3D synthetic tissue hydrogels

Patent metadata

Field	Value
Publication number	US-11312950-B2
Application number	US-201815895710-A
Country	US
Kind code	B2
Filing date	Feb 13, 2018
Priority date	Feb 16, 2017
Publication date	Apr 26, 2022
Grant date	Apr 26, 2022

Abstract

A method to prepare synthetic hydrogels having tissue-specific properties, and a hydrogel comprising a polymer matrix comprising a plurality of peptide, are provided.

First claim

What is claimed is:

1. A hydrogel comprising a polymer matrix comprising a plurality of peptides, wherein one of the peptides comprises VTCG (SEQ ID NO:26) and another peptide comprises LRE and the hydrogel optionally includes peptides from two or more of entactin/nidogen; vitronectin; vWF; netrin 1; fibronectin; collagen 1; fibrinogen alpha; osteopontin; fibrinogen gamma; thrombospondin; collagen IX; tenascin C; laminin-alpha; laminin-beta; laminin gamma; MMP-1, MMP-14, MMP-2, MMP-3, MMP-7, MMP-9, or MMP-13, wherein the peptide comprising LRE in the hydrogel is about 1% to about 2% and the peptide comprising VTCG (SEQ ID NO:26) is about 4% to about 6%.

2. The hydrogel of claim 1 wherein the peptides further include one or more of peptides comprising RGD, YIGSR (SEQ ID NO: 22), IKVAV (SEQ ID NO: 23), AEIDGIEL (SEQ ID NO: 24), DGEA (SEQ ID NO: 25), YSMKKTTMKIIPFNRLTIG (SEQ ID NO: 27), SVVYLR (SEQ ID NO: 28), GPR, GFXaaGER (SEQ ID NO: 74), PHSRN(G)6RGD (SEQ ID NO: 73), or QWRDTWARRLRICFQQREKKGKCRKA (SEQ ID NO: 31).

3. The hydrogel of claim 2 , wherein the peptide comprising RGD is about 25% to about 35%, comprising YIGSR (SEQ ID NO: 22) is about 1% to about 3%, comprising IKVAV (SEQ ID NO: 23) is about 2% to about 4%, comprising AEIDGIEL (SEQ ID NO: 24) is about 2% to about 4%, comprising DGEA (SEQ ID NO: 25) is about 2% to about 4%, the YSMKKTTMKIIPFNRLTIG (SEQ ID NO: 27) is about 4% to about 6%, comprising SVVYLR (SEQ ID NO: 28) is about 7% to about 9%, comprising GPR is about 7% to about 9%, comprising GFXaaGER (SEQ ID NO: 74) is about 7% to about 9%, comprising PHSRN(G)6RGD is about 10% to about 12%, or comprising QWRDTWARRLRICFQQREKKGKCRKA (SEQ ID NO: 31) is about 10% to about 12%.

4. The hydrogel of claim 1 wherein the peptides further include one or more peptides comprising VPMSMRGG (SEQ ID NO: 32), SGESPAYYTA (SEQ ID NO: 33), RPFSMIMG (SEQ ID NO: 34), VPLSLTMG (SEQ ID NO: 35), VPLSLYSG (SEQ ID NO: 36), GPLGLWAR (SEQ ID NO: 37), or IPESLRAG (SEQ ID NO: 38).

5. A hydrogel comprising a polymer matrix comprising a plurality of peptides, wherein the peptides comprise VTCG (SEQ ID NO:26) and LRE and one or more of VPMSMRGG (SEQ ID NO: 32), SGESPAYYTA (SEQ ID NO: 33), RPFSMIMG (SEQ ID NO: 34), VPLSLTMG (SEQ ID NO: 35), VPLSLYSG (SEQ ID NO: 36), GPLGLWAR (SEQ ID NO: 37), or IPESLRAG (SEQ ID NO: 38), wherein the VPMSMRGG (SEQ ID NO: 32) is about 15% to about 20%, SGESPAYYTA (SEQ ID NO: 33) is about 15% to about 25%, RPFSMIMG (SEQ ID NO: 34) is about 15% to about 25%, VPLSLTMG (SEQ ID NO: 35) is about 10% to about 20%, VPLSLYSG (SEQ ID NO: 36) is about 5% to about 15%, GPLGLWAR (SEQ ID NO: 37) is about 7% to about 13%, or IPESLRAG (SEQ ID NO: 38) is about 7% to about 13%.

6. The hydrogel of claim 1 , wherein the polymer matrix comprises PEG, agarose, collagen, fibrin, silk, or methylcellulose.

7. The hydrogel of claim 1 wherein the polymer matrix is cross-linked.

8. The hydrogel of claim 1 which has peptides from laminin A/C, laminin β1, laminin γ, fibrinogen α, fibrinogen β, fibrinogen γ, thrombospondin-1, vitronectin, fibronectin, collagen α1, collagen 1, collagen αI, collagen II, collagen III, collagen IV, collagen α21, collagen I, collagen V, collagen IV, vWf, fibrinogen α, fibrinogen β, fibrinogen γ, vitronectin, and/or fibronectin, tenascin R, or Galectin 1.

9. The hydrogel of claim 1 which has peptides from collagen αI, collagen II, collagen III, collagen IV, collagen α21, collagen I, collagen V, collagen IV, vWf, fibrinogen α, fibrinogen β, fibrinogen γ, vitronectin, and/or fibronectin, tenascin R, or Galectin 1.

10. The hydrogel of claim 1 wherein the peptides in the hydrogel further include one or more of IPVSLRSGDRCG (SEQ ID NO:52), RPFSMIMG (SEQ ID NO:34), VPLSLTMG (SEQ ID NO: 35), VPLSLYSG (SEQ ID NO:36), IPESLRAG (SEQ ID NO:38), DGEA (SEQ ID NO:25), IKVAV (SEQ ID NO:23), YIGSR (SEQ ID NO:22), PHSRN-RGD (SEQ ID NO:30), GPR or RGD.

Assignees

• Univ Massachusetts

Inventors

• Jansen Lauren
• Peyton Shelly

Classifications

• C12N11/04 Primary

  entrapped within the carrier, e.g. gel or hollow fibres · CPC title

• C12N2533/30

  Synthetic polymers · CPC title

• C12N2533/90

  Substrates of biological origin, e.g. extracellular matrix, decellularised tissue · CPC title

• C12N11/12

  Cellulose or derivatives thereof · CPC title

• C12N2533/76

  Agarose, agar-agar · CPC title