3d synthetic tissue hydrogels

Patent metadata

Field	Value
Publication number	US-2018346902-A1
Application number	US-201815895710-A
Country	US
Kind code	A1
Filing date	Feb 13, 2018
Priority date	Feb 16, 2017
Publication date	Dec 6, 2018
Grant date	—

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

1 . A method to prepare synthetic hydrogels having tissue-specific properties, comprising:
a) selecting one or more integrin binding proteins and/or one or more matrix metalloproteinase (MMP) substrate proteins in a selected mammalian tissue, or a peptide thereof; b) selecting one or more monomers for a polymer matrix that provides a selected polymer density; and c) combining the one or more monomers and the one or more selected integrin binding proteins and/or MMP substrate proteins, or the peptide thereof, under conditions that form a tissue-specific hydrogel comprising the polymer matrix having the selected polymer density and the one or more selected proteins or peptides.

2 . The method of claim 1 wherein the polymer comprises PEG, agarose, collagen, fibrin, silk, matrigel, methylcellulose, alginate, poly lactic acid, polyacrylamide, cellulose, or cellulose acetate.

3 . The method of claim 2 wherein the polymer is formed of 2K, 10K, 20K, or 40K PEG star PEG with 4, 6, or 8 arms.

4 . The method of claim 1 wherein the integrin binding proteins bind integrin heterodimers.

5 . The method of claim 1 wherein the selected mammalian tissue is bone marrow, heart, brain or lung tissue.

6 . The method of claim 1 wherein the selected peptides include peptides of 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; or laminin gamma.

7 . The method of claim 1 wherein the peptides include one or more of RGD, LRE, YIGSR (SEQ ID NO:22), IKVAV (SEQ ID NO:23), AEIDGIEL (SEQ ID NO:24), DGEA (SEQ ID NO:25), VTCG (SEQ ID NO:54), YSMKKTTMKIIPFNRLTIG (SEQ ID NO:27), SVVYLR (SEQ ID NO:28), GPR, GFOGER (SEQ ID NO:29), PHSRN-RGD (SEQ ID NO:42), or QWRDTWARRLRICFQQREKKGKCRKA (SEQ ID NO:31).

8 . The method of claim 1 wherein the peptides include one or more of VPMS/MRGG (SEQ ID NO:32), SGESPAY/YTA (SEQ ID NO:33), RPFS/MIMG (SEQ ID NO:34), VPLS/LTMG (SEQ ID NO:35), VPLS/LYSG (SEQ ID NO:36), GPLG/LWAR (SEQ ID NO:37), or IPES/LRAG (SEQ ID NO:38).

9 . The method of claim 1 further comprising combining cells with the whydrogel.

10 . A hydrogel comprising a polymer matrix comprising a plurality of peptides, wherein the peptides include 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-1, MMP-2, MMP-3, MMP-7, MMP-9, or MMP-13.

11 . The hydrogel of claim 10 wherein the peptides include one or more of RGD, LRE, YIGSR, IKVAV, AEIDGIEL, DGEA, VTCG, YSMKKTTMKIIPFNRLTIG, SVVYLR, GPR, GFOGER, PHSRN-RGB, or QWRDTWARRLRICFQQREKKGKCRKA.

12 . The hydrogel of claim 11 wherein RGD is about 25% to about 35%, LRE is about 1% to about 2%, YIGSR is about 1% to about 3%, IKVAV is about 2% to about 4%, AEIDGIEL is about 2% to about 4%, DGEA is about 2% to about 4%, VTCG is about 4% to about 6%, YSMKKTTMKIIPFNRLTIG is about 4% to about 6%, SVVYLR is about 7% to about 9%, GPR is about 7% to about 9%, GFOGER is about 7% to about 9%, PHSRN(G)6RGD is about 10% to about 12%, or QWRDTWARRLRICFQQREKKGKCRKA is about 10% to about 12%.

13 . The hydrogel of claim 10 wherein the peptides include one or more VPMS/MRGG, SGESPAY/YTA, RPFS/MIMG, VPLS/LTMG, VPLS/LYSG, GPLG/LWAR, or IPES/LRAG.

14 . The hydrogel of claim 13 wherein the VPMS/MRGG is about 15% to about 20%, SGESPAY/YTA is about 15% to about 25%, RPFS/MIMG is about 15% to about 25%, VPLS/LTMG is about 10% to about 20%, VPLS/LYSG is about 5% to about 15%, GPLG/LWAR is about 7% to about 13%, or IPES/LRAG is about 7% to about 13%.

15 . The hydrogel of claim 10 wherein the polymer matrix comprises PEG, agarose, collagen, fibrin, silk, matrigel or methylcellulose.

16 . The hydrogel of claim 10 wherein the polymer matrix is cross-linked.

17 . The hydrogel of claim 10 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 1, collagen V, collagen IV, vWf, fibrinogen α, fibrinogen β, fibrinogen γ, vitronectin, and/or fibronectin, tenascin R, or Galectin 1.

18 . The hydrogel of claim 10 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.

Assignees

• Univ Massachusetts

Inventors

• Jansen Lauren
• Peyton Shelly

Classifications

• C12N2533/80

  Hyaluronan · CPC title

• C12N2533/78

  Cellulose · CPC title

• C12N2533/30

  Synthetic polymers · CPC title

• C12N2533/76

  Agarose, agar-agar · CPC title

• C12N2513/00

  3D culture · CPC title