Materials with improved properties

Abstract

Products, such as devices, prostheses, and materials, whose surfaces have been modified in order to impart beneficial properties to these products are disclosed. The surface-modified products have improved biocompatibility compared to a corresponding product that lacks the modification. Following implantation in a subject, the surface-modified products induce a lower foreign-body response, compared to a corresponding unmodified product.

1 - 20 . (canceled) 
     
     
         21 . A macroscopic device comprising a cell that produces a therapeutically effective substance, wherein a surface of the macroscopic device is modified with a structure —X—R 1 , wherein:
 X is oxygen, sulfur, or NR 2 ; 
 R 2  is hydrogen; 
 R 1  has the structure
   -A-B(—C) δ ,  Formula XII
 
 
 A is 
 
       
         
           
           
               
               
           
         
         wherein R 18  in A is —(CR 19 R 19 ) p —; p is an integer from 0 to 5; each R 19  is hydrogen; each R d  is independently alkyl, alkenyl, alkynyl, substituted alkyl, substituted alkenyl, substituted alkynyl, alkoxy, alkylamino, dialkylamino, hydroxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, substituted alkoxy, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, or substituted heterocyclic; z is an integer from 0 to 11; R 12 , R 13 , R 14 , R 15 , R 16 , and R 17  are independently C or N, wherein the bonds between adjacent R 12  to R 17  are double or single according to valency, and wherein R 12  to R 17  are bound to none, one, or two hydrogens according to valency; or 
       
       
         
           
           
               
               
           
         
         wherein R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , and R 28  in A are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, substituted arylalkyl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, substituted heterocyclic, poly(ethylene glycol), or poly(lactic-co-glycolic acid); k is an integer from 0 to 20; each X d  is independently absent, O, or S; and R c  is B; 
         B is 
       
       
         
           
           
               
               
           
         
         wherein R 18  in B is —(CR 19 R 19 ) p —; p is an integer from 0 to 5; each R 19  is hydrogen; each R d  is independently alkyl, alkenyl, alkynyl, substituted alkyl, substituted alkenyl, substituted alkynyl, alkoxy, alkylamino, dialkylamino, hydroxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, substituted alkoxy, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, or substituted heterocyclic; w is an integer from 0 to 4; each R 12 , R 13 , R 14 , R 15 , and R 16 , are independently C or N, wherein the bonds between adjacent R 12  to R 16  are double or single according to valency, and wherein R 12  to R 16  are bound to none, one, or two hydrogens according to valency; 
         C is 
       
       
         
           
           
               
               
           
         
         wherein R 18  in C is —(CR 19 R 19 ) p — or —(CR 19 R 19 ) p —X b —(CR 19 R 19 ) q —, wherein p and q are independently integers from 0 to 5; X b  is absent, —O—, —S—, —S(O)—, —S(O) 2 —, or NR 20 ; each R 19  is hydrogen; R 20  is alkyl or substituted alkyl; R d  are independently alkyl, alkenyl, alkynyl, substituted alkyl, substituted alkenyl, substituted alkynyl, alkoxy, alkylamino, dialkylamino, hydroxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, substituted alkoxy, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, or substituted heterocyclic; z is an integer from 0 to 11; wherein R 12 , R 13 , R 14 , R 15 , R 16 , and R 17  are independently C, O, N, S, S(O), or S(O) 2 , wherein the bonds between adjacent R 12  to R 17  are double or single according to valency, and wherein R 12  to R 17  are bound to none, one, or two hydrogens according to valency; and 
         wherein δ is 1. 
       
     
     
         22 . The macroscopic device of  claim 21 , wherein the surface of the macroscopic device has at least 10 chemical derivatizations per μm 2  on the surface or a surface of the products. 
     
     
         23 . The macroscopic device of  claim 21 , wherein the concentration of surface modifications of the macroscopic device is in the range of 0.1 to 50 percent surface modifications. 
     
