Microporous annealed particle gel system
A hydrogel material for use in a human subject or other mammal includes a collection of microgel particles having one or more network cross linker components, wherein the microgel particles, when exposed to an endogenous or exogenous annealing agent, links the microgel particles together in situ to form a covalently-stabilized scaffold of microgel particles having pores formed between the microgel particles wherein the pores are substantially devoid of hydrogel.
1. A system, comprising:
(a) a plurality of microgel particles, wherein at least one microgel particle of the plurality of microgel particles comprises a hydrogel backbone and one or more annealing components; and
(b) an annealing agent configured to couple the one or more annealing components of two or more microgel particles of the plurality of microgel particles to form a covalently-stabilized scaffold of microgel particles having pores formed between the microgel particles, wherein the pores are on the 10 micrometer scale and are substantially devoid of hydrogel.
2. The system of claim 1 , wherein at least one pore of the pores formed between the plurality of microgel particles comprises a diameter of about 10 micrometers.
3. The system of claim 1 , wherein at least one microgel particle of the plurality of microgel particles comprises a diameter that is at least or about 50 micrometers.
4. The system of claim 1 , wherein the hydrogel backbone comprises a Matrix Metalloprotease (MMP) target substrate, or a portion thereof.
5. The system of claim 1 , wherein the annealing agent comprises Eosin Y, a thiol group, or a combination thereof.
6. The system of claim 1 , wherein the annealing agent comprises Factor XIII.
7. The system of claim 1 , wherein a microgel particle of the plurality of microgel particles is substantially spherical in shape.
8. The system of claim 1 , wherein at least one pore of the pores formed between the plurality of microgel particles comprises a diameter of about 2 to about 20 micrometers.
9. The system of claim 1 , wherein at least one microgel particle of the plurality of microgel particles comprises a diameter that is about 50 to about 200 micrometers.
10. The system of claim 1 , further comprising a light source configured to initiate the coupling of the one or more annealing components of the two or more microgel particles by the annealing agent.
11. The system of claim 1 , wherein the plurality of microgel particles comprise a coefficient of variation less than 25% in size.
12. The system of claim 1 , wherein one or more microgel particles of the plurality comprises an antigen, an adjuvant, or a combination thereof.
13. The system of claim 12 , wherein the antigen, the adjuvant, or the combination thereof comprises an immunosuppressive agent.
14. The system of claim 12 , wherein the antigen, the adjuvant, or the combination thereof is chemically bound to or loaded within the one or more microgel particles.
15. The system of claim 1 , further comprising one or more living cells configured to be incorporated into the pores formed between the microgel particles.
16. The system of claim 1 , wherein the plurality of microgel particles comprises a first type of microgel particle that is non-degradable and a second type of microgel particle that is degradable.
17. The system of claim 16 , wherein the second type of microgel particle comprises an antigen, an adjuvant, or a combination thereof.
18. A pharmaceutical formulation comprising the system of claim 1 , formulated for administration to a subject by injection.