Journal
JOURNAL OF CONTROLLED RELEASE
Volume 316, Issue -, Pages 93-104Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2019.11.003
Keywords
Controlled release; Extracellular vesicles; Self-assembling peptide; Tissue repair; Mesenchymal stem cells; MMP2
Funding
- National Natural Science Foundation of China [81571808, 31871001, 31200754]
- Sichuan Science and Technology Program [2019YJ0069]
- 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University [ZYGD18014]
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Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown great potential for tissue repair, but their therapeutic capacity is limited by rapid clearance and short half-life. Herein, we purposed a hydrogel-based slow release strategy to enhance the therapeutic potency of EVs. A matrix metalloproteinase-2 (MMP2) sensitive self-assembling peptide (KMP2) hydrogel was used for the local delivery of MSC-EVs. The structure and controlled release properties of the KMP2 hydrogel were analyzed. The effects of the EV-loaded KMP2 hydrogel (KMP2-EVs) on cell apoptosis, inflammation and angiogenesis were evaluated in mice with renal ischemia-reperfusion (I/R) injury. In vitro, KMP2 formed a cross-linked nanofiber hydrogel to encapsulate MSC-EVs. KMP2 showed greater degradation and EV release in response to MMP2. The released EVs had similar structures and bioactivities as fresh, isolated EVs. In vivo, I/R mice treated with KMP2-EVs showed improved renal function by reducing tubular cell apoptosis, pro-inflammatory cytokine expression, and macrophage infiltration than mice receiving either EVs or KMP2. Moreover, KMP2-EVs showed better efficacy on promoting endothelial cell proliferation and angiogenesis than KMP2 or EVs alone, which subsequently decreased chronic renal fibrosis in I/R mice. This study highlighted that the EV-released KMP2 hydrogel is a promising cell-free therapy for tissue repair.
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