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

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ID: 1893
2019
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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.
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farah2019longtermnature Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Farah, Shady;Doloff, Joshua C;Müller, Peter;Sadraei, Atieh;Han, Hye Jung;Olafson, Katy;Vyas, Keval;Tam, Hok Hei;Hollister-Lock, Jennifer;Kowalski, Piotr S;Griffin, Marissa;Meng, Ashley;McAvoy, Malia;Graham, Adam C;McGarrigle, James;Oberholzer, Jose;Weir, Gordon C;Greiner, Dale L;Langer, Robert;Anderson, Daniel G;
Journal Nature Materials
Year 2019
DOI
10.1038/s41563-019-0377-5
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