Farah, Shady and Doloff, Joshua C and Müller, Peter and Sadraei, Atieh and Han, Hye and Olafson, Katy and Vyas, Keval and Tam, Hok and Hollister-Lock, Jennifer and Kowalski, Piotr S and Griffin, Marissa and Meng, Ashley and McAvoy, Malia and Graham, Adam C and McGarrigle, James and Oberholzer, Jose and Weir, Gordon C and Greiner, Dale L and Langer, Robert and Anderson, Daniel G

2019

January

Nature Materials

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

Validated

Altmetric: 46 ()

18

8

892

904

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.

10.1038/s41563-019-0377-5