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Macrophage-hitchhiking Anisotropic Microparticles for Diagnostic Applications
Immune cells have gained significant attention owing to their inflammation-homing ability as well as inherently critical roles in disease progression and tissue regeneration. The prosperity of immune cell-based therapies in the clinic has fueled the efforts in immune cell engineering. Material-assisted cellular platforms (MACP), marrying the strengths of biomaterials and leukocytes, become a new pillar of immune cell engineering and possess the potential to be used for both therapeutic and diagnostic applications.
Here, we present a novel MACP – cellular backpacks, composed of anisotropic microparticles (also called “backpacks”) and inflammation-homing macrophages for diagnosis of mild traumatic brain injury (mTBI), a brain disorder that is significantly underdiagnosed in the current clinical settings. Given that circulating immune cells are likely to infiltrate across the perturbed brain barriers after trauma, we hypothesized that imaging of cellular backpack infiltration into the brain can potentially offer a new sensitive imaging modality for mTBI diagnosis.
Backpacks are hydrogel-based micro-disks, which bind to macrophages yet resist phagocytosis due to their anisotropic morphology, enabling stable loading of MRI contrast agent (i.e., gadolinium (Gd(III)), on the cell surface. Studies in a porcine mTBI model confirm that cellular backpacks provide a differential signal in injured brains, while clinical comparator Gadavist® cannot even at Gd(III) doses 500-1000-fold higher than those used in cellular backpacks. This MACP takes advantage of inflammation-homing capability of macrophages and enables stable loading of therapeutic and imaging agents in the extracellular space, paving the way for a myriad of applications in the body.
Thesis Supervisor:
Samir Mitragotri, PhD
Hiller Professor of Bioengineering at the John A. Paulson School of Engineering and Applied Sciences, Harvard University
Thesis Committee Chair:
Sangeeta Bhatia, MD, PhD
John J. and Dorothy Wilson Professor at the Electrical Engineering & Computer Science and Institute for Medical Engineering & Science, MIT
Thesis Readers:
David J. Mooney, PhD
Robert P. Pinkas Family Professor of Bioengineering at the John A. Paulson School of Engineering and Applied Sciences, Harvard University
Jeffrey Karp, PhD
Professor, Anaesthesia, Brigham and Women’s Hospital and Harvard Medical School
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Topic: Lily Wang’s PhD Thesis Defense
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