Controllable self-annealing microgel particles for biomedical applications

Abstract

A microporous gel system for certain applications, including biomedical applications, includes an aqueous solution containing plurality of microgel particles including a biodegradable crosslinker. In some aspects, the microgel particles act as gel building blocks that anneal to one another to form a covalently-stabilized scaffold of microgel particles having interstitial spaces therein. In certain aspects, annealing of the microgel particles occurs after exposure to an annealing agent that is endogenously present or exogenously added. In some embodiments, annealing of the microgel particles requires the presence of an initiator such as exposure to light. In particular embodiments, the chemical and physical properties of the gel building blocks can be controlled to allow downstream control of the resulting assembled scaffold. In one or more embodiments, cells are able to quickly infiltrate the interstitial spaces of the assembled scaffold.

1 - 66 . (canceled) 
     
     
         67 . A method of providing a scaffold for living tissue comprising:
 delivering to the living tissue a flowable solution comprising a plurality of spherical microgel building blocks, wherein the spherical microgel building blocks have a molecular mass between 481 teradaltons and 60 petadaltons;   exposing the spherical microgel building blocks to an annealing agent that crosslinks the spherical microgel building blocks to adjacent spherical microgel building blocks and adjacent living tissue at points of contact to form a covalently-stabilized scaffold with a molecular mass greater than 60 petadaltons and having interstitial spaces throughout; and   promoting cells from the living tissue to migrate into the interstitial spaces of the covalently-stabilized scaffold.   
     
     
         68 . The method of  claim 67 , wherein the flowable solution of spherical microgel building blocks is delivered to the living tissue by injection from a syringe. 
     
     
         69 . The method of  claim 67 , wherein the plurality of spherical microgel building blocks have a distribution of diameters with a coefficient of variation less than 50%. 
     
     
         70 . The method of  claim 67 , wherein the volume fraction of the swollen spherical microgel building blocks before crosslinking is between 30% and 99%. 
     
     
         71 . The method of  claim 67 , wherein the spherical microgel building blocks comprise a polyethylene glycol component and peptide component. 
     
     
         72 . The method of  claim 71 , wherein the plurality of spherical microgel building blocks comprise a first plurality of spherical microgel building blocks comprising L amino acids and a second plurality of spherical microgel building blocks comprising D amino acids. 
     
     
         73 . The method of  claim 71 , wherein the peptide component comprises an MMP-degradable peptide. 
     
     
         74 . The method of  claim 72 , wherein the ratio between the first plurality of spherical microgel building blocks and the second plurality of spherical microgel building blocks is substantially 1:1. 
     
     
         75 . The method of  claim 74 , wherein a portion of the spherical microgel building blocks remain in the living tissue after 21 days. 
     
     
         76 . The method of  claim 75 , wherein the living tissue comprises an epidermal wound and wherein the covalently-stabilized scaffold increases the formation of sweat glands and hair follicles in the covalently-stabilized scaffold after 21 days. 
     
     
         77 . The method of  claim 75 , wherein the living tissue comprises an epidermal wound and wherein the migrated cells increase dermal thickness in the covalently-stabilized scaffold after 21 days. 
     
     
         78 . The method of  claim 77 , wherein the dermal thickness increases at least 2-fold. 
     
     
         79 . The method of  claim 67 , wherein exposing the spherical microgel building blocks to an annealing agent comprises exposing the spherical microgel building blocks to light, and wherein the flowable solution of spherical microgel building blocks further comprises Eosin Y. 
     
     
         80 . A method of providing a scaffold for living tissue comprising:
 delivering to the living tissue a flowable solution of polymer building blocks to form a pack of polymer building blocks in physical contact with each other and adjacent living tissue, wherein the polymer building blocks have a molecular mass between 481 teradaltons and 60 petadaltons, wherein the polymer building blocks comprise a polyethylene glycol component and peptide component;   exposing the polymer building blocks to light that crosslinks the polymer building blocks to adjacent polymer building blocks and adjacent living tissue at points of physical contact to form a covalently-stabilized scaffold having interstitial spaces therein; and   promoting cells from the living tissue to migrate into the interstitial spaces of the covalently-stabilized scaffold.   
     
     
         81 . The method of  claim 80 , wherein the interstitial spaces comprise an interconnected network of continuously connected voids. 
     
     
         82 . The method of  claim 81 , wherein the volume of the interconnected network of voids is between 10% and 50% of the entire volume of the covalently-stabilized scaffold. 
     
     
         83 . The method of  claim 81 , wherein the characteristic length scale of each void is between 12 μm and 27 μm. 
     
     
         84 . The method of  claim 81 , wherein the voids have walls exhibiting negative concavity. 
     
     
         85 . The method of  claim 80 , wherein the polymer building blocks comprise a first type of polymer building block with a first peptide component and a second type of polymer building block with a second peptide component. 
     
     
         86 . The method of  claim 85 , wherein the ratio of the first type of polymer building blocks and the second type of polymer building blocks is substantially equal. 
     
     
         87 . The method of  claim 85 , wherein the first peptide component comprises at least one D amino acid and wherein the second peptide component comprises L amino acids.