Electrosprayed zein nanoparticles as antibacterial and anti-thrombotic coatings for ureteral stents.

Ureteral stents are among the most frequently used human implants, with urothelium trauma, blood clots, and bacterial colonization being their main reasons for failure. In this study, berberine-loaded zein (ZB) nanoparticles with high drug encapsulation efficiency (>90 %) were fabricated via electrospray on flat and 3D stainless steel structures. Physico-chemical characterization revealed that the ZB nanoparticles created a highly hydrophilic, antioxidant, and scratch-resistant continuous coating over the metal structure. Results showed that the drug release rate was faster at neutral pH (i.e., PBS pH 7.4) than in an artificial urine medium (pH 5.3) due to the different swelling behavior of the zein polymeric matrix. In vitro evaluation of ZB particles onto human dermal fibroblasts and blood cells demonstrated good cell proliferation and enhanced anti-thrombotic properties compared to bare stainless steel. The ability of the electrosprayed zein particles to resist bacterial adherence and proliferation was evaluated with Gram-negative (Escherichia coli) bacteria, showing high inhibition rates (-29 % and -46 % for empty and berberine-loaded particles, respectively) compared to the medical-grade metal substrates. Overall, the proposed composite coating fulfilled the requirements for ureteral applications, and can advance the development of innovative biocompatible, biodegradable, and antibacterial coatings for drug-eluting stents.

Plant-Based, Hydrogel-like Microfibers as an Antioxidant Platform for Skin Burn Healing.

Natural polymers from organic wastes have gained increasing attention in the biomedical field as resourceful second raw materials for the design of biomedical devices which can perform a specific bioactive function and eventually degrade without liberating toxic residues in the surroundings. In this context, patches and bandages, that need to support the skin wound healing process for a short amount of time to be then discarded, certainly constitute good candidates in our quest for a more environmentally friendly management. Here, we propose a plant-based microfibrous scaffold, loaded with vitamin C (VitC), a bioactive molecule which acts as a protecting agent against UV damages and as a wound healing promoter. Fibers were fabricated via electrospinning from various zein/pectin formulations, and subsequently cross-linked in the presence of Ca2+ to confer them a hydrogel-like behavior, which we exploited to tune both the drug release profile and the scaffold degradation. A comprehensive characterization of the physico-chemical properties of the zein/pectin/VitC scaffolds, either pristine or cross-linked, has been carried out, together with the bioactivity assessment with two representative skin cell populations (human dermal fibroblast cells and skin keratinocytes, HaCaT cells). Interestingly, col-1a gene expression of dermal fibroblasts increased after 3 days of growth in the presence of the microfiber extraction media, indicating that the released VitC was able to stimulate collagen mRNA production overtime. Antioxidant activity was analyzed on HaCaT cells via DCFH-DA assay, highlighting a fluorescence intensity decrease proportional to the amount of loaded VitC (down to 50 and 30%), confirming the protective effect of the matrices against oxidative stress. Finally, the most performing samples were selected for the in vivo test on a skin UVB-burn mouse model, where our constructs demonstrated to significantly reduce the inflammatory cytokines expression in the injured area (50% lower than the control), thus constituting a promising, environmentally sustainable alternative to skin patches.

Wool Keratin Nanoparticle-Based Micropatterns for Cellular Guidance Applications.

The waste stream of low-grade wool is an underutilized source of keratin-rich materials with appropriate methods for upcycling into high value-added products still being an open challenge. In the present work, keratins were precipitated from their water solution to produce hierarchical keratin particles via isoelectric precipitation. Matrix-assisted laser desorption/ionization coupled with time-of-flight tandem mass spectrometry analysis (MALDI-TOF/TOF MS/MS) showed the presence of the amino acid sequence leucine-aspartic acid-valine (LDV) in the extracted keratin. This well-known cell adhesion motif is recognized by the cell adhesion molecule α4ß1 integrin. We showed that keratin particles had this tripeptide exposed on the surface and that it could be leveraged, via patterns obtained with microcontact printing, to support and facilitate dermal fibroblast cell adhesion and direct their growth orientation. The zeta potential, isoelectric point, morphological structures, chemical composition, and biocompatibility of keratin particles and the influence of the surfactant sodium dodecyl sulfate (SDS) were investigated. An appropriate ink for microcontact printing of the keratin particles was developed and micron-sized patterns were obtained. Cells adhered preferentially to the patterns, showing how this strategy could be used to functionalize biointerfaces.

