{"doi":"10.1002/smll.202200060","title":"Sustained Exosome‐Guided Macrophage Polarization Using Hydrolytically Degradable PEG Hydrogels for Cutaneous Wound Healing: Identification of Key Proteins and MiRNAs, and Sustained Release Formulation","abstract":"Macrophages (Mφs) are characterized by remarkable plasticity, an essential component of chronic inflammation. Thus, an appropriate and timely transition from proinflammatory (M1) to anti-inflammatory (M2) Mφs during wound healing is vital to promoting resolution of acute inflammation and enhancing tissue repair. Herein, exosomes derived from M2-Mφs (M2-Exos), which contain putative key regulators driving Mφ polarization, are used as local microenvironmental cues to induce reprogramming of M1-Mφs toward M2-Mφs 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-Mφs to M2-Mφs 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 Mφs, which is crucial for tissue homeostasis and wound repair.","journal":"Small","year":2022,"id":233350,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":132,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":254060,"name":"Jing Cheng","orcid":"0000-0002-5379-2203","position":1,"is_corresponding":false},{"id":846338,"name":"Hyo‐Suk Kim","orcid":"0000-0003-3239-3147","position":2,"is_corresponding":false},{"id":846339,"name":"Sukyung Song","orcid":"0009-0004-0710-7078","position":3,"is_corresponding":false},{"id":846340,"name":"Su Jin Lee","orcid":"0000-0003-3405-9935","position":4,"is_corresponding":false},{"id":846341,"name":"Yoosoo Yang","orcid":"0000-0003-3279-4362","position":5,"is_corresponding":false},{"id":846342,"name":"Ji Hoon Jeong","orcid":"0000-0002-4836-3551","position":6,"is_corresponding":false},{"id":846343,"name":"Ji Eun Lee","orcid":"0000-0002-4455-2259","position":7,"is_corresponding":false},{"id":245083,"name":"Phillip B. Messersmith","orcid":"0000-0002-1197-333X","position":8,"is_corresponding":false},{"id":846344,"name":"Sun Hwa Kim","orcid":"0000-0002-2076-111X","position":9,"is_corresponding":false},{"id":703830,"name":"Gijung Kwak","orcid":"0000-0001-6908-9638","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T00:21:25.223756Z","pmid":"35229462","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}