Anti-inflammatory nanofibers

Abstract

Provided herein are anti-inflammatory nanofibers and methods of use thereof. In particular methods are provided for the use of anti-inflammatory nanofibers in the promotion of tissue (e.g., urinary bladder tissue) regeneration.

1 . A peptide amphiphile comprising:
 (a) a hydrophobic non-peptidic segment;   (b) a structural peptide segment;   (c) a charged peptide segment; and   (d) an anti-inflammatory peptide segment;   wherein the hydrophobic non-peptidic segment is covalently attached to the N-terminus of the structural peptide segment;   wherein the C-terminus of the structural peptide segment is covalently attached to the N-terminus of the charged peptide segment; and   wherein the C-terminus of the charged peptide segment is covalently attached to the N-terminus of the anti-inflammatory peptide segment.   
     
     
         2 . The peptide amphiphile of  claim 1 , wherein the comprises at least 50% sequence identity with one of MQMKKVLDS (SEQ ID NO:7), HDMNKVLDL (SEQ ID NO:8), KVLDPVKG (SEQ ID NO:9), KVLDGQDP (SEQ ID NO:10), and DPVKG (SEQ ID NO:11). 
     
     
         3 . The peptide amphiphile of  claim 1 , wherein the comprises at least 70% sequence similarity with one of MQMKKVLDS (SEQ ID NO:7), HDMNKVLDL (SEQ ID NO:8), KVLDPVKG (SEQ ID NO:9), KVLDGQDP (SEQ ID NO:10), and DPVKG (SEQ ID NO:11). 
     
     
         4 . The peptide amphiphile of  claim 1 , wherein the hydrophobic non-peptidic segment comprises an acyl chain. 
     
     
         5 . The peptide amphiphile of  claim 4 , wherein the acyl chain comprises C 6 -C 20 . 
     
     
         6 . The peptide amphiphile of  claim 5 , wherein the acyl chain comprises C 16 . 
     
     
         7 . The peptide amphiphile of  claim 1 , wherein the structural peptide segment comprises a β-sheet-forming peptide segment. 
     
     
         8 . The peptide amphiphile of  claim 7 , wherein the β-sheet-forming peptide segment comprises alanine (A) and valine (V). 
     
     
         9 . The peptide amphiphile of  claim 8 , wherein the β-sheet-forming peptide segment comprises AV. 
     
     
         10 . The peptide amphiphile of  claim 9 , wherein the β-sheet-forming peptide segment comprises AAVV (SEQ ID NO:15). 
     
     
         11 . The peptide amphiphile of  claim 10 , wherein the β-sheet-forming peptide segment comprises AAAVVV (SEQ ID NO:16). 
     
     
         12 . The peptide amphiphile of  claim 1 , wherein the charged peptide segment comprises a plurality of Lys (K), Arg (R), Glu (E) and/or Asp (D) residues. 
     
     
         13 . The peptide amphiphile of  claim 12 , wherein the charged peptide segment comprises 2-7 amino acids in length with 50% or more amino acids selected from Lys (K), Arg (R), Glu (E) and/or Asp (D) residues. 
     
     
         14 . The peptide amphiphile of  claim 13 , wherein the charged peptide segment comprises EE. 
     
     
         15 . The peptide amphiphile of  claim 14 , wherein the charged peptide segment comprises EEE. 
     
     
         16 . The peptide amphiphile of  claim 1 , comprising: 
       
         
           
                 
                 
               
                     
                   (i) 
                 
                     
                   (CH 2 ) 10-20 -V 2-3 A 2-3 E 2-3   
                 
                     
                   (SEQ ID NOS: 1, 17-23) 
                 
                     
                   MQMKKVLDS; 
                 
                     
                     
                 
                     
                   (ii) 
                 
                     
                   (CH 2 ) 10-20 -V 2-3 A 2-3 E 2-3   
                 
                     
                   (SEQ ID NOS: 2, 24-30) 
                 
                     
                   HDMNKVLDL; 
                 
                     
                     
                 
                     
                   (iii) 
                 
                     
                   (CH 2 ) 10-20 -V 2-3 A 2-3 E 2-3   
                 
                     
                   (SEQ ID NOS: 3, 31-37) 
                 
                     
                   KVLDPVKG; 
                 
                     
                     
                 
                     
                   (iv) 
                 
                     
                   (CH 2 ) 10-20 -V 2-3 A 2-3 E 2-3   
                 
                     
                   (SEQ ID NOS: 4, 38-44) 
                 
                     
                   KVLDGQDP; 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   (v) 
                 
                     
                   (CH 2 ) 10-20 -V 2-3 A 2-3 E 2-3   
                 
                     
                   (SEQ ID NOS: 5, 45-51) 
                 
                     
                   DPVKG. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         17 . A nanofiber comprising a peptide amphiphile of  claim 1 . 
     
     
         18 . A method of promoting tissue regeneration in a subject comprising administering a peptide amphiphile of  claim 1  to a subject. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 18 , wherein inflammation is reduced in the subject. 
     
     
         21 . The method of  claim 18 , wherein both innate and adaptive immune responses are modulated.