Systems to promote healing at a site of a medical device

Abstract

Disclosed herein are systems for promoting healing of a wound or surgical incision at a medical device site (e.g., implanted medical device) in a subject, by administering a microporous gel to the medical implant site. Also disclosed are systems for the treatment and prevention of infection at a medical implant site in a subject, by administering a microporous gel to the medical implant site. The microporous gel may be fluidic during application and annealed or crosslinked after application. The microporous gels may contain various therapeutic agents, including antibiotics and analgesics, throughout the gel.

1 .- 20 . (canceled) 
     
     
         21 . A system comprising:
 (a) a porous hydrogel matrix inserted in tissue of a subject at a wound site, the porous hydrogel matrix comprising:
 (1) a plurality of annealed microgel particles comprising a microgel particle having an annealing component bonded to an adjacent annealing component of another microgel particle; 
 (2) pores between the annealed microgel particles, the pores having a median diameter of at least 10 micrometers; and 
 (3) a compressive modulus of between 1,500 and 200,000 Pascal (Pa); and 
   (b) newly formed tissue at the wound site substantially integrated into the porous hydrogel matrix, wherein the newly formed tissue is substantially non-fibrous tissue when determined using a standard histological scoring system.   
     
     
         22 . The system of  claim 21 , wherein the newly formed tissue at the wound site has reduced acute inflammation as compared to newly formed tissue at a second wound site having a comparable substantially non-porous hydrogel matrix inserted in tissue at the second would site. 
     
     
         23 . The system of  claim 21 , wherein the porous hydrogel matrix comprises an annealing agent comprising Eosin Y or Factor XIII. 
     
     
         24 . The system of  claim 21 , wherein the annealing component is bonded covalently to the adjacent annealing component. 
     
     
         25 . The system of  claim 21 , wherein the annealing components are a functional group selected from a vinyl sulfone, thiol, amine, imidazole, aldehyde, ketone, hydroxyl, azide, alkyne, vinyl, alkene, maleimide, carboxyl, N-hydroxysuccinimide (NHS) ester, isocyanate, isothiocyanate, hydroxylamine, thione, catechol, sialic acid, boronic acid, molecular cage, adamantane, biotin, and streptavidin. 
     
     
         26 . The system of  claim 21 , wherein each of the microgel particles comprises a backbone polymer comprising poly(ethylene glycol). 
     
     
         27 . The system of  claim 26 , wherein the backbone polymer is functionalized with a functional group selected from a vinyl sulfone, thiol, amine, imidazole, aldehyde, ketone, hydroxyl, azide, alkyne, vinyl, alkene, maleimide, carboxyl, N-hydroxysuccinimide (NHS) ester, isocyanate, isothiocyanate, hydroxylamine, thione, catechol, sialic acid, boronic acid, molecular cage, adamantane, biotin, and streptavidin. 
     
     
         28 . The system of  claim 21 , wherein the pores make up about 10-40% of the porous hydrogel matrix. 
     
     
         29 . The system of  claim 21 , wherein the annealing component is a photoinitiated annealing component. 
     
     
         30 . The system of  claim 21 , wherein the porous hydrogel matrix further comprises a therapeutic agent. 
     
     
         31 . The system of  claim 21 , wherein the wound tissue is soft tissue or cardiac tissue. 
     
     
         32 . The system of  claim 31 , wherein the soft tissue is a neural tissue. 
     
     
         33 . The system of  claim 21 , wherein the porous hydrogel matrix is stable in the tissue for about 50 days following delivery of the porous hydrogel matrix to the wound site. 
     
     
         34 . The system of  claim 21 , wherein the wound site comprises an implanted medical device selected from a cardiac device and a neurological device. 
     
     
         35 . A method comprising:
 (a) delivering a fluid composition to a tissue at a wound site of a subject, the fluid composition comprising:
 (1) a plurality of microgel particles comprising a first microgel particle having a first annealing component and a second microgel particle having a second annealing component; and 
 (2) pores between microgel particles of the plurality; 
   (b) delivering an annealing agent to the tissue at the wound site of the subject; and   (c) exposing the fluid composition of (a) and the annealing agent of (b) to light causing the first annealing component to bond to the second annealing component to form a porous hydrogel matrix having a compressive modulus of between 1,500 and 200,000 Pascal (Pa).   
     
     
         36 . The method of  claim 35  wherein the annealing agent and the fluid composition are delivered to the tissue at the wound site simultaneously. 
     
     
         37 . The method of  claim 35 , further comprising substantially integrating new tissue at the wound site into the porous hydrogel matrix about 5 days following delivery in (a) and (b). 
     
     
         38 . The method of  claim 35 , further comprising reducing a risk of developing fibrosis in newly formed tissue at the wound site following delivery in (a) and (b), as compared to the risk of developing fibrosis in newly formed tissue at a wound site to which a comparable substantially non-porous hydrogel matrix was delivered. 
     
     
         39 . The method of  claim 35 , further comprising forming new tissue that is substantially non-fibrous tissue when determined using a standard histological scoring system. 
     
     
         40 . The method of  claim 35 , wherein the annealing agent is Eosin Y or Factor XIII.