Engineered scaffolds for vascularized tissue repair

Abstract

The present invention provides scaffolds that include a polymer and a cyclic peptide ligand. The peptide ligand increases the attachment of endothelial cells and/or progenitor cells to the scaffold. The present invention also provides engineered tissues that include the provided scaffolds. The present invention also provides coatings that include a coating polymer and a cyclic peptide ligand. The present invention also provides methods of improving endothelialization and vascularization of endothelial cells and/or progenitor cells for tissue regeneration in a subject and of repairing bone defects in a subject, by implanting a provided scaffold.

1 - 33 . (canceled) 
     
     
         34 . A medical device comprising:
 a scaffold; and   a coating on a surface of the scaffold, wherein the coating comprises:
 a coating polymer, hydroxyapatite, or a combination thereof; and 
 a peptide ligand selected from the group consisting of cGRGDdvc, cGRGDsfc, cGRGDdfc, cGRGDsec, cGRGDdsc, cGRGDd-DBug-c, cGRGDd-DBta-c, Ac-cGRGDdvc, (β-alanine)-cGRGDdvc, (Ebes)-cGRGDdvc, cGRGDd-DAgl-c, cGRGDd-DPra-c, cGRGDd-D(NMe)Val-c, cGRGDd-D(CαMe)Val-c, cGRGDd-DAbu-c, cGRGDd-DNal1-c, cGRGDd-DNal2-c, and functionalized derivatives thereof. 
   
     
     
         35 . The medical device of  claim 34 , wherein the scaffold comprises a scaffold polymer. 
     
     
         36 . The medical device of  claim 35 , wherein the scaffold polymer is selected from the group consisting of poly (L-lactic acid) (PLLA), polycaprolactone (PCL), poly (lactic-co-glycolic acid) (PLGA), poly(lactide-co-ε-caprolactone) (PLCL), polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), and combinations thereof. 
     
     
         37 . The medical device of  claim 36 , wherein the scaffold polymer comprises PTFE. 
     
     
         38 . The medical device of  claim 34 , wherein the scaffold has a form of a vascular graft, a stent, a shunt, a patch, a cardiac valve, or a catheter. 
     
     
         39 . The medical device of  claim 38 , wherein the scaffold has the form of a vascular graft. 
     
     
         40 . The medical device of  claim 39 , wherein the vascular graft is an arteriovenous dialysis graft. 
     
     
         41 . The medical device of  claim 34 , wherein the coating comprises a coating polymer. 
     
     
         42 . The medical device of  claim 41 , wherein the coating polymer comprises a parylene polymer. 
     
     
         43 . The medical device of  claim 41 , wherein the peptide ligand is covalently attached to the coating polymer. 
     
     
         44 . The medical device of  claim 34 , wherein the peptide ligand is selected from the group consisting of cGRGDdvc, cGRGDsfc, cGRGDdfc, cGRGDsec, cGRGDdsc, cGRGDd-DBug-c, cGRGDd-DBta-c, and functionalized derivatives thereof. 
     
     
         45 . The medical device of  claim 44 , wherein the peptide ligand is cGRGDdvc (LXW7) or a functionalized derivative thereof. 
     
     
         46 . The medical device of  claim 34 , further comprising:
 endothelial cells or endothelial progenitor cells seeded on the medical device.   
     
     
         47 . The medical device of  claim 34 , wherein
 the scaffold comprises PTFE,   the scaffold has a form of an arteriovenous dialysis graft,   the coating comprises a coating polymer,   the coating polymer comprises a parylene polymer,   the peptide ligand is covalently attached to the parylene polymer, and   the peptide ligand comprises LXW7 or a functionalized derivative thereof.   
     
     
         48 . A method of treating a subject in need of hemodialysis, the method comprising creating a vascular access for the subject, wherein the vascular access includes a medical device comprising:
 a scaffold having a form of an arteriovenous dialysis graft; and   a coating on a surface of the scaffold, wherein the coating comprises:
 a coating polymer, hydroxyapatite, or a combination thereof; and 
 a peptide ligand selected from the group consisting of cGRGDdvc, cGRGDsfc, cGRGDdfc, cGRGDsec, cGRGDdsc, cGRGDd-DBug-c, cGRGDd-DBta-c, Ac-cGRGDdvc, (β-alanine)-cGRGDdvc, (Ebes)-cGRGDdvc, cGRGDd-DAgl-c, cGRGDd-DPra-c, cGRGDd-D(NMe)Val-c, cGRGDd-D(CαMe)Val-c, cGRGDd-DAbu-c, cGRGDd-DNal1-c, cGRGDd-DNal2-c, and functionalized derivatives thereof. 
   
     
     
         49 . The method of  claim 48  wherein
 the scaffold comprises PTFE, 
 the coating comprises a coating polymer, 
 the coating polymer comprises a parylene polymer, 
 the peptide ligand is covalently attached to the parylene polymer, and 
 the peptide ligand comprises cGRGDdvc (LXW7) or a functionalized derivative thereof. 
 
     
     
         50 . A method of manufacturing a medical device, the method comprising:
 providing a scaffold;   applying a coating polymer to a surface of the scaffold;   functionalizing the coating polymer; and   covalently attaching a peptide ligand to the coating polymer, wherein the peptide ligand is selected from the group consisting of cGRGDdvc, cGRGDsfc, cGRGDdfc, cGRGDsec, cGRGDdsc, cGRGDd-DBug-c, cGRGDd-DBta-c, Ac-cGRGDdvc, (β-alanine)-cGRGDdvc, (Ebes)-cGRGDdvc, cGRGDd-DAgl-c, cGRGDd-DPra-c, cGRGDd-D(NMe)Val-c, cGRGDd-D(CαMe)Val-c, cGRGDd-DAbu-c, cGRGDd-DNal1-c, cGRGDd-DNal2-c, and functionalized derivatives thereof.   
     
     
         51 . The method of  claim 50 , further comprising:
 activating the surface of the scaffold prior to the applying of the coating polymer to the surface.   
     
     
         52 . The method of  claim 50 , further comprising:
 functionalizing the coating polymer prior to the covalent attaching of the peptide ligand to the coating polymer.   
     
     
         53 . The method of  claim 50 , wherein
 the scaffold comprises PTFE,   the scaffold has a form of an arteriovenous dialysis graft,   the coating polymer comprises a parylene polymer,   the peptide ligand is covalently attached to the parylene polymer, and   the peptide ligand comprises cGRGDdvc (LXW7) or a functionalized derivative thereof.