Biomaterials comprising hyaluronic acid binding peptides and bifunctional biopolymer molecules for hyaluronic acid retention and tissue engineering applications

Patent metadata

Field	Value
Publication number	US-9795686-B2
Application number	US-201314372258-A
Country	US
Kind code	B2
Filing date	Jan 22, 2013
Priority date	Jan 19, 2012
Publication date	Oct 24, 2017
Grant date	Oct 24, 2017

Abstract

The present invention provides novel biomaterial compositions and methods having a technology to improve retention of hyaluronic acid (HA). The biomaterial compositions utilize small HA binding peptides that is tethered to synthetic biocompatible polymers. When tethered to the polymers, the peptide region allows the polymers to bind to HA. The biocompatible polymers are modified to contain a crosslinking group so that the HA can be incorporated into a scaffold and retained in place. The novel biomaterial 1 compositions can be made into hydrogel compositions and used in a variety of tissue applications, using mild crosslinking conditions and they also have the ability to be degraded with hyaluronidase if needed. Furthermore, the novel biomaterial compositions will enable enhanced interaction between the scaffold and encapsulated cells for a wide variety of tissue engineering applications. Methods of making hydrogel compositions and their use are also provided. The present invention also provides bifunctional biopolymer compositions comprising a biologically compatible polymer having at least one amine reactive moiety and at least one thiol reactive moiety and provides thiolated HA binding peptides which can be used together to coat or chemically modify cartilage or tissues having amine reactive residues with a biologically compatible polymer having HA binding peptides, which allow HA to bind to the surface of the cartilage or tissues. Methods of using same are also provided.

First claim

The invention claimed is:

1. A hydrogel composition comprising:
(a) a biomaterial comprising at least one biologically compatible polymer having one or more hyaluronic acid (HA) binding peptides selected from the group consisting of: GAHWQFNALTVR (SEQ ID NO: 1), CRRDDGAHWQFNALTVR (SEQ ID NO: 2) or a conservative amino acid substitution thereof at a residue position other than 4, 5, 6, 9, 10 or 11, GAAWQFNALTVR (SEQ ID NO: 3) or a conservative amino acid substitution thereof at a residue position other than 4, 5, 6, 9, 10 or 11, GAHWQFAALTVR (SEQ ID NO: 4) or a conservative amino acid substitution thereof at a residue position other than 4, 5, 6, 9, 10 or 11, and iv) GAHWQFNALTVA (SEQ ID NO: 5) or a conservative amino acid substitution thereof at a residue position other than 4, 5, 6, 9, 10 or 11,
wherein said one or more HA binding peptides are covalently linked to the biologically compatible polymer, and
(b) at least one other component, wherein the at least one other component is one or more second biocompatible polymers;
wherein the first or second biocompatible polymer is selected from the group consisting of: poly(ethylene glycol), poly(propylene glycol), poly(methyl vinyl ether), oligoethylene, poly(isobutylene), poly(tetrahydrofuran), poly(oxytrimethylene), poly(dimethylsiloxsane), poly(dimethylsilane), nylon 6, nylon 11, poly(acrylonitrile), squalane, poly(1,3-dioxolane), poly(iminooligomethylene), poly(L-lysine), polyethyleneimine, poly(adipate), poly(L-caprolactone), poly(L-lactic acid), and derivatives thereof; and

wherein the biocompatible polymers are cross linked together to form a hydrogel.

2. The hydrogel composition of claim 1 , wherein the biocompatible polymers are cross linked using a photoinitiator.

3. The hydrogel composition of claim 2 , wherein the one or more first or second biocompatible polymers are mono- or disubstituted with an acrylate group.

4. The hydrogel composition of claim 1 , wherein the hydrogel further comprises one or more isolated stem cells.

5. The hydrogel composition of claim 4 , wherein said one or more isolated stem cells are selected from the group consisting of a mesenchymal stem cell, a cardiac stem cell, a liver stem cell, a retinal stem cell, a chondrocyte, an adipose tissue derived stem cell, and an epidermal stem cell.

6. A method of filling a tissue void on or in a subject in need thereof, said method comprising contacting said void with a therapeutically effective amount of the hydrogel composition of claim 4 .

7. The method of claim 6 , wherein the one or more isolated stem cells are autologous to the subject.

8. The method of claim 6 , wherein the one or more isolated stem cells are allogeneic to the subject.

9. A therapeutic method for the treatment of eye diseases by means of an eye surgery treatment, comprising applying to the eye of a subject in need of such treatment a therapeutically effective amount of the hydrogel composition of claim 1 .

10. The therapeutic method of claim 9 , wherein the surgery treatment is selected from the group consisting of corneal transplantation, cataract surgery, glaucoma surgery, and surgery to repair retinal detachment.

11. A therapeutic method for the treatment of dry eye in a subject, comprising applying to the eye of a subject in need of such treatment a therapeutically effective amount of the hydrogel composition of claim 1 .

12. A method of treating a cartilage defect in a tissue of a subject comprising administering to the tissue of the subject in need of treatment, a therapeutically effective amount of the hydrogel composition of claim 1 .

13. The method of claim 12 , wherein the defect is in cartilage in a joint or ligament of the subject.

14. A coating for a tissue surface comprising the hydrogel composition of claim 1 .

15. The coating of claim 14 , wherein the HA binding peptide (HABPep) is a peptide comprising the following amino acid sequence: GAHWQFNALTVR (SEQ ID NO: 1).

Assignees

• Univ Johns Hopkins

Inventors

• Lee Janice
• Elisseeff Jennifer H
• Unterman Shimon A

Classifications

• A61L27/3834

  Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells · CPC title

• A61L2430/10

  for reconstruction of tendons or ligaments · CPC title

• A61K47/48338 Primary

  Human Necessities · mapped topic

• A61K35/12

  Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00) · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title