Long-term implant fibrosis prevention in rodents and non-human primates using crystallized drug formulations
UMass Chan AffiliationsProgram in Molecular Medicine
Document TypeJournal Article
Biomedical Devices and Instrumentation
Immunoprophylaxis and Therapy
Translational Medical Research
MetadataShow full item record
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 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.
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
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/44398
Full author list omitted for brevity. For the full list of authors, see article.