Bi-functional arginine-glycine-aspartic acid (RGD) peptides and methods to promote angiogenesis

1. A hydrogel composition comprising:

(a) an integrin-binding peptide comprising the amino acid sequence TFALRGDNP (SEQ ID NO:1), TFALRADNP (SEQ ID NO:2), DVEKRGDREEAHVP (SEQ ID NO:3), IQRGDIDAMIS (SEQ ID NO:4), DAVKQLQAAERGDA (SEQ ID NO:5), PMQKMRGDVFSP (SEQ ID NO6), RSDGTG (SEQ ID NO:7), EAPRGDVYQG (SEQ ID NO:8), GLOGERGRO (SEQ ID NO:9), GFOGERGVQ (SEQ ID NO:10), DGEA (SEQ ID NO:11), GFOGER (SEQ ID NO:12), GLKGEN (SEQ ID NO:13), LDV (SEQ ID NO:14), REDV (SEQ ID NO:15), PEDGIHE (SEQ ID NO:16), PHSRN (SEQ ID NO:17), ALNGR (SEQ ID NO:18), IAFQRN (SEQ ID NO:19), IKLLI (SEQ ID NO:20), AGQWHRVSVRWG (SEQ ID NO:22), TWSQKALHHRVP (SEQ ID NO:23), SIYITRF (SEQ ID NO:24), SYWYRIEASRTG (SEQ ID NO:25), YIGSR (SEQ ID NO:26), RDIAEIIKDI (SEQ ID NO:27), VFDNFVLK (SEQ ID NO:28), AEIDGIEL (SEQ ID NO:29), SETQRGDVFVP (SEQ ID NO:30), PASYRGDSC (SEQ ID NO:31), VTGRGDSPAS (SEQ ID NO:32), PQVTRGDVFTMP (SEQ ID NO:37), or variants at least 90% identical thereto;

(b) a pro-angiogenic growth factor and/or a VEGF mimetic peptide comprising the amino acid sequence KLTWQELYQLKYKGI (SEQ ID NO:38); and

(c) a biocompatible polymer, wherein the integrin-binding peptide is linked to the biocompatible polymer.

2. The hydrogel composition of claim 1 , wherein the linkage is a covalent or non-covalent linkage.

3. The hydrogel composition of claim 1 , wherein the biocompatible polymer is functionalized with a VEGF or the VEGF mimetic peptide, which comprises the amino acid sequence KLTWQELYQLKYKGI (SEQ ID NO:38), and the integrin-binding peptide binds at least one type of endothelial cell integrin.

4. The hydrogel composition of claim 2 , wherein the pro-angiogenic growth factor or the VEGF mimetic peptide is attached to the biocompatible polymer through a matrix metalloproteinase (MMP) degradable peptide linkage.

5. The hydrogel composition of claim 1 , wherein the biocompatible polymer is functionalized with a VEGF or the VEGF mimetic peptide, which comprises the amino acid sequence KLTWQELYQLKYKGI (SEQ ID NO:38), and the integrin binding peptide binds to an αvβ3 and/or VLA-6 integrin.

6. The hydrogel composition of claim 1 , wherein the biocompatible polymer comprises an agarose gel, polyethylene glycol, alginate, hyaluronic acid, polyacrylic acid, polyacrylic amide, polyvinyl alcohol, polyhydroxyethyl methacrylate, methacrylated dextrans, poly(N-isopropylacrylamide), or any combination thereof.

7. The hydrogel composition of claim 1 , wherein the biocompatible polymer is oxidized alginate.

8. The hydrogel composition of claim 1 , wherein the hydrogel composition is an injectable composition.

9. A method of promoting angiogenesis in a subject in need thereof, comprising administering to the subject the hydrogel composition of claim 1 , in an amount effective to promote angiogenesis.

10. A method of promoting endothelial cell adhesion, endothelial cell spreading, endothelial cell migration and/or endothelial cell proliferation, comprising administering to the subject the hydrogel composition of claim 1 , in an amount effective to promote endothelial cell adhesion, endothelial cell spreading, endothelial cell migration and/or endothelial cell proliferation.

11. A method of treating ischemic injury in a subject in need thereof, comprising administering to the subject the hydrogel composition of claim 1 , in an amount effective to treat ischemic injury.

12. A method of promoting tissue regeneration in a subject in need thereof, comprising administering to the subject the hydrogel composition of claim 1 , in an amount effective to promote tissue regeneration.

13. A method of bioprinting, comprising administering the hydrogel composition of claim 1 to a substrate in an amount effective to promote tissue regeneration.

14. A biomaterial product for bioprinting, comprising the hydrogel composition of claim 1 .