Dual-function nanoparticles enzymatically conjugated with a custom-made polyurethane hydrogel for chronic wound treatment

Hydrogels are attractive drug delivery systems with the potential to protect their cargo and control its release. In particular, hydrogels based on synthetic polymers are gaining increasing interest by virtue of their controllable chemistry, ease of modification, and reproducibility. Moreover, the presence of specific side chains and pending functional groups in the polymer structure allows for the conjugation of drugs and other compounds resulting in improved control over drug release. Enzymes that catalyse reactions in a very specific way could also be used to control the conjugation of compounds to the polymeric chains to improve reproducibility and biocompatibility of the conjugation process. This contribution describes an innovative system for drug delivery comprising a bioartificial supramolecular hydrogel based on a customised polyurethane and α- cyclodextrins, and nanoparticles, for application in the treatment of chronic wounds. The system has the potential to reduce inflammation and eradicate infection by virtue of dual-function nanoparticles which incorporate cobalt as antimicrobial agent, and phenolated lignin as antioxidant. The nanoparticles are enzymatically conjugated to the hydrogel by means of the amine side groups exposed along the backbone of the ad-hoc synthesised polyurethane. The oxidase enzyme laccase is exploited to oxidize the phenol groups of lignin, to allow their interaction with the amines on the hydrogel. The effects of nanoparticles conjugation to the hydrogel are studied through gelification tests, stability tests, and rheology. Moreover, the release of nanoparticles from the hydrogel and their effects on patients’ wound fluids and against relevant bacterial strains are analysed in vitro

Reproducibility in the absence of selective reporting: An illustration from large‐scale brain asymmetry research

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p‐hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left–right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta‐analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an “ideal publishing environment,” that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically‐used sample sizes

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Lignin–Cobalt Nano-Enabled Poly(pseudo)rotaxane Supramolecular Hydrogel for Treating Chronic Wounds

Chronic wounds (CWs) are a growing issue for the health care system. Their treatment requires a synergic approach to reduce both inflammation and the bacterial burden. In this work, a promising system for treating CWs was developed, comprising cobalt-lignin nanoparticles (NPs) embedded in a supramolecular (SM) hydrogel. First, NPs were obtained through cobalt reduction with phenolated lignin, and their antibacterial properties were tested against both Gram-negative and Gram-positive strains. The anti-inflammatory capacity of the NPs was proven through their ability to inhibit myeloperoxidase (MPO) and matrix metalloproteases (MMPs), which are enzymes involved in the inflammatory process and wound chronicity. Then, the NPs were loaded in an SM hydrogel based on a blend of α-cyclodextrin and custom-made poly(ether urethane)s. The nano-enabled hydrogel showed injectability, self-healing properties, and linear release of the loaded cargo. Moreover, the SM hydrogel’s characteristics were optimized to absorb proteins when in contact with liquid, suggesting its capacity to uptake harmful enzymes from the wound exudate. These results render the developed multifunctional SM material an interesting candidate for the management of CWs