Title

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

UMMS Affiliation

Program in Molecular Medicine

Publication Date

2019-08-01

Document Type

Article

Disciplines

Biochemistry | Biomaterials | Biomedical Devices and Instrumentation | Immunopathology | Immunoprophylaxis and Therapy | Molecular Biology | Therapeutics | Translational Medical Research

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.

Keywords

Biomedical engineering, Drug delivery, Implants, Translational research

DOI of Published Version

10.1038/s41563-019-0377-5

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

Journal/Book/Conference Title

Nature materials

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

31235902

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