Hydroxycinnamic Acids and Derivatives Formulations for Skin Damages and Disorders: A Review.

Alterations of skin homeostasis are widely diffused in our everyday life both due to accidental injuries, such as wounds and burns, and physiological conditions, such as late-stage diabetes, dermatitis, or psoriasis. These events are locally characterized by an intense inflammatory response, a high generation of harmful free radicals, or an impairment in the immune response regulation, which can profoundly change the skin tissue' repair process, vulnerability, and functionality. Moreover, diabetes diffusion, antibiotic resistance, and abuse of aggressive soaps and disinfectants following the COVID-19 emergency could be causes for the future spreading of skin disorders. In the last years, hydroxycinnamic acids and derivatives have been investigated and applied in several research fields for their anti-oxidant, anti-inflammatory, and anti-bacterial activities. First, in this study, we give an overview of these natural molecules' current source and applications. Afterwards, we review their potential role as valid alternatives to the current therapies, supporting the management and rebalancing of skin disorders and diseases at different levels. Also, we will introduce the recent advances in the design of biomaterials loaded with these phenolic compounds, specifically suitable for skin disorders treatments. Lastly, we will suggest future perspectives for introducing hydroxycinnamic acids and derivatives in treating skin disorders.

From fabric to tissue: Recovered wool keratin/polyvinylpyrrolidone biocomposite fibers as artificial scaffold platform.

Keratin extracted from wool fibers has recently gained attention as an abundant source of renewable, biocompatible material for tissue engineering and drug delivery applications. However, keratin extraction and processing generally require a copious use of chemicals, not only bearing consequences for the environment but also possibly compromising the envisioned biological outcome. In this study, we present, for the first time, keratin-PVP biocomposite fibers obtained via an all-water co-electrospinning process and explored their properties modulation as a result of different thermal crosslinking treatments. The protein-based fibers featured homogenous morphologies and average diameters in the range of 170-290 nm. The thermomechanical stability and response to a wet environment can be tuned by acting on the curing time; this can be achieved without affecting the 3D fibrous network nor the intrinsic hydrophilic behavior of the material. More interestingly, our protein-based membranes treated at 170 °C for 18 h successfully sustained the attachment and growth of primary human dermal fibroblasts, a cellular model which can recapitulate more faithfully the physiological human tissue conditions. Our proposed approach can be viewed as pivotal in designing tunable protein-based scaffolds for the next generation of skin tissue growth devices.

Role of CpALS4790 and CpALS0660 in Candida parapsilosis Virulence: Evidence from a Murine Model of Vaginal Candidiasis.

The Candida parapsilosis genome encodes for five agglutinin-like sequence (Als) cell-wall glycoproteins involved in adhesion to biotic and abiotic surfaces. The work presented here is aimed at analyzing the role of the two still uncharacterized ALS genes in C. parapsilosis, CpALS4790 and CpALS0660, by the generation and characterization of CpALS4790 and CpALS066 single mutant strains. Phenotypic characterization showed that both mutant strains behaved as the parental wild type strain regarding growth rate in liquid/solid media supplemented with cell-wall perturbing agents, and in the ability to produce pseudohyphae. Interestingly, the ability of the CpALS0660 null mutant to adhere to human buccal epithelial cells (HBECs) was not altered when compared with the wild-type strain, whereas deletion of CpALS4790 led to a significant loss of the adhesion capability. RT-qPCR analysis performed on the mutant strains in co-incubation with HBECs did not highlight significant changes in the expression levels of others ALS genes. In vivo experiments in a murine model of vaginal candidiasis indicated a significant reduction in CFUs recovered from BALB/C mice infected with each mutant strain in comparison to those infected with the wild type strain, confirming the involvement of CpAls4790 and CpAls5600 proteins in C. parapsilosis vaginal candidiasis in mice.