{\rtf1\adeflang1025\ansi\ansicpg1252\uc1\adeff31507\deff0\stshfdbch31506\stshfloch31506\stshfhich31506\stshfbi31507\deflang2057\deflangfe2052\themelang2057\themelangfe2052\themelangcs1025{\fonttbl{\f0\fbidi \froman\fcharset0\fprq2{\*\panose 02020603050405020304}Times New Roman;}{\f1\fbidi \fswiss\fcharset0\fprq2{\*\panose 020b0604020202020204}Arial;}
{\f3\fbidi \froman\fcharset2\fprq2{\*\panose 05050102010706020507}Symbol;}{\f13\fbidi \fnil\fcharset134\fprq2{\*\panose 02010600030101010101}SimSun{\*\falt \'cb\'ce\'cc\'e5};}
{\f23\fbidi \fswiss\fcharset222\fprq2{\*\panose 020b0304020202020204}Cordia New;}{\f34\fbidi \froman\fcharset0\fprq2{\*\panose 02040503050406030204}Cambria Math;}{\f37\fbidi \fswiss\fcharset0\fprq2{\*\panose 020f0502020204030204}Calibri;}
{\f44\fbidi \froman\fcharset0\fprq2{\*\panose 00000000000000000000}Times;}{\f45\fbidi \fswiss\fcharset0\fprq2{\*\panose 00000000000000000000}Segoe UI{\*\falt Sylfaen};}{\f46\fbidi \fswiss\fcharset0\fprq2{\*\panose 020b0603020202020204}Trebuchet MS;}
{\f48\fbidi \fnil\fcharset134\fprq2{\*\panose 02010600030101010101}@SimSun;}{\flomajor\f31500\fbidi \froman\fcharset0\fprq2{\*\panose 02020603050405020304}Times New Roman;}
{\fdbmajor\f31501\fbidi \fnil\fcharset134\fprq2{\*\panose 02010600030101010101}SimSun{\*\falt \'cb\'ce\'cc\'e5};}{\fhimajor\f31502\fbidi \fswiss\fcharset0\fprq2{\*\panose 020f0302020204030204}Calibri Light;}
{\fbimajor\f31503\fbidi \froman\fcharset0\fprq2{\*\panose 02020603050405020304}Times New Roman;}{\flominor\f31504\fbidi \froman\fcharset0\fprq2{\*\panose 02020603050405020304}Times New Roman;}
{\fdbminor\f31505\fbidi \fnil\fcharset134\fprq2{\*\panose 02010600030101010101}SimSun{\*\falt \'cb\'ce\'cc\'e5};}{\fhiminor\f31506\fbidi \fswiss\fcharset0\fprq2{\*\panose 020f0502020204030204}Calibri;}
{\fbiminor\f31507\fbidi \fswiss\fcharset0\fprq2{\*\panose 020b0604020202020204}Arial;}{\f49\fbidi \froman\fcharset238\fprq2 Times New Roman CE;}{\f50\fbidi \froman\fcharset204\fprq2 Times New Roman Cyr;}
{\f52\fbidi \froman\fcharset161\fprq2 Times New Roman Greek;}{\f53\fbidi \froman\fcharset162\fprq2 Times New Roman Tur;}{\f54\fbidi \froman\fcharset177\fprq2 Times New Roman (Hebrew);}{\f55\fbidi \froman\fcharset178\fprq2 Times New Roman (Arabic);}
{\f56\fbidi \froman\fcharset186\fprq2 Times New Roman Baltic;}{\f57\fbidi \froman\fcharset163\fprq2 Times New Roman (Vietnamese);}{\f59\fbidi \fswiss\fcharset238\fprq2 Arial CE;}{\f60\fbidi \fswiss\fcharset204\fprq2 Arial Cyr;}
{\f62\fbidi \fswiss\fcharset161\fprq2 Arial Greek;}{\f63\fbidi \fswiss\fcharset162\fprq2 Arial Tur;}{\f64\fbidi \fswiss\fcharset177\fprq2 Arial (Hebrew);}{\f65\fbidi \fswiss\fcharset178\fprq2 Arial (Arabic);}
{\f66\fbidi \fswiss\fcharset186\fprq2 Arial Baltic;}{\f67\fbidi \fswiss\fcharset163\fprq2 Arial (Vietnamese);}{\f181\fbidi \fnil\fcharset0\fprq2 SimSun Western{\*\falt \'cb\'ce\'cc\'e5};}{\f281\fbidi \fswiss\fcharset0\fprq2 Cordia New;}
{\f419\fbidi \fswiss\fcharset238\fprq2 Calibri CE;}{\f420\fbidi \fswiss\fcharset204\fprq2 Calibri Cyr;}{\f422\fbidi \fswiss\fcharset161\fprq2 Calibri Greek;}{\f423\fbidi \fswiss\fcharset162\fprq2 Calibri Tur;}
{\f424\fbidi \fswiss\fcharset177\fprq2 Calibri (Hebrew);}{\f425\fbidi \fswiss\fcharset178\fprq2 Calibri (Arabic);}{\f426\fbidi \fswiss\fcharset186\fprq2 Calibri Baltic;}{\f427\fbidi \fswiss\fcharset163\fprq2 Calibri (Vietnamese);}
{\f489\fbidi \froman\fcharset238\fprq2 Times CE;}{\f490\fbidi \froman\fcharset204\fprq2 Times Cyr;}{\f492\fbidi \froman\fcharset161\fprq2 Times Greek;}{\f493\fbidi \froman\fcharset162\fprq2 Times Tur;}
{\f494\fbidi \froman\fcharset177\fprq2 Times (Hebrew);}{\f495\fbidi \froman\fcharset178\fprq2 Times (Arabic);}{\f496\fbidi \froman\fcharset186\fprq2 Times Baltic;}{\f497\fbidi \froman\fcharset163\fprq2 Times (Vietnamese);}
{\f499\fbidi \fswiss\fcharset238\fprq2 Segoe UI CE{\*\falt Sylfaen};}{\f500\fbidi \fswiss\fcharset204\fprq2 Segoe UI Cyr{\*\falt Sylfaen};}{\f502\fbidi \fswiss\fcharset161\fprq2 Segoe UI Greek{\*\falt Sylfaen};}
{\f503\fbidi \fswiss\fcharset162\fprq2 Segoe UI Tur{\*\falt Sylfaen};}{\f504\fbidi \fswiss\fcharset177\fprq2 Segoe UI (Hebrew){\*\falt Sylfaen};}{\f505\fbidi \fswiss\fcharset178\fprq2 Segoe UI (Arabic){\*\falt Sylfaen};}
{\f506\fbidi \fswiss\fcharset186\fprq2 Segoe UI Baltic{\*\falt Sylfaen};}{\f507\fbidi \fswiss\fcharset163\fprq2 Segoe UI (Vietnamese){\*\falt Sylfaen};}{\f509\fbidi \fswiss\fcharset238\fprq2 Trebuchet MS CE;}
{\f510\fbidi \fswiss\fcharset204\fprq2 Trebuchet MS Cyr;}{\f512\fbidi \fswiss\fcharset161\fprq2 Trebuchet MS Greek;}{\f513\fbidi \fswiss\fcharset162\fprq2 Trebuchet MS Tur;}{\f516\fbidi \fswiss\fcharset186\fprq2 Trebuchet MS Baltic;}
{\f531\fbidi \fnil\fcharset0\fprq2 @SimSun Western;}{\flomajor\f31508\fbidi \froman\fcharset238\fprq2 Times New Roman CE;}{\flomajor\f31509\fbidi \froman\fcharset204\fprq2 Times New Roman Cyr;}
{\flomajor\f31511\fbidi \froman\fcharset161\fprq2 Times New Roman Greek;}{\flomajor\f31512\fbidi \froman\fcharset162\fprq2 Times New Roman Tur;}{\flomajor\f31513\fbidi \froman\fcharset177\fprq2 Times New Roman (Hebrew);}
{\flomajor\f31514\fbidi \froman\fcharset178\fprq2 Times New Roman (Arabic);}{\flomajor\f31515\fbidi \froman\fcharset186\fprq2 Times New Roman Baltic;}{\flomajor\f31516\fbidi \froman\fcharset163\fprq2 Times New Roman (Vietnamese);}
{\fdbmajor\f31520\fbidi \fnil\fcharset0\fprq2 SimSun Western{\*\falt \'cb\'ce\'cc\'e5};}{\fhimajor\f31528\fbidi \fswiss\fcharset238\fprq2 Calibri Light CE;}{\fhimajor\f31529\fbidi \fswiss\fcharset204\fprq2 Calibri Light Cyr;}
{\fhimajor\f31531\fbidi \fswiss\fcharset161\fprq2 Calibri Light Greek;}{\fhimajor\f31532\fbidi \fswiss\fcharset162\fprq2 Calibri Light Tur;}{\fhimajor\f31533\fbidi \fswiss\fcharset177\fprq2 Calibri Light (Hebrew);}
{\fhimajor\f31534\fbidi \fswiss\fcharset178\fprq2 Calibri Light (Arabic);}{\fhimajor\f31535\fbidi \fswiss\fcharset186\fprq2 Calibri Light Baltic;}{\fhimajor\f31536\fbidi \fswiss\fcharset163\fprq2 Calibri Light (Vietnamese);}
{\fbimajor\f31538\fbidi \froman\fcharset238\fprq2 Times New Roman CE;}{\fbimajor\f31539\fbidi \froman\fcharset204\fprq2 Times New Roman Cyr;}{\fbimajor\f31541\fbidi \froman\fcharset161\fprq2 Times New Roman Greek;}
{\fbimajor\f31542\fbidi \froman\fcharset162\fprq2 Times New Roman Tur;}{\fbimajor\f31543\fbidi \froman\fcharset177\fprq2 Times New Roman (Hebrew);}{\fbimajor\f31544\fbidi \froman\fcharset178\fprq2 Times New Roman (Arabic);}
{\fbimajor\f31545\fbidi \froman\fcharset186\fprq2 Times New Roman Baltic;}{\fbimajor\f31546\fbidi \froman\fcharset163\fprq2 Times New Roman (Vietnamese);}{\flominor\f31548\fbidi \froman\fcharset238\fprq2 Times New Roman CE;}
{\flominor\f31549\fbidi \froman\fcharset204\fprq2 Times New Roman Cyr;}{\flominor\f31551\fbidi \froman\fcharset161\fprq2 Times New Roman Greek;}{\flominor\f31552\fbidi \froman\fcharset162\fprq2 Times New Roman Tur;}
{\flominor\f31553\fbidi \froman\fcharset177\fprq2 Times New Roman (Hebrew);}{\flominor\f31554\fbidi \froman\fcharset178\fprq2 Times New Roman (Arabic);}{\flominor\f31555\fbidi \froman\fcharset186\fprq2 Times New Roman Baltic;}
{\flominor\f31556\fbidi \froman\fcharset163\fprq2 Times New Roman (Vietnamese);}{\fdbminor\f31560\fbidi \fnil\fcharset0\fprq2 SimSun Western{\*\falt \'cb\'ce\'cc\'e5};}{\fhiminor\f31568\fbidi \fswiss\fcharset238\fprq2 Calibri CE;}
{\fhiminor\f31569\fbidi \fswiss\fcharset204\fprq2 Calibri Cyr;}{\fhiminor\f31571\fbidi \fswiss\fcharset161\fprq2 Calibri Greek;}{\fhiminor\f31572\fbidi \fswiss\fcharset162\fprq2 Calibri Tur;}
{\fhiminor\f31573\fbidi \fswiss\fcharset177\fprq2 Calibri (Hebrew);}{\fhiminor\f31574\fbidi \fswiss\fcharset178\fprq2 Calibri (Arabic);}{\fhiminor\f31575\fbidi \fswiss\fcharset186\fprq2 Calibri Baltic;}
{\fhiminor\f31576\fbidi \fswiss\fcharset163\fprq2 Calibri (Vietnamese);}{\fbiminor\f31578\fbidi \fswiss\fcharset238\fprq2 Arial CE;}{\fbiminor\f31579\fbidi \fswiss\fcharset204\fprq2 Arial Cyr;}
{\fbiminor\f31581\fbidi \fswiss\fcharset161\fprq2 Arial Greek;}{\fbiminor\f31582\fbidi \fswiss\fcharset162\fprq2 Arial Tur;}{\fbiminor\f31583\fbidi \fswiss\fcharset177\fprq2 Arial (Hebrew);}
{\fbiminor\f31584\fbidi \fswiss\fcharset178\fprq2 Arial (Arabic);}{\fbiminor\f31585\fbidi \fswiss\fcharset186\fprq2 Arial Baltic;}{\fbiminor\f31586\fbidi \fswiss\fcharset163\fprq2 Arial (Vietnamese);}}{\colortbl;\red0\green0\blue0;\red0\green0\blue255;
\red0\green255\blue255;\red0\green255\blue0;\red255\green0\blue255;\red255\green0\blue0;\red255\green255\blue0;\red255\green255\blue255;\red0\green0\blue128;\red0\green128\blue128;\red0\green128\blue0;\red128\green0\blue128;\red128\green0\blue0;
\red128\green128\blue0;\red128\green128\blue128;\red192\green192\blue192;\red0\green0\blue0;\red0\green0\blue0;\caccentone\ctint255\cshade191\red47\green84\blue150;\caccentone\ctint255\cshade127\red31\green55\blue99;
