease (COPD) in individuals exposed to cigarette smoke (CS), but their mechanism of release ...and function remain unknown. We assessed biochemical and functional characteristics of EMPs and circulating microparticles (cMPs) released by CS. CS exposure was sufficient to increase microparticle levels in plasma of humans and mice, and in supernatants of primary human lung microvascular endothelial cells. CS-released EMPs contained predominantly exosomes that were significantly enriched in let-7d, miR-191; miR-126; and miR125a, microRNAs that reciprocally decreased intracellular in CS-exposed endothelium. CS-released EMPs and cMPs were ceramide-rich and required the ceramide-synthesis enzyme acid sphingomyelinase (aSMase) for their release, an enzyme which was found to exhibit significantly higher activity in plasma of COPD patients or of CS-exposed mice. The ex vivo or in vivo engulfment of EMPs or cMPs by peripheral blood monocytes-derived macrophages was associated with significant inhibition of efferocytosis. Our results indicate that CS, via aSMase, releases circulating EMPs with distinct microRNA cargo and that EMPs affect the clearance of apoptotic cells by specialized macrophages. These targetable effects may be important in the pathogenesis of diseases linked to endothelial injury and inflammation in smokers.
Recent reports highlighted several novel applications for the
silk fibroin (SF), as edible coatings for the preservation of food freshness, smart labels, or packaging materials. This study ...complements these reports and additionally describes the colorimetric sensing properties of the natural protein that could be explored to enhance the practical value of such applications. Our data show that in response to pH changes, reconstituted SF is able to undergo visible color changes that correlate with the intensity of the stimuli, regardless of its physical format or physical cross-linking state. The intensity of the developed color was proportional to the extent of the protein's hydrolytic degradation. We also found that these pH-driven color changes were reversible and interchangeable, with colorless samples at neutral pH, purple in acidic environments, and yellow under basic conditions. Our mechanistic studies identified tryptophan as being responsible for these colorimetric responses, which could be further intensified by the presence of ionized tyrosine functionalities. In addition, we determined that SF's sensing properties also applied to ultraviolet light exposure. Finally, we showed that the innate sensing capabilities of activated SF can be enhanced via the covalent incorporation of additional tryptophan into the protein. Overall, our results further support the utility of SF for sensing applications.
Hearing loss affects roughly 466 million people worldwide. While the causes of hearing loss are diverse, mechanistically, inflammation and oxidative stress have been identified as major players in ...hearing loss regardless of pathogenesis. Treatment options remain extremely limited and there is currently no FDA approved drug therapy. Studies indicate that antioxidants such as
d
-Methionine have shown some protective effects; however, these studies involved systemic or invasive localized delivery methods and highlighted the need for the development of minimally invasive localized therapeutic approaches. Described herein is the development of an antioxidant-conjugated system that shows prophylactic potential against oxidative damage and appears suitable for topical delivery. Specifically, our covalent conjugate of hyaluronan with
d
-Methionine shows cytocompatibility and protection from oxidative stress in two mouse cochlear cell lines (HEI-OC1 and SV-k1). Mechanistically, the data indicate that the protective effects of the conjugate are due to the hyaluronan-mediated cellular internalization of the antioxidant. Most notably, the conjugate can efficiently permeate through an
in vitro
round window membrane model without the loss of the attached antioxidant, for subsequent delivery of the therapeutic cargo to the hearing sensory cells. Collectively these findings show that the novel conjugate could be a potential topical preventive agent against hearing loss.
Silk fibroin is a natural polymer with a unique repetitive structure that translates to extraordinary properties in terms of processability and mechanical properties. The
silk has a molecular weight ...of ∼415 kDa and consists of a light chain and a heavy chain. Its heavy chain is organized into 12 crystalline domains. Each of these crystalline domains contains subdomains of ∼70 amino acid containing blocks. It is well understood that the heavy chain of the protein is responsible for its processing versatility and excellent mechanical properties; however, the need for the high number of monomeric repeating units is unclear, and the individual properties of crystalline regions compared to those of the full-length protein are not understood. The work described herein assessed the possibility of using recombinant crystalline regions as alternative biomaterials for applications such as tissue adhesives. Our results indicate that while the two tested substructures do not fully recapitulate the native silk fibroin's properties, they appear to be a suitable alternative for the production of silk-based medical adhesives.
World Health Organization estimates that 30–50% of cancers are preventable by healthy lifestyle choices, early detection and adequate therapy. When the conventional therapeutic strategies are still ...regulated by the lack of selectivity, multidrug resistance and severe toxic side effects, nanotechnology grants a new frontier for cancer management since it targets cancer cells and spares healthy tissues. This review highlights recent studies using biotin molecule combined with functional nanomaterials used in biomedical applications, with a particular attention on biotinylated chitosan-based nanosystems. Succinctly, this review focuses on five areas of recent advances in biotin engineering: (a) biotin features, (b) biotinylation approaches, (c) biotin functionalized chitosan based nanosystems for drug and gene delivery functions, (d) diagnostic and theranostic perspectives, and (e) author's inputs to the biotin-chitosan based tumour-targeting drug delivery structures. Precisely engineered biotinylated-chitosan macromolecules shaped into nanosystems are anticipated to emerge as next-generation platforms for treatment and molecular imaging modalities applications.
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