Schiff Base-Based Hydrogel Embedded with In Situ Generated Silver Nanoparticles Capped by a Hyaluronic Acid-Diethylenetriamine Derivative for Wound Healing Application.

In this study, hydrogels were produced using a Schiff base reaction between two hyaluronic acid derivatives: one containing aldehyde groups (HA-Ald) and the other holding a diethylenetriamine with terminal amino groups (HA-DETA). The DETA portion promotes the in situ growth, complexation, and stabilization of silver nanoparticles (AgNPs), eliminating the need for external reducing agents. The reaction between HA-DETA and HA-Ald leads to the formation of imine bonds, which results in dynamically pH-responsive cross-linking. While the DETA capping ability helped in embedding the AgNPs, the on/off pH environmental responsivity of the hydrogel allows for a controlled and on-demand release of the drug, mainly when bacterial infections cause pH variation of the wound bed. The injectable hydrogels resulted in being highly compatible in contact with blood red cells, fibroblasts, and keratinocytes and capable of having a proliferative effect on an in vitro wound scratch model. The pH-responsive hydrogels showed proper antibacterial activity againstPseudomonas aeruginosaandStaphylococcus aureus, common bacterial strains presented in wound infections. Finally, in vivo wound model studies demonstrated an overall speeding up in the wound healing rate and advanced wound conditions in the experimental group treated with the hydrogels compared to control samples.

From laboratory- to industrial-scale plants: Future of anaerobic digestion of olive mill solid wastes.

In this review, the main properties of olive mill solid waste, the primary by-product of olive oil production, and its feasibility as a feedstock for anaerobic digesters operating at laboratory-, pilot- and industrial-scales are discussed in detail. Nutrient addition and thermal pretreatments were found to have the potential to address the challenges arising from the high carbon-to-nitrogen ratio, the low pH, and the high concentration of phenolic compounds. Furthermore, anaerobic co-digestion with different organic feedstocks has been identified as one of the most promising options to solve the aforementioned problems and the seasonality nature of olive waste, while improving the efficiency of anaerobic treatment plants that operate throughout the whole year. The insights generated from this study show co-digestion with wastes from animal farming to be the most environmentally and economically sustainable method for improving anaerobic digestion processes with olive mill solid waste.

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.

Combining Alginate/PVPI-Based Film with Frequency Rhythmic Electrical Modulation System (FREMS) Technology as an Advanced Strategy for Diabetic Wounds.

Diabetes is rising as one of the most diffused diseases of the century with the related urgent necessity to face its systemic and local effects on the patients, such as cardiovascular problems, degeneration of limbs, and dysfunction of the wound healing process. The diffusion of leg ulcers has been estimated to be 1.51 for 1000 population, and these non-resolved wounds can produce several social, economic, and mental health issues in diabetic patients. At the same time, these people experience neuropathic pain that causes morbidity and a further decrease in their quality of life. Here, a new study is presented where asodium alginate/Polyvinylpyrrolidone-Iodine complex (PVPI)-based wound dressing is combined with the Frequency Rhythmic Electrical Modulation System (FREMS) technology, an established medical device for the treatment of neuropathic pain and diabetic ulcers. The produced Alginate/PVPI-based films are characterized in terms of morphology, chemistry, wettability, bio-/hemo-compatibility, and clotting capacity. Next, the Alginate/PVPI-based films are used together with FREMS technology in diabetic mice models, and synergism of their action in the wound closure rate and anti-inflammatory properties is found. Hence, how the combination of electrical neurostimulation devices and advanced wound dressings can be a new approach to improve chronic wound treatment is demonstrated.

Polysaccharide-protein microparticles based-scaffolds to recover soft tissue loss in mild periodontitis.

