title: Minimally invasive, longitudinal monitoring of biomaterial-associated inflammation by fluorescence imaging.
abstract: Implant-associated inflammation is a major cause for the reduced performance/lifetime and failure of numerous medical devices. Therefore, the ability to non-invasively and quantitatively monitor implant-associated inflammation is critically important. Here we show that implant-associated inflammation can be imaged via fluorescence imaging using near-infrared hydrocyanine dyes delivered either locally or intravenously in living mice. This imaging strategy allowed quantitative longitudinal monitoring of inflammation by detecting reactive oxygen species (ROS) released by inflammatory cells in response to implanted poly(ethylene terephthalate) (PET) disks or injected poly (lactic-co-glycolic acid) (PLGA) microparticles, and exhibited a strong correlation to conventional analysis of inflammation. Furthermore, modulation of inflammatory responses via controlled release of the anti-inflammatory agent dexamethasone was detected using this sensitive imaging approach. Thus, hydrocyanine-based fluorescence imaging of ROS could serve as a surrogate measure for monitoring implant-associated inflammation as well as evaluating the efficacy of therapeutic approaches to modulate host responses to implanted medical devices.
authors.affiliation: Petit Institute for Bioengineering and Bioscience, Atlanta, GA 30332, USA.
authors.forename: Shivaram
authors.initials: S
authors.lastname: Selvam
authors.forename: Kousik
authors.initials: K
authors.lastname: Kundu
authors.forename: Kellie L
authors.initials: KL
authors.lastname: Templeman
authors.forename: Niren
authors.initials: N
authors.lastname: Murthy
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: García
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects*; D003907:Dexamethasone / Q000494:pharmacology; D005453:Fluorescence; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007150:Immunohistochemistry; D020007:Implants, Experimental / Q000009:adverse effects; D007208:Indocyanine Green / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000209:etiology* / Q000473:pathology*; D019344:Lactic Acid / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008863:Microspheres; D009504:Neutrophils / Q000187:drug effects; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017382:Reactive Oxygen Species / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared
chemical_list: D001672:Biocompatible Materials; D017382:Reactive Oxygen Species; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone; D007208:Indocyanine Green