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.
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