US2016040121A1PendingUtilityA1

Thermally responsive cell culture surfaces

Assignee: INNOVATIVE SURFACE TECHNOLOGIES INCPriority: Jun 22, 2007Filed: Jul 20, 2015Published: Feb 11, 2016
Est. expiryJun 22, 2027(~0.9 yrs left)· nominal 20-yr term from priority
A61L 27/16C12N 2539/00C12N 2533/30C12M 25/14C12M 23/08C12N 5/0068C12M 23/20C12N 2537/10A61L 29/041D01F 6/625D01F 1/10D01D 5/0007A61L 31/16A61L 27/50A61L 31/14A61L 2400/12A61L 27/54A61L 27/34A61L 2300/00D01F 6/26G01N 33/48A61L 31/048A61L 29/14A61L 29/16D06M 2400/01A61L 31/10D01F 6/22D06M 15/285A61L 29/085
50
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Claims

Abstract

A stimuli responsive nanofiber that includes a stimuli responsive polymer, such as a thermally responsive polymer, and a cross-linking agent having at least two latent reactive activatable groups. The nanofiber may also include a biologically active material or a functional polymer. The stimuli responsive nanofiber can be used to modify the surface of a substrate. When the nanofiber includes a thermally responsive polymer, the physical properties of the surface can be controlled by controlling the temperature of the system, thus controlling the ability of the surface to bind to a biologically active material of interest.

Claims

exact text as granted — not AI-modified
1 .- 52 . (canceled) 
     
     
         53 . A cell culture article comprising a surface and a coating composition in contact with the surface, the coating composition comprising:
 (a) a thermally responsive polymer, and   (b) a monomeric or polymeric crosslinking agent having at least two latent photoreactive groups capable of forming covalent bonds when the coating composition is subjected to electromagnetic energy, thereby coupling the thermally responsive polymer to the surface of the cell culture article in a manner in which at least some of the latent photoreactive groups remain in an inactive state.   
     
     
         54 . The article according to  claim 53  wherein the latent photoreactive groups are capable of forming a covalent bond with the surface. 
     
     
         55 . The article according to  claim 54  wherein the covalent bond is formed by carbon or nitrogen bond insertion, hydrogen abstraction followed by radical recombination, or dimerization. 
     
     
         56 . The article according to  claim 53  wherein the latent photoreactive groups are aryl ketones. 
     
     
         57 . The article according to  claim 56  wherein the aryl ketones are selected from acetophenones, benzophenones, anthraquinones, anthrones, and anthrone-like heterocycles. 
     
     
         58 . The article according to  claim 53  wherein the crosslinking agent is a compound having a formula selected from (a) to (g):
 (a) L-(D-T-C(R 1 )(XP)CHR 2 GR 3 C(═O)R 4 ) m  
 wherein L is a linking group; 
 D is O, S, SO, SO 2 , NR 5  or CR 6 R 7 ; 
 T is (—CH 2 —) x , (—CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 CH 2 —O—) x  or forms a bond; 
 R 1  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 X is O, S, or NR 8 R 9 ; 
 P is a hydrogen atom or a protecting group, with the proviso that P is absent when X is NR 8 R 9 ; 
 R 2  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 R 3  and R 4  are each independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (—CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 R 5  and R 10  are a hydrogen atom or an alkyl, aryl or arylalkyl group; 
 R 6  and R 7  are each independently a hydrogen atom, an alkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl group; 
 R 8  and R 9  are each independently a hydrogen atom, an alkyl, aryl, or arylalkyl group; 
 R is a hydrogen atom, an alkyl or an aryl group; 
 q is an integer from 1 to about 7; 
 r is an integer from 0 to about 3; 
 s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; 
 t is an integer from 1 to about 10; and 
 x is an integer from 1 to about 500; 
 
