	US 11,806,441 B2
	Viscoelastic hydrogels with fast stress relaxation
Luo Gu, Cambridge, MA (US); Ovijit Chaudhuri, San Mateo, CA (US); Nathaniel D. Huebsch, Colma, CA (US); David J. Mooney, Sudbury, MA (US); Max Carlton Darnell, Somerville, MA (US); and Simon Young, Cambridge, MA (US)
Assigned to President and Fellows of Harvard College, Cambridge, MA (US)
Filed by President and Fellows of Harvard College, Cambridge, MA (US)
Filed on Jun. 15, 2021, as Appl. No. 17/347,915.
Application 17/347,915 is a division of application No. 14/738,294, filed on Jun. 12, 2015, granted, now 11,065,362.
Claims priority of provisional application 62/011,512, filed on Jun. 12, 2014.
Prior Publication US 2021/0308322 A1, Oct. 7, 2021
Int. Cl. A61L 27/20 (2006.01); A61L 27/56 (2006.01); A61L 27/52 (2006.01); A61L 27/54 (2006.01); C12N 5/077 (2010.01); A61L 27/38 (2006.01)

CPC A61L 27/20 (2013.01) [A61L 27/3834 (2013.01); A61L 27/52 (2013.01); A61L 27/54 (2013.01); A61L 27/56 (2013.01); C12N 5/0654 (2013.01); A61L 2400/12 (2013.01); A61L 2430/02 (2013.01); C12N 2506/1346 (2013.01); C12N 2513/00 (2013.01); C12N 2533/74 (2013.01)]

19 Claims

1. A method of enhancing proliferation or differentiation of a cell, the method comprising contacting the cell with a fast-relaxing hydrogel, wherein:

the hydrogel is characterized by a stress relaxation rate (τ_1/2) of 800 seconds or less;

the hydrogel comprises a plurality of alginate polymer chains and a plurality of linear spacer molecules,

wherein the plurality of alginate polymer chains have an average molecular weight of about 80 kDa or less;

wherein the plurality of alginate polymer chains are ionically cross-linked to each other using Ca²⁺, wherein Ca²⁺ is present in said hydrogel at a concentration of about 2 mM to about 60 mM;

wherein each of the plurality of linear spacer molecules comprises a first end and a second end, wherein the first end is covalently attached to an alginate polymer chain and the second end is not attached to an alginate polymer chain, wherein each of the plurality of linear spacer molecules does not cross-link the alginate polymer chains, and wherein the plurality of linear spacer molecules physically separate the alginate polymer chains;

wherein the plurality of alginate polymer chains and the plurality of spacer molecules are present in the hydrogel at a ratio of at least 2:1 spacer molecule:alginate polymer chain; and

wherein the length of each of the plurality of linear spacer molecules ranges from about 80 Angstroms to about 1500 Angstroms, thereby enhancing proliferation or differentiation of a cell.