\ctextone\ctint216\cshade255\red39\green39\blue39;\chyperlink\ctint255\cshade255\red5\green99\blue193;\red8\green46\blue255;\red32\green31\blue30;}{\*\defchp \f31506\fs22\lang2057\langfe1033\langfenp1033 }{\*\defpap \ql \li0\ri0\sa160\sl259\slmult1
\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 }\noqfpromote {\stylesheet{\ql \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0
\f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 \snext0 \sqformat \spriority0 \styrsid621002 Normal;}{\s1\ql \fi-432\li432\ri0\sb240\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\outlinelevel0\adjustright\rin0\lin432\itap0
\rtlch\fcs1 \af31503\afs32\alang1025 \ltrch\fcs0 \b\fs28\cf19\lang1033\langfe1033\loch\f31503\hich\af31503\dbch\af31501\cgrid\langnp1033\langfenp1033 \sbasedon0 \snext0 \slink16 \sqformat \spriority9 \styrsid728116 heading 1;}{
\s2\ql \fi-576\li576\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl1\outlinelevel1\adjustright\rin0\lin576\itap0 \rtlch\fcs1 \af31503\afs26\alang1025 \ltrch\fcs0
\b\fs24\lang1033\langfe1033\loch\f1\hich\af1\dbch\af31501\cgrid\langnp1033\langfenp1033 \sbasedon0 \snext0 \slink17 \sunhideused \sqformat \spriority9 \styrsid1775240 heading 2;}{
\s3\ql \fi-720\li720\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl2\outlinelevel2\adjustright\rin0\lin720\itap0 \rtlch\fcs1 \af31503\afs24\alang1025 \ltrch\fcs0
\b\fs24\lang1033\langfe1033\loch\f1\hich\af1\dbch\af31501\cgrid\langnp1033\langfenp1033 \sbasedon0 \snext0 \slink23 \sunhideused \sqformat \spriority9 \styrsid7408068 heading 3;}{
\s4\ql \fi-864\li864\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl3\outlinelevel3\adjustright\rin0\lin864\itap0 \rtlch\fcs1 \ai\af31503\afs24\alang1025 \ltrch\fcs0
\i\fs24\cf19\lang1033\langfe1033\loch\f31502\hich\af31502\dbch\af31501\cgrid\langnp1033\langfenp1033 \sbasedon0 \snext0 \slink37 \ssemihidden \sunhideused \sqformat \spriority9 \styrsid10178777 heading 4;}{
\s5\ql \fi-1008\li1008\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl4\outlinelevel4\adjustright\rin0\lin1008\itap0 \rtlch\fcs1 \af31503\afs24\alang1025 \ltrch\fcs0
\fs24\cf19\lang1033\langfe1033\loch\f31502\hich\af31502\dbch\af31501\cgrid\langnp1033\langfenp1033 \sbasedon0 \snext0 \slink38 \ssemihidden \sunhideused \sqformat \spriority9 \styrsid10178777 heading 5;}{
\s6\ql \fi-1152\li1152\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl5\outlinelevel5\adjustright\rin0\lin1152\itap0 \rtlch\fcs1 \af31503\afs24\alang1025 \ltrch\fcs0
\fs24\cf20\lang1033\langfe1033\loch\f31502\hich\af31502\dbch\af31501\cgrid\langnp1033\langfenp1033 \sbasedon0 \snext0 \slink39 \ssemihidden \sunhideused \sqformat \spriority9 \styrsid10178777 heading 6;}{
\s7\ql \fi-1296\li1296\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl6\outlinelevel6\adjustright\rin0\lin1296\itap0 \rtlch\fcs1 \ai\af31503\afs24\alang1025 \ltrch\fcs0
\i\fs24\cf20\lang1033\langfe1033\loch\f31502\hich\af31502\dbch\af31501\cgrid\langnp1033\langfenp1033 \sbasedon0 \snext0 \slink22 \ssemihidden \sunhideused \sqformat \spriority9 \styrsid7357425 heading 7;}{
\s8\ql \fi-1440\li1440\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl7\outlinelevel7\adjustright\rin0\lin1440\itap0 \rtlch\fcs1 \af31503\afs21\alang1025 \ltrch\fcs0
\fs21\cf21\lang1033\langfe1033\loch\f31502\hich\af31502\dbch\af31501\cgrid\langnp1033\langfenp1033 \sbasedon0 \snext0 \slink40 \ssemihidden \sunhideused \sqformat \spriority9 \styrsid10178777 heading 8;}{
\s9\ql \fi-1584\li1584\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl8\outlinelevel8\adjustright\rin0\lin1584\itap0 \rtlch\fcs1 \ai\af31503\afs21\alang1025 \ltrch\fcs0
\i\fs21\cf21\lang1033\langfe1033\loch\f31502\hich\af31502\dbch\af31501\cgrid\langnp1033\langfenp1033 \sbasedon0 \snext0 \slink41 \ssemihidden \sunhideused \sqformat \spriority9 \styrsid10178777 heading 9;}{\*\cs10 \additive
\ssemihidden \sunhideused \spriority1 Default Paragraph Font;}{\*
\ts11\tsrowd\trftsWidthB3\trpaddl108\trpaddr108\trpaddfl3\trpaddft3\trpaddfb3\trpaddfr3\trcbpat1\trcfpat1\tblind0\tblindtype3\tsvertalt\tsbrdrt\tsbrdrl\tsbrdrb\tsbrdrr\tsbrdrdgl\tsbrdrdgr\tsbrdrh\tsbrdrv \ql \li0\ri0\sa160\sl259\slmult1
\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \rtlch\fcs1 \af31507\afs22\alang1025 \ltrch\fcs0 \f31506\fs22\lang2057\langfe1033\cgrid\langnp2057\langfenp1033 \snext11 \ssemihidden \sunhideused Normal Table;}{
\s15\ql \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f1\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 \snext15 \sqformat \spriority1 \styrsid2899302
No Spacing;}{\*\cs16 \additive \rtlch\fcs1 \af31503\afs32 \ltrch\fcs0 \b\fs32\cf19\lang1033\langfe0\loch\f31503\hich\af31503\dbch\af31501\langnp1033 \sbasedon10 \slink1 \slocked \spriority9 \styrsid728116 Heading 1 Char;}{\*\cs17 \additive \rtlch\fcs1
\af31503\afs26 \ltrch\fcs0 \b\fs26\lang1033\langfe0\loch\f1\hich\af1\dbch\af31501\langnp1033 \sbasedon10 \slink2 \slocked \spriority9 \styrsid1775240 Heading 2 Char;}{
\s18\ql \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \rtlch\fcs1 \af45\afs18\alang1025 \ltrch\fcs0 \f45\fs18\lang1033\langfe1033\cgrid\langnp1033\langfenp1033
\sbasedon0 \snext18 \slink19 \ssemihidden \sunhideused \styrsid4204766 Balloon Text;}{\*\cs19 \additive \rtlch\fcs1 \af45\afs18 \ltrch\fcs0 \f45\fs18\lang1033\langfe0\langnp1033 \sbasedon10 \slink18 \slocked \ssemihidden \styrsid4204766
Balloon Text Char;}{\s20\qj \li1890\ri0\sb240\sa360\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin1890\itap0\contextualspace \rtlch\fcs1 \af23\afs28\alang1054 \ltrch\fcs0
\fs24\lang1033\langfe1033\loch\f46\hich\af46\dbch\af37\cgrid\langnp1033\langfenp1033 \sbasedon0 \snext20 \sqformat \spriority34 \styrsid7491472 List Paragraph,Subcaption;}{
\s21\qj \fi-1890\li1890\ri0\sb360\sa240\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin1890\itap0 \rtlch\fcs1 \af31507\afs24\alang1054 \ltrch\fcs0
\b\fs28\lang1024\langfe1024\loch\f1\hich\af1\dbch\af31505\cgrid\noproof\langnp1033\langfenp1033 \sbasedon0 \snext0 \sunhideused \sqformat \spriority35 \styrsid7491472 caption;}{\*\cs22 \additive \rtlch\fcs1 \ai\af31503\afs24 \ltrch\fcs0
\i\fs24\cf20\lang1033\langfe0\loch\f31502\hich\af31502\dbch\af31501\langnp1033 \sbasedon10 \slink7 \slocked \ssemihidden \spriority9 \styrsid7357425 Heading 7 Char;}{\*\cs23 \additive \rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\b\fs24\lang1033\langfe0\loch\f1\hich\af1\dbch\af31501\langnp1033 \sbasedon10 \slink3 \slocked \spriority9 \styrsid7408068 Heading 3 Char;}{\*\cs24 \additive \rtlch\fcs1 \af0\afs18 \ltrch\fcs0 \fs18 \sbasedon10 \ssemihidden \sunhideused \styrsid5836263
annotation reference;}{\*\ts25\tsrowd\trbrdrt\brdrs\brdrw10 \trbrdrl\brdrs\brdrw10 \trbrdrb\brdrs\brdrw10 \trbrdrr\brdrs\brdrw10 \trbrdrh\brdrs\brdrw10 \trbrdrv\brdrs\brdrw10
\trftsWidthB3\trpaddl108\trpaddr108\trpaddfl3\trpaddft3\trpaddfb3\trpaddfr3\trcbpat1\trcfpat1\tblind0\tblindtype3\tsvertalt\tsbrdrt\tsbrdrl\tsbrdrb\tsbrdrr\tsbrdrdgl\tsbrdrdgr\tsbrdrh\tsbrdrv
\ql \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \rtlch\fcs1 \af31507\afs24\alang1054 \ltrch\fcs0 \f31506\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 \sbasedon11 \snext25 \spriority59 \styrsid5836263
Table Grid;}{\s26\ql \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \rtlch\fcs1 \af31507\afs20\alang1025 \ltrch\fcs0 \f1\fs20\lang1033\langfe1033\cgrid\langnp1033\langfenp1033
\sbasedon0 \snext26 \slink27 \ssemihidden \sunhideused annotation text;}{\*\cs27 \additive \rtlch\fcs1 \af0\afs20 \ltrch\fcs0 \f1\fs20\lang1033\langfe0\langnp1033 \sbasedon10 \slink26 \slocked \ssemihidden Comment Text Char;}{\s28\ql \li0\ri0\widctlpar
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header;}{\*\cs29 \additive \rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \f1\fs24\lang1033\langfe0\langnp1033 \sbasedon10 \slink28 \slocked \styrsid8071785 Header Char;}{\s30\ql \li0\ri0\widctlpar
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\par }}{\*\aftnsepc \ltrpar \pard\plain \ltrpar\ql \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid8071785 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10356976 \chftnsepc
\par }}\ltrpar \sectd \ltrsect\sbknone\linex0\headery709\footery709\colsx708\endnhere\sectlinegrid360\sectdefaultcl\sectrsid2239836\sftnbj {\headerr \ltrpar \pard\plain \ltrpar
\ql \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid2171879 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \ab\af37\afs22 \ltrch\fcs0
\b\f37\fs22\cf24\lang2057\langfe2057\chshdng0\chcfpat0\chcbpat8\langnp2057\langfenp2057\insrsid1258920 Paper link }{\rtlch\fcs1 \af0\afs20 \ltrch\fcs0 \f0\fs20\cf23\lang2057\langfe1033\langnp2057\insrsid1258920
https://pubs.acs.org/doi/10.1021/acsnano.0c03130}{\rtlch\fcs1 \af0\afs20 \ltrch\fcs0 \f0\fs20\cf1\lang2057\langfe1033\langnp2057\insrsid1258920 .
