Generation of a novel human dermal substitute functionalized with antibiotic-loaded nanostructured lipid carriers (NLCs)
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urnal of Nanobiotechnology Open Access
RESEARCH
Generation of a novel human dermal substitute functionalized with antibiotic‑loaded nanostructured lipid carriers (NLCs) with antimicrobial properties for tissue engineering Jesús Chato‑Astrain1,2, Isabel Chato‑Astrain1, David Sánchez‑Porras1,2, Óscar‑Darío García‑García1,2, Fabiola Bermejo‑Casares1, Claudia Vairo3, María Villar‑Vidal4, Garazi Gainza3, Silvia Villullas3, Roke‑Iñaki Oruezabal5, Ángela Ponce‑Polo5, Ingrid Garzón1,2, Víctor Carriel1,2, Fernando Campos1,2* and Miguel Alaminos1,2
Abstract 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 immunohistochemi‑ cal 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 character‑ ized, 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 detect‑ able side effects. This opens the door to future clinical use of functionalized tissues. Keywords: Tissue engineering, Functionalization, Dermal substitute, Severe burns, Human skin, Nanostructured lipid carriers, Colistimethate, Amikacin
*Correspondence: [email protected] 1 Tissue Engineering Group, Department of Histology, Faculty of Medicine, University of Granada, Avenida de la Investigación 11, 18016 Granada, Spain Full list of author information is available at the end of the article
Background Tissue engineering strategies attempt to generate biologically active tissue-like substitutes to restore and maintain the normal function of damaged tissues and organs [1]. Tissue engineering protocols combine the principles of
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