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Chitosan (CS), a biopolymer known for its wound-healing properties, has garnered significant interest in biomedical research. This study explores the potential of two Hermetia illucens-derived CS types-unbleached CS and bleached CS-as novel biomaterials for wound-healing applications, in comparison with commercial CS derived from the shells of Pandalus borealis (cold-water shrimp). CS was extracted from pupal exuviae, a byproduct of insect farming, which supports a circular economy by converting waste into valuable molecules for biomedical applications. Unbleached CS exhibited viscosity and viscoelastic properties comparable to those of commercial CS. The critical entanglement concentration (CEC) of unbleached CS (1.15 ± 0.05 % w/v) was similar to that of commercial CS (1.18 ± 0.09 % w/v). Moreover, both Hermetia illucens-derived CS types (unbleached and bleached) demonstrated a greater capability to enhance fibroblast viability (135 ± 7 % and 123 ± 6 %, respectively) compared to commercial CS (115 ± 7 %). Further investigation revealed that unbleached CS exhibited increased antioxidant activity, reversing >30 % of the loss of viability caused by H 2 O 2 treatment, and demonstrated anti-inflammatory properties, decreasing IL-6 levels by 66 ± 2 %. Sponge-like scaffolds based on unbleached CS and commercial CS were prepared via freeze-drying. When comparing structural and functional properties of commercial and unbleached CS scaffolds, the unbleached CS scaffolds exhibited higher porosity (67.9 ± 2.7 %), smaller pore size (216 ± 35 nm), higher swelling ratio (25.4 ± 1.9), greater resistance to degradation, and enhanced fibroblast proliferation. These findings underscore the potential of insect-derived CS as a sustainable and bioactive material for wound healing. However, further research is required to fully understand its interactions and mechanisms in tissue repair., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Respiratory tract infections (RTIs) represent a significant global health issue, particularly for vulnerable population, such as children, the elderly, or patients with immunosuppression. In this context, the aim of the present work was the development of Chitosan/Hydrolyzed Collagen-based microparticles (Mps) as a pulmonary drug delivery system (PDDS) for the treatment of RTIs. Mps were produced via spray-drying and composed of chitosan (Cs), one of the most widely used polysaccharides in PDDS, and hydrolyzed collagen (HC), another promising material for the development of PDDS that has not yet been fully explored. The formation of an interaction product between Cs and HC occurred during the spray-drying process and was confirmed by infrared spectroscopy and thermal analysis. Mps were characterized in terms of morphology, particle size, zeta potential, aerodynamic performance, swelling behavior and biodegradation profile in simulated lung fluid. Mps biocompatibility was also assessed on adenocarcinomic human alveolar basal epithelial (A549) cells. Finally, Mps were characterized in vitro for antibacterial properties and their ability to inhibit bacterial adhesion to S. aureus and P. aeruginosa. An enhanced antibacterial effect was observed for Mps with respect to the pristine materials (Cs and HC) and their physical mixture. Moreover, Mps were also able to inhibit bacteria adhesion to epithelial cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The work aims to develop mucoadhesive and thermo-responsive in situ gelling systems, using hydrophobically-modified hydroxypropyl-methyl cellulose (Sangelose, SG) and beta-cyclodextrin (β-CD) derivatives, for preventing viral respiratory infections. Eight SG/CD systems with varying CD concentrations were evaluated for rheological properties, mucoadhesiveness, spreadability and sprayability via nasal devices; cytotoxicity was in vitro investigated on reconstituted nasal epithelia. Additionally, droplet size distribution and spray deposition were assessed for the most promising systems. The addition of β-CD derivatives to SG solution was responsible for a rapid sol-gel transition within a physiological temperature range (29-34 °C). SG/CD systems were characterized by a prevalence of the elastic properties on the viscous ones at 37 °C, functional to the formation of a protective gel barrier on the mucosa. The most promising systems showed sprayability and spreadability suitable for nasal administration, while in vitro tests demonstrated their non-toxicity. All the sprays were characterized by droplets with size >100 μm, functional to avoid droplet exhalation or lung deposition; spray deposition studies confirmed uniform distribution across nasal turbinates, crucial for trapping inhaled particles. In conclusion, a mucoadhesive and thermo-responsive in situ gelling system consisting of SG and β-CD derivatives was successfully developed as promising nasal spray for the prevention of respiratory infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Chronic wounds represent silent epidemic affecting a large portion of the world population, especially the elders; in this context, the development of advanced bioactive dressings is imperative to accelerate wound healing process, while contrasting or preventing infections. The aim of the present work was to provide a deep characterization of the functional and biopharmaceutical properties of a sustainable thin and flexible films, composed of whey proteins alone (WPI) and added with nanostructured zinc oxide (WPZ) and intended for the management of chronic wounds. The potential of whey proteins-based films as wound dressings has been confirmed by their wettability, hydration properties, elastic behavior upon hydration, biodegradation propensity and, when added with nanostructured zinc oxide, antibacterial efficacy against both Gram-positive and Gram-negative pathogens, i.e. Staphylococcus aureus and Escherichia coli. In-vitro experiments, performed on normal human dermal fibroblasts, confirmed film cytocompatibility, also revealing the possible role of Zn 2+ ions in promoting fibroblast proliferation. Finally, in-vivo studies on rat model confirmed film suitability to act as wound dressing, since able to ensure a regular healing process while providing effective protection from infections. In particular, both films WPI and WPZ are responsible for the formation in the wound bed of a continuous collagen layer similar to that of healthy skin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Herein we developed a hydrogel based porous cross-linked scaffold intended for the treatment of chronic skin ulcers. It is made of collagen, the most abundant protein of mammals ECM, and chitosan, a natural polysaccharide endowed with numerous positive cues for wound repair. Different cross-linking methods, namely UV irradiation with the addition of glucose, addition of tannic acid as cross-linking agent and ultrasonication, were employed to prepare a cross-linked hydrogel with a highly interconnected 3D internal structure. The variables considered critical to obtain a suitable system for the envisaged application are the composition of hydrogels, especially the concentration of chitosan, and the concentration ratio between chitosan and collagen. Stable systems, characterized by high porosity, were obtained thanks to the use of freeze-drying process. To assess the influence of the above-mentioned variables on scaffold mechanical properties, a Design of Experiments (DoE) approach was exploited, which resulted in the identification of the best hydrogel composition. In vitro and in vivo assays on a fibroblast model cell line and on a murine model, respectively, demonstrated scaffold biocompatibility, biomimicry, and safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)