Mater. Res. Soc. Symp. Proc. Vol. 1718 © 2015 Materials Research Society DOI: 10.1557/opl.2015.490
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`î 7KHVXUIDFHZHWWDELOLW\RIVFDIIROGVZDVVWXGLHGXVLQJVWDWLFFRQWDFWDQJOHWHVWLQJ6DPSOHVZHUH PRXQWHGRQJODVVVOLGHVLQD.H\HQFH9+;GLJLWDOPLFURVFRSHDQGZHUHZHWWHGZLWKDʅ/ GURSRIZDWHU$IWHUVWKHLQQHU DQJOHEHWZHHQWKHVFDIIROGVXUIDFHDQGHGJHRIWKHZDWHU GURSOHWZDVPHDVXUHG7KHVWDELOLW\RIWKH+%FRDWLQJLQDTXHRXVHQYLURQPHQWVZDVVWXGLHGE\ VWDLQLQJVFDIIROGVZLWKSLFURVLULXVUHG365 DQGDJLQJWKHPLQ3%6>@)LQDOO\KXPDQ XPELOLFDOYHLQHQGRWKHOLDOFHOOV+89(&V ZHUHFXOWXUHGîFHOOVFP RQWRWKHVFDIIROGVWR VWXG\WKHHIIHFWRIFRDWLQJRQFHOOVFDIIROGLQWHUDFWLRQ
80
5(68/76$1'',6&866,21 3&/3*&
[('&
6(0PLFURJUDSKV)LJXUH ZHUH DQDO\]HGWRGHWHUPLQHWKHILEHU GLDPHWHUGLVWULEXWLRQDQGVWXG\WKH ILEHUPRUSKRORJ\RI3&/3*& ELRK\EULGDQGFURVVOLQNHG VFDIIROGV7KHILEHUGLDPHWHU GLVWULEXWLRQVRIWKHVFDIIROGVDUH VKRZQLQ)LJXUH7KHPDMRULW\RI ILEHUVLQ3&/3*&VFDIIROGVZHUH IRXQGWRKDYHGLDPHWHUVLQWKH UDQJHRI±ʅPWKLV PDWFKHVWKHGLDPHWHUVRIFROODJHQ ILEHUVLQWKHQDWLYHH[WUDFHOOXODU PDWUL[±QPGLDPHWHU &RDWLQJZLWK+%LQFUHDVHGWKH GLDPHWHUVRIILEHUVWKHPDMRULW\RI ILEHUVKDYHGLDPHWHUVLQWKHUDQJH RI±ʅP
%LRK\EULG
[*HQLSLQ
('&FURVVOLQNLQJIXUWKHULQFUHDVHGILEHU GLDPHWHULQWKHUDQJHRI±ʅP 7KHDSSDUHQWGHQVLW\RIVFDIIROGVDQGWKH GHQVLW\RIEXON3&/3*&ZHUHXVHGWR REWDLQWKHHVWLPDWHGSRURVLW\RIVDPSOHV 7DEOH, (IIHFWRIFURVVOLQNLQJRQWKH VXUIDFHZHWWDELOLW\DQGK\GUDWLRQZHUH IXUWKHUVWXGLHGE\PHDVXULQJWKHZDWHU FRQWDFWDQJOHDQGWKH3%6XSWDNHRI VFDIIROGVDIWHUK\GUDWLRQIRUK7DEOH, ,QWKHFDVHRISRURXVVFDIIROGVWKH3%6 XSWDNHYDOXHLVWKHUHVXOWRILQWUXVLRQRI 3%6LQWKHVFDIIROGSRUHYROXPHDQGEXON DEVRUSWLRQE\WKHSRO\PHU 7DEOH,3RURVLW\WKHUPDODQGK\GUDWLRQHIIHFWV 6DPSOH 3&/3*& %LRK\EULG ('&FURVVOLQNHG *SFURVVOLQNHG
3RURVLW\
&RQWDFW$QJOH GHJUHH
81
3%68SWDNH ZW
0HOW(QWKDOS\ -J
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î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
83
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iomater. Appl. >@ 433KDP86KDUPDDQG$*0LNRVTissue Eng. >@ ;=KDQJ97KRPDV@ &3%DUQHV&:3HPEOH''%UDQG'*6LPSVRQDQG*/%RZOLQTissue Eng. >@ 0()URKEHUJK$.DWVPDQ*3%RWWD3/D]DURYLFL&/6FKDXHU8*:HJVW, DQG3,/HONHVBiomaterials >@ .=KDQJ@ $2*HH%0%DNHU$06LOYHUVWHLQ*0RQWHUR-/(VWHUKDLDQG5/0DXFN Cell Tissue Res.
84