Human umbilical cord mesenchymal stem cell-derived exosomes combined with low-intensity pulsed ultrasound for the treatment of chronic burn wounds infected with methicillin-resistant Staphylococcus aureus.

Abstract

Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exosomes) have a short half-life and low bioavailability in vivo, which consequently limits their therapeutic efficacy in the treatment of chronic burn wounds infected with methicillin-resistant Staphylococcus aureus (MRSA). Low-intensity pulsed ultrasound (LIPUS), as a non-invasive physical stimulus, helps to enhance the bioavailability of exosomes, thereby improving their therapeutic efficacy. In this study, hUCMSC-Exosomes were extracted, purified, and characterized, and combined with LIPUS for the treatment of chronic burn wounds infected with MRSA. The results demonstrated that we successfully extracted and purified hUCMSC-Exosomes, which exhibited a spherical vesicle morphology and expressed the specific proteins TSG101 and CD63. In vitro, hUCMSC-Exosomes combined with LIPUS promoted the growth and proliferation of HSF and HMEC-1 cells, significantly enhancing the expression of key factors such as miR-21, EGF, VEGF, and TGF-β, while inhibiting the expression of PI3K and AKT. In vivo, the combination of hUCMSC-Exosomes and LIPUS facilitated the healing of severe burn wounds, including those infected with MRSA, by promoting skin wound regeneration and suppressing the expression of inflammatory factors such as IL-1β, IL-6, IL-12, and CRP. Histopathological analysis revealed evident epidermal regeneration and a marked resolution of the inflammatory response. Additionally, the treatment significantly increased the expression of miR-21, EGF, VEGF, and TGF-β in wound tissues, while inhibiting PI3K and AKT. Taken together, hUCMSC-Exosomes combined with LIPUS demonstrate significant clinical potential for the treatment of chronic burn wounds infected with MRSA.