\par Data link }{\rtlch\fcs1 \ab\af37\afs22 \ltrch\fcs0 \b\f37\fs22\cf24\lang2057\langfe2057\chshdng0\chcfpat0\chcbpat8\langnp2057\langfenp2057\insrsid2171879\charrsid2171879 10.5525/gla.researchdata.1037}{\rtlch\fcs1 \af0 \ltrch\fcs0
\f0\lang2057\langfe2057\langnp2057\langfenp2057\insrsid2171879\charrsid2171879
\par }\pard\plain \ltrpar\s28\ql \li0\ri0\widctlpar\tqc\tx4513\tqr\tx9026\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f1\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1
\af31507 \ltrch\fcs0 \insrsid2171879
\par }}{\*\pnseclvl1\pnucrm\pnqc\pnstart1\pnindent720\pnhang {\pntxta .}}{\*\pnseclvl2\pnucltr\pnqc\pnstart1\pnindent720\pnhang {\pntxta .}}{\*\pnseclvl3\pndec\pnqc\pnstart1\pnindent720\pnhang {\pntxta .}}{\*\pnseclvl4\pnlcltr\pnqc\pnstart1\pnindent720\pnhang
{\pntxta )}}{\*\pnseclvl5\pndec\pnqc\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}{\*\pnseclvl6\pnlcltr\pnqc\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}{\*\pnseclvl7\pnlcrm\pnqc\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}
{\*\pnseclvl8\pnlcltr\pnqc\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}{\*\pnseclvl9\pnlcrm\pnqc\pnstart1\pnindent720\pnhang {\pntxtb (}{\pntxta )}}{\listtext\pard\plain\ltrpar \s1 \rtlch\fcs1 \af31503 \ltrch\fcs0
\b\cf19\lang1033\langfe1033\loch\af31503\hich\af31503\dbch\af31501\langnp1033\insrsid15735271\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503 1\tab}\pard\plain \ltrpar
\s1\qj \fi-432\li432\ri0\sb240\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\outlinelevel0\adjustright\rin0\lin432\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs32\alang1025 \ltrch\fcs0
\b\fs28\cf19\lang1033\langfe1033\loch\af31503\hich\af31503\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \fs24\insrsid15735271\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503 Title}{\rtlch\fcs1 \af31503\afs24
\ltrch\fcs0 \fs24\insrsid2899302\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \ab\af1
\ltrch\fcs0 \b\cf19\dbch\af31501\insrsid2899302\charrsid11824744
\par }\pard \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid2171879 {\rtlch\fcs1 \ab\af31507 \ltrch\fcs0 \b\insrsid2171879\charrsid11824744 Nanovibrational
Stimulation of Mesenchymal Stem Cells Induces Therapeutic Reactive Oxygen Species and Inflammation for Three- Dimensional Bone Tissue Engineering
\par {\listtext\pard\plain\ltrpar \s1 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\cf19\lang1033\langfe1033\loch\af31503\hich\af31503\dbch\af31501\langnp1033\insrsid15735271\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503 2\tab}}\pard\plain \ltrpar
\s1\qj \fi-432\li432\ri0\sb240\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\outlinelevel0\adjustright\rin0\lin432\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs32\alang1025 \ltrch\fcs0
\b\fs28\cf19\lang1033\langfe1033\loch\af31503\hich\af31503\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \fs24\insrsid15735271\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503 Authors}{\rtlch\fcs1
\af31503\afs24 \ltrch\fcs0 \fs24\lang2057\langfe1033\langnp2057\insrsid15735271\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503 :
\par }\pard\plain \ltrpar\ql \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid728116 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31507
\ltrch\fcs0 \lang2057\langfe1033\langnp2057\insrsid728116\charrsid11824744
\par }\pard\plain \ltrpar\s46\ql \li0\ri0\sa240\sl480\slmult1\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid621002 \rtlch\fcs1 \af0\afs20\alang1025 \ltrch\fcs0 \i\f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 Wich Orapiriyakul}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 1,2}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744
, Penelope M. Tsimbouri}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 1}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 ,}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0
\i0\super\insrsid728116\charrsid11824744 }{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 Peter G. Childs}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 3}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0
\i0\insrsid728116\charrsid11824744 , Paul Campsie}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 4}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 , Julia Wells}{\rtlch\fcs1 \ai\af0\afs24
\ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 5}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 , Marc Fernandez-Yague}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 6}{\rtlch\fcs1
\ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 , Karl Burgess}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 7}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 , K. Elizabeth Tanner}{
\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 3,8}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 , Manlio Tassieri}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744
3}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 , R.M. Dominic Meek}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 9}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 ,}{
\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 }{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 Massimo Vassali}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 3}{
\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 , Manus JP Biggs}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 6}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744
, Manuel Salmer\'f3n-S\'e1nchez}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 3}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 , Richard O.C. Oreffo}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0
\i0\super\insrsid728116\charrsid11824744 5}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 , Stuart Reid}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 4}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0
\i0\insrsid728116\charrsid11824744 , Matthew J Dalby}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\super\insrsid728116\charrsid11824744 1*}{\rtlch\fcs1 \ai\af0\afs24 \ltrch\fcs0 \i0\insrsid728116\charrsid11824744 .
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af1
\ltrch\fcs0 \insrsid2899302\charrsid11824744
\par }\pard\plain \ltrpar\s44\ql \li0\ri0\sa240\sl480\slmult1\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid621002 \rtlch\fcs1 \af0\afs20\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \super\insrsid728116\charrsid11824744 1}{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \insrsid728116\charrsid11824744 Centre for the Cellular
Microenvironment, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
\par }{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \super\insrsid728116\charrsid11824744 2}{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \insrsid728116\charrsid11824744 Department of Orthopedics, Faculty of Medicine, Prince of Songkla University, Songkhla, }{\rtlch\fcs1
\af0\afs24 \ltrch\fcs0 \insrsid621002\charrsid11824744 90110, }{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \insrsid728116\charrsid11824744 Thailand}{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \insrsid621002\charrsid11824744 .}{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0
\insrsid728116\charrsid11824744
\par }{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \super\insrsid728116\charrsid11824744 3}{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \insrsid728116\charrsid11824744
Centre for the Cellular Microenvironment, Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, UK.
\par }{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \super\insrsid728116\charrsid11824744 4}{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \insrsid728116\charrsid11824744 SUPA Department of Biomedical Engineering, University of Strathclyde, Glasgow G1 1QE, UK.
\par }{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \super\insrsid728116\charrsid11824744 5}{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \insrsid728116\charrsid11824744 Bone a
nd Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD, UK.
\par }{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \super\insrsid728116\charrsid11824744 6}{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \f497\insrsid728116\charrsid11824744 Centre for Research in Medical Devices (CU\'ecRAM), National University of Ireland G}{\rtlch\fcs1
\af0\afs24 \ltrch\fcs0 \insrsid728116\charrsid11824744 alway, Galway, Ireland.
\par }{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \super\insrsid728116\charrsid11824744 7}{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \insrsid728116\charrsid11824744
Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, University of Glasgow, Switchback Rd, Bearsden, Glasgow G61 1BD, UK.
\par }{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \super\insrsid728116\charrsid11824744 8}{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \insrsid728116\charrsid11824744 School of Engineering and Materials Science, Queen Mary University of London, Mile End Road
, London E1 4NS, UK.
\par }{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \super\insrsid728116\charrsid11824744 9}{\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \insrsid728116\charrsid11824744 Department of Orthopedics, Queen Elizabeth II University Hospital, Glasgow G51 4TF, UK.
