期刊
SMALL
卷 18, 期 15, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202200060
关键词
cutaneous wound healing; exosomal miRNA sequencing; exosome proteomics; exosome-guided cell reprogramming; hydrogels; macrophage-derived exosomes
类别
资金
- Samsung Research Funding & Incubation Center of Samsung Electronics [SRFC-MA1901-10]
- USA National Institutes of Health [R01 DE021104]
- International Research & Development Program of the National Research Foundation of Korea (NRF) - Ministry of Science and ICT [2019K1A4A7A02102530]
- Intramural Research Program of the Korea Institute of Science and Technology (KIST)
- National Research Foundation of Korea [2019K1A4A7A02102530] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
In this study, a hydrolytically degradable PEG hydrogel-based exosome delivery system was designed to induce macrophages to transition from proinflammatory to anti-inflammatory state, promoting cutaneous wound healing.
Macrophages (M phi s) are characterized by remarkable plasticity, an essential component of chronic inflammation. Thus, an appropriate and timely transition from proinflammatory (M1) to anti-inflammatory (M2) M phi s during wound healing is vital to promoting resolution of acute inflammation and enhancing tissue repair. Herein, exosomes derived from M2-M phi s (M2-Exos), which contain putative key regulators driving M phi polarization, are used as local microenvironmental cues to induce reprogramming of M1-M phi s toward M2-M phi s for effective wound management. As an injectable controlled release depot for exosomes, hydrolytically degradable poly(ethylene glycol) (PEG) hydrogels (Exogels) are designed and employed for encapsulating M2-Exos to maximize their therapeutic effects in cutaneous wound healing. The degradation time of the hydrogels is adjustable from 6 days or up to 27 days by controlling the crosslinking density and tightness. The localization of M2-Exos leads to a successful local transition from M1-M phi s to M2-M phi s within the lesion for more than 6 days, followed by enhanced therapeutic effects including rapid wound closure and increased healing quality in an animal model for cutaneous wound healing. Collectively, the hydrolytically degradable PEG hydrogel-based exosome delivery system may serve as a potential tool in regulating local polarization state of M phi s, which is crucial for tissue homeostasis and wound repair.
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