Natural tissue scaffolds as tissue fillers

Abstract

Tissue fillers derived from decellularized tissues are provided. The tissue fillers can include acellular tissue matrices that have reduced inflammatory responses when implanted in a body. Also provided are methods of making and therapeutic uses for the tissue fillers.

1 . A tissue filler, comprising:
 an acellular tissue matrix having the ability to maintain the same shape, size, and sponge property after being implanted for one week as was observed prior to application to a tissue site; and   exogenous hyaluronic acid (HA) on a surface of the acellular tissue matrix at a concentration that reduces an inflammatory response or fibrosis when the tissue filler is applied to the tissue site the concentration between approximately 0.5 mg and approximately 5.0 mg per gram of tissue filler.   
     
     
         2 . The tissue filler of  claim 1 , further comprising at least one growth factor. 
     
     
         3 . The tissue filler of  claim 2 , wherein the at least one growth factor is selected from at least one of FGF, VEGF, PDGF, Angiopoitin-2, or Follistatin. 
     
     
         4 . The tissue filler of  claim 1 , wherein the tissue filler has been treated to reduce a bioburden. 
     
     
         5 . The tissue filler of  claim 1 , further comprising an antimicrobial agent. 
     
     
         6 . The tissue filler of  claim 5 , wherein the antimicrobial agent includes at least one of chlorhexidine (CHX) and silver. 
     
     
         7 . The tissue filler of  claim 6 , wherein the CHX has a concentration between approximately 0.1 mg and approximately 3.0 mg per gram of tissue filler. 
     
     
         8 . The tissue filler of  claim 6 , wherein the silver has a concentration between approximately 0.1 mg and approximately 1.0 mg per gram of tissue filler. 
     
     
         9 . The tissue filler of  claim 1 , wherein the tissue filler is capable of being compressed up to approximately ⅔ of its length or width. 
     
     
         10 . The tissue filler of  claim 9 , wherein the tissue filler is capable of returning to its original dimensions after release of compression. 
     
     
         11 . The tissue filler of  claim 1 , wherein the acellular tissue matrix has a stable three-dimensional structure. 
     
     
         12 . The tissue filler of  claim 1 , wherein the acellular tissue matrix comprises a dermal matrix. 
     
     
         13 . The tissue filler of  claim 12 , wherein the acellular tissue matrix is derived from skin. 
     
     
         14 . The tissue filler of  claim 12 , wherein the acellular tissue matrix is derived from dermis. 
     
     
         15 . The tissue filler of  claim 1 , wherein the acellular tissue matrix is derived from at least one of lung, liver, bladder, muscle, and fat tissue. 
     
     
         16 . The tissue filler of  claim 1 , wherein the acellular tissue matrix is derived from porcine tissue. 
     
     
         17 . The tissue filler of  claim 1 , wherein the acellular tissue matrix comprises an adipose matrix. 
     
     
         18 . A method of treatment, comprising:
 removing native tissue from a tissue site; and   applying a tissue filler to the tissue site, the tissue filler comprising:
 an acellular tissue matrix having the ability to maintain the same shape, size, and sponge property after being implanted for one week as was observed prior to application to a tissue site; and 
 exogenous hyaluronic acid (HA) on a surface of the acellular tissue matrix at a concentration that reduces an inflammatory response or fibrosis when the tissue filler is applied to the tissue site, the concentration between approximately 0.5 mg and approximately 5.0 mg per gram of tissue filler. 
   
     
     
         19 . A method of producing a tissue filler, comprising:
 selecting a tissue;   decellularizing the tissue to produce an acellular tissue matrix; and   contacting a surface of the acellular tissue matrix with exogenous hyaluronic acid (HA) at a concentration between approximately 0.5 mg and approximately 5.0 mg per gram of tissