TECHNOLOGICAL PLATFORMS CONTAINING NATURAL COMPOUNDS TO MAINTAIN AND RESTORE TISSUE INTEGRITY

Aim of PhD project was the development of bioactive systems based on natural compounds (as matrix forming components or as functional ingredients) to achieve tissue reparation. In particular, two different targets were considered: 1) skin: acute wounds with massive bleeding and non-healing cutaneous lesions as chronic wounds and severe burns, 2) heart: myocardial infarction. Chapter 1 of the thesis focuses on the development of hemostatic dressings loaded tranexamic acid (TA) to be used in case of massive bleedings. The biopolymers employed were chitosan in association with glycosaminoglycans, GAGs, (Hyaluronic acid, HA, Chondroitin sulfate, CS), leading to a polyelectrolyte complex formation able to induce a better fluid absorption from the wound and higher dressing bioadhesion properties. The fast release of TA makes the dressings able to be used during massive bleeding occurring during surgery, allowing procoagulant function as quickly as possible. Since multi-resistant bacteria represent a serious problem worldwide, a therapeutic option consists in the use of essential oils. These compounds possess an antimicrobial effect against multi-resistant bacteria but they are also extremely volatile. Due to this problem, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) based on cocoa butter, as solid lipid, and olive oil or sesame oil, as liquid lipids were developed for the encapsulation of eucalyptus and rosemary essential oils (Chapter 2). NLC based on olive oil and eucalyptus essential oil allowed a high fibroblast proliferation in an in vitro wound healing model, confirmed also by in vivo application on a murine burn model. Furthermore, the encapsulation protected the essential oils allowing the antimicrobial properties against gram-positive bacterial strain. Chapter 3 and 4 of the thesis focus on the development of therapeutic strategies for the treatment of myocardial infarction. Two different systems were studied: in situ gelling systems and electrospun nanofibrous scaffolds. In situ gelling systems were prepared by using two different polymers: poloxamer 407, a thermosensitive material, and sodium alginate, an ion-dependent polymer. Scaffolds were obtained by electrospinning of gelatin solutions. Both systems were associated to chondroitin sulfate, a glycosaminoglycan negatively charged able to interact with positively charged molecules such as growth factors. The therapeutic use of platelet lysate (PL) as hemoderivative rich in growth factors was investigated. PL allowed to improve cardiomyocytes viability isolated from rat fetuses.