Microporous annealed particle gels and methods of use
A hydrogel material for modulating an immune response 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 interstitial spaces formed between the microgel particles and wherein the collection of microgel particles further includes at least one of an antigen and an adjuvant.
1. A method of delivering a microgel system to a subject, the method comprising:
(a) delivering to the subject a plurality of microgel particles, wherein at least one microgel particle of the microgel particles comprises
(i) a core comprising one or more hydrogel polymer components; and
(ii) one or more annealing components in a presence of an annealing agent, wherein the one or more annealing components comprises a vinyl unsaturated double bond, a K-peptide, a Q-peptide, or any combination thereof; and
(b) exposing the plurality of microgel particles to the annealing agent, thereby coupling adjacent microgel particles of the plurality of microgel particles together, to form a covalently-stabilized scaffold of microgel particles comprising pores between the adjacent microgel particles, wherein the pores are on the 10 micrometer scale and are substantially devoid of the hydrogel polymer.
2. The method of claim 1 , wherein exposing in (b) is performed after the delivering in (a).
3. The method of claim 1 , wherein delivering in (a) comprises injecting or implanting the plurality of microgel particles into the subject.
4. The method of claim 1 , wherein the pores formed between the microgel particles comprise a diameter of about 10 micrometers.
5. The method of claim 1 , wherein the plurality of microgel particles comprises diameters that are at least or about 50 micrometers.
6. The method of claim 1 , wherein the core further comprises one or more degradable crosslinker components comprising a peptide sequence of:
(a) a Matrix Metalloprotease (MMP) target substrate
(b) an OMI substrate;
(c) a Heat-Shock protein substrate;
(d) a portion of any one of (a)-(c) capable of crosslinking the core of at least two of the microgel particles together; or
(e) any combination of (a)-(d).
7. The method of claim 1 , wherein the annealing agent comprises Factor XIII, Eosin Y, a free radical transfer agent, or any combination thereof.
8. The method of claim 1 , further comprising exposing the plurality of microgel particles and the annealing agent to light.
9. The method of claim 1 , wherein the microgel particles of the plurality of microgel particles are substantially spherical in shape.