Comprehensive genetic analysis of early host body reactions to the bioactive and bio-inert porous scaffolds.
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)-1β and IL-10 are important cytokines in tissue responses to biomaterials because IL-1β promotes both inflammation and wound healing and IL-10 suppresses both of them. IL-1β 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.
Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan ; Core Research Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan.
Tomo
T
Ehashi
Nanotechnology Innovation Station, National Institute for Materials Science, Ibaraki, Japan.
Taro
T
Takemura
Nanotechnology Innovation Station, National Institute for Materials Science, Ibaraki, Japan.
Nobutaka
N
Hanagata
Nanotechnology Innovation Station, National Institute for Materials Science, Ibaraki, Japan.
Takashi
T
Minowa
Biomaterials Center, National Institute for Materials Science, Ibaraki, Japan.
Hisatoshi
H
Kobayashi
Department of Materials Engineering and Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan.
Kazuhiko
K
Ishihara
Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan ; Core Research Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan.
Tetsuji
T
Yamaoka
D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects* / Q000737:chemistry; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000009:adverse effects* / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008422:Materials Testing / Q000379:methods*; D008689:Methacrylates / Q000009:adverse effects* / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010767:Phosphorylcholine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry; D020959:Polyethylene / Q000737:chemistry; D016062:Porosity; D013499:Surface Properties; D013997:Time Factors; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000009:adverse effects* / Q000737:chemistry
D001672:Biocompatible Materials; D008689:Methacrylates; D010767:Phosphorylcholine; C079200:poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate); D020959:Polyethylene; D003094:Collagen