Influence of degradation on inflammatory profile of polyphosphazene coated PMMA and trisacryl gelatin microspheres in a sheep uterine artery embolization model
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- 作者：Valentin Verret ; Michel Wassef ; Jean-Pierre Pelage ; Saï ; da H. Ghegediban ; Luc Jouneau ; Laurence Moine ; Denis Labarre ; Jafar Golzarian ; Isabelle Schwartz-Cornil ; Alex ; re Laurent
- 关键词：Embolization ; Inflammation ; Foreign body response ; Degradation ; Gene expression
- 刊名：Biomaterials
- 出版年：2011
- 出版时间：January 2011
- 年：2011
- 卷：32
- 期：2
- 页码：339-351
- 全文大小：1739 K
文摘
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.