Composite viscoelastic hydrogel, and uses thereof for sealing a channel in tissue

Abstract

A composite viscoelastic hydrogel comprises a continuous phase of non-crosslinked hyaluronic acid gel and a dispersed phase of dehydrothermally-crosslinked micron-sized gelatin hydrogel particles. The hydrogel exhibits a storage modulus (G′) of greater than 400 Pa and a tan δ (G″/G′) from 0.1 to 0.8 in dynamic viscoelasticity measured by a rheometer at 1 Hz and 1% strain rate at 25° C. The dehydrothermally crosslinked micron-sized gelatin hydrogel particles have an average dimension of less than 100 microns prior to hydration.

1 . A composite viscoelastic hydrogel comprising:
 a continuous phase of non-crosslinked biodegradable hyaluronic acid gel; and   a dispersed phase of dehydrothermally-crosslinked micron-sized gelatin hydrogel particles.   
     
     
         2 . A composite viscoelastic hydrogel according to  claim 1  that exhibits a storage modulus (G′) of greater than 400 Pa and a tan δ (G″/G′) from 0.1 to 0.8 in dynamic viscoelasticity measured by a rheometer at 1 Hz and 1% strain rate at 25° C. 
     
     
         3 . A composite viscoelastic hydrogel according to  claim 1  that exhibits an axial compressive stiffness of greater than 800 Pa, as measured using an axial compression testing machine. 
     
     
         4 . A composite viscoelastic hydrogel according to  claim 1 , in which the dehydrothermally crosslinked micron-sized gelatin hydrogel particles have an average dimension of less than 100 microns prior to hydration. 
     
     
         5 . A composite viscoelastic hydrogel according to  claim 1 , that possesses an in vivo degradation period in the lung tissue of at least 2 weeks. 
     
     
         6 . A composite viscoelastic hydrogel according to  claim 1 , in which the dehydrothermally-crosslinked micron-sized gelatin hydrogel particles have an in-vivo degradation period in the lung tissue of less than 2 months. 
     
     
         7 . A composite viscoelastic hydrogel according to  claim 1  which is shear-thinning. 
     
     
         8 . A composite viscoelastic hydrogel according to  claim 1 , that is shear-thinning and demonstrates a storage modulus G′ of less than 200 Pa at 100% strain as measured by a rheometer under strain control and at a test frequency of 1 Hz. 
     
     
         9 . A composite viscoelastic hydrogel according to  claim 1 , comprising 8-25% gelatin (w/v). 
     
     
         10 . A composite viscoelastic hydrogel according to  claim 1 , comprising about 0.4-6% of hyaluronic acid (w/v). 
     
     
         11 . A composite viscoelastic hydrogel according to  claim 1 , whereby the hydrogel is terminally sterilized via steam sterilization. 
     
     
         12 . A composite viscoelastic shear-thinning hydrogel according to  claim 1 , comprising:
 a continuous phase of non-crosslinked biodegradable hyaluronic gel; and   a dispersed phase of dehydrothermally-crosslinked micron-sized gelatin hydrogel particles,   in which the hydrogel exhibits a storage modulus (G′) of greater than 400 Pa and a tan δ (G″/G′) from 0.01 to 0.8 in dynamic viscoelasticity measured by a rheometer at 1 Hz and 1% strain rate at 25° C.   
     
     
         13 . A composite viscoelastic shear-thinning hydrogel according to  claim 1 , comprising:
 a continuous phase of non-crosslinked biodegradable hyaluronic gel; and   a dispersed phase of dehydrothermally-crosslinked micron-sized gelatin hydrogel particles,   in which the hydrogel comprises 8-25% gelatin hydrogel particles (w/v) having an average dimension of less than 100 microns in a dehydrated state, and about 0.5-2.0% of hyaluronic acid (w/v).   
     
     
         14 . A composite viscoelastic shear-thinning hydrogel according to  claim 1 , comprising:
 a continuous phase of non-crosslinked biodegradable hyaluronic gel; and   a dispersed phase of dehydrothermally-crosslinked micron-sized gelatin or collagen hydrogel particles,   
       in which the hydrogel exhibits an in vivo degradation period in the lung tissue of at least 2 weeks, and in which dehydrothermally-crosslinked micron-sized gelatin hydrogel particles exhibit an in-vivo degradation period in the lung tissue of less than 2 months. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . (canceled)