title: In vivo and in vitro evaluation of hydroxyapatite nanoparticle morphology on the acute inflammatory response.
abstract: Biomedical implants have been widely used in bone repair applications. However, nanosized degradation products from these implants could elicit an inflammatory reaction, which may lead to implant failure. It is well known that the size, chemistry, and charge of these nanoparticles can modulate this response, but little is known regarding the role that the particle's morphology plays in inducing inflammation. The present study aims to investigate the effect of hydroxyapatite nanoparticle (HANPs) morphology on inflammation, in-vitro and in-vivo. Four distinct HANP morphologies were fabricated and characterized: long rods, dots, sheets, and fibers. Primary human polymorphonuclear cells (PMNCs), mononuclear cells (MNCs), and human dermal fibroblasts (hDFs) were exposed to HANPs and alterations in cell viability, morphology, apoptotic activity, and reactive oxygen species (ROS) production were evaluated, in vitro. PMNCs and hDFs experienced a 2-fold decrease in viability following exposure to fibers, while MNC viability decreased 5-fold after treatment with the dots. Additionally, the fibers stimulated an elevated ROS response in both PMNCs and MNCs, and the largest apoptotic behavior for all cell types. Furthermore, exposure to fibers and dots resulted in greater capsule thickness when implanted subcutaneously in mice. Collectively, these results suggest that nanoparticle morphology can significantly impact the inflammatory response.
authors.affiliation: Applied Material Science, Department of Engineering Sciences, The Ångström Laboratory, Uppsala University, SE-751 21, Uppsala, Sweden.
authors.forename: Shiuli
authors.initials: S
authors.lastname: Pujari-Palmer
authors.affiliation: Applied Material Science, Department of Engineering Sciences, The Ångström Laboratory, Uppsala University, SE-751 21, Uppsala, Sweden.
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Physics, University of Oslo, Oslo, Norway.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rubino
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, Arlington, TX, 76019-0138, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Weng
authors.affiliation: Applied Material Science, Department of Engineering Sciences, The Ångström Laboratory, Uppsala University, SE-751 21, Uppsala, Sweden.
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.affiliation: Applied Material Science, Department of Engineering Sciences, The Ångström Laboratory, Uppsala University, SE-751 21, Uppsala, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Engqvist
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, Arlington, TX, 76019-0138, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Tang
authors.affiliation: Applied Material Science, Department of Engineering Sciences, The Ångström Laboratory, Uppsala University, SE-751 21, Uppsala, Sweden. Electronic address: marjam.ott@angstrom.uu.se.
authors.forename: Marjam Karlsson
authors.initials: MK
authors.lastname: Ott
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000276:immunology; D002470:Cell Survival; D002478:Cells, Cultured; D017886:Durapatite / Q000009:adverse effects* / Q000276:immunology; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008297:Male; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000009:adverse effects* / Q000648:ultrastructure*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology
chemical_list: D017382:Reactive Oxygen Species; D017886:Durapatite; D020169:Caspases
keywords: Hydroxyapatite nanoparticles; In vivo; Mononuclear cells; Morphology; Polymorphonuclear cells; Reactive oxygen species