 (b) L-(T-C(R 1 )(XP)CHR 2 GR 3 C(═O)R 4 ) m  
 wherein L is a linking group; 
 T is (—CH 2 —) x , (—CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 CH 2 —O—) x  or forms a bond; 
 R 1  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 X is O, S, or NR 8 R 9 ; 
 P is a hydrogen atom or a protecting group, with the proviso that P is absent when X is NR 8 R 9 ; 
 R 2  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 R 3  and R 4  are each independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group, or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (—CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 R 10  is a hydrogen atom or an alkyl, aryl or arylalkyl group; 
 R 8  and R 9  are each independently a hydrogen atom, an alkyl, aryl, or arylalkyl group; 
 R is a hydrogen atom, an alkyl or aryl group; 
 q is an integer from 1 to about 7; 
 r is an integer from 0 to about 3; 
 s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; 
 t is an integer from 1 to about 10; and 
 x is an integer from 1 to about 500; 
 
 (c) L-(GTZR 3 C(═O)R 4 ) m  
 wherein L is a linking group; 
 T is (—CH 2 —) x , (—CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 CH 2 —O—) x  or forms a bond; 
 G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 Z is C═O, COO, or CONH when T is (—CH 2 —) x ; 
 R 3  and R 4  are each independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group, or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (—CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 R 10  is a hydrogen atom or an alkyl, aryl or arylalkyl group; 
 R is a hydrogen atom or an alkyl or aryl group; 
 q is an integer from 1 to about 7; 
 r is an integer from 0 to about 3; 
 s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; 
 t is an integer from 1 to about 10; and 
 x is an integer from 1 to about 500; 
 
 (d) L-(TGQR 3 C(═O)R 4 ) m  
 wherein L is a linking group; 
 T is (—CH 2 —) x , (—CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 CH 2 —O—) x  or forms a bond; 
 G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 Q is (—CH 2 —) p , (—CH 2 CH 2 —O—) p , (—CH 2 CH 2 CH 2 —O—) p  or (—CH 2 CH 2 CH 2 CH 2 —O—) p ; 
 R 3  and R 4  are each independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group, or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (—CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 R 10  is a hydrogen atom or an alkyl, aryl, or an arylalkyl group; 
 R is a hydrogen atom or an alkyl or aryl group; 
 q is an integer from 1 to about 7; 
 r is an integer from 0 to about 3; 
 s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; 
 p is an integer from 1 to about 10; 
 t is an integer from 1 to about 10; and 
 x is an integer from 1 to about 500; 
 
 (e) L-(—CH 2 —) xx C(R 1 )(GR 3 C(═O)R 4 ) m  
 wherein L is a linking group; 
 R 1  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl, or aryloxyaryl group; 
 each G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 each R 3  and R 4  is independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group, or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (—CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 each R 10  is a hydrogen atom or an alkyl, aryl, or an arylalkyl group; 
 each R is a hydrogen atom or an alkyl or aryl group; 
 each q is an integer from 1 to about 7; 
 each r is an integer from 0 to about 3; 
 each s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; 
 each t is an integer from 1 to about 10; and 
 xx is an integer from 1 to about 10; 
 
 (f) L-(C(R 1 )(XP)CHR 2 GR 3 C(═O)R 4 ) m  
 wherein L is a linking group; 
 R 1  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 X is O, S, or NR 8 R 9 ; 
 P is a hydrogen atom or a protecting group, with the proviso that P is absent when X is NR 8 R 9 ; 
 R 2  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 R 3  and R 4  are each independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group, or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (—CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 R 8  and R 9  are each independently a hydrogen atom, an alkyl, aryl, or arylalkyl group; 
 R 10  is a hydrogen atom or an alkyl, aryl, or an arylalkyl group; 
 R is a hydrogen atom, an alkyl or an aryl group; 
 q is an integer from 1 to about 7; 
 r is an integer from 0 to about 3; 
 s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; and 
 t is an integer from 1 to about 10; and 
 
 (g) L-(GR 3 C(═O)R 4 ) m ;
 wherein L is a linking group; 
 G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 R 3  and R 4  are each independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group, or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (—CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 R 10  is a hydrogen atom or an alkyl, aryl or arylalkyl group; 
 R is a hydrogen atom, an alkyl or an aryl group; 
 q is an integer from 1 to about 7; 
 r is an integer from 0 to about 3; 
 s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; and 
 t is an integer from 1 to about 10. 
 
