Generation of a novel human dermal substitute functionalized with antibiotic-loaded nanostructured lipid carriers (NLCs) with antimicrobial properties for tissue engineering

• Published in: Journal of nanobiotechnology 2020-11, Vol.18 (1), p.174-174, Article 174
• Main Authors: Chato-Astrain, Jesús, Chato-Astrain, Isabel, Sánchez-Porras, David, García-García, Óscar-Darío, Bermejo-Casares, Fabiola, Vairo, Claudia, Villar-Vidal, María, Gainza, Garazi, Villullas, Silvia, Oruezabal, Roke-Iñaki, Ponce-Polo, Ángela, Garzón, Ingrid, Carriel, Víctor, Campos, Fernando, Alaminos, Miguel
• Format: Article
• Language: English
• Subjects: Amikacin; Amikacin - chemistry; Amikacin - pharmacology; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-infective agents; Antibacterial activity; Antibiotics; Antimicrobial agents; Artificial tissues; Biocompatibility; Biocompatible Materials - chemistry; Biomaterials; Biomechanics; Biomedical materials; Caspase-7; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell viability; Cells, Cultured; Colistin - analogs & derivatives; Colistin - chemistry; Colistin - pharmacology; Collagen; Deoxyribonucleic acid; Dermis; DNA; Dosage and administration; Drug Carriers - chemistry; Drug Carriers - toxicity; Drug delivery systems; Drug dosages; Drugs; Efficiency; Fibrin; Fibroblasts; Fibroblasts - cytology; Health aspects; Health risks; Histochemistry; Humans; Immunohistochemistry; Lipids; Lipids - chemistry; Mechanical properties; Metabolism; Methods; Morphology; Multidrug resistant organisms; Nanoparticles; Nanostructure; Nanostructures - chemistry; Nanostructures - toxicity; Proliferating cell nuclear antigen; Properties (attributes); Proteoglycans; Pseudomonas; Side effects; Skin, Artificial; Substitutes; Tissue engineering; Tissue Engineering - methods; Vehicles
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-020-00732-0

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 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. These results suggest that functionalization of fibrin-agarose human dermal substitutes with antibiotic-loaded 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.