Bioactive Insulin-Loaded Electrospun Wound Dressings for Localized Drug Delivery and Stimulation of Protein Expression Associated with Wound Healing.

Effective therapy of wounds is difficult, especially for chronic, non-healing wounds, and novel therapeutics are urgently needed. This challenge can be addressed with bioactive wound dressings providing a microenvironment and facilitating cell proliferation and migration, ideally incorporating actives, which initiate and/or progress effective healing upon release. In this context, electrospun scaffolds loaded with growth factors emerged as promising wound dressings due to their biocompatibility, similarity to the extracellular matrix, and potential for controlled drug release. In this study, electrospun core-shell fibers were designed composed of a combination of polycaprolactone and polyethylene oxide. Insulin, a proteohormone with growth factor characteristics, was successfully incorporated into the core and was released in a controlled manner. The fibers exhibited favorable mechanical properties and a surface guiding cell migration for wound closure in combination with a high uptake capacity for wound exudate. Biocompatibility and significant wound healing effects were shown in interaction studies with human skin cells. As a new approach, analysis of the wound proteome in treated ex vivo human skin wounds clearly demonstrated a remarkable increase in wound healing biomarkers. Based on these findings, insulin-loaded electrospun wound dressings bear a high potential as effective wound healing therapeutics overcoming current challenges in the clinics.

Best Practice Recommendations for the Safe use of Lung Ultrasound.

The safety of ultrasound is of particular importance when examining the lungs, due to specific bioeffects occurring at the alveolar air-tissue interface. Lung is significantly more sensitive than solid tissue to mechanical stress. The causal biological effects due to the total reflection of sound waves have also not been investigated comprehensively.On the other hand, the clinical benefit of lung ultrasound is outstanding. It has gained considerable importance during the pandemic, showing comparable diagnostic value with other radiological imaging modalities.Therefore, based on currently available literature, this work aims to determine possible effects caused by ultrasound on the lung parenchyma and evaluate existing recommendations for acoustic output power limits when performing lung sonography.This work recommends a stepwise approach to obtain clinically relevant images while ensuring lung ultrasound safety. A special focus was set on the safety of new ultrasound modalities, which had not yet been introduced at the time of previous recommendations.Finally, necessary research and training steps are recommended in order to close knowledge gaps in the field of lung ultrasound safety in the future.These recommendations for practice were prepared by ECMUS, the safety committee of the EFSUMB, with participation of international experts in the field of lung sonography and ultrasound bioeffects.

Electrospun fibers loaded with antimicrobial peptides for treatment of wound infections.

The widespread resistance of clinically relevant bacteria against established antibiotics emphasizes the urgent need for novel therapeutics. In this context, wound infections constitute a specific challenge, as most systemically applied antibiotics are insufficiently available at the site of infection. Therefore, the local treatment of infected wounds poses a particular challenge regarding the appropriate release kinetics of actives and their residence time in the wound bed. Consequently, design and development of novel, drug-loaded wound dressings constitute a major research focus for the effective treatment of wound infections. In this study, we employed electrospinning to design drug-loaded wound dressings, incorporating the therapeutically promising antimicrobial peptide tyrothricin. By parallel electrospinning, we combined different ratios of water-soluble polyvinylpyrrolidone and water-insoluble methacrylate copolymer (EudragitE), in order to take advantage of their specific mechanical stability and dissolution properties. We fabricated fiber mats constituting mechanically stable wound dressings with a controlled drug release profile, combining an initial burst release above the minimal inhibitory concentration of known wound pathogens and a subsequent prolonged antimicrobial effect of the active ingredient. Antimicrobial activity against Staphylococcusaureus and Staphylococcusepidermidis was successfully proven, thereby introducing our tyrothricin-loaded fiber mats as a promising prospective therapy against typical wound-associated pathogens.

SEDDS-loaded mucoadhesive fiber patches for advanced oromucosal delivery of poorly soluble drugs.

To date, buccal administration of lipophilic drugs is still a major challenge due to their poor solubility in saliva and limited penetration into mucosal tissues. To overcome these limitations, we developed electrospun patches combining the benefits of mucoadhesive fibers and self-emulsifying drug delivery systems (SEDDS). The fiber system comprises a combination of mucoadhesive thiolated polyacrylic acid fibers and SEDDS-loaded fibers fabricated by parallel electrospinning. The resulting mucoadhesive electrospun SEDDS patches were systemically investigated for fiber characteristics, self-emulsification, mucoadhesion, drug penetration into porcine buccal tissue and biocompatibility. The patches showed high encapsulation efficiency for SEDDS without causing fiber defects or leakage. SEDDS incorporation enhanced the spinning process and reduced the fiber diameter and fiber size distribution. Hydration-dependent self-emulsification provided a controlled release of curcumin being encapsulated in nano-scaled o/w emulsion for over 3 h. Due to the thiolated polyacrylic acid fibers, the buccal residence time of patches was 200-fold prolonged. Further, they promoted a significantly increased drug penetration into buccal tissue compared to fiber patches without SEDDS. Finally, biocompatibility and improved therapeutic effects of curcumin-loaded patches on human keratinocytes and fibroblasts were confirmed. Mucoadhesive electrospun SEDDS patches represent a promising approach to overcome current challenges in the oromucosal delivery of lipophilic drugs to unlock their full therapeutic potential.