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.