Bioadhesive Microcarriers Encapsulated with IL-27 High Expressive MSC Extracellular Vesicles for Inflammatory Bowel Disease Treatment

Abstract

Mesenchymal stem cell (MSC) therapy is a promising candidate for inflammatory bowel disease (IBD) treatment, while overcoming the limitations of naive seeding cells function and realizing efficient intestinal targeting remains a challenge. Here, a bioadhesive microparticle carrying interleukin-27 (IL-27) MSC-derived extracellular vesicles (MSC^IL-27 EVs) is developed to treat IBD. The MSC^IL-27 EVs prepared through lentivirus-mediated gene transfection technology show ideal anti-inflammatory and damage repair function. By encapsulating MSC^IL-27 EVs into dopamine methacrylamide-modified hydrogel, a bioadhesive EVs microcarrier via microfluidic technology is fabricated. The resultant microcarriers exhibit ideal MSC^IL-27 EVs sustained release effect and effective wet adhesion property. Furthermore, the therapeutic potential of MSC^IL-27 EVs-loaded microcarriers in treating IBD is demonstrated. Through giving IBD rats a rectal administration, it is found that the microcarriers can firmly anchor to the surface of colon, reduce the inflammatory response, and repair the damaged barrier. Therefore, the bioadhesive MSC^IL-27 EVs-loaded microcarriers provide a promising strategy for the biomedical application of MSC-derived EVs, and broaden the clinical potential of MSC therapy.

Keywords: IL-27; adhesion; extracellular vesicle; inflammatory bowel disease; mesenchymal stem cell; microcarrier.