 
     
     
         59 . The article according to  claim 53  wherein the cell culture article is selected from slides, multi-well plates, Petri dishes, tissue culture plates, tissue culture flasks, and coverslips. 
     
     
         60 . A cell culture article having a thermally responsive surface, the cell culture article comprising a thermally responsive polymer covalently coupled to a surface of the cell culture article via a monomeric or polymeric crosslinking agent,
 wherein the crosslinking agent includes at least two latent photoreactive groups,   wherein at least one of the latent photoreactive groups has undergone activation when subjected to a suitable energy source to form a covalent bond with the surface of the cell culture article, and remaining latent photoreactive groups are present at a ground state energy level.   
     
     
         61 . The article according to  claim 60  wherein the latent photoreactive groups are capable of forming a covalent bond with the surface. 
     
     
         62 . The article according to  claim 61  wherein the covalent bond is formed by carbon or nitrogen bond insertion, hydrogen abstraction followed by radical recombination, or dimerization. 
     
     
         63 . The article according to  claim 60  wherein the latent photoreactive groups are aryl ketones. 
     
     
         64 . The article according to  claim 60  wherein the crosslinking agent is a compound having a formula selected from (a) to (g):
 (a) L-(D-T-C(R 1 )(XP)CHR 2 GR 3 C(═O)R 4 ) m  
 wherein L is a linking group; 
 D is O, S, SO, SO 2 , NR 5  or CR 6 R 7 ; 
 T is (—CH 2 —) x , (—CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 CH 2 —O—) x  or forms a bond; 
 R 1  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 X is O, S, or NR 8 R 9 ; 
 P is a hydrogen atom or a protecting group, with the proviso that P is absent when X is NR 8 R 9 ; 
 R 2  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 
 R 3  and R 4  are each independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (—CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ;
 R 5  and R 19  are a hydrogen atom or an alkyl, aryl or arylalkyl group; 
 R 6  and R 7  are each independently a hydrogen atom, an alkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl group; 
 R 8  and R 9  are each independently a hydrogen atom, an alkyl, aryl, or arylalkyl group; 
 R is a hydrogen atom, an alkyl or an aryl group; 
 q is an integer from 1 to about 7; 
 r is an integer from 0 to about 3; 
 s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; 
 t is an integer from 1 to about 10; and 
 x is an integer from 1 to about 500; 
 
 (b) L-(T-C(R 1 )(XP)CHR 2 GR 3 C(═O)R 4 ) m  
 wherein L is a linking group; 
 T is (—CH 2 —) x , (—CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 CH 2 —O—) x  or forms a bond; 
 R 1  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 X is O, S, or NR 8 R 9 ; 
 P is a hydrogen atom or a protecting group, with the proviso that P is absent when X is NR 8 R 9 ; 
 R 2  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 R 3  and R 4  are each independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group, or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (—CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 R 10  is a hydrogen atom or an alkyl, aryl or arylalkyl group; 
 R 8  and R 9  are each independently a hydrogen atom, an alkyl, aryl, or arylalkyl group; 
 R is a hydrogen atom, an alkyl or aryl group; 
 q is an integer from 1 to about 7; 
 r is an integer from 0 to about 3; 
 s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; 
 t is an integer from 1 to about 10; and 
 x is an integer from 1 to about 500; 
 
 (c) L-(GTZR 3 C(═O)R 4 ) m  
 wherein L is a linking group; 
 T is (—CH 2 —) x , (—CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 CH 2 —O—) x  or forms a bond; 
 G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 Z is C═O, COO, or CONH when T is (—CH 2 —) x ; 
 R 3  and R 4  are each independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group, or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (—CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 R 10  is a hydrogen atom or an alkyl, aryl or arylalkyl group; 
 R is a hydrogen atom or an alkyl or aryl group; 
 q is an integer from 1 to about 7; 
 r is an integer from 0 to about 3; 
 s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; 
 t is an integer from 1 to about 10; and 
 x is an integer from 1 to about 500; 
 
