Long-Term Implant Fibrosis Prevention in Rodents and Non-Human Primates Using Localized Deliverable Crystals
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Han, Hye Jung
Tam, Hok Hei
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CitationFarah, Shady, Joshua Doloff, Peter Müller, Atieh Sadraei, Katy Olafson, Keval Vyas, Hok Tam, Jennifer Hollister-Lock, Piotr Kowalski, Marissa Griffin, Ashley Meng, Malia McAvoy, Adam Graham, James McGarrigle, Jose Oberholzer, Gordon Weir, Dale Greiner, Robert Langer, and Daniel Anderson. 2019. Long-term Implant Fibrosis Prevention in Rodents and Non-human Primates Using Crystallized Drug Formulations. Nature Materials 18, no. 8: 892-904.
AbstractImplantable 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.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37374255
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