\par
\par }\pard\plain \ltrpar\s45\ql \li0\ri0\sa200\sl480\slmult1\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid621002 \rtlch\fcs1 \af0\afs20\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {
\rtlch\fcs1 \af0\afs24 \ltrch\fcs0 \insrsid728116\charrsid11824744 KEYWORDS: Mesenchymal stem cells, nanovibration, mechanotransduction, bioreactor, bone tissue engineering
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid2119456\charrsid11824744
\par }\pard \ltrpar\qj \li0\ri0\sl360\slmult1\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid2171879 {\rtlch\fcs1 \af1 \ltrch\fcs0 \i\insrsid2171879\charrsid11824744 *corresponding author }{\field\fldedit{\*\fldinst {
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10356976 HYPERLINK "mailto:matthew.dalby@glasgow.ac.uk" }}{\fldrslt {\rtlch\fcs1 \af1 \ltrch\fcs0 \cs36\i\ul\cf22\insrsid2171879\charrsid11824744 matthew.dalby@glasgow.ac.uk}}}\sectd \ltrsect
\sbknone\linex0\headery709\footery709\colsx708\endnhere\sectlinegrid360\sectdefaultcl\sectrsid2239836\sftnbj {\rtlch\fcs1 \af1 \ltrch\fcs0 \i\ul\cf2\lang2057\langfe1033\langnp2057\insrsid2171879\charrsid11824744
\par }\pard \ltrpar\ql \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid6570804 {\rtlch\fcs1 \af31507 \ltrch\fcs0 \ul\cf2\lang2057\langfe1033\langnp2057\insrsid12205707\charrsid11824744
\par {\listtext\pard\plain\ltrpar \s1 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\cf19\lang1033\langfe1033\loch\af31503\hich\af31503\dbch\af31501\langnp1033\insrsid9794680\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503 3\tab}}\pard\plain \ltrpar
\s1\qj \fi-432\li432\ri0\sb240\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\outlinelevel0\adjustright\rin0\lin432\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs32\alang1025 \ltrch\fcs0
\b\fs28\cf19\lang1033\langfe1033\loch\af31503\hich\af31503\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \fs24\insrsid9794680\charrsid11824744 \page }{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\fs24\insrsid13379221\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503 Funder information:}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \fs24\insrsid9794680\charrsid11824744
\par }\pard\plain \ltrpar\ql \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid4197696 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af0
\ltrch\fcs0 \f0\lang2057\langfe1033\langnp2057\insrsid2171879\charrsid11824744
W.O. was supported by a scholarship from the Royal Thai Government and Faculty of medicine, Prince of Songkla University. The work was supported by grants to M.J.D. from BBSRC (BB/P00220X/1, BB/S018808/1) and EPSRC (EP/ N013905/1, EP/P001114/1) and }{
\rtlch\fcs1 \af0 \ltrch\fcs0 \f0\lang2057\langfe2057\langnp2057\langfenp2057\insrsid4197696\charrsid4197696 and the Sir Bobby Charlton Foundation}{\rtlch\fcs1 \af0 \ltrch\fcs0 \f0\lang2057\langfe2057\langnp2057\langfenp2057\insrsid4197696 and }{
\rtlch\fcs1 \af0 \ltrch\fcs0 \f0\lang2057\langfe1033\langnp2057\insrsid2171879\charrsid11824744 to M.J.P.B from Science Foundation Ireland (16/BBSRC/3317).}{\rtlch\fcs1 \af0 \ltrch\fcs0
\f0\lang2057\langfe2057\langnp2057\langfenp2057\insrsid2171879\charrsid4197696
\par }\pard \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 {\rtlch\fcs1 \af31507 \ltrch\fcs0 \lang2057\langfe1033\langnp2057\insrsid13379221\charrsid11824744
\par {\listtext\pard\plain\ltrpar \s1 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\cf19\lang1033\langfe1033\loch\af31503\hich\af31503\dbch\af31501\langnp1033\insrsid2171879\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503 4\tab}}\pard\plain \ltrpar
\s1\qj \fi-432\li432\ri0\sb240\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\outlinelevel0\adjustright\rin0\lin432\itap0\pararsid2171879 \rtlch\fcs1 \af31503\afs32\alang1025 \ltrch\fcs0
\b\fs28\cf19\lang1033\langfe1033\loch\af31503\hich\af31503\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \fs24\insrsid2171879\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503 Abstract:
\par }\pard\plain \ltrpar\ql \li0\ri0\widctlpar\wrapdefault\faauto\rin0\lin0\itap0\pararsid2171879 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af0 \ltrch\fcs0
\f0\lang2057\langfe1033\langnp2057\insrsid2171879\charrsid11824744 ABSTRACT: There is a pressing clinical need to develop cell-based bone therapies due to a lack of viable, autologous bone grafts and a growing demand
for bone grafts in musculoskeletal surgery. Such therapies can be tissue engineered and cellular, such as osteoblasts, combined with a material scaffold. Because mesenchymal stem cells (MSCs) are both available and fast growing compared to mature osteobla
s
ts, therapies that utilize these progenitor cells are particularly promising. We have developed a nanovibrational bioreactor that can convert MSCs into bone-forming osteoblasts in two- and three-dimensional, but the mechanisms involved in this osteoinduct
i
on process remain unclear. Here, to elucidate this mechanism, we use increasing vibrational amplitude, from 30 nm (N30) to 90 nm (N90) amplitudes at 1000 Hz and assess MSC metabolite, gene, and protein changes. These approaches reveal that dose-dependent
changes occur in MSCs\rquote
responses to increased vibrational amplitude, particularly in adhesion and mechanosensitive ion channel expression and that energetic metabolic pathways are activated, leading to low-level reactive oxygen species (ROS) production and
to low-level infl ammation as well as to ROS- and infl ammation-balancing pathways.These events are analogous to those that occur in the natural bone-healing processes. We have also developed a tissue engineered MSC-laden scaffold designed using cells
\rquote mechanical memory, driven by the stronger N90 stimulation. These mechanistic insights and cell-scaff old design are underpinned by a process that is free of inductive chemicals.
\par }\pard \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 {\rtlch\fcs1 \af31507 \ltrch\fcs0 \lang2057\langfe1033\langnp2057\insrsid7950296\charrsid11824744
\par {\listtext\pard\plain\ltrpar \s1 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\cf19\lang1033\langfe1033\loch\af31503\hich\af31503\dbch\af31501\langnp1033\insrsid13379221\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503 5\tab}}\pard\plain \ltrpar
\s1\qj \fi-432\li432\ri0\sb240\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\outlinelevel0\adjustright\rin0\lin432\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs32\alang1025 \ltrch\fcs0
\b\fs28\cf19\lang1033\langfe1033\loch\af31503\hich\af31503\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \fs24\insrsid13379221\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503 Dataset and re}{\rtlch\fcs1
\af31503\afs24 \ltrch\fcs0 \fs24\insrsid4988280\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503 adme information}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \fs24\insrsid7950296\charrsid11824744 \hich\af31503\dbch\af31501\loch\f31503 :}{\rtlch\fcs1
\af31503\afs24 \ltrch\fcs0 \fs24\insrsid12864857\charrsid11824744
\par {\listtext\pard\plain\ltrpar \s2 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\langnp1033\insrsid13109444\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 5.1\tab}}\pard\plain \ltrpar
\s2\qj \fi-576\li576\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl1\outlinelevel1\adjustright\rin0\lin576\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs26\alang1025 \ltrch\fcs0
\b\fs24\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid13109444\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 Scanning electron microscopy (}{\rtlch\fcs1 \af31503\afs24
\ltrch\fcs0 \insrsid1537183\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 SEM}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid13109444\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 )}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\insrsid354522\charrsid11824744 .}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid8861477\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 }{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid14440819\charrsid11824744
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid12346167\charrsid11824744 Data Folder: }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid12534694\charrsid11824744 \tab }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid12346167\charrsid11824744 \tab Figure6 (6A)
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12346167\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744
The samples were prepared for SEM using the sputter coating technique. The samples were mounted onto SEM stubs using double sided conductive tape and silver paint. They were then coated with Gold/ Palladium (approximately 10-20
nm) using a SEM coating system (Q150T ES, Quorum, UK). The samples were viewed on a JEOL6400. SEM running at 10 kV and Tif image captured using Olympus Scandium Software. Porosity diameter was analysed by ImageJ software.}{\rtlch\fcs1 \af31503
\ltrch\fcs0 \insrsid13109444\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744
\par {\listtext\pard\plain\ltrpar \s2 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\langnp1033\insrsid3555329\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 5.2\tab}}\pard\plain \ltrpar
\s2\qj \fi-576\li576\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl1\outlinelevel1\adjustright\rin0\lin576\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs26\alang1025 \ltrch\fcs0
\b\fs24\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid3555329\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 Hydrogels-CHSCs c}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\insrsid2899302\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 ontraction meas\hich\af1\dbch\af31501\loch\f1 urement}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid3555329\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 and time lapse microscopy}{
\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid354522\charrsid11824744 .}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid4987155\charrsid11824744
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid13256549\charrsid11824744 Data Folder: }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid12534694\charrsid11824744 \tab }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid13256549\charrsid11824744 \tab Figure6 (}{\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid11872360\charrsid11824744 6}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid13256549\charrsid11824744 C}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid2835438\charrsid11824744 , 6F, 6G}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid13256549\charrsid11824744 )
\par }\pard \ltrpar\qj \fi720\li1440\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin1440\itap0\pararsid3748957 {\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid13256549\charrsid11824744 Figure}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid6569003\charrsid11824744 S}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid2171982\charrsid11824744 2}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid13256549\charrsid11824744 (}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid5975342\charrsid11824744 S}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid2171982\charrsid11824744 2}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid5975342\charrsid11824744 B)}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid13256549\charrsid11824744
\par }\pard \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 {\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid354522\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14440819\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 In order to monitor the hydrogel }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15225882\charrsid11824744 or CHSCs }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744
contraction without NS, the percentage of the hydrogel contraction comparing to initial }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid11358996\charrsid11824744 hydro}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 gel }{\rtlch\fcs1
\af31507 \ltrch\fcs0 \insrsid13574185\charrsid11824744 or CHSCs }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 surface area in top view. }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10318035\charrsid11824744 T}{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid5836263\charrsid11824744 he hydrogel}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9576043\charrsid11824744 or CHSCs }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 image}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid8139185\charrsid11824744 s were}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 taken in top view every 3-4 days}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5339486\charrsid11824744 . }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid5836263\charrsid11824744 The hydrogel }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid6963218\charrsid11824744 or CHSCs }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 surface areas in top view were measured and a}{\rtlch\fcs1
\af31507 \ltrch\fcs0 \insrsid3363468\charrsid11824744 nalysed}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 by ImageJ software.}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2192085\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid13109444\charrsid11824744 To evaluate cell migration, CHSCs were cultured for 6 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10225181\charrsid11824744 (pre-}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12651203\charrsid11824744 CHSC}{\rtlch\fcs1
\af31507 \ltrch\fcs0 \insrsid14703965\charrsid11824744 s}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12651203\charrsid11824744 contraction) }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744 and 10 days}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid14703965\charrsid11824744 (post-CHSCs contraction)}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744 . CHSCs were imaged using a 10x objective lens at 120 sec intervals for 24 hours at 37\'b0C. Cell velocity
and migration directions were analysed using imageJ plugin (manual tracking) and Chemotaxis and Migration tool (Ibidi). }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid6626910\charrsid11824744
Data and calculation were provided in .xlsx files (Microsoft Excel) and .pzfx file (GraphPad Prism software)}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7883175\charrsid11824744 .}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744
\par
\par {\listtext\pard\plain\ltrpar \s2 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\langnp1033\insrsid13109444\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 5.3\tab}}\pard\plain \ltrpar
\s2\qj \fi-576\li576\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl1\outlinelevel1\adjustright\rin0\lin576\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs26\alang1025 \ltrch\fcs0
\b\fs24\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid13109444\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 Cryosection}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\insrsid4590093\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 and immunost\hich\af1\dbch\af31501\loch\f1 aining}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid15549157\charrsid11824744 .}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\insrsid14440819\charrsid11824744
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid12408137\charrsid11824744 Data Folder:}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid12534694\charrsid11824744 \tab }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid12408137\charrsid11824744 \tab Figure}{\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid8796336\charrsid11824744 6}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid12408137\charrsid11824744 (}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid1455497\charrsid11824744 6H}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid12408137\charrsid11824744 )
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14552713\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744 After CHSCs were stimulated with NS, the samples were fixed in 4% formadehyde and infused in 30% sucrose in PBS for cryoprotection, overnight at 4 }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid13109444\charrsid11824744 {\field{\*\fldinst SYMBOL 176 \\f "Symbol" \\s 12}{\fldrslt\f3\fs24}}}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744
C. The samples were then transferred to embedding molds and O.C.T. (Tissue-Tek, Sakura) was aliquoted to cover the samples. The samples were then frozen in liquid nitrogen and kept at -80 }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid13109444\charrsid11824744 {\field{\*\fldinst SYMBOL 176 \\f "Symbol" \\s 12}{\fldrslt\f3\fs24}}}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744 C. The frozen samples were sliced into 60 mm thickness and attached
onto adhesive slides (9597, Tissue-Tek, Sakura, Netherlands). Immunofluorescent staining was then carried out.}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7866425\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4590093\charrsid11824744
Samples were rinse}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2295422\charrsid11824744 d}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4590093\charrsid11824744 with 1xPBS and fixed with fixative}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid1708926\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4590093\charrsid11824744 at 37\'b0C for 15 minutes. After that, permeabilisation buffer was added and incubated at 4\'b0C for 5 minutes. Samples were then blocked with 1% BSA in
}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7890179\charrsid11824744 1x}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4590093\charrsid11824744 PBS at 37\'b0
C for 5 minutes. Primary antibody (P-myosin light chain 2, cell signaling, 3671S, rabbit, 1:50) and rhodamine-phalloidin (Invitrogen, Thermo fisher, 1:500) diluted in 1% BSA in }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid1512018\charrsid11824744 1x}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4590093\charrsid11824744 PBS were added and incubated at 37\'b0C for 1 hour. Samples were then washed with }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13500952\charrsid11824744 1x}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid491143\charrsid11824744 PBS/}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4590093\charrsid11824744 0.5% }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10697704\charrsid11824744 T}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid488649\charrsid11824744 ween}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid491143\charrsid11824744 -20}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4590093\charrsid11824744
