Sustained Exosome-Guided Macrophage Polarization Using Hydrolytically Degradable PEG Hydrogels for Cutaneous Wound Healing: Identification of Key Proteins and MiRNAs, and Sustained Release Formulation

Kwak, GijungCheng, JingKim, HyosukSong, SukyungLee, Su JinYang, YoosooJeong, Ji HoonLee, Ji EunMessersmith, Phillip B.Kim, Sun Hwa
Issue Date
Wiley - V C H Verlag GmbbH & Co.
Small, v.18, no.15, pp.1 - 15
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.
EXTRACELLULAR VESICLES; INFLAMMATORY RESPONSE; COMMUNICATION; INNATE; exosome-guided cell reprogramming; hydrogels; macrophage-derived exosomes; cutaneous wound healing; exosomal miRNA sequencing; exosome proteomics
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KIST Article > 2022
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