BIMODAL - Bi-layers antI polyMicrobial 3D printed patches lOaded with yeAst-Derived exosome for wound heaLing

Skin defects are amongst the main causes of morbidity and mortality worldwide, which account for significantly high socioeconomic costs. Today, much attention is being paid to tissue engineering and biomaterials strategies for skin regeneration, and among them, there is increasing interest in using multi layered biomaterials. Extracellular vesicles (EVs) originated from all the cells of all kinds of organisms and recently got a lot more attention because of their potential in regenerative medicine. Many studies have been performed on mammalian-derived vesicles, but little attention has been paid to yeast as valuable sources of EVs. Recently researchers discovered that yeast contains biological properties beneficial for human tissue regeneration such as EVs or exosomes (EXo) able to dialogue directly with Candida species infecting the wounds. Based on the above, this project proposal intends to integrate, with the collaboration of leading research centres in these areas such as National Research Council (CNR), University of Ferrara (UNIFE) and University of Padova (UNIPD) multi-functional hydrogels, 3D Bioprinting and yeast derived EVs to develop innovative therapeutic protocols for the treatment of chronic wounds. BIMODAL aims to develop a bi-layered exosome loaded patch that combines 3D bioprinting, semi-IPN hydrogels and yeast derived EVs for wound healing and tissue regeneration applications. The technological and socio-economic value of the developed patch will be proven by integrating different EVs-functionalities and innovative hydrogels into the patch for reconstructive surgery.The different levels of multifunctionality (i.e., molecular, engineering and biological) will be integrated to achieve histo-specific regeneration processes by 3D bioprinting. BIMODAL technology will eliminate the need for the harvesting of large sections of autologous tissue from another anatomical area thus reducing invasiveness, risks of failure and hospitalization costs. BIMODAL will have a significant impact on the global bioink and 3D bioprinting markets that are projected to grow at a CAGR of 18%. As a result, this innovative approach will bring the research and knowledge far beyond the current state-of-the-art and will lead, through a carefully planned validation programme, to a proof-of-concept of multifunctional hydrogels and 3D bioprinting technology with a broader application in regenerative medicine.