for 3 times (5 minutes each). Biotinylated secondary antibody (anti-rabbit; Vector Laboratories, USA, 1:50) diluted in 1% BSA in }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid1512018\charrsid11824744 1x}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid4590093\charrsid11824744 PBS was added and incubated at 37\'b0C for 1 hour. Samples were washed again with }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13500952\charrsid11824744 1xPBS/}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid4590093\charrsid11824744 0.5% }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13500952\charrsid11824744 Tween }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4590093\charrsid11824744
for 3 times. Streptavidin-FITC (Vector Laboratories, USA, 1:50) diluted in 1% BSA in }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14765735\charrsid11824744 1x}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4590093\charrsid11824744 PBS was incubated at 4\'b0
C for 30 minutes. Samples were washed for 3 times. A small drop of DAPI (4\rquote ,6-diamidino-2 phenylindole, Vectashield) was placed onto the samples and covered with coverslips. FITC/TRITC channel images were taken (Olympus, US) operated
on Surveyor software version 9.0.1.4 (Objective Imaging, UK). Images were processed using ImageJ (Version 1.50g, USA) and Photoshop CS4 (Adobe, version11 extended, Ireland). }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12727866\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9056612\charrsid11824744
\par {\listtext\pard\plain\ltrpar \s2 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\langnp1033\insrsid2899302\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 5.4\tab}}\pard\plain \ltrpar
\s2\qj \fi-576\li576\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl1\outlinelevel1\adjustright\rin0\lin576\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs26\alang1025 \ltrch\fcs0
\b\fs24\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid2899302\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 Interferometr}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\insrsid13582404\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 ic measurement}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid16538502\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 . }{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\insrsid14440819\charrsid11824744
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid2510711\charrsid11824744 Data }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid13461222\charrsid11824744 Folder}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid9844695\charrsid11824744 s: }{\rtlch\fcs1 \ai\af31507
\ltrch\fcs0 \i\insrsid938730\charrsid11824744 \tab }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid3753212\charrsid11824744 Figure1}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid938730\charrsid11824744 (}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid9660466\charrsid11824744 1B}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid15542063\charrsid11824744 , 1C, 1D, 1E and }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid9660466\charrsid11824744 1F}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid938730\charrsid11824744 )}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid13461222\charrsid11824744
\par }\pard \ltrpar\qj \fi720\li1440\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin1440\itap0\pararsid3748957 {\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid990584\charrsid11824744 Figure}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid7998254\charrsid11824744 6}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid938730\charrsid11824744 (}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid7412878\charrsid11824744 6D, 6E}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid938730\charrsid11824744 )}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid12059834\charrsid11824744
\par }\pard \ltrpar\qj \li720\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin720\itap0\pararsid3748957 {\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid938730\charrsid11824744
\par }\pard \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 {\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15536494\charrsid11824744
0.8 mg/ml or 1.8 mg/ml collagen hydrogels were prepared. The hydrogel nanovibration}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \f492\insrsid15536494\charrsid11824744 was measured by laser interferometric vibrometer (wavelength = 632.8 nm, CW power; 5mW; SIOS, Me
\'e2technik GmbH, Germany). The vibration distance was analysed using INFAS Vibro 1.8.4 software (SIOS, Me\'e2technik GmbH, Germany)}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12391183\charrsid11824744 and recorded }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid16674125\charrsid11824744 in .xls file.}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4931629\charrsid11824744 Data and calculation were provided in .xlsx files (Microsoft Excel) and .pzfx file (GraphPad Prism software)}{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid6626910\charrsid11824744 .}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15536494\charrsid11824744
\par
\par {\listtext\pard\plain\ltrpar \s2 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\langnp1033\insrsid15028312\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 5.5\tab}}\pard\plain \ltrpar
\s2\qj \fi-576\li576\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl1\outlinelevel1\adjustright\rin0\lin576\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs26\alang1025 \ltrch\fcs0
\b\fs24\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid15028312\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 Rheology}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\insrsid12269249\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 . }{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid14440819\charrsid11824744
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid8091790\charrsid11824744 Data Folder:}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid12534694\charrsid11824744 \tab }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid8091790\charrsid11824744 }{\rtlch\fcs1 \ai\af31507
\ltrch\fcs0 \i\insrsid938730\charrsid11824744 \tab }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid8091790\charrsid11824744 FigureS}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid2171982\charrsid11824744 2}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid938730\charrsid11824744 (}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid8091790\charrsid11824744 S}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid2171982\charrsid11824744 2}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid8091790\charrsid11824744 A}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid938730\charrsid11824744 )}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid8091790\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid8091790\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7357425\charrsid11824744 To investigate viscoelastic property of the hydrogels,}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15430397\charrsid11824744 a modular compact rheometer (MCR 302, Anton Paar, Aus
tria) with parallel plate method (}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3434717\charrsid11824744 25 mm of }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15430397\charrsid11824744 P}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3434717\charrsid11824744 ara}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10186220\charrsid11824744 l}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3434717\charrsid11824744 lel plate)}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15430397\charrsid11824744 was used.}{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid3504461\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid11471593\charrsid11824744 The s}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7357425\charrsid11824744 train sweep }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid11471593\charrsid11824744 test }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7357425\charrsid11824744 was measured to evaluate the breaking point of the hydrogels}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid808436\charrsid11824744 . Following that, }{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7357425\charrsid11824744 hydrogel }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid11210456\charrsid11824744 viscoelasticity}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid949546\charrsid11824744
was assessed by frequency sweep test}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7357425\charrsid11824744 . }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid795217\charrsid11824744 H}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3504461\charrsid11824744
ydrogels were prepared 24 hours prior to study}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10619073\charrsid11824744 and }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid16062199\charrsid11824744 transferred}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid7357425\charrsid11824744 on the rheometer plate. }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4720734\charrsid11824744 At 23\'b0C of }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14633479\charrsid11824744 controlled temperature, p}{\rtlch\fcs1
\af31507 \ltrch\fcs0 \insrsid724359\charrsid11824744 aralell plate was }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid8217897\charrsid11824744 applied }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15355748\charrsid11824744 with }{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid8217897\charrsid11824744 a }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3226364\charrsid11824744 0.01 N of }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3110875\charrsid11824744 normal force compression }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid6049205\charrsid11824744 and }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4526483\charrsid11824744 1.5 mm gap size. }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7357425\charrsid11824744 The strain sweep was measured from 0.01 to 1% }{\rtlch\fcs1
\af31507 \ltrch\fcs0 \insrsid1835536\charrsid11824744 (of 0.8 mg/ml hydrogel) }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid339817\charrsid11824744 and }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid1835536\charrsid11824744 0.1 to 10% (of 1.8 mg/ml hydrogel) }{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7357425\charrsid11824744 at 10 rad/sec in order to select the strain which was in linear-viscoelastic regime. Consequently, the frequency sweep test was measured at 1% strain starting from 100-0.1 rad/sec}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14773410\charrsid11824744 .}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14576293\charrsid11824744 Data and calculation were provided in .xlsx files (Microsoft Excel) and .pzfx file (GraphPad Prism software)}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7357425\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12738355\charrsid11824744
\par {\listtext\pard\plain\ltrpar \s2 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\langnp1033\insrsid15028312\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 5.6\tab}}\pard\plain \ltrpar
\s2\qj \fi-576\li576\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl1\outlinelevel1\adjustright\rin0\lin576\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs26\alang1025 \ltrch\fcs0
\b\fs24\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid15028312\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 Alamar}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\insrsid13972629\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 B}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid15028312\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 lue}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid12269249\charrsid11824744
\hich\af1\dbch\af31501\loch\f1 assay.}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid14440819\charrsid11824744
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid5114084\charrsid11824744 Data Folders: \tab FigureS}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid2171982\charrsid11824744 2}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid5114084\charrsid11824744 (S}{\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid2171982\charrsid11824744 2}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid5114084\charrsid11824744 C)}{\rtlch\fcs0 \ai\alang2057 \ltrch\fcs1 \i\f23\fs24\lang1054\langnp2057\insrsid5114084\charrsid11824744
\par }\pard \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid2171982 {\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid5114084\charrsid11824744
\par }\pard \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 {\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5114084\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 4x10}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid5836263\charrsid11824744 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 cells/ml }{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid13852445\charrsid11824744 of Stro1 selected MSCs in }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid1539731\charrsid11824744 CHSCs and }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13852445\charrsid11824744 hydrogels}{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid1539731\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 were}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2257348\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5249010\charrsid11824744
prepared}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3810513\charrsid11824744 and stimulate}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid16342507\charrsid11824744 d for }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14948153\charrsid11824744 1 and }{\rtlch\fcs1
\af31507 \ltrch\fcs0 \insrsid16342507\charrsid11824744 2 week}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2710170\charrsid11824744 . }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2640828\charrsid11824744 The previous culture media were removed}{\rtlch\fcs1
\af31507 \ltrch\fcs0 \insrsid16585003\charrsid11824744 . Samples were}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2640828\charrsid11824744 washed with }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid935807\charrsid11824744 warm }{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid16196922\charrsid11824744 1x}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2640828\charrsid11824744 PBS}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid11867871\charrsid11824744 .}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid10301077\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 10% }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid1054061\charrsid11824744 (v/v)}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744
of Alamar}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13972629\charrsid11824744 B}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 lue resazurin (Bio-Rad, }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid8137351\charrsid11824744 Watford, }{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 UK) diluted in phenol-red free media (D5030, Sigma) was }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid6780043\charrsid11824744 prepared and }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid5836263\charrsid11824744 added into each sampl}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15680360\charrsid11824744 e. }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid1140267\charrsid11824744 After}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid12347455\charrsid11824744 i}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 ncubat}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid16534201\charrsid11824744 ed}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 at 37
\'b0C}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid11424128\charrsid11824744 and}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 5%}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid1649747\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid5836263\charrsid11824744 CO2}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13834202\charrsid11824744 for 5 hours,}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2173591\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid16459495\charrsid11824744 t}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 he supernatant containing the up-taken }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14254048\charrsid11824744 A}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid5836263\charrsid11824744 lamar}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14254048\charrsid11824744 B}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 lue was pipetted and transferred into 96 well plates. A microplate r
eader (Clariostar, }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid22917\charrsid11824744 BMG Labtech, }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744
Germany) was used to detect light absorbance at wavelengths of 570 nm and 600 nm. The percentage of }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13331976\charrsid11824744 A}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 lamar}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12589902\charrsid11824744 B}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 lue reduction was calculated }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3370616\charrsid11824744
as Tsimbouri et al, 201}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid16007555\charrsid11824744 7 }{\field{\*\fldinst {\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid275077\charrsid11824744
ADDIN EN.CITE Tsimbouri P.M.2017960(1)96096017Tsimbouri P.M., Childs P.G., Pemberton G.D., Yang J, Jayawarna V., Orapiriyakul W., Burgess K., Gonzalez-Garcia C., Thomas D., Giraldo C.V., Biggs M.P
.
