Class of biomaterials for promoting large blood vessel growth

Patent metadata

Field	Value
Publication number	US-2024050627-A1
Application number	US-202118268009-A
Country	US
Kind code	A1
Filing date	Dec 17, 2021
Priority date	Dec 18, 2020
Publication date	Feb 15, 2024
Grant date	—

Abstract

Provided are biomaterials and methods useful for promoting large blood vessel growth in a subject. An example biomaterial includes a crosslinked hydrogel and a peptide chemically attached to the hydrogel wherein the peptide comprises an extracellular epitope of a cadherin protein. An example method includes administering to an area of the subject a therapeutically effective amount of the biomaterial, wherein the biomaterial provides artery growth, arteriole growth, a combination thereof in the area of administration.

First claim

What is claimed is:

1 . A method of promoting arteriogenesis for treating a disorder in a subject, the method comprising administering to an area of the subject in need thereof a therapeutically effective amount of a biomaterial, the biomaterial comprising
a crosslinked hydrogel, and a peptide chemically attached to the hydrogel and comprising an extracellular epitope of a cadherin protein,
wherein the biomaterial provides artery growth, arteriole growth, or a combination thereof in the area of administration.

2 . The method of claim 1 , wherein the artery growth, arteriole growth, or a combination thereof occurs within about 1 day to about 14 days.

3 . The method of claim 1 , wherein the artery growth, arteriole growth, or a combination thereof corresponds to providing a vessel having a diameter of about 0.1 mm to about 1 mm.

4 . The method of claim 1 , wherein the biomaterial increases blood flow in the area of administration compared to blood flow in the area prior to administration as measured by perfusion index.

5 . The method of claim 1 , wherein the area of administration is an area of the subject having impaired blood flow.

6 . The method of claim 1 , wherein the administration of the biomaterial repairs damage caused by ischemia in said subject as measured by modified ischemia score.

7 . The method of claim 1 , wherein the disorder is selected from the group consisting of ischemic heart disease, coronary artery disease, ischemic heart failure, peripheral artery disease, critical limb ischemia, diabetic foot ulcer, organ transplant, skin wound, and bone fracture.

8 . The method of claim 1 , wherein the subject is human.

9 . The method of claim 1 , wherein the hydrogel comprises a polymeric material at about 1% to about 20% by weight of the hydrogel.

10 . The method of claim 9 , wherein the polymeric material comprises gelatin.

11 . The method of claim 1 , wherein the peptide comprises SEQ ID NO: 1, SEQ ID NO: 2, a variant of SEQ ID NO: 1 or SEQ ID NO: 2, or a combination thereof.

12 . The method of claim 1 , wherein the hydrogel is crosslinked via a crosslinker comprising an acrylate group, a phenol group, a multivalent polyethylene glycol (PEG), or a combination thereof, or via non-covalent interactions.

13 . The method of claim 1 , wherein the biomaterial has a stiffness of about 800 Pa to about 5 kPa.

14 . The method of claim 1 , wherein the biomaterial comprises a plurality of pores, each individual pore having a diameter of about 20 μm to about 80 μm.

15 . The method of claim 1 , wherein the biomaterial further comprises a plurality of cells, a growth factor, or a combination thereof.

16 . The method of claim 1 , wherein the biomaterial is administered without any cells.

17 . A biomaterial comprising:
a crosslinked hydrogel comprising a multivalent polyethylene glycol (PEG) crosslinker; and a peptide chemically attached to the hydrogel and comprising an extracellular epitope of a cadherin protein.

18 . The biomaterial of claim 17 , wherein the hydrogel comprises a polymeric material at about 1% to about 20% by weight of the hydrogel.

19 . The biomaterial of claim 18 , wherein the polymeric material comprises gelatin.

20 . The biomaterial of claim 19 , wherein the hydrogel comprises the peptide at a degree of functionalization of about 10% to about 70% as measured by the amount of valine of the peptide relative to the amount of phenylalanine of the hydrogel per nuclear magnetic resonance.

21 . The biomaterial of claim 17 , wherein the multivalent PEG crosslinker is a multivalent PEG succinimidyl glutarate.

22 . The biomaterial of claim 17 , wherein the multivalent PEG crosslinker has a number average molecular weight of about 1 kDa to about 40 kDa.

23 . The biomaterial of claim 17 , wherein the peptide comprises SEQ ID NO: 1, SEQ ID NO:
2, a variant of SEQ ID NO: 1 or SEQ ID NO: 2, or a combination thereof.

24 . The biomaterial of claim 17 , having a stiffness of about 800 Pa to about 5 kPa.

25 . The biomaterial of claim 17 , comprising a plurality of pores, each individual pore having a diameter of about 20 μm to about 80 μm.

Assignees

• Univ Vanderbilt

Inventors

• Lippmann Ethan S
• O'Grady Brian
• Florian David C
• Guelcher Scott A

Classifications

• A61L27/507 Primary

  for artificial blood vessels (apparatus for applying cells on a blood vessel prosthesis A61F2/062) · CPC title

• A61L27/52

  Hydrogels or hydrocolloids · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61L27/222

  Gelatin · CPC title

• A61L27/18

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