US 11,752,237 B2
Bioactive agent spatial patterned biodegradable hydrogels
Eben Alsberg, Cleveland, OH (US); and Oju Jeon, Cleveland, OH (US)
Assigned to CASE WESTERN RESERVE UNIVERSITY, Cleveland, OH (US)
Filed by CASE WESTERN RESERVE UNIVERSITY, Cleveland, OH (US)
Filed on Aug. 21, 2018, as Appl. No. 16/107,756.
Claims priority of provisional application 62/548,243, filed on Aug. 21, 2017.
Prior Publication US 2019/0054206 A1, Feb. 21, 2019
Int. Cl. A61L 27/20 (2006.01); A61L 27/54 (2006.01); A61L 27/44 (2006.01); A61L 27/36 (2006.01); A61L 27/52 (2006.01); A61L 27/58 (2006.01); C08L 89/06 (2006.01); C08L 5/04 (2006.01); C08B 37/00 (2006.01); C08H 1/06 (2006.01); A61L 27/26 (2006.01); A61L 27/38 (2006.01); C08G 65/00 (2006.01)
CPC A61L 27/44 (2013.01) [A61L 27/20 (2013.01); A61L 27/26 (2013.01); A61L 27/3608 (2013.01); A61L 27/3834 (2013.01); A61L 27/52 (2013.01); A61L 27/54 (2013.01); A61L 27/58 (2013.01); C08B 37/0084 (2013.01); C08G 65/002 (2013.01); C08H 1/06 (2013.01); C08L 5/04 (2013.01); C08L 89/06 (2013.01); A61L 2300/236 (2013.01); A61L 2300/252 (2013.01); A61L 2300/412 (2013.01); A61L 2300/414 (2013.01); A61L 2400/16 (2013.01); A61L 2430/40 (2013.01); C08L 2205/04 (2013.01); C08L 2312/00 (2013.01)] 12 Claims
 
1. A method for forming a spatially patterned biodegradable hydrogel having discrete portions and/or patterns of immobilized bioactive agent, the method comprising:
a) combining (i) aoxidized, methacrylated natural polymer macromers, which include at least one first photocrosslinkable group; (ii) bioactive agent-coupling polymer macromers, which include at least one second photocrosslinkable group reactive with the first crosslinkable group; (iii) at least one bioactive agent that couples to the bioactive agent:coupling natural polymer macromers; and (iv) at least one cell;
b) crosslinking the oxidized, methacrylated natural polymer macromers to form a photocrosslinkable hydrogel that includes photocrosslinkable base polymer, the bioactive agent-coupling polymer macromers, the at least one bioactive agent, and the at least one cell encapsulated in the photocrosslinkable hydrogel;
c) selectively exposing discrete portions of the photocrosslinkable hydrogel to actinic radiation effective to initiate cross-linking of the photocrosslinkable base polymer and the bioactive agent-coupling polymer macromers at the exposed portions to provide the hydrogel with discrete portions and/or patterns of immobilized bioactive agent;
d) removing bioactive agent-coupling polymer macromers that are not crosslinked with the base polymer and optionally, bioactive agent that is not coupled to the crosslinked bioactive agent-coupling polymer macromers; and
e) further exposing the hydrogel to actinic radiation effective to initiate cross-linking of the methacrylate groups of the base polymer in regions of the hydrogel not previously exposed to actinic radiation;
wherein the discrete portions and/or patterns of immobilized bioactive agent modulate a function and/or characteristic of the at least one cell encapsulated therein and elicit location specific control over cellular function.