, Curtis A.G., Salmeron-Sanchez M., Reid S., Dalby M.J.3D osteogenesis of mesenchymal stem cells stimulated by nanovibrational bioreactor in vitro.Nature Biomedical engineeringNature Biomedical engineering758-77012017}}{\fldrslt {\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid275077\charrsid11824744 (1)}}}\sectd \ltrsect\sbknone\linex0\headery709\footery709\colsx708\endnhere\sectlinegrid360\sectdefaultcl\sectrsid2239836\sftnbj {\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid6912887\charrsid11824744 .}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4614580\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2444967\charrsid11824744 Data }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7283075\charrsid11824744 and calculation were }{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid2444967\charrsid11824744 provided in .xls}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid6715076\charrsid11824744 x}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2444967\charrsid11824744 files}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid7283075\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4159455\charrsid11824744 (}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7945247\charrsid11824744 Mi}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4159455\charrsid11824744 crosoft Excel}
{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid8677243\charrsid11824744 ) }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7283075\charrsid11824744 and}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3172144\charrsid11824744 .pzfx file}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid12342040\charrsid11824744 (Grap}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7604743\charrsid11824744 h}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9790027\charrsid11824744 P}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7604743\charrsid11824744 ad Prism}
{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13920542\charrsid11824744 software}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12342040\charrsid11824744 )}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3172144\charrsid11824744 . }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid5836263\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7550803\charrsid11824744
\par {\listtext\pard\plain\ltrpar \s2 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\langnp1033\insrsid8724908\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 5.7\tab}}\pard\plain \ltrpar
\s2\qj \fi-576\li576\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl1\outlinelevel1\adjustright\rin0\lin576\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs26\alang1025 \ltrch\fcs0
\b\fs24\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid8724908\charrsid11824744 \hich\af1\dbch\af31501\loch\f1
Quantitative polymerase chain reaction with reverse transcription }{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid15664808\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 (q}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid2899302\charrsid11824744
\hich\af1\dbch\af31501\loch\f1 RT-PCR}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid15664808\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 )}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid3808132\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 }{
\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid14440819\charrsid11824744
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid2430551\charrsid11824744 Data Folders: \tab }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid4202474\charrsid11824744 Folder: Figure1 (1G, 1H)
\par }\pard \ltrpar\qj \fi720\li1440\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin1440\itap0\pararsid3748957 {\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid2430551\charrsid11824744 Figure}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid16154349\charrsid11824744 2}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid2430551\charrsid11824744 (}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid7153622\charrsid11824744 2B}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid2430551\charrsid11824744 , }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid7153622\charrsid11824744 2C}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid2430551\charrsid11824744 )
\par }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid3678889\charrsid11824744 Figure4 (4E)
\par }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid9254912\charrsid11824744 Figure5 (5A}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid3615826\charrsid11824744 , 5B, 5C}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid9254912\charrsid11824744 )
\par }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid12351595\charrsid11824744 Figure7 }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid8153231\charrsid11824744 (7A, 7B, 7}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid6257925\charrsid11824744 E}{\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid8153231\charrsid11824744 )}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid12351595\charrsid11824744
\par }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid8667631\charrsid11824744 FigureS}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid10044305\charrsid11824744 5}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid8667631\charrsid11824744
\par }\pard \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 {\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2430551\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 To assess gene expression changes, hydrogels }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10098811\charrsid11824744 or CHSCs }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid5836263\charrsid11824744 were prepared for quantitative RT-PCR (qRT-PCR). Real time PCR was }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10098811\charrsid11824744 carried out}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10636513\charrsid11824744 }{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 (7500 Real Time PCR system, Applied Biosystem, USA)}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid8529697\charrsid11824744 and quantified by}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid5836263\charrsid11824744 2}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid5836263\charrsid11824744 -\u8710\'3f\u8710\'3fCT}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 method }{\field{\*\fldinst {\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid275077\charrsid11824744
ADDIN EN.CITE Livak2001967(2)967967<
/
key>17Livak, K. J.Schmittgen, T. D.Applied Biosystems, Foster City, California 94404, USA.Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) MethodMethodsMethods402
-
8254AlgorithmsBrain/metabolismCell LineDNA, Complementary/metabolismHumansPolymerase Chain Reaction
/
*methods*Reverse Transcriptase Polymerase Chain ReactionTime Factors2001Dec1046-2023 (Print)
1046-2023 (Linking)11846609https://www.ncbi.nlm.nih.gov/pubmed/1184660910.1006/meth.2001.1262}}{\fldrslt {
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid275077\charrsid11824744 (2)}}}\sectd \ltrsect\sbknone\linex0\headery709\footery709\colsx708\endnhere\sectlinegrid360\sectdefaultcl\sectrsid2239836\sftnbj {\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid5836263\charrsid11824744 . }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7550803\charrsid11824744 Data and calculation were provided in .xlsx files (Microsoft Excel) and .pzfx file (GraphPad Prism software)}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid2361201\charrsid11824744 .}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744
\par }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid16006932\charrsid11824744
\par }{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid16006932\charrsid11824744 Folder}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid3348320\charrsid11824744 : }{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid16006932\charrsid11824744 Figure1 (1G
}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid3348320\charrsid11824744 )}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid16006932\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14290279\charrsid11824744 4x10}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid14290279\charrsid11824744 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14290279\charrsid11824744 cells/ml of }{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid11799726\charrsid11824744 MSCs (2 donors) }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid16128912\charrsid11824744 were cultured in hydrogel}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9657168\charrsid11824744 s}{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid16128912\charrsid11824744 . }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2254882\charrsid11824744 qRT-PCR at day 9 compar}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7539967\charrsid11824744 ed}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid2254882\charrsid11824744 between }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid8938391\charrsid11824744 with (}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2254882\charrsid11824744 N30 and N90}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid8938391\charrsid11824744 ) and without NS}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7491884\charrsid11824744 were carried out}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2254882\charrsid11824744 . }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid7094272\charrsid11824744 Osteogenic markers were tested}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid1072391\charrsid11824744 .}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid16006932\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid1072391\charrsid11824744
\par }{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid3348320\charrsid11824744 {\*\bkmkstart _Toc27404080}Folder: Figure1 (1H)}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid3958725\charrsid11824744 , Figure5 (5C)}{\rtlch\fcs1 \ab\ai\af31507
\ltrch\fcs0 \b\i\insrsid3348320\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9657168\charrsid11824744 4x10}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid9657168\charrsid11824744 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9657168\charrsid11824744
cells/ml of MSCs (3 donors) were cultured in hydrogels. Temporal study of qRT-PCR at day 7, 14 and 21 were performed}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4354161\charrsid11824744 to compare}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid9657168\charrsid11824744 N90}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9582070\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4354161\charrsid11824744 with }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2121503\charrsid11824744
non-stimulated group (control)}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9657168\charrsid11824744 . Osteogenic}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid6293046\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12131965\charrsid11824744 (1H) }{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid6293046\charrsid11824744 and inflammatory}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10440717\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12131965\charrsid11824744 (5C) }{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid10440717\charrsid11824744 markers}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9657168\charrsid11824744 were tested.
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15890212\charrsid11824744
\par }{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid4070576\charrsid11824744 Folder: Figure2 (2B}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid8996933\charrsid11824744 , 2C}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0
\b\i\insrsid8289033\charrsid11824744 )}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid4070576\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15028928\charrsid11824744 4x10}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid15028928\charrsid11824744 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15028928\charrsid11824744
cells/ml of MSCs (2 donors) were cultured in hydrogels. qRT-PCR at day 9 compar}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7539967\charrsid11824744 ed }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15028928\charrsid11824744
between with (N30 and N90) and without NS were carried out. Osteogenic}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4655297\charrsid11824744 -}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid6107664\charrsid11824744 related pathways }{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid15028928\charrsid11824744 markers were tested.}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14187769\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15028928\charrsid11824744
\par }{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid8289033\charrsid11824744
\par Folder: Figure2 (2}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid795277\charrsid11824744 D}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid8289033\charrsid11824744 )}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid10621527\charrsid11824744
and }{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid2297522\charrsid11824744 Figure 4 (4E)}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid8289033\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15164980\charrsid11824744 4x10}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid15164980\charrsid11824744 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15164980\charrsid11824744
cells/ml of MSCs in hydrogels were cultured with }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3564457\charrsid11824744 ROCK }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2297522\charrsid11824744 (2}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid13119230\charrsid11824744 D}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2297522\charrsid11824744 ) and ROS (4E) }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3564457\charrsid11824744 inhibitor}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid15164980\charrsid11824744 . qRT-PCR at day }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid11762776\charrsid11824744 9}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14966343\charrsid11824744 was}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid15164980\charrsid11824744 performed to compare }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14966343\charrsid11824744 NS}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid16280172\charrsid11824744 (N30 and }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid15164980\charrsid11824744 N90}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid16280172\charrsid11824744 )}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15164980\charrsid11824744 with non-stimulated group (control). }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid723702\charrsid11824744 RUNX2 and OSX}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15164980\charrsid11824744 were }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid8021207\charrsid11824744 studied}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid15164980\charrsid11824744 .
