Broadly Accessible\n3D <i>In Vitro</i> Skin\nModel as a Comprehensive Platform for Antibacterial Therapy Screening

Skin infections are currently a worldwide emergency as\nantibiotic-resistant\nbacteria are spreading, leading to the ineffectiveness of most antibiotics\nand antibacterial strategies. Consequently, there is an urgency of\ndeveloping and testing innovative antibacterial therapies. As traditional\n2D cell culture and planktonic bacteria culture can be obsolete due\nto their incapability of resembling the complex infection environment,\n3D <i>in vitro</i> skin models can be a powerful tool to\ntest and validate therapies. In this article, a 3D <i>in vitro</i> epidermis–dermis skin model has been developed and biofabricated\nto be broadly available, reaching a balance between the simplicity\nand reproducibility of the model and its complexity in terms of wound,\ninfection, and treatment response. The results are really promising,\nas the skin model developed a comprehensive physical barrier. To further\ninvestigate the skin model, controlled wounding, infection, and antibiotic\ntreatments were performed. The results were remarkable: Not only was\nthe unwounded epidermal barrier able to partially stop the bacterial\nproliferation, but the entire system reacted to both wound and infection\nin a complex and complete way. Extracellular matrix deposition and\nremodeling, inflammatory response, antimicrobial peptide production,\nand change in cellular behaviors, from epithelial to mesenchymal and\nfrom fibroblasts to myofibroblasts, were witnessed, with different\nextents depending on the bacterial strain. In addition, the inflammatory\nresponse to the antibiotic administration was opposite for the two\nbacterial infections, probably revealing the release of inflammatory\nendotoxins during Escherichia coli death.\nIn conclusion, the presented 3D <i>in vitro</i> skin model\nhas all the characteristics to be a future landmark as a platform\nfor antibacterial strategy therapy testing.