Engineered scaffolds for vascularized tissue repair

Patent metadata

Field	Value
Publication number	US-11246961-B2
Application number	US-201816124505-A
Country	US
Kind code	B2
Filing date	Sep 7, 2018
Priority date	Mar 11, 2016
Publication date	Feb 15, 2022
Grant date	Feb 15, 2022

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.

First claim

What is claimed is:

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.

Assignees

• Univ California

Inventors

• Wang Aijun
• Lam Kit

Classifications

• C07K14/78 Primary

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] · CPC title

• C08L67/04

  Polyesters derived from hydroxycarboxylic acids, e.g. lactones (C08L67/06 takes precedence) · CPC title

• C08L27/18

  Homopolymers or copolymers or tetrafluoroethene · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61L27/18

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds · CPC title