Exosome-like vesicles encapsulated with specific microRNAs accelerate burn wound healing and ameliorate scarring

Abstract

Abstract Burn injuries are prevalent, yet effective treatments remain elusive. Exosomes derived from mesenchymal stem cells (MSC-Ex) possess remarkable pro-regenerative properties for wound healing. Despite their potential, the challenge of mass production limits their clinical application. To address this, preparing exosome-like vesicles has become an international trend. In this study, 28 key microRNAs (miRNAs) with significant pro-proliferation, anti-inflammation, and anti-fibrosis functions were screened from MSC-Ex. These miRNAs were encapsulated into liposomes and then hybridized with extracellular vesicles derived from watermelon to create synthetic exosome-like vesicles. The fabricated vesicles exhibited similar particle size and zeta potential to MSC-Ex, demonstrating high serum stability and effectively resisting the degradation of miRNA by RNase. They were efficiently internalized by cells and enabled a high rate of lysosomal escape for miRNAs post cellular uptake, thereby effectively exerting their pro-proliferative, anti-inflammatory, and anti-fibrotic functions. Further experiments demonstrated that these vesicles efficiently accelerated burn wound healing and reduced scarring, with effects comparable to those of natural MSC-Ex. Based on these findings, the exosome-like vesicles fabricated in this study present a promising alternative to MSC-Ex in burn wound treatment. Graphical Abstract

Keywords

• microRNA
• Exosome-like vesicles
• Mesenchymal stem cells
• Exosomes
• Wound
• Scar