MARINE-DERIVED BIOMATERIALS IN REGENERATIVE MEDICINE: TREATMENT OF CUTANEOUS INJURIES WITH COLLAGEN AND ANTIOXIDANTS FROM PARACENTROTUS LIVIDUS - IN VITRO AND PRECLINICAL ASSESSMENT

Skin injuries place a substantial clinical and economic burden on healthcare systems worldwide. Due to the limited intrinsic healing capacity of the skin, surgical interventions and rapid wound coverage are often necessary to promote optimal healing. In fact, despite the considerable medical need, currently available treatments show limited efficacy and are associated with high costs, making the management of skin wounds an ongoing area of research. In recent years, Regenerative Medicine and Tissue Engineering have opened pathways to innovative therapies, which are now being widely investigated. In this thesis, following the principles of the circular economy, the potential of novel wound dressings was explored as a tool for the cure of large skin defects involving both epidermal and dermal layers. The purple sea urchin (Paracentrotus lividus) of the Mediterranean Sea was studied as a sustainable and cost-effective source of bioactive molecules with potential medical application. Native collagen and antioxidants extracted from the non-edible parts of the animal were evaluated in vitro for their therapeutic properties. Following promising results, these materials were used to develop novel wound dressings -a collagen-based scaffold, termed Marine Collagen Wound Dressing, and a collage-based scaffold added with polyhydroxynaphthoquinones antioxidants, termed Antioxidants-enriched Marine Collagen Wound Dressing- which were subsequently tested in vitro, then ex vivo and in vivo to assess their ability to prevent excessive inflammation and promote wound closure. In vitro studies indicated that both dressings are biocompatible. The Antioxidants-enriched Marine Collagen Wound Dressing exhibited superior chemical stability and slower degradation rates compared to the Marine Collagen Wound Dressing, owing to strong interactions between collagen and polyhydroxynaphthoquinones. Moreover, the antioxidant activity of polyhydroxynaphthoquinones was preserved within the composite scaffolds, providing additional therapeutic benefits in the context of regenerative medicine. Polyhydroxynaphthoquinones were demonstrated to be efficient antioxidant pigments. Results clearly showed that their antioxidant activity is not restricted to direct scavenging or reactive oxygen species; rather, it is also associated with an upregulating effect on the expression of components of the endogenous antioxidant enzymes defense system. Given the promising results obtained with the novel wound dressings, preclinical studies were extended to ex vivo and in vivo rodent models on full-thickness skin lesions. In the ex vivo setting, both dressing effectively maintained a moist wound environment and accelerated keratinocytes migration, thereby promoting fast wound closure. In addition, the Antioxidants-enriched Marine Collagen Wound Dressing significantly reduced inflammation and enhanced extracellular matrix regeneration. In the in vivo model, the wound dressings supported tissue repair by providing effective wound coverage to prevent infections and maintaining a moist environment that sustains epidermal barrier restoration and facilitates the exchange of soluble mediators. Furthermore, the Antioxidants-enriched Marine Collagen Wound Dressing reduced elevated levels of reactive oxygen species and counteracted inflammation, promoting the progression to the subsequent phases of healing. Overall, the results highlight the potential of marine-derived, eco-sustainable biomaterials as a valuable resource for medical applications, particularly in the field of dermatology, by promoting wound healing.