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Griffin, Marissa

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Griffin, Marissa

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    Long-Term Implant Fibrosis Prevention in Rodents and Non-Human Primates Using Localized Deliverable Crystals
    (Nature Publishing Group, 2019-06-24) Farah, Shady; Doloff, Joshua; Han, Hye Jung; Olafson, Katy; McAvoy, Malia; Graham, Adam; Langer, Robert; Anderson, Daniel; Sadraei, Atieh; Vyas, Keval; Tam, Hok Hei; Holliser-Locke, Jennifer; Kowalski, Piotr; Griffin, Marissa; Ashley, Meng; McGarrigle, James; Oberholzer, Jose; Weir, Gordon; Greiner, Dale
    Implantable medical devices have revolutionized modern medicine. However, immune-mediated foreign body response (FBR) to the materials of these devices can limit their function or even induce failure. Here we describe long-term controlled release formulations for local anti-inflammatory release through the development of compact, solvent-free crystals. The compact lattice structure of these crystals allows for very slow, surface dissolution and high drug density. These formulations suppress FBR in both rodents and non-human primates for at least 1.3 years and 6 months, respectively. Formulations inhibited fibrosis across multiple implant sites—subcutaneous, intraperitoneal and intramuscular. In particular incorporation of GW2580, a Colony Stimulating Factor 1 Receptor (CSF1R) inhibitor, into a range of devices including human islet microencapsulation systems, electrode-based continuous glucose-sensing monitors and muscle-stimulating devices, inhibits fibrosis, thereby allowing for extended function. We believe that local, long-term controlled release with the crystal formulations described here enhances and extends function in a range of medical devices and provides a generalized solution to the local immune response to implanted biomaterials.