Periodontal regeneration is extremely limited and unpredictable due to structural complications, as it requires the simultaneous restoration of different tissues, including cementum, gingiva, bone, and periodontal ligament. In this work, spray-dried microparticles based on green materials (polysaccharides - gums - and a protein - silk fibroin) are proposed to be implanted in the periodontal pocket as 3D scaffolds during non-surgical treatments, to prevent the progression of periodontal disease and to promote the healing in mild periodontitis. Arabic or xanthan gum have been associated to silk fibroin, extracted from Bombyx mori cocoons, and loaded with lysozyme due to its antibacterial properties. The microparticles were prepared by spray-drying and cross-linked by water vapor annealing, inducing the amorphous to semi-crystalline transition of the protein component. The microparticles were characterized in terms of their chemico-physical features (SEM, size distribution, structural characterization - FTIR and SAXS, hydration and degradation properties) and preclinical properties (lysozyme release, antibacterial properties, mucoadhesion, in vitro cells adhesion and proliferation and in vivo safety on a murine incisional wound model). The encouraging preclinical results highlighted that these three-dimensional (3D) microparticles could provide a biocompatible platform able to prevent periodontitis progression and to promote the healing of soft tissues in mild periodontitis.

Dynamic investigation of zein-based degradable and hemocompatible coatings for drug-eluting stents: a microfluidic approach.

Biodegradable stent coatings have shown great potential in terms of delivering drugs to a damaged vessel wall, and their release profiles are key elements governing the overall performance of drug-eluting stents (DESs). However, release and degradation kinetics are usually not tested under simulated physiological conditions or in dynamic environments, both essential aspects in the design of novel DESs. To bridge this gap, fused silica-based microfluidic systems, with either round or square channel cross-sections, were designed to mimic the microenvironment of a stented vessel. In particular, we fabricated and characterized microfluidic chips based on customizable channels, which were spray-coated with a naturally-derived, rutin-loaded zein solution, to perform a comprehensive study under flow conditions. Dynamic assays after 6 hours showed how the degradation of the zein matrix was affected by the cross-sectional conformation (∼69% vs. ∼61%, square and round channel, respectively) and the simulated blood fluid components (∼55%, round channel with a more viscous solution). The released amount of rutin was ∼81% vs. ∼77% and ∼78% vs. ∼74% from the square and round channels, using the less and more viscous blood-simulated fluids, respectively. Fitting the drug release data to Korsmeyer-Peppas and first-order mathematical models provided further insight into the mechanism of rutin release and coating behavior under flowing conditions. More importantly, whole blood tests with our newly developed microfluidic platforms confirmed the hemocompatibility of our zein-based coating. In detail, in-flow and static studies on the blood cell behavior showed a significant reduction of platelet adhesion (∼73%) and activation (∼93%) compared to the stainless-steel substrate, confirming the benefits of using such naturally-derived coatings to avoid clogging. Overall, our microfluidic designs can provide a key practical tool for assessing polymer degradation and drug release from degradable matrices under flowing conditions, thus aiding future studies on the development of hemocompatible, controlled-release coatings for DESs.

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.

Development of biodegradable zein-based bilayer coatings for drug-eluting stents.

Drug-eluting stents (DES) have been widely used for the treatment of cardiovascular diseases. Nevertheless, chronic inflammation and delayed re-endothelialization still represent challenges for their clinical use. In the present work, we developed novel bilayer coatings for stent applications that could overcome these limitations, exclusively using biodegradable plant-based drugs and polymers. In particular, stainless steel surfaces were coated with rutin-loaded zein (the active layer) and cross-linked alginate (the sacrificial layer) via facile dip and spray coating methods. Various mechanical tests and analysis tools, such as infrared spectroscopy, water contact angle measurements, and scanning electron microscopy were used to characterize the coated surfaces. Degradation and release studies of the films were extensively carried out and compared. The release rate of rutin from the bilayer coating reached 66.1 ± 3.2% within 24 hours of incubation (initial burst period), while the rest of the drug was released over 21 days in a sustained manner. Antioxidant assays confirmed that rutin retained its free radical scavenging ability after being eluted in phosphate buffer at 37 °C. In vitro results with human fibroblasts and endothelial cells suggested that the coating materials and their degradation products are highly biocompatible. In conclusion, our novel drug-eluting coatings, fabricated with natural biodegradable polymers, are promising materials for DES applications, allowing a sustained drug delivery and improving the biocompatibility of cardiovascular implanted devices.