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4070576\charrsid11824744
\par }{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid4356492\charrsid11824744 Folder: Figure}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid12542975\charrsid11824744 5}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid4356492\charrsid11824744 (}{
\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid5012726\charrsid11824744 5A}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid4356492\charrsid11824744 )
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4356492\charrsid11824744 4x10}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid4356492\charrsid11824744 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4356492\charrsid11824744
cells/ml of MSCs were cultured in hydrogels. qRT-PCR at day 9 compar}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid162117\charrsid11824744 ed}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4356492\charrsid11824744 between with}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid9651858\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4356492\charrsid11824744 N90}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9651858\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4356492\charrsid11824744 and}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9651858\charrsid11824744 non-stimulated group }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4356492\charrsid11824744 w}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid162117\charrsid11824744 as}{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid4356492\charrsid11824744 carried out. }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12542975\charrsid11824744 Inflammatory }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4356492\charrsid11824744 markers were }{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid12542975\charrsid11824744 investigated}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4356492\charrsid11824744 .
\par }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid788566\charrsid11824744
\par }{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid12542975\charrsid11824744 Folder: Figure5 (5B)}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid8063688\charrsid11824744 , Figure S}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0
\b\i\insrsid10044305\charrsid11824744 5}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid11366175\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7101864\charrsid11824744 4x10}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid7101864\charrsid11824744 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7101864\charrsid11824744
cells/ml of MSCs in hydrogels were cultured with }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13270542\charrsid11824744 NF}{\rtlch\fcs1 \af1 \ltrch\fcs0 \f492\insrsid11547091\charrsid11824744 \'ea}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid13270542\charrsid11824744 B}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5518440\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7101864\charrsid11824744 inhibitor}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid16612729\charrsid11824744 s}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7101864\charrsid11824744 . qRT-PCR at day 9 was }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5518440\charrsid11824744 carried }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid8467638\charrsid11824744 out }{\rtlch\fcs1
\af31507 \ltrch\fcs0 \insrsid7101864\charrsid11824744 to compare NS (N30 and N90) with non-stimulated group (control). RUNX2}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10044305\charrsid11824744 , O}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid7101864\charrsid11824744 SX}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10044305\charrsid11824744 and OPN}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7101864\charrsid11824744 were studied.}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid15601884\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5524755\charrsid11824744 Effect of }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13121434\charrsid11824744 dependent pathways were calculated.}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid7101864\charrsid11824744
\par }{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid12542975\charrsid11824744
\par }{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid225999\charrsid11824744 Folder: }{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid11366175\charrsid11824744 Figure7 (7A, 7B}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0
\b\i\insrsid225999\charrsid11824744 )
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2903598\charrsid11824744 4x10}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid2903598\charrsid11824744 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2903598\charrsid11824744
cells/ml of MSCs (3 donors) were cultured in }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3106932\charrsid11824744 CHSCs}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2903598\charrsid11824744
. Temporal study of qRT-PCR at day 7, 14 and 21 were performed to compare }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3106932\charrsid11824744 NS (N30 and }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2903598\charrsid11824744 N90}{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid3106932\charrsid11824744 )}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2903598\charrsid11824744 with non-stimulated group (control). Osteogenic (7A) and inflammatory (7B) markers were tested.
\par }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid225999\charrsid11824744
\par }{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid2056944\charrsid11824744 Folder: Figure7 (7E)}{\rtlch\fcs1 \ab\ai\af31507 \ltrch\fcs0 \b\i\insrsid11366175\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2056944\charrsid11824744 4x, 10x and 20x 10}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid2056944\charrsid11824744 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2056944\charrsid11824744 cells/ml of MSCs}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13959611\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2056944\charrsid11824744 in }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13959611\charrsid11824744 CHSCs were prepared}{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid8328201\charrsid11824744 and stimulated with N30 and N90 for 1 and 2 weeks}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2056944\charrsid11824744 . qRT-PCR}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7890047\charrsid11824744
was studied at }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3344818\charrsid11824744 week 2 and 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid16220137\charrsid11824744 .}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2056944\charrsid11824744
Osteogenic markers were tested.
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 {\*\bkmkend _Toc27404080}
\par {\listtext\pard\plain\ltrpar \s2 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\langnp1033\insrsid5836263\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 5.8\tab}}\pard\plain \ltrpar
\s2\qj \fi-576\li576\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl1\outlinelevel1\adjustright\rin0\lin576\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs26\alang1025 \ltrch\fcs0
\b\fs24\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid5836263\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 Protein antibody microarrays}{\rtlch\fcs1 \af31503\afs24
\ltrch\fcs0 \insrsid3808132\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 . }{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid14440819\charrsid11824744
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid9182266\charrsid11824744 Data Folder:}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid12534694\charrsid11824744 \tab }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid9182266\charrsid11824744 \tab Figure}{\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid15340516\charrsid11824744 2}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid9182266\charrsid11824744 (}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid15340516\charrsid11824744 2A}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid9182266\charrsid11824744 )
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9182266\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid8666409\charrsid11824744 4x}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5836263\charrsid11824744 10}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid5836263\charrsid11824744 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid5836263\charrsid11824744 cells/ml of Stro1 selected MSCs in 1.8 mg/ml collagen hydrogels were stimulated with N30 and N90. After stimulation for 1 and 2 weeks,}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9980960\charrsid11824744 }{\rtlch\fcs1
\af31507 \ltrch\fcs0 \insrsid11481866\charrsid11824744 samples were processed. D}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3285625\charrsid11824744 ata was analysed by }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid556304\charrsid11824744 Microsoft }{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3285625\charrsid11824744 Excels. Heatmaps were generated by Hierarchical Clustering Explorer v3.0 (}{\field\fldedit{\*\fldinst {\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10356976
HYPERLINK "http://www.cs.umd.edu/hcil/hce/hce3.html" }}{\fldrslt {\rtlch\fcs1 \af31507 \ltrch\fcs0 \cs36\ul\cf22\insrsid3285625\charrsid11824744 http://www.cs.umd.edu/hcil/hce/hce3.html}}}\sectd \ltrsect
\sbknone\linex0\headery709\footery709\colsx708\endnhere\sectlinegrid360\sectdefaultcl\sectrsid2239836\sftnbj {\rtlch\fcs1 \af31507 \ltrch\fcs0 \cs36\ul\cf22\insrsid14032589\charrsid11824744 )}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid3285625\charrsid11824744 .}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3299888\charrsid11824744 Data and calculation were provided in .xlsx files (Microsoft Excel)}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid282966\charrsid11824744 .}{\rtlch\fcs1
\af31507 \ltrch\fcs0 \insrsid3285625\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid8071785\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid1642366\charrsid11824744 \sect }\sectd \ltrsect\sbknone\linex0\headery708\footery708\colsx708\endnhere\sectlinegrid360\sectdefaultcl\sectrsid2239836\sftnbj {\listtext\pard\plain\ltrpar \s2 \rtlch\fcs1 \af31503
\ltrch\fcs0 \b\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\langnp1033\insrsid1642366\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 5.9\tab}\pard\plain \ltrpar
\s2\qj \fi-576\li576\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl1\outlinelevel1\adjustright\rin0\lin576\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs26\alang1025 \ltrch\fcs0
\b\fs24\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid1642366\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 M}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\insrsid2899302\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 etabolomics}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid9445599\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 . }{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\insrsid14440819\charrsid11824744
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid10038310\charrsid11824744 Data Folders: \tab Figure}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid16598176\charrsid11824744 3}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid10038310\charrsid11824744 (}{\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid14617097\charrsid11824744 3A, }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid10514267\charrsid11824744 3}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid10038310\charrsid11824744 B, }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid10514267\charrsid11824744 3}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid10038310\charrsid11824744 C}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid15224674\charrsid11824744 , 3}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid3476414\charrsid11824744 D}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid10038310\charrsid11824744 )
\par }\pard \ltrpar\qj \fi720\li1440\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin1440\itap0\pararsid3748957 {\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid10038310\charrsid11824744 Figure}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid4281002\charrsid11824744 4}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid10038310\charrsid11824744 (}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid4281002\charrsid11824744 4A, 4B, 4C, }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid6647600\charrsid11824744 4F}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid10038310\charrsid11824744 )
\par }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid13441658\charrsid11824744 FigureS}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid2171982\charrsid11824744 3, S4}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid13372962\charrsid11824744
\par }\pard \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 {\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10038310\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744 Stro1-selected MSCs seeded with 4 x10}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid13109444\charrsid11824744 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744
cells/ml density in 1.8 mg/ml collagen hydrogels were stimulated with N30 and N90. After 1 and 2 week}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9774898\charrsid11824744 s}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744
NS the gels were homogenized on ice and metabolites were then extracted using a Chloroform/Methanol/ water (1:3:1 ratio) extraction buffer. Samples were agitated on a shaker at 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744
{\field{\*\fldinst SYMBOL 176 \\f "Symbol" \\s 12}{\fldrslt\f3\fs24}}}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744 C for 1 hour and in turn centrifuged at 13,000xg at 4 }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid13109444\charrsid11824744 {\field{\*\fldinst SYMBOL 176 \\f "Symbol" \\s 12}{\fldrslt\f3\fs24}}}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744
C for 5 minutes. Supernatants were transferred to and analysed by the Glasgow Polyomics team. Hydrophilic interaction liquid chromatography-mass spectrometry was performed (D
ionex, UltiMate 3000 RSCL system, Thermo Fisher Scientific, Hemel Hempstead, UK) using a ZIC-pHILIC column (150 mm x 4.6 mm, 5 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744 {\field{\*\fldinst SYMBOL 109 \\f "Symbol" \\s 12}{\fldrslt
\f3\fs24}}}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744 m. column, Merck Sequant). The datasets were processed using XCMS (peak picking), MzMatch (filter and grouping), IDEOM (post pro
cessing filtering and identification). Metaboanalyst was used to generate heatmaps and PCA analysis. KEGG database and Ingenuity Pathway Analysis (IPA) software were used for metabolomic pathway analysis.
