Long-term implant fibrosis prevention in rodents and non-human primates using crystallized drug formulations
dc.contributor.author | Farah, Shady | |
dc.contributor.author | Greiner, Dale L. | |
dc.contributor.author | Anderson, Daniel G. | |
dc.date | 2022-08-11T08:10:18.000 | |
dc.date.accessioned | 2022-08-23T17:03:19Z | |
dc.date.available | 2022-08-23T17:03:19Z | |
dc.date.issued | 2019-08-01 | |
dc.date.submitted | 2019-10-07 | |
dc.identifier.citation | <p>Nat Mater. 2019 Aug;18(8):892-904. doi: 10.1038/s41563-019-0377-5. Epub 2019 Jun 24. <a href="https://doi.org/10.1038/s41563-019-0377-5">Link to article on publisher's site</a></p> | |
dc.identifier.issn | 1476-1122 (Linking) | |
dc.identifier.doi | 10.1038/s41563-019-0377-5 | |
dc.identifier.pmid | 31235902 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/44398 | |
dc.description | <p>Full author list omitted for brevity. For the full list of authors, see article.</p> | |
dc.description.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. | |
dc.language.iso | en_US | |
dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31235902&dopt=Abstract">Link to Article in PubMed</a></p> | |
dc.relation.url | https://doi.org/10.1038/s41563-019-0377-5 | |
dc.subject | Biomedical engineering | |
dc.subject | Drug delivery | |
dc.subject | Implants | |
dc.subject | Translational research | |
dc.subject | Biochemistry | |
dc.subject | Biomaterials | |
dc.subject | Biomedical Devices and Instrumentation | |
dc.subject | Immunopathology | |
dc.subject | Immunoprophylaxis and Therapy | |
dc.subject | Molecular Biology | |
dc.subject | Therapeutics | |
dc.subject | Translational Medical Research | |
dc.title | Long-term implant fibrosis prevention in rodents and non-human primates using crystallized drug formulations | |
dc.type | Journal Article | |
dc.source.journaltitle | Nature materials | |
dc.source.volume | 18 | |
dc.source.issue | 8 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/pmm_pp/132 | |
dc.identifier.contextkey | 15503632 | |
html.description.abstract | <p>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.</p> | |
dc.identifier.submissionpath | pmm_pp/132 | |
dc.contributor.department | Program in Molecular Medicine | |
dc.source.pages | 892-904 |