IP Library Granted Patent US 10,723,783
Granted Patent B2
US 10,723,783 · App. 15/559,481 · Granted Jul 28, 2020

Polypeptide compositions and methods of using the same

Inventors: Nasim Annabi (Cambridge, MA); Ali Khademhosseini (Cambridge, MA)
Assignee: The Brigham and Women's Hospital, Inc.
C07K14/78A61L24/0015A61L24/0031A61L24/108A61L26/008A61L26/0047A61L26/0066A61L27/227A61L27/52A61L27/54A61L2300/404A61L2300/418A61L2300/64A61L2400/04
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Quick Facts
Patent No.
US 10,723,783
App. No.
15/559,481
Granted
Jul 28, 2020
Kind
B2
Abstract

Disclosed herein are polypeptides comprising an amino acid sequence of {[VPGVG] 4 IPGVG} n , wherein n is an integer greater than 1. The polypeptides can be crosslinked to from biocompatible hydrogels with tunable and desirable mechanical properties. The polypeptides and hydrogels can be used in a variety of biomedical applications including treatment of bleeding, treatment of soft tissue injury, injectable filler, and tissue adhesives.

Claims (19)

1. A composition comprising:

a) a polypeptide comprising the amino acid sequence of {[VPGVG] 4 IPGVG} n , wherein n is an integer greater than 1 (SEQ ID NO: 2), and wherein the polypeptide comprises a first cysteine-containing peptide linked to a first side of the amino acid sequence of {[VPGVG] 4 IPGVG} n (SEQ ID NO: 2); and

b) 2-hydroxy-1-(4-(hydroxyethoxy) phenyl)-2-methyl-1-propanone.

2. The composition of claim 1 , wherein n is in the range of 10-28.

3. The composition of claim 1 , further comprising a second cysteine-containing peptide linked to a second side of the amino acid sequence of {[VPGVG] 4 IPGVG} n (SEQ ID NO: 2).

4. The composition of claim 3 , wherein the first cysteine-containing peptide or the second cysteine-containing peptide comprises an amino acid sequence of KCTS (SEQ ID NO: 6).

5. The composition of claim 1 , further comprising an amino acid sequence of RGD.

6. A hydrogel comprising a photo-crosslinked composition of claim 1 .

7. The hydrogel of claim 6 , wherein the polypeptide is present at a concentration between 5% and 30% (w/v).

8. The hydrogel of claim 6 , having extensibility up to 500%.

9. The hydrogel of claim 6 , having an elastic modulus in the range of 0.5-10 kPa.

10. The hydrogel of claim 6 , having a tensile strength in the range of 4 to 20 kPa.

11. The hydrogel of claim 6 , having a compressive modulus of 1 to 20 kPa.

12. The hydrogel of claim 6 , further comprising a hemostatic agent selected from the group consisting of silica nanoparticles, blood coagulation factors, prothrombin, thrombin, fibrinogen, fibrin, gelatin, collagen, polysaccharide, and cellulose.

13. The hydrogel of claim 6 , further comprising an antibacterial agent selected from the group consisting of silver nanoparticles, copper oxide nanoparticles, nanoparticle-carried antibiotic drugs, penicillins, cephalosporins, penems, carbapenems, monobactams, aminoglycosides, sulfonamides, macrolides, tetracyclins, lincosides, quinolones, chloramphenicol, vancomycin, metronidazole, rifampin, isoniazid, spectinomycin, trimethoprim, and sulfamethoxazole.

14. The hydrogel of claim 6 , further comprising one or more biological cells.

15. The hydrogel of claim 6 , produced by crosslinking the polypeptide in the presence of the photoinitiator under light irradiation.

16. A tissue scaffold comprising a hydrogel of claim 6 and at least one biological cell.

17. A method of treating bleeding or soft-tissue injury, the method comprising contacting a site of bleeding or soft-tissue injury with a hydrogel of claim 6 and a hemostatic agent.

Assignments (1)
CONFIRMATORY LICENSE Recorded Dec 11, 2018
From: BRIGHAM AND WOMEN'S HOSPITAL
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 047769/0817 →
Continuity (3)
Provisional Application 62135405 · Mar 19, 2015
Provisional Application 62173653 · Jun 10, 2015
Related Publication 20180111978A1 · Apr 26, 2018