     
         24 . The macroscopic device of  claim 21 , wherein the cell comprises a retinal epithelial cell. 
     
     
         25 . The macroscopic device of  claim 21 , wherein the cell comprises a genetically engineered cell. 
     
     
         26 . The macroscopic device of  claim 21 , wherein the therapeutically effective agent comprises an agent from a row in Table 2. 
     
     
         27 . The macroscopic device of  claim 21 , wherein the therapeutically effective agent is provided in sufficient amount to treat a disorder from a row in Table 2. 
     
     
         28 . The macroscopic device of  claim 27 , wherein the disorder is selected from diabetes or a lysosomal storage disease. 
     
     
         29 . The macroscopic device of  claim 21 , wherein the therapeutically effective substance comprises a protein. 
     
     
         30 . The macroscopic device of  claim 21 , wherein the therapeutically effective substance comprises protein comprising a hormone, growth factor, enzyme, antibody, peptide, or cytokine. 
     
     
         31 . The macroscopic device of  claim 21 , wherein for the moiety of structure —X—R 1 :
 R 1  is, independently in one or more sites of chemical modification, 
 
       
         
           
           
               
               
           
         
         R a  is alkylamino, dialkylamino, hydroxy, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, polyaryl, substituted polyaryl, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, substituted heterocyclic, amino acid, poly(ethylene glycol), peptide, polypeptide group, arylalkyl substituted arylalkyl, sulfonyl, substituted sulfonyl, sulfonic acid, phosphoryl, substituted phosphoryl, phosphonyl, and substituted phosphonyl, or poly(lactic-co-glycolic acid); 
         R 4 , and R 5 , are, independently, hydrogen methyl, or —CH 2 —OH; 
         C is methyl, —COCH 3 , —CH 2 —N(CH 2 —CH 3 ) 2 , 
       
       
         
           
           
               
               
           
         
         a is an integer from 1 to 30; 
         z is an integer from 0-5; 
         n is an integer from 1 to 12; and 
         m is an integer from 3 to 16. 
       
     
     
         32 . The macroscopic device of  claim 21 , wherein the moiety of structure —X—R 1  comprises: 
       
         
           
           
               
               
           
         
       
     
     
         33 . A method of providing a therapeutically effective substance to a subject comprising implanting in the subject a macroscopic device comprising a cell that produces the therapeutically effective substance, wherein a surface of the macroscopic device is modified with a structure —X—R 1 , wherein:
 X is oxygen, sulfur, or NR 2 ; 
 R 2  is hydrogen; 
 R 1  has the structure
   -A-B(—C) δ ,  Formula XII
 
 
 A is 
 
       
         
           
           
               
               
           
         
         wherein R 18  in A is —(CR 19 R 19 ) p —; p is an integer from 0 to 5; each R 19  is hydrogen; each R d  is independently alkyl, alkenyl, alkynyl, substituted alkyl, substituted alkenyl, substituted alkynyl, alkoxy, alkylamino, dialkylamino, hydroxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, substituted alkoxy, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, or substituted heterocyclic; z is an integer from 0 to 11; R 12 , R 13 , R 14 , R 15 , R 16 , and R 17  are independently C or N, wherein the bonds between adjacent R 12  to R 17  are double or single according to valency, and wherein R 12  to R 17  are bound to none, one, or two hydrogens according to valency; or 
       
       
         
           
           
               
               
           
         
         wherein R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , and R 28  in A are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, substituted arylalkyl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, substituted heterocyclic, poly(ethylene glycol), or poly(lactic-co-glycolic acid); k is an integer from 0 to 20; each X d  is independently absent, O, or S; and R c  is B; 
         B is 
       
       
         
           
           
               
               
