{"doi":"10.1002/btm2.10697","title":"In situ‐crosslinked <scp>Zippersomes</scp> enhance cardiac repair by increasing accumulation and retention","abstract":"Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction (MI), but their therapeutic efficacy is limited by inefficient accumulation at the target site. A minimally invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post-infarct cardiac regeneration. Here, we show that EVs decorated with the next-generation of high-affinity (HiA) heterodimerizing leucine zippers, termed HiA Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ~7-fold enhanced accumulation within the infarcted myocardium in mice after 3 days and continued to be retained up to Day 21, surpassing the performance of unmodified EVs. After MI in mice, HiA Zippersomes increase the ejection fraction by 53% and 100% compared with unmodified EVs and phosphate-buffered saline (PBS), respectively. This notable improvement in cardiac function played a crucial role in restoring healthy heart performance. HiA Zippersomes also robustly decrease infarct size by 52% and 60% compared with unmodified EVs and PBS, respectively, thus representing a promising platform for minimally invasive vesicle delivery to the infarcted heart compared to intramyocardial injections.","journal":"Bioengineering & Translational Medicine","year":2024,"id":445401,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":639098,"name":"Kuo‐Ching Mei","orcid":"0000-0001-6045-2154","position":1,"is_corresponding":false},{"id":918965,"name":"Hannah M. Oh","orcid":null,"position":2,"is_corresponding":false},{"id":253761,"name":"Emily E. Bonacquisti","orcid":"0000-0001-6091-9834","position":3,"is_corresponding":false},{"id":1109813,"name":"Ameya Chaudhari","orcid":"0000-0003-0456-5677","position":4,"is_corresponding":false},{"id":1261816,"name":"Camryn Byrum","orcid":null,"position":5,"is_corresponding":false},{"id":535379,"name":"Brian C. Jensen","orcid":"0000-0001-6430-8344","position":6,"is_corresponding":false},{"id":253763,"name":"Juliane Nguyen","orcid":"0000-0002-8578-7396","position":7,"is_corresponding":false},{"id":349354,"name":"Natalie E. Jasiewicz","orcid":null,"position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T02:01:42.089235Z","pmid":"39545082","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":[]}