 (d) L-(TGQR 3 C(═O)R 4 ) m  
 wherein L is a linking group; 
 T is (—CH 2 —) x , (—CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 —O—) x , (—CH 2 CH 2 CH 2 CH 2 —O—) x  or forms a bond; 
 G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 Q is (—CH 2 —) p , (—CH 2 CH 2 —O—) p , (—CH 2 CH 2 CH 2 —O—) p  or (—CH 2 CH 2 CH 2 CH 2 —O—) p ; 
 R 3  and R 4  are each independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group, or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (—CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 R 10  is a hydrogen atom or an alkyl, aryl, or an arylalkyl group; 
 R is a hydrogen atom or an alkyl or aryl group; 
 q is an integer from 1 to about 7; 
 r is an integer from 0 to about 3; 
 s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; 
 p is an integer from 1 to about 10; 
 t is an integer from 1 to about 10; and 
 x is an integer from 1 to about 500; 
 
 (e) L-(—CH 2 —) xx C(R 1 )(GR 3 C(═O)R 4 ) m  
 wherein L is a linking group; 
 R 1  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl, or aryloxyaryl group; 
 each G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 each R 3  and R 4  is independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group, or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (—CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 each R 10  is a hydrogen atom or an alkyl, aryl, or an arylalkyl group; 
 each R is a hydrogen atom or an alkyl or aryl group; 
 each q is an integer from 1 to about 7; 
 each r is an integer from 0 to about 3; 
 each s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; 
 each t is an integer from 1 to about 10; and 
 xx is an integer from 1 to about 10; 
 
 (f) L-(—C(R 1 )(XP)CHR 2 GR 3 C(═O)R 4 ) m  
 wherein L is a linking group; 
 R 1  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 X is O, S, or NR 8 R 9 ; 
 P is a hydrogen atom or a protecting group, with the proviso that P is absent when X is NR 8 R 9 ; 
 R 2  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 R 3  and R 4  are each independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group, or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (—CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 R 8  and R 9  are each independently a hydrogen atom, an alkyl, aryl, or arylalkyl group; 
 R 10  is a hydrogen atom or an alkyl, aryl, or an arylalkyl group; 
 R is a hydrogen atom, an alkyl or an aryl group; 
 q is an integer from 1 to about 7; 
 r is an integer from 0 to about 3; 
 s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; and 
 t is an integer from 1 to about 10; and 
 
 (g) L-(GR 3 C(═O)R 4 ) m ;
 wherein L is a linking group; 
 G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 R 3  and R 4  are each independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group, or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , —(CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 R 10  is a hydrogen atom or an alkyl, aryl or arylalkyl group; 
 R is a hydrogen atom, an alkyl or an aryl group; 
 q is an integer from 1 to about 7; 
 r is an integer from 0 to about 3; 
 s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; and 
 t is an integer from 1 to about 10. 
 
 
     
     
         65 . The article according to  claim 60  wherein the cell culture article is selected from slides, multi-well plates, Petri dishes, tissue culture plates, tissue culture flasks, and coverslips. 
     
     
         66 . The article according to  claim 53  wherein the surface of the cell culture article further comprises a biologically active material. 
     
     
         67 . A coating composition for coating a substrate, the coating composition comprising:
 (a) a thermally responsive polymer, and   (b) a monomeric or polymeric crosslinking agent having at least two latent photoreactive groups capable of forming covalent bonds with a surface of the substrate when the coating composition is subjected to electromagnetic energy,   thereby coupling the thermally responsive polymer to the surface of the substrate in a manner in which at least some of the latent photoreactive groups remain in an inactive state.   
     
     
         68 . The article according to  claim 67  wherein the latent photoreactive groups are capable of forming a covalent bond with the surface. 
     
     
         69 . The article according to  claim 68  wherein the covalent bond is formed by carbon or nitrogen bond insertion, hydrogen abstraction followed by radical recombination, or dimerization. 
     
     
         70 . The coating composition according to  claim 67  wherein the photoreactive groups are aryl ketones. 
     
     
         71 . The coating composition according to  claim 70  wherein the aryl ketone aryl ketones are selected from acetophenones, benzophenones, anthraquinones, anthrones, and anthrone-like heterocycles. 
     
     
         72 . The article according to  claim 60  wherein the surface of the cell culture article further comprises a biologically active material.

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