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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)892-904
Number of pages13
JournalNature Materials
Volume18
Issue number8
DOIs
StatePublished - Aug 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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