title: Influence of degradation on inflammatory profile of polyphosphazene coated PMMA and trisacryl gelatin microspheres in a sheep uterine artery embolization model.
abstract: Embolization with microspheres is widely applied to treat uterine fibroids. However, the foreign body reaction that could result from the degradation of the microspheres remains to be evaluated to adequately appreciate the tissular tolerance to such biomaterials. We compared herein the in situ degradation of PMMA microspheres coated with polyphosphazene (PMMA-PPms) and trisacryl gelatin microspheres (TGms) and we thoroughly investigated the induced local inflammatory responses, at 1 and 4 weeks after uterine artery embolization in sheep, by using immunohistochemistry and microarray analyses. PMMA-PPms underwent an acute and partial degradation that was associated with the early recruitment of phagocytic cells (CD172a+ and MHCII+), and with the up-regulated expression of genes involved in the movement of phagocytes (ALOX5AP, CXCL2, CXCL5, IL8, PTGS2, YARS). By contrast, TGms were not degraded and triggered a different inflammation profile including the recruitment of FBR Giant Cells and T-lymphocytes (CD4+) and the increased expression of genes involved in lymphocyte activation (CXCL10, IL2RG, IRAK4, MALT1). Our results indicate that, in contrast to a non-degradable microsphere such as TGms which is associated to a poorly inflammatory foreign body reaction that rapidly resolves, PMMA-PPms, which is partially degradable, rapidly recruits and activates inflammatory phagocytes, thus delaying the resolution of the foreign body reaction.
authors.affiliation: ArchimMed, ParisBiotech, 24 rue du Faubourg Saint-Jacques, Paris, France.
authors.forename: Valentin
authors.initials: V
authors.lastname: Verret
authors.forename: Michel
authors.initials: M
authors.lastname: Wassef
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pelage
authors.forename: Saïda H
authors.initials: SH
authors.lastname: Ghegediban
authors.forename: Luc
authors.initials: L
authors.lastname: Jouneau
authors.forename: Laurence
authors.initials: L
authors.lastname: Moine
authors.forename: Denis
authors.initials: D
authors.lastname: Labarre
authors.forename: Jafar
authors.initials: J
authors.lastname: Golzarian
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schwartz-Cornil
authors.forename: Alexandre
authors.initials: A
authors.lastname: Laurent
mesh_terms: D000180:Acrylic Resins; D000818:Animals; D005260:Female; D005549:Foreign-Body Reaction / Q000139:chemically induced / Q000276:immunology; D005780:Gelatin / Q000276:immunology*; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000628:therapy; D022423:Myeloid Cells / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000276:immunology*; D010586:Phagocytes / Q000378:metabolism; D011108:Polymers / Q000737:chemistry*; D019904:Polymethyl Methacrylate / Q000737:chemistry / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D055357:Uterine Artery Embolization / Q000379:methods*
chemical_list: D000180:Acrylic Resins; D009943:Organophosphorus Compounds; D011108:Polymers; C108974:poly(phosphazene); C496735:trisacryl gelatin microspheres; D005780:Gelatin; D019904:Polymethyl Methacrylate