Generation of a novel human dermal substitute functionalized with antibiotic‑loaded nanostructured lipid carriers (NLCs) with antimicrobial properties for tissue engineering Chato Astrain, Jesús Chato Astrain, Isabel Sánchez Porras, David García García, Óscar Darío Bermejo Casares, Fabiola Garzón Bello, Ingrid Johanna Carriel Araya, Víctor Campos, Fernando Alaminos Mingorance, Miguel Tissue engineering Functionalization Dermal substitute Severe burns Human skin Nanostructured lipid carriers Colistimethate Amikacin Background: Treatment of patients affected by severe burns is challenging, especially due to the high risk of Pseudomonas infection. In the present work, we have generated a novel model of bioartificial human dermis substitute by tissue engineering to treat infected wounds using fibrin-agarose biomaterials functionalized with nanostructured lipid carriers (NLCs) loaded with two anti-Pseudomonas antibiotics: sodium colistimethate (SCM) and amikacin (AMK). Results: Results show that the novel tissue-like substitutes have strong antibacterial effect on Pseudomonas cultures, directly proportional to the NLC concentration. Free DNA quantification, WST-1 and Caspase 7 immunohistochemical assays in the functionalized dermis substitute demonstrated that neither cell viability nor cell proliferation were affected by functionalization in most study groups. Furthermore, immunohistochemistry for PCNA and KI67 and histochemistry for collagen and proteoglycans revealed that cells proliferated and were metabolically active in the functionalized tissue with no differences with controls. When functionalized tissues were biomechanically characterized, we found that NLCs were able to improve some of the major biomechanical properties of these artificial tissues, although this strongly depended on the type and concentration of NLCs. Conclusions: These results suggest that functionalization of fibrin-agarose human dermal substitutes with antibioticloaded NLCs is able to improve the antibacterial and biomechanical properties of these substitutes with no detectable side effects. This opens the door to future clinical use of functionalized tissues. 2021-02-04T11:13:26Z 2021-02-04T11:13:26Z 2020-11-23 journal article Chato-Astrain, J., Chato-Astrain, I., Sánchez-Porras, D., García-García, Ó. D., Bermejo-Casares, F., Vairo, C., ... & Alaminos, M. (2020). Generation of a novel human dermal substitute functionalized with antibiotic-loaded nanostructured lipid carriers (NLCs) with antimicrobial properties for tissue engineering. Journal of Nanobiotechnology, 18(1), 1-13. [https://doi.org/10.1186/s12951-020-00732-0] http://hdl.handle.net/10481/66287 10.1186/s12951-020-00732-0 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España Bmc