{"doi":"10.1002/advs.202501036","title":"Neutrophil Macrophage Crosstalk via Extracellular Vesicles Drives Reverse Migration in a Fully Human Model of Wound Healing","abstract":"Persistent neutrophilic inflammation can lead to tissue damage and chronic inflammation, contributing to non-healing wounds. The resolution phase of neutrophilic inflammation is critical to preventing tissue damage. Animal models have provided insight into resolution of neutrophilic inflammation via efferocytosis and reverse migration (rM); however, species-specific differences and complexity of innate immune responses make translation to humans challenging. Thus, there is a need for in vitro systems that can elucidate mechanisms of resolution of human neutrophilic inflammation. Here, a human microphysiological system (MPS) is developed to mimic an inflammatory sterile injury (SI) microenvironment to study the role of macrophage-derived extracellular vesicles (M-EVs) in the resolution of inflammation via neutrophil rM. The MPS integrates a blood vessel mimic, injury site spheroid, human neutrophils, macrophages, and macrophage-derived EVs to investigate the role of M-EVs in neutrophil rM in vitro. The MPS enabled demonstration that EVs derived from macrophage subsets modulate migratory behavior in primary neutrophils differently in specific inflammatory microenvironments. A new mechanism is identified underlying neutrophil rM, where neutrophils exposed to M2-EV-derived-IL-8 migrate away from the SI site. Overall, the SI MPS system demonstrates a reverse migratory pattern in human primary neutrophils, advancing the study of the resolution of inflammation via M-EVs.","journal":"Advanced Science","year":2025,"id":521315,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1391635,"name":"Oluwatoyin Babatunde","orcid":"0000-0003-4608-5874","position":1,"is_corresponding":false},{"id":686472,"name":"Adeel Ahmed","orcid":"0000-0003-4511-8208","position":2,"is_corresponding":false},{"id":294333,"name":"Wilmara Salgado‐Pabón","orcid":"0000-0003-0854-1568","position":3,"is_corresponding":false},{"id":282370,"name":"David J. Beebe","orcid":"0000-0002-0415-9006","position":4,"is_corresponding":false},{"id":401581,"name":"Sheena C. Kerr","orcid":"0000-0002-4404-3382","position":5,"is_corresponding":false},{"id":645052,"name":"Kehinde Adebayo Babatunde","orcid":"0000-0001-9091-0953","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:49:44.558743Z","pmid":"40448602","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":[]}