Hetero-assembling, tunable, and injectable hydrogels for cell encapsulation

Patent metadata

Field	Value
Publication number	US-9399068-B2
Application number	US-201514690589-A
Country	US
Kind code	B2
Filing date	Apr 20, 2015
Priority date	Jun 10, 2008
Publication date	Jul 26, 2016
Grant date	Jul 26, 2016

Abstract

A viscoelastic hydrogel based on a protein hetero-assembled with a polymer is provided. The protein cannot self-assemble with itself and the polymer cannot self-assemble with itself. The protein has a first association sequence (1stA) and a first spacer (1stSp). The polymer has a second association sequence (2ndA) and a second spacer (2ndSp). The first association sequence and the second association sequence are physically cross-linked to interact with each other with a 1:1 known and specific stoichiometry to form a three dimensional scaffold. The protein is represented by {1stA(1stSp)} x 1stA, where x is ≧2, and the polymer is represented by {2ndA(2ndSp)} y 2ndA, where y≧2.

First claim

What is claimed is:

1. A viscoelastic hydrogel, comprising: a protein hetero-assembled with a polymer, wherein the protein cannot self-assemble with itself, wherein the polymer cannot self-assemble with itself, wherein the protein includes a first association sequence (1stA) and a first spacer (1stSp), wherein the polymer includes a second association sequence (2ndA) and a second spacer (2ndSp), wherein the first association sequence and the second association sequence are physically cross-linked to interact with each other with a 1:1 known and specific stoichiometry to form a three dimensional scaffold, wherein the protein is represented by {1stA(1stSp)} x 1stA, where x is ≧2, and the polymer is represented by {2ndA(2ndSp)} y 2ndA, where y≧2.

2. The viscoelastic hydrogel as set forth in claim 1 , wherein the protein is represented by {1stA(1stSp) m } x 1stA, where m is 1 to 50, and x is 2 to 15; and the polymer is represented by {2ndA(2ndSp)} y 2ndA, where y is 2 to 64.

3. The viscoelastic hydrogel as set forth in claim 1 , wherein the first association sequence is a WW protein sequence.

4. The viscoelastic hydrogel as set forth in claim 1 , wherein the second association sequence is 1, 2, 3 or 4 repeats of a polyproline-rich peptide sequence in series.

5. The viscoelastic hydrogel as set forth in claim 1 , wherein the second spacer is a branched polyethylene glycol.

6. The viscoelastic hydrogel as set forth in claim 1 , wherein the second spacer is a linear polyethylene glycol.

7. The viscoelastic hydrogel as set forth in claim 4 , wherein the second spacer has a molecular range in the order of 10-200 kDa.

8. The viscoelastic hydrogel as set forth in claim 1 , wherein the second spacer is a polypeptide or a polysaccharide.

9. The viscoelastic hydrogel as set forth in claim 1 , wherein the second spacer is a biopolymer alginate.

10. The viscoelastic hydrogel as set forth in claim 1 , wherein the polymer comprises a copolymer block of a stimuli-responsive polymer.

11. The viscoelastic hydrogel as set forth in claim 1 , wherein the polymer comprises a copolymer block, wherein the copolymer block is a poly(n-isopropylacrylamide) and the resulting hydrogel contains 0-10 wt/vol % of poly(n-isopropylacrylamide).

Assignees

• Univ Leland Stanford Junior

Inventors

• Heilshorn Sarah C
• Mulyasasmita Widya
• Cai Lei

Classifications

• C12N2533/50

  Proteins · 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

• C12N5/0012

  Cell encapsulation · CPC title

• A61K47/42 Primary

  Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) · CPC title

• A61K9/0024

  Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L) · CPC title