Comprehensive Genetic Analysis of Early Host Body Reactions to the Bioactive and Bio-Inert Porous Scaffolds

被引:15
作者
Ehashi, Tomo [1 ,2 ]
Takemura, Taro [3 ]
Hanagata, Nobutaka [3 ]
Minowa, Takashi [3 ]
Kobayashi, Hisatoshi [4 ]
Ishihara, Kazuhiko [5 ,6 ]
Yamaoka, Tetsuji [1 ,2 ]
机构
[1] Natl Cerebral & Cardiovasc Ctr Res Inst, Dept Biomed Engn, Osaka, Japan
[2] Japan Sci & Technol Agcy, CREST, Tokyo, Japan
[3] Natl Inst Mat Sci, Nanotechnol Innovat Stn, Ibaraki, Japan
[4] Natl Inst Mat Sci, Biomat Ctr, Ibaraki, Japan
[5] Univ Tokyo, Dept Mat Engn, Sch Engn, Tokyo, Japan
[6] Univ Tokyo, Sch Engn, Dept Bioengn, Tokyo, Japan
关键词
IN-VIVO; MACROPHAGE ACTIVATION; PHOSPHOLIPID POLYMERS; ADHERENT CELLS; TISSUE; ANGIOGENESIS; EXPRESSION; IMPLANT; BIOMATERIALS; ADHESION;
D O I
10.1371/journal.pone.0085132
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
To design scaffolds for tissue regeneration, details of the host body reaction to the scaffolds must be studied. Host body reactions have been investigated mainly by immunohistological observations for a long time. Despite of recent dramatic development in genetic analysis technologies, genetically comprehensive changes in host body reactions are hardly studied. There is no information about host body reactions that can predict successful tissue regeneration in the future. In the present study, porous polyethylene scaffolds were coated with bioactive collagen or bio-inert poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) and were implanted subcutaneously and compared the host body reaction to those substrates by normalizing the result using control non-coat polyethylene scaffold. The comprehensive analyses of early host body reactions to the scaffolds were carried out using a DNA microarray assay. Within numerous genes which were expressed differently among these scaffolds, particular genes related to inflammation, wound healing, and angiogenesis were focused upon. Interleukin (IL)-1 beta and IL-10 are important cytokines in tissue responses to biomaterials because IL-1 beta promotes both inflammation and wound healing and IL-10 suppresses both of them. IL-1 beta was up-regulated in the collagen-coated scaffold. Collagen-specifically up-regulated genes contained both M1-and M2-macrophage- related genes. Marked vessel formation in the collagen-coated scaffold was occurred in accordance with the up-regulation of many angiogenesis-inducible factors. The DNA microarray assay provided global information regarding the host body reaction. Interestingly, several up-regulated genes were detected even on the very bio-inert PMB-coated surfaces and those genes include inflammation-suppressive and wound healing-suppressive IL-10, suggesting that not only active tissue response but also the inert response may relates to these genetic regulations.
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页数:11
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