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

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 15; no. 36; pp. e1902232 - n/a
• Main Authors: Saleh, Bahram, Dhaliwal, Harkiranpreet Kaur, Portillo‐Lara, Roberto, Shirzaei Sani, Ehsan, Abdi, Reza, Amiji, Mansoor M., Annabi, Nasim
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-09-2019
• Subjects: Acceleration; Adhesion tests; adhesive hydrogels; Adhesives; Animals; CD44 targeting hyaluronic acid nanoparticles; Cell Line; Gene expression; Hyaluronic acid; Hyaluronic Acid - chemistry; Hydrogels; Hydrogels - chemistry; Immunomodulation - physiology; local immunomodulation; localized delivery; macrophage polarization; Macrophages; Macrophages - metabolism; Macrophages - ultrastructure; Magnetic Resonance Spectroscopy; Male; Mice; MicroRNAs; MicroRNAs - chemistry; MicroRNAs - genetics; MicroRNAs - metabolism; Microscopy, Electron, Scanning; miRNA‐223; Nanoparticles; Nanoparticles - chemistry; Nanotechnology; Polarization; Polymerase chain reaction; Wound healing; Wound Healing - genetics; Wound Healing - physiology; wound healing; CD44 targeting hyaluronic acid nanoparticles; adhesive hydrogels; macrophage polarization; localized delivery; local immunomodulation; miRNA-223
• ISSN: 1613-6810; 1613-6829; 1613-6829
• DOI: 10.1002/smll.201902232

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.
RNAi delivery has great potential for the treatment of different diseases. However, there are multiple challenges such as intracellular delivery, stability, and toxicity when using RNAi therapy. To overcome these limitations, miRNAs are encapsulated in macrophage targeting nanoparticles and delivered locally to the wounds using an adhesive hydrogel. The adhesive seals the wound and promotes tissue healing in vivo.