\par
\par {\listtext\pard\plain\ltrpar \s2 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\langnp1033\insrsid4733222\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 5.10\tab}}\pard\plain \ltrpar
\s2\qj \fi-576\li576\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl1\outlinelevel1\adjustright\rin0\lin576\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs26\alang1025 \ltrch\fcs0
\b\fs24\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid4733222\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 Reactive oxygen species }{\rtlch\fcs1 \af31503\afs24
\ltrch\fcs0 \insrsid6253571\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 measurement}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid6717018\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 . }{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\insrsid14440819\charrsid11824744
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid9333324\charrsid11824744 Data Folder:}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid11430552\charrsid11824744 \tab }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid9333324\charrsid11824744 \tab Figure4 (}{\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid8018570\charrsid11824744 4}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid9333324\charrsid11824744 D)
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9333324\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744 Stro1-selected MSCs seeded with 4 x10}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid13109444\charrsid11824744 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744
cells/ml density in hydrogels }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid6301064\charrsid11824744 (3 donors) }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744 were stimulated with N30 and N90 for 7 day}{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid4743964\charrsid11824744 s}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744 . The samples were incubated in 2.5 mg/ml collagenase for }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13578545\charrsid11824744 an}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744 hour and were then centrifuged at 200xg for 4 minutes. Following that, the cell pellets were incubated for }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid7762975\charrsid11824744 an}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744 hour in 2 uM 2\rquote ,7\rquote - dichlorodihydrogen-fluorescein diacetate (H2DCF-DA, Invitrogen) in phenol red free media (Sigma, D5030). In the positive control group, 500 uM hydroge}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid1998334\charrsid11824744 n}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744
peroxide was added. After incubation, the samples were then centrifuged and resuspended in 250 ul of flow cytometry buffer (2% FBS, 2 mM EDTA in }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13525006\charrsid11824744 1x}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid13109444\charrsid11824744 PBS) and transferred t
o 96 well plates. Resuspended MSCs in 96 well plates were incubated for 30 minutes. Signal of H2DCF-DA fluorescein was detected by using flow cytometry at 492-295 nm of excitation and 517-527 nm of emission. }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid10817085\charrsid11824744 Data and calculation were provided in .xlsx files (Microsoft Excel) and .pzfx file (GraphPad Prism software)}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13109444\charrsid11824744
\par
\par {\listtext\pard\plain\ltrpar \s2 \rtlch\fcs1 \af31503 \ltrch\fcs0 \b\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\langnp1033\insrsid2899302\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 5.11\tab}}\pard\plain \ltrpar
\s2\qj \fi-576\li576\ri0\sb40\keep\keepn\widctlpar\wrapdefault\aspalpha\aspnum\faauto\ls7\ilvl1\outlinelevel1\adjustright\rin0\lin576\itap0\pararsid3748957 \rtlch\fcs1 \af31503\afs26\alang1025 \ltrch\fcs0
\b\fs24\lang1033\langfe1033\loch\af1\hich\af1\dbch\af31501\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid2899302\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 ELISA}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0
\insrsid2360362\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 of interleukin}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid3954266\charrsid11824744 -}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \f62\insrsid2360362\charrsid11824744
\hich\af62\dbch\af31501\loch\f62 \hich\f62 1\'e2}{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid6717018\charrsid11824744 \hich\af1\dbch\af31501\loch\f1 . }{\rtlch\fcs1 \af31503\afs24 \ltrch\fcs0 \insrsid14440819\charrsid11824744
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 {\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid5592302\charrsid11824744 Data Folder:}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid5851153\charrsid11824744 \tab }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid5592302\charrsid11824744 \tab Figure}{\rtlch\fcs1
\ai\af31507 \ltrch\fcs0 \i\insrsid16648521\charrsid11824744 5 }{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid5592302\charrsid11824744 (}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0 \i\insrsid16648521\charrsid11824744 5}{\rtlch\fcs1 \ai\af31507 \ltrch\fcs0
\i\insrsid5592302\charrsid11824744 D)
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid5592302\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid16457323\charrsid11824744 Stro1-selected MSCs seeded with 4 x10}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \super\insrsid16457323\charrsid11824744 4}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid16457323\charrsid11824744
cells/ml density in 1.8 mg/ml collagen hydrogels}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10167669\charrsid11824744 were }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9110814\charrsid11824744 nano}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid10167669\charrsid11824744 stimulate}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9110814\charrsid11824744 d for 7 days. }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid8341443\charrsid11824744 Hydrogels were digested with }{\rtlch\fcs1 \af31507
\ltrch\fcs0 \insrsid8551176\charrsid11824744 c}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 ollagenase}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12989780\charrsid11824744 (Sigma-Aldrich, UK)}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid2360362\charrsid11824744 . Protein was extracted using RIPA lysis buffer containing phosphatase and protease inhibitors}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid4091501\charrsid11824744 .}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\f492\insrsid2360362\charrsid11824744 Total protein concentration was quantified using BCA kits (Pierce, ThermoFisher). Human IL-1\'e2 kits (}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744
DY201-05, R&D systems) was used. Working concentration of reagents (Human IL-1}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 {\field{\*\fldinst SYMBOL 98 \\f "Symbol" \\s 12}{\fldrslt\f3\fs24}}}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid2360362\charrsid11824744 capture antibody; 840168, Human IL-1}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 {\field{\*\fldinst SYMBOL 98 \\f "Symbol" \\s 12}{\fldrslt\f3\fs24}}}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid2360362\charrsid11824744 detection Antibody; 840169, Human IL-1}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 {\field{\*\fldinst SYMBOL 98 \\f "Symbol" \\s 12}{\fldrslt\f3\fs24}}}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid2360362\charrsid11824744 standard; 840170, Streptavidin-HRP; 893975) was prepared as Certificate of Analysis (COA) sheet.}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid8924423\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid2360362\charrsid11824744 T}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \f492\insrsid2360362\charrsid11824744 o coat the captured antibody onto ELISA plate, 100 \'ecl captured antibody was added into 96}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid7418140\charrsid11824744 -}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 well plate and incubated overnight at 4\'b0C. }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid6311744\charrsid11824744 A captured antibodies}{\rtlch\fcs1
\af31507 \ltrch\fcs0 \insrsid8928965\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid6311744\charrsid11824744 coated p}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744
late was then washed with washing buffer (0.05% Tween 20 in }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10825135\charrsid11824744 1x}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 PBS (pH 7.4) for 3 times using }{\rtlch\fcs1 \af31507
\ltrch\fcs0 \f492\insrsid2360362\charrsid11824744 multichannel pipettes. 300 \'ecl of reagent diluent (Reagent diluent concentrate 2, DY995, R&D systems) was added and incubated for }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid15418463\charrsid11824744 an }
{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 hour to block the }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid926569\charrsid11824744 coated }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 plate.}{\rtlch\fcs1
\af31507 \ltrch\fcs0 \insrsid15667304\charrsid11824744 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 100 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 {\field{\*\fldinst SYMBOL 109 \\f "Symbol" \\s 12}{\fldrslt
\f3\fs24}}}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 l samples and standard in reagent diluent (Human IL-1}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 {\field{\*\fldinst SYMBOL 98 \\f "Symbol"
\\s 12}{\fldrslt\f3\fs24}}}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 , 840170) w}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12066108\charrsid11824744 ere}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744
added and incubated for 2 hours at room temperature. Samples were washed 3 times with washing buffer. 100 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 {\field{\*\fldinst SYMBOL 109 \\f "Symbol" \\s 12}{\fldrslt\f3\fs24}}}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 l of streptavidin-HRP was added and incubated for 30 minutes at room temperature. Samples were washed 3 times. 100 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744
{\field{\*\fldinst SYMBOL 109 \\f "Symbol" \\s 12}{\fldrslt\f3\fs24}}}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 l substrate solution (1:1 of col
our reagent A; H2O2 and colour reagent B; Tetramethylbenzidine) was added and incubated for 20 minutes. 50 }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 {\field{\*\fldinst SYMBOL 109 \\f "Symbol" \\s 12}{\fldrslt\f3\fs24}}}{
\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid2360362\charrsid11824744 l stop solution (2NH2SO4, DY994, R&D systems) was added. Microplate reader was used to determine the optical density at 450 nm and 570 nm.}{\rtlch\fcs1 \af31507 \ltrch\fcs0
\insrsid5995246\charrsid11824744 Data and calculation were provided in .xlsx files (Microsoft Excel) and .pzfx file (GraphPad Prism software)}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid10031274\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid14440819\charrsid11824744
\par
\par 5.}{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9787938\charrsid11824744 The date the dataset can be made publicly would be once the paper is out on publication
\par
\par 6. No restrictions
\par 7. No preference
\par }\pard \ltrpar\ql \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid13184132 {\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid9787938\charrsid11824744 8. }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid13184132 paper link}{
\rtlch\fcs1 \af0\afs20 \ltrch\fcs0 \f0\fs20\cf23\lang2057\langfe1033\langnp2057\insrsid13184132\charrsid13184132 }{\rtlch\fcs1 \af0\afs20 \ltrch\fcs0 \f0\fs20\cf23\lang2057\langfe1033\langnp2057\insrsid13184132 https://pubs
.acs.org/doi/10.1021/acsnano.0c03130}{\rtlch\fcs1 \af0\afs20 \ltrch\fcs0 \f0\fs20\cf1\lang2057\langfe1033\langnp2057\insrsid13184132 .}{\rtlch\fcs1 \af0\afs20 \ltrch\fcs0 \f0\fs20\cf1\lang2057\langfe1033\langnp2057\insrsid9787938
\par }{\rtlch\fcs1 \af0\afs20 \ltrch\fcs0 \f0\fs20\cf1\lang2057\langfe1033\langnp2057\insrsid13184132
\par }{\rtlch\fcs1 \af0\afs20 \ltrch\fcs0 \f0\fs20\cf1\lang2057\langfe1033\langnp2057\insrsid13184132\charrsid13184132
\par }\pard \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 {\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid16535477\charrsid11824744
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid12000317\charrsid11824744
\par }{\rtlch\fcs1 \ab\af31507 \ltrch\fcs0 \b\insrsid275077\charrsid11824744 References
\par }{\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid275077\charrsid11824744
\par }\pard\plain \ltrpar\s34\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af1\afs24\alang1025 \ltrch\fcs0 \f1\fs24\lang1024\langfe1024\cgrid\noproof\langnp1033\langfenp1033
{\field{\*\fldinst {\rtlch\fcs1 \af1 \ltrch\fcs0 \insrsid275077\charrsid11824744 ADDIN EN.REFLIST }}{\fldrslt {\rtlch\fcs1 \af1 \ltrch\fcs0 \insrsid275077\charrsid11824744 1.\tab
Tsimbouri P.M. CPG, Pemberton G.D., Yang J, Jayawarna V., Orapiriyakul W., Burgess K., Gonzalez-Garcia C., Thomas D., Giraldo C.V., Biggs M.P., Curtis A.G.,
Salmeron-Sanchez M., Reid S., Dalby M.J. 3D osteogenesis of mesenchymal stem cells stimulated by nanovibrational bioreactor in vitro. Nature Biomedical engineering. 2017;1:758-70.
\par 2.\tab Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8.
\par }\pard\plain \ltrpar\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 }}\pard\plain \ltrpar
\qj \li0\ri0\widctlpar\wrapdefault\aspalpha\aspnum\faauto\adjustright\rin0\lin0\itap0\pararsid3748957 \rtlch\fcs1 \af31507\afs24\alang1025 \ltrch\fcs0 \f44\fs24\lang1033\langfe1033\cgrid\langnp1033\langfenp1033 \sectd \ltrsect
\sbknone\linex0\headery708\footery708\colsx708\endnhere\sectlinegrid360\sectdefaultcl\sectrsid2239836\sftnbj {\rtlch\fcs1 \af31507 \ltrch\fcs0 \insrsid3156265\charrsid11824744
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