           
         
         wherein R 18  in B is —(CR 19 R 19 ) p —; p is an integer from 0 to 5; each R 19  is hydrogen; each R d  is independently alkyl, alkenyl, alkynyl, substituted alkyl, substituted alkenyl, substituted alkynyl, alkoxy, alkylamino, dialkylamino, hydroxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, substituted alkoxy, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, or substituted heterocyclic; w is an integer from 0 to 4; each R 12 , R 13 , R 14 , R 15 , and R 16 , are independently C or N, wherein the bonds between adjacent R 12  to R 16  are double or single according to valency, and wherein R 12  to R 16  are bound to none, one, or two hydrogens according to valency; 
         C is 
       
       
         
           
           
               
               
           
         
         wherein R 18  in C is —(CR 19 R 19 ) p — or —(CR 19 R 19 ) p —X b —(CR 19 R 19 ) q —, wherein p and q are independently integers from 0 to 5; X b  is absent, —O—, —S—, —S(O)—, —S(O) 2 —, or NR 20 ; each R 19  is hydrogen; R 20  is alkyl or substituted alkyl; R d  are independently alkyl, alkenyl, alkynyl, substituted alkyl, substituted alkenyl, substituted alkynyl, alkoxy, alkylamino, dialkylamino, hydroxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, substituted alkoxy, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, or substituted heterocyclic; z is an integer from 0 to 11; wherein R 12 , R 13 , R 14 , R 15 , R 16 , and R 17  are independently C, O, N, S, S(O), or S(O) 2 , wherein the bonds between adjacent R 12  to R 17  are double or single according to valency, and wherein R 12  to R 17  are bound to none, one, or two hydrogens according to valency; and 
         wherein δ is 1. 
       
     
     
         34 . The method of  claim 33 , wherein the surface of the macroscopic device has at least 10 chemical derivatizations per μm 2  on the surface or a surface of the products. 
     
     
         35 . The method of  claim 33 , wherein the concentration of surface modifications of the macroscopic device is in the range of 0.1 to 50 percent surface modifications. 
     
     
         36 . The method of  claim 33 , wherein the cell comprises a retinal epithelial cell. 
     
     
         37 . The method of  claim 33 , wherein the cell comprises a genetically engineered cell. 
     
     
         38 . The method of  claim 33 , wherein the therapeutically effective agent comprises an agent from a row in Table 2. 
     
     
         39 . The method of  claim 33 , wherein the therapeutically effective agent is provided in sufficient amount to treat a disorder from a row in Table 2. 
     
     
         40 . The method of  claim 39 , wherein the disorder is selected from diabetes or a lysosomal storage disease. 
     
     
         41 . The method of  claim 33 , wherein the therapeutically effective substance comprises a protein. 
     
     
         42 . The method of  claim 33 , wherein the therapeutically effective substance comprises protein comprises hormone, growth factor, enzyme, antibody, peptide, or cytokine. 
     
     
         43 . The method of  claim 33 , wherein for the moiety of structure —X—R 1 :
 R 1  is, independently in one or more sites of chemical modification, 
 
       
         
           
           
               
               
           
         
         R a  is alkylamino, dialkylamino, hydroxy, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, polyaryl, substituted polyaryl, C 3 -C 20  cyclic, substituted C 3 -C 20  cyclic, heterocyclic, substituted heterocyclic, amino acid, poly(ethylene glycol), peptide, polypeptide group, arylalkyl substituted arylalkyl, sulfonyl, substituted sulfonyl, sulfonic acid, phosphoryl, substituted phosphoryl, phosphonyl, and substituted phosphonyl, or poly(lactic-co-glycolic acid); 
         R 3 , and R 4 , are, independently, hydrogen methyl, or —CH 2 —OH; 
         C is methyl, —COCH 3 , —CH 2 —N(CH 2 —CH 3 ) 2 , 
       
       
         
           
           
               
               
           
         
         a is an integer from 1 to 30; 
         z is an integer from 0-5; 
         n is an integer from 1 to 12; and 
         m is an integer from 3 to 16. 
       
     
     
         44 . The method of  claim 33 , wherein the moiety of structure —X—R 1  comprises: