Therapeutic polymer gel system to promote healing and prevent fibrosis at a wound or surgical site

Abstract

Disclosed herein are therapeutic polymer gel systems for promoting healing of a wound or surgical site in a subject. The therapeutic polymer gel forms a microporous network and may be applied or injected in a fluid form and annealed or crosslinked after application to the wound or surgical site. The microporous gel may optionally contain various therapeutic agents throughout the therapeutic polymer gel which are released.

1 . A therapeutic polymer gel system for use in a wound or surgical site comprising:
 a collection of substantially monodisperse spherical microgel particles having diameters within the range of 35 μm to 1,000 μm comprising a synthetic polymer backbone and annealing components comprising K-peptides and Q-peptides and exhibiting a stiffness within the range of about 10 to 1,000 pascals (Pa) that when exposed to an annealing agent covalently links adjacent spherical microgel particles to form an interconnected porous network from the substantially monodisperse spherical microgels having a mean pore diameter of at least 10 μm.   
     
     
         2 . The therapeutic polymer gel system of  claim 1 , wherein the annealing agent comprises activated Factor XIII. 
     
     
         3 . The therapeutic polymer gel system of  claim 1 , wherein the annealing agent comprises Eosin Y, that when exposed to light, covalently links adjacent spherical microgel particles. 
     
     
         4 . The therapeutic polymer gel system of  claim 1 , wherein the synthetic polymer backbone comprises poly(ethylene glycol). 
     
     
         5 . The therapeutic polymer gel system of  claim 1 , wherein the collection of substantially monodisperse spherical microgel particles, when exposed to the annealing agent, further covalently links the spherical microgel particles to adjacent tissue in the wound or surgical site. 
     
     
         6 . The therapeutic polymer gel system of  claim 1 , wherein the collection of substantially monodisperse spherical microgel particles has a coefficient of variation of less than 35% in diameter. 
     
     
         7 . The therapeutic polymer gel system of  claim 1 , wherein the monodisperse spherical microgel particles further comprise an MMP-degradable crosslinker. 
     
     
         8 . The therapeutic polymer gel system of  claim 7 , wherein the MMP-degradable crosslinker comprises D-amino acids.