# Magnetically propelled microwheels for rapid thrombolysis in small arteries

> **NIH NIH R01** · COLORADO SCHOOL OF MINES · 2021 · $495,794

## Abstract

Project Summary: In small vessel stroke (SVS), which accounts for 20% of ischemic strokes, tissue
plasminogen activator (tPA) is ineffective because it can take a prohibitively long time to diffuse to the clot, and
catheter-based thrombectomy devices cannot access small vessels. Moreover, treatment associated
hemorrhaging limits tPA use to within a few hours of the onset of symptoms for all ischemic strokes. As a
result, there is an urgent need for strategies that overcome these limitations, particularly in SVS, while reducing
the risks associated with tPA. Building on a successful previous work, a drug delivery strategy is proposed that
can selectively target small artery occlusions and deliver mechanical force to accelerate thrombolysis. The
objective of this proposal is to investigate and test within realistic models an approach where injected,
dispersed magnetic beads are assembled into blood cell sized microwheels (µwheels) capable of targeting
occlusive clots located in small vessels and lysing them with a combination of mechanical and biochemical
action. The central hypothesis is that µwheels can (i) target occluded small arteries by exploiting the low flow
regions at the entrance of these vessels, (ii) achieve reperfusion at rates an order-of-magnitude faster than
soluble tPA, and (iii) improve outcomes in murine models of stroke. This hypothesis will be tested with the
following specific aims: Aim 1. Identify magnetic field conditions for µwheels targeting of occlusions. µWheels
will be assembled in flowing blood and directed to occluded channels or vessels. Microfluidic, zebrafish, and
3D human cerebrovascular models will be used to test the assembly and targeting. Aim 2. Determine rates for
thrombolysis of occlusive thrombi using tPA functionalized µwheels. It is postulated that tPA functionalized
µwheels can dissolve fibrin- and platelet-rich clots within microfluidic models and achieve reperfusion in
zebrafish and 3D human cerebrovascular models, at rates significantly faster than soluble tPA. Aim 3. Measure
the functional benefit of µwheel thrombolysis in vivo. In comparison to soluble tPA, µwheel mediated
thrombolysis will improve safety, motor, and neurological outcomes in murine stroke models and can be
visualized using high-resolution MRI and micro-CT. In Aims 1 and 2 the expected outcomes are identifying the
operating conditions for µwheel assembly, targeting, and fibrinolysis that provide faster reperfusion compared
to tPA and can be scaled-up to human-size vascular networks. In Aim 3, it will be shown that µwheel
thrombolysis is a superior strategy to systemic administration of tPA in terms of neurobehavioral outcomes in a
stroke model and can be imaged in vivo. This approach is significant because it could lead to the development
of a more rapid and less invasive strategy for alleviating ischemia than methods currently available. This
approach is innovative because of the use of external magnetic fields to propel fibrinolyti...

## Key facts

- **NIH application ID:** 10135155
- **Project number:** 5R01NS102465-04
- **Recipient organization:** COLORADO SCHOOL OF MINES
- **Principal Investigator:** DAVID WM MARR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $495,794
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135155

## Citation

> US National Institutes of Health, RePORTER application 10135155, Magnetically propelled microwheels for rapid thrombolysis in small arteries (5R01NS102465-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135155. Licensed CC0.

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