ArticleJournal of thrombosis and haemostasis : JTH2022
Breaking the fibrinolytic speed limit with microwheel co-delivery of tissue plasminogen activator and plasminogen.
Article in Journal of thrombosis and haemostasis : JTH, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Plasminogen supplementation enhances alteplase fibrinolysis efficacy in a systemic embolization rat model.Journal of thrombosis and thrombolysis · 2026Article
- Optimized TELIP, an Echogenic Liposomal Nano-Carrier Loaded with Alteplase for Preclinical Studies.Pharmaceutics · 2026Article
- Thermally assisted microbot transport through high-viscosity media.Scientific reports · 2025Article
- Smart magnetic nanoparticles under electromagnetic stimulation: a synergistic approach to targeted chemotherapy and hyperthermia.Nanomedicine (London, England) · 2025Review
- Micrometer-scale tPA beads amplify plasmin generation for enhanced thrombolytic therapy.Bioengineering & translational medicine · 2025Article
- Bioprinted Micro-Clots for Kinetic Analysis of Endothelial Cell-Mediated Fibrinolysis.Advanced healthcare materials · 2025Article
- Emerging Elastic Micro-Nano Materials for Diagnosis and Treatment of Thrombosis.Research (Washington, D.C.) · 2025Review
- Magnetically powered microwheel thrombolysis of occlusive thrombi in zebrafish.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Advances in smart delivery of magnetic field-targeted drugs in cardiovascular diseases.Drug delivery · 2023Review
- Coupling magnetic torque and force for colloidal microbot assembly and manipulation.Advanced intelligent systems (Weinheim an der Bergstrasse, Germany) · 2023Article
- Magnetically Powered Microwheel Thrombolysis of Occlusive Thrombi in Zebrafish.bioRxiv : the preprint server for biology · 2023Article
- Fibrinolytic system and COVID-19: From an innovative view of epithelial ion transport.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Review
- Article
- Fibrinolysis: an illustrated review.Research and practice in thrombosis and haemostasis · 2023Review
- An aquatic microrobot for microscale flow manipulation.Scientific reports · 2022Article
- "Going with the flow" in modeling fibrinolysis.Frontiers in cardiovascular medicine · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTo reestablish blood flow in vessels occluded by clots, tissue plasminogen activator (tPA) can be used; however, its efficacy is limited by transport to and into a clot and by the depletion of its substrate, plasminogen.
objectivesTo overcome these rate limitations, a platform was designed to co-deliver tPA and plasminogen based on microwheels (µwheels), wheel-like assemblies of superparamagnetic colloidal beads that roll along surfaces at high speeds.
methodsThe biochemical speed limit was determined by measuring fibrinolysis of plasma clots at varying concentrations of tPA (10-800 nM) and plasminogen (1-6 µM). Biotinylated magnetic mesoporous silica nanoparticles were synthesized and bound to streptavidin-coated superparamagnetic beads to make studded beads. Studded beads were loaded with plasminogen and tPA was immobilized on their surface. Plasminogen release and tPA activity were measured on the studded beads. Studded beads were assembled into µwheels with rotating magnetic fields and fibrinolysis of plasma clots was measured in a microfluidic device.
resultsThe biochemical speed limit for plasma clots was ~15 µm/min. Plasminogen-loaded, tPA-immobilized µwheels lyse plasma clots at rates comparableto the biochemical speed limit. With the addition of a corkscrew motion, µwheels penetrate clots, thereby exceeding the biochemical speed limit (~20 µm/min) and achieving lysis rates 40-fold higher than 50 nM tPA.
conclusionsCo-delivery of an immobilized enzyme and its substrate via a microbot capable of mechanical work has the potential to target and rapidly lyse clots that are inaccessible by mechanical thrombectomy devices or recalcitrant to systemic tPA delivery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.