Engineered scaffolds for vascularized tissue repair
View Patent ↗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. A scaffold sculpted or molded into a form of at least a portion of a stent, a shunt, a vascular graft, a patch, a cardiac valve, or a catheter, the scaffold comprising:
a biopolymer functionalized with chemical groups facilitating covalent attachment of the biopolymer to a peptide ligand; and
the peptide ligand, wherein the peptide ligand is covalently immobilized on the surface of the biopolymer, wherein the peptide ligand increases a number of endothelial cells and/or endothelial progenitor cells attached to the scaffold relative to a number of endothelial cells and/or endothelial progenitor cells attached to a corresponding scaffold not comprising the peptide ligand, and
wherein the peptide ligand is cGRGDdvc (LXW7) (SEQ ID No. 1).
2. The scaffold of claim 1 , wherein the biopolymer 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.
3. The scaffold of claim 1 , wherein the biopolymer is a coating on at least a portion of a surface of the scaffold.
4. The scaffold of claim 3 , wherein the coating is a parylene polymer.
5. The scaffold of claim 1 , wherein endothelial cells, endothelial progenitor cells, and/or osteogenic cells are seeded on the scaffold.
6. The scaffold of claim 1 , wherein the scaffold is an electrospun microfibrous scaffold.
7. The scaffold of claim 1 , wherein the scaffold is a bony construct.
8. An engineered tissue comprising the scaffold of claim 1 .
9. A coating on a surface of a scaffold sculpted or molded into a form of at least a portion of a stent, a shunt, a vascular graft, a patch, a cardiac valve, or a catheter comprising:
a coating polymer; and
the peptide ligand of claim 1 , wherein the peptide ligand is covalently attached to the coating polymer.
10. The coating of claim 9 , wherein the coating polymer is a parylene polymer.
11. A method for improving endothelialization and vascularization of endothelial cells and/or endothelial progenitor cells for tissue regeneration in a subject, the method comprising implanting the scaffold of claim 1 into the subject.
12. The method of claim 11 , wherein the peptide ligand increases the recruitment of endothelial cells and/or endothelial progenitor cells to the scaffold.
13. The method of claim 11 , wherein the peptide ligand increases the proliferation of endothelial cells and/or endothelial progenitor cells on the scaffold.
14. A method for repairing a bone defect in a subject, the method comprising implanting the scaffold of claim 1 into the subject.
15. The method of claim 14 , wherein endothelial cells and osteogenic cells are seeded on the scaffold prior to implantation.
16. A method of coating a surface of a scaffold sculpted or molded into a form of at least a portion of a stent, a shunt, a vascular graft, a patch, a cardiac valve, or a catheter, the method comprising:
functionalizing a coating biopolymer with chemical groups facilitating covalent attachment of the coating biopolymer to a peptide ligand;
adhering the coating biopolymer to the surface; and
covalently attaching the peptide ligand to the coating biopolymer, wherein the peptide ligand is the peptide ligand of claim 1 or a functionalized derivative thereof.
17. The method of claim 16 , wherein the coating biopolymer is a parylene polymer.
18. The method of claim 16 , wherein the functionalizing of the coating biopolymer includes introducing alkyne functional groups to the coating biopolymer.
19. The method of claim 18 , wherein the peptide ligand is functionalized with an azide functional group.
20. The method of claim 16 , wherein the scaffold comprises a scaffold polymer, a plastic, a metal, or a glass.
21. The method of claim 20 , 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.
22. The method of claim 16 , wherein the adhering of the coating biopolymer to the surface includes chemical vapor deposition (CVD).
23. The method of claim 16 , further comprising:
activating the surface prior to the adhering of the coating biopolymer to the surface.
24. The method of claim 23 , wherein the activating of the surface includes applying microwave plasma.