Genetically Engineered Stromal Cell Exosomes from High-Throughput Herringbone Microfluidics

Stromal cell-derived exosomes have demonstrated their value in the field of biomedical engineering. However, the low production and specific requirements of different diseases limited the practical efficacy of these exosomes and restricted their wider applications. Here, we presented a method to culture genetically engineered mesenchymal stromal cells (MSC) that overexpressed the hepatocyte growth factor (HGF) in microfluidics and harvest mass HGF overexpressed exosomes for wound healing. The microfluidic chips were featured with herringbone grooves and micropillar arrays, where sufficient fluidic mechanical stimuli and efficient nutrient delivery were promoted by a turbulent vortex. It was demonstrated that the production of exosomes was much higher than by the traditional flask cell culture, along with higher HGF content. In addition, the MSC^HGF-secreted exosomes were applied for wound healing in diabetic rat model, showing superior angiogenesis, cell migration, and immune modulation capabilities. These features indicated that the genetically engineered MSC^HGF exosomes from high-throughput herringbone microfluidics possess great potential for wound healing and related biomedical applications.