Hydrogel Microneedle Patches Loaded with Stem Cell Mitochondria-Enriched Microvesicles Boost the Chronic Wound Healing

作者：Wende Yao, Junnian Zhou, Chao Tang, Julei Zhang, Zhaoyang Chen, Yan Li, Xiaojing Gong, Mingyi Qu, Quan Zeng, Yi Jia, Haiyang Wang, Tao Fan, Jing Ren, Lingli Guo, Jiafei Xi, Xuetao Pei, Yan Han, Wen Yue · 发表于：ACS Nano · 年份：2024 · DOI：10.1021/acsnano.4c06921 · 被引用次数：119 · 研究领域：Advancements in Transdermal Drug Delivery、Extracellular vesicles in disease、Wound Healing and Treatments

High Resolution Image Download MS PowerPoint Slide Rescuing or compensating mitochondrial function represents a promising therapeutic avenue for radiation-induced chronic wounds. Adult stem cell efficacies are primarily dependent on the paracrine secretion of mitochondria-containing extracellular vesicles (EVs). However, effective therapeutic strategies addressing the quantity of mitochondria and mitochondria-delivery system are lacking. Thus, in this study, we aimed to design an effective hydrogel microneedle patch (MNP) loaded with stem cell-derived mitochondria-rich EVs to gradually release and deliver mitochondria into the wound tissues and boost wound healing. We, first, used metformin to enhance mitochondrial biogenesis and thereby increasing the secretion of mitochondria-containing EVs (termed “Met-EVs”) in adipose-derived stem cells. To verify the therapeutic effects of Met-EVs, we established an in vitro and an in vivo model of X-ray-induced mitochondrial dysfunction. The Met-EVs ameliorated the mitochondrial dysfunction by rescuing mitochondrial membrane potential, increasing adenosine 5′-triphosphate levels, and decreasing reactive oxygen species production by transferring active mitochondria. To sustain the release of EVs into damaged tissues, we constructed a Met-EVs@Decellularized Adipose Matrix (DAM)/Hyaluronic Acid Methacrylic Acid (HAMA)-MNP. Met-EVs@DAM/HAMA-MNP can load and gradually release Met-EVs and their contained mitochondria into wound tissues to all...