Catheter injectable cyclic peptide pro-gelators for myocardial tissue engineering
Cyclic peptide pro-gelator compositions, and methods of therapeutic use, which assemble into macromolecular hydrogel when administered through cleavage by endogenous enzymes upregulated at a site of tissue injury, such as a myocardial infarction.
1. A tissue scaffolding composition comprising a pharmaceutically acceptable carrier and a cyclic peptide having a substrate recognition sequence that when enzymatically cleaved linearizes and self-assembles with like-kind peptides into a hydrogel, wherein the cyclic peptide is disulfide bonded by terminal cysteine residues and comprises repeating amino acid sequence KFDF (SEQ ID NO:1) and wherein the peptide self-assembles into a hydrogel via beta-sheets.
2. The composition of claim 1 , wherein the substrate recognition sequence is specific for inflammatory-related enzymes, matrix metalloproteinases (MMP)-2/9 and/or elastase.
3. The composition of claim 1 , wherein therapeutic peptide comprises a MMP-2/9 cleavable substrate recognition amino acid sequence PLGLAG (SEQ ID NO:2).
4. The composition of claim 1 , wherein the peptide is labeled for detection.
5. The composition of claim 1 , wherein the composition further comprises a therapeutic agent, a chemotactic agent, an antibiotic, or a growth factor.
6. The composition of claim 1 , wherein the peptide comprises the amino acid sequence CKFDFKFDFKFDFPLGLAGC (SEQ ID NO:7).
7. A method of creating a scaffold for tissue repair in a patient in need thereof comprising administering to the patient a cyclic peptide having a substrate recognition sequence that when enzymatically cleaved linearizes and self-assembles with like-kind peptides into a hydrogel, wherein the cyclic peptide has a disulfide bonded by terminal cysteine residues and comprises repeating amino acid sequence KFDF (SEQ ID NO:1) and wherein the peptide self-assembles into a hydrogel via beta-sheets.
8. The method of claim 7 , wherein the substrate recognition sequence is specific for inflammatory-related enzymes, matrix metalloproteinases (MMP)-2/9 and/or elastase.
9. The method of claim 7 , wherein the peptide comprises a MMP-2/9 cleavable substrate recognition amino acid sequence PLGLAG (SEQ ID NO:2).
10. The method of claim 7 , wherein the peptide is labeled for detection.
11. The method of claim 7 , wherein the composition further comprises a therapeutic agent, a chemotactic agent, an antibiotic, or a growth factor.
12. The method of claim 7 , wherein the tissue being repaired is ischemic tissue.
13. The method of claim 7 , wherein the tissue being repaired is left ventricular tissue for remodeling post-myocardial infarction.
14. The method claim 7 , wherein the administration is via a catheter, parenteral injection, or implantation.
15. The method of claim 7 , wherein the composition is a liquid when administered and gels upon in situ enzymatic cleavage.
16. The method of claim 7 , wherein the peptide comprises the amino acid sequence CKFDFKFDFKFDFPLGLAGC (SEQ ID NO:7).
17. A peptide comprising the amino acid sequence CKFDFKFDFKFDFPLGLAGC (SEQ ID NO:7).
18. The peptide of claim 17 , wherein the peptide is cyclic.