{"doi":"10.1002/btm2.70012","title":"Micrometer‐scale <scp>tPA</scp> beads amplify plasmin generation for enhanced thrombolytic therapy","abstract":"Rapid restoration of blood flow is critical in treating acute ischemic stroke. Current thrombolytic therapies using tissue plasminogen activator (tPA) are limited by low recanalization rates and risks of off-target bleeding. Here, we demonstrate that a remarkably simple adjustment-using micrometer-scale rather than sub-micrometer particles to immobilize tPA-fundamentally improves thrombolysis. By merely increasing the particle diameter from 0.1 to 1.0 μm, we achieve a dramatic shift in lysis dynamics: 1.0 μm tPA-beads generate higher plasmin flux, readily overcome antiplasmin inhibition, and trigger a self-propagating cascade of fibrinolysis. This leads to near-complete clot dissolution at tPA doses nearly 100-fold lower than standard free tPA, both in vitro and in a murine model of acute ischemic stroke. Within minutes, low-dose 1.0 μm tPA beads fully restore blood flow, outperforming conventional therapies. Our results show that simply scaling up particle size can resolve kinetic and transport barriers in thrombolysis, offering a promising advancement in stroke treatment with potential applications in other thrombotic disorders.","journal":"Bioengineering & Translational Medicine","year":2025,"id":540614,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9423,"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":1002377,"name":"Fabrice Dabertrand","orcid":"0000-0003-2541-9185","position":1,"is_corresponding":false},{"id":345716,"name":"Nidia Quillinan","orcid":"0000-0002-5708-8395","position":2,"is_corresponding":false},{"id":877414,"name":"Enming J. Su","orcid":"0000-0002-7781-5924","position":3,"is_corresponding":false},{"id":316366,"name":"Daniel A. Lawrence","orcid":"0000-0003-3126-1935","position":4,"is_corresponding":false},{"id":307003,"name":"David W. M. Marr","orcid":"0000-0002-6820-761X","position":5,"is_corresponding":false},{"id":325873,"name":"Keith B. Neeves","orcid":"0000-0001-7546-4588","position":6,"is_corresponding":false},{"id":738817,"name":"Matthew J. Osmond","orcid":"0000-0002-4778-9067","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T02:52:38.861025Z","pmid":"40708974","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":[]}