Extremely compliant yet tough hydrogel systems as ultrasound transmission agents

Abstract

A method for making a tough and compliant hydrogel. A precursor hydrogel is made of a first polymer selected to maintain high elasticity and a second polymer selected to dissipate mechanical energy. The precursor hydrogel is stretched to a multiple of its original length to form a pre-stretched hydrogel. The pre-stretched hydrogel is allowed to relax and is soaked in a biocompatible solvent to reach equilibrium swelling of the pre-stretched hydrogel whereby shear modulus of the hydrogel is reduced.

1 . An ultrasound transmission agent comprising:
 a tough and compliant hydrogel comprising a long chain polymer network and a sacrificial chain polymer network,   wherein the hydrogel is provided with a low shear modulus and a high fracture toughness,   and wherein the hydrogel is conformable to various shapes.   
     
     
         2 . The ultrasound transmission agent of  claim 1 , wherein the hydrogel has a shear modulus below 10 kPa. 
     
     
         3 . The ultrasound transmission agent of  claim 1 , wherein the hydrogel has a shear modulus of about 5 kPa or less. 
     
     
         4 . The ultrasound transmission agent of  claim 1 , wherein the hydrogel has a shear modulus of about 1 kPa or less. 
     
     
         5 . The ultrasound transmission agent of  claim 1 , wherein the long chain network is selected from the group consisting of polyacrylamide, polyethylene glycol, poly (vinyl alcohol), poly (N-isopropyl acrylamide), and poly (2-hydroxyethyl methacrylate). 
     
     
         6 . The ultrasound transmission agent of  claim 1 , wherein the sacrificial chain network is selected from the group consisting of alginate, hyaluronic acid, collagen, agarose, gelatin, fibrin and chitosan. 
     
     
         7 . The ultrasound transmission agent of  claim 1 , wherein the volume concentration of the long chain network in the hydrogel ranges from 5% to 40%, and the volume concentration of the sacrificial chain network ranges from 0.15% to 10%. 
     
     
         8 . The ultrasound transmission agent of  claim 1 , wherein the volume concentration of the sacrificial chain network is lower than the volume concentration of the long chain network. 
     
     
         9 . The ultrasound transmission agent of  claim 1 , wherein polymers of the long chain network are crosslinked by free-radical polymerization, UV crosslinking, gamma irradiation, electron beam irradiation and/or freeze thawing. 
     
     
         10 . The ultrasound transmission agent of  claim 1 , wherein polymers of the sacrificial chain network are crosslinked by adding multivalent ions, changing ambient temperature and/or varying pH of the solution. 
     
     
         11 . The ultrasound transmission agent of  claim 1 , wherein the hydrogel has a shear modulus of about 1 kPa or lower, and can be stretched over 11 times its original length without fracture or flow. 
     
     
         12 . The ultrasound transmission agent of  claim 1 , wherein the hydrogel conforms to various regions of a body and/or is conformable to wrap around ultrasound probes of various shapes without flow or fracture. 
     
     
         13 . An ultrasound transmission agent comprising a tough and compliant hydrogel comprising a long chain polymer network and a sacrificial chain polymer network, wherein the hydrogel is formed by (a) combining the long chain polymer network and the sacrificial chain polymer network to form an interpenetrating hydrogel; (b) stretching the interpenetrating hydrogel a first time to a multiple of its original length to form a pre-stretched hydrogel; (c) allowing the pre-stretched hydrogel to relax; (c) soaking the relaxed hydrogel in a biocompatible solvent to reach equilibrium swelling of the hydrogel; (d) stretching the interpenetrating hydrogel a second time to a second multiple of its original length wherein the second multiple is greater than the first multiple, whereby shear modulus of the hydrogel is reduced. 
     
     
         14 . The ultrasound transmission agent of  claim 13 , wherein the multiple of its original length is in the range of 2-10. 
     
     
         15 . The ultrasound transmission agent of  claim 13 , wherein the shear modulus of the hydrogel is reduced from over 10 kPa to about 5 kPa or below. 
     
     
         16 . The ultrasound transmission agent of  claim 13 , wherein the shear modulus of the hydrogel is reduced from over 10 kPa to about 1 kPa or below. 
     
     
         17 . The ultrasound transmission agent of  claim 13 , wherein the long chain polymer network is selected from the group consisting of polyacrylamide, polyethylene glycol, poly (vinyl alcohol), poly (N-isopropyl acrylamide), and poly (2-hydroxyethylmethacrylate). 
     
     
         18 . The ultrasound transmission agent of  claim 13 , wherein the sacrificial chain polymer network is selected from the group consisting of alginate, hyaluronic acid, collagen, agarose, gelatin, fibrin and chitosan. 
     
     
         19 . The ultrasound transmission agent of  claim 13 , wherein the volume concentration of the long chain network in the hydrogel ranges from 5% to 40%, and the volume concentration of the sacrificial chain network ranges from 0.15% to 10%. 
     
     
         20 . The ultrasound transmission agent of  claim 13 , wherein the volume concentration of the sacrificial chain network is lower than the volume concentration of the long chain network. 
     
     
         21 . The ultrasound transmission agent of  claim 13 , wherein the hydrogel has a shear modulus of about 1 kPa or lower, and can be stretched over 11 times its original length without fracture or flow. 
     
     
         22 . The ultrasound transmission agent of  claim 13 , wherein the hydrogel conforms to various regions of a body and/or is conformable to wrap around ultrasound probes of various shapes without flow or fracture.