Local Immunomodulation Using an Adhesive Hydrogel Loaded with miRNA-Laden Nanoparticles Promotes Wound Healing.

Autor: Saleh B; Department of Chemical Engineering, Northeastern University, Boston, MA, 02115, USA., Dhaliwal HK; Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, 02115, USA., Portillo-Lara R; Department of Chemical Engineering, Northeastern University, Boston, MA, 02115, USA.; Technologico de Monterrey, Escuela de Ingenieria y Ciencias, Zapopan, JAL 45138, Mexico., Shirzaei Sani E; Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA., Abdi R; Department of Medicine Renal, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA., Amiji MM; Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, 02115, USA., Annabi N; Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.; Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2019 Sep; Vol. 15 (36), pp. e1902232. Date of Electronic Publication: 2019 Jul 22.
DOI: 10.1002/smll.201902232
Abstrakt: Chronic wounds are characterized by impaired healing and uncontrolled inflammation, which compromise the protective role of the immune system and may lead to bacterial infection. Upregulation of miR-223 microRNAs (miRNAs) shows driving of the polarization of macrophages toward the anti-inflammatory (M2) phenotype, which could aid in the acceleration of wound healing. However, local-targeted delivery of microRNAs is still challenging, due to their low stability. Here, adhesive hydrogels containing miR-223 5p mimic (miR-223*) loaded hyaluronic acid nanoparticles are developed to control tissue macrophages polarization during wound healing processes. In vitro upregulation of miR-223* in J774A.1 macrophages demonstrates increased expression of the anti-inflammatory gene Arg-1 and a decrease in proinflammatory markers, including TNF-α, IL-1β, and IL-6. The therapeutic potential of miR-223* loaded adhesive hydrogels is also evaluated in vivo. The adhesive hydrogels could adhere to and cover the wounds during the healing process in an acute excisional wound model. Histological evaluation and quantitative polymerase chain reaction (qPCR) analysis show that local delivery of miR-223* efficiently promotes the formation of uniform vascularized skin at the wound site, which is mainly due to the polarization of macrophages to the M2 phenotype. Overall, this study demonstrates the potential of nanoparticle-laden hydrogels conveying miRNA-223* to accelerate wound healing.
(© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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