Anagrafe della ricerca

Chronic skin wounds (CSWs) affect more than 40M patients globally and represent a growing burden for the healthcare systems (costs > $18.5B in 2022). Among the different factors contributing to wound chronicity, bacterial infections and biofilms represent the most severe issues to face in wound management (over 60% of CSWs contain biofilm). In this scenario, the gold standard treatment encompasses biofilm eradication and bacterial burden reduction through debridement and antibiotic administration. However, antibiotic administration should not be used indiscriminately as their wide application increases the risk of selection of multidrug-resistant organisms, resulting in adverse events and treatment failure. To provide significant breakthroughs in the available therapeutic approaches for an CSW treatment, HERO will engineer a smart injectable multifunctional hydrogel able to dislodge biofilm, while preventing its relapse, reducing the overall microbial burden, and creating a favorable environment for the healing process. To gather all these features within a single injectable formulation HERO will combine a lactoferrin-loaded thermo-sensitive and alkaline pH-responsive bioartificial hydrogel based on a custom-made amphiphilic poly(ether urethane) bearing pendant -COOH and hyaluronic acid, with farnesol-loaded quaternary ammonium palmitoyl glycol chitosan (F-GCPQ) micelles. Micelle nano-size and chemical nature will favour biofilm infiltration and dislodging, further enhanced by the antibiofilm effect of the progressively released farnesol. The concurrent release of lactoferrin will provide additional antimicrobial, anti-inflammatory, and pro-healing properties. Furthermore, the inclusion on hyaluronic acid is expected to further stimulate the creation of a favorable environment to initiate the healing cascade, while providing an acidifying effect of the wound bed pH that is expected to contribute to microbial load decrease. Lastly, HERO alkaline pH-responsiveness will accelerate payload release in response to the absorption of CSW alkaline exudate, thus resulting in a prompt adaptation of system behavior to the wound status. HERO formulation will be easy to prepare, handle and inject, thus answering to the need of new antibiotic-free wound care products suitable for auto-medication too. It will be engineered to remain in loco for up to 72h thus avoiding the need for a daily dressing replacement and will be easy to remove by simple irrigation with water solutions, with significant advantages in terms of patient comfort and healthy tissue preservation. Lastly, the use of the scented farnesol will enhance patient psychological wellness, being smell a recurrent issue in CSWs. HERO has thus been conceived to significantly impact the biomedical field, providing a new approach for CSW treatment. Finally, its multi-component nature will allow a flexible design of the therapeutic approach that might be adapted to patient-specific strategies.