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    Long-term implant fibrosis prevention in rodents and non-human primates using crystallized drug formulations

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    Authors
    Farah, Shady
    Greiner, Dale L.
    Anderson, Daniel G.
    UMass Chan Affiliations
    Program in Molecular Medicine
    Document Type
    Journal Article
    Publication Date
    2019-08-01
    Keywords
    Biomedical engineering
    Drug delivery
    Implants
    Translational research
    Biochemistry
    Biomaterials
    Biomedical Devices and Instrumentation
    Immunopathology
    Immunoprophylaxis and Therapy
    Molecular Biology
    Therapeutics
    Translational Medical Research
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    Link to Full Text
    https://doi.org/10.1038/s41563-019-0377-5
    Abstract
    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 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.
    Source

    Nat Mater. 2019 Aug;18(8):892-904. doi: 10.1038/s41563-019-0377-5. Epub 2019 Jun 24. Link to article on publisher's site

    DOI
    10.1038/s41563-019-0377-5
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/44398
    PubMed ID
    31235902
    Notes

    Full author list omitted for brevity. For the full list of authors, see article.

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    ae974a485f413a2113503eed53cd6c53
    10.1038/s41563-019-0377-5
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