Long-term implant fibrosis prevention in rodents and non-human primates using crystallized drug formulations
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2019-08-01Keywords
Biomedical engineeringDrug delivery
Implants
Translational research
Biochemistry
Biomaterials
Biomedical Devices and Instrumentation
Immunopathology
Immunoprophylaxis and Therapy
Molecular Biology
Therapeutics
Translational Medical Research
Metadata
Show full item recordAbstract
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.Source
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
DOI
10.1038/s41563-019-0377-5Permanent Link to this Item
http://hdl.handle.net/20.500.14038/44398PubMed ID
31235902Notes
Full author list omitted for brevity. For the full list of authors, see article.
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10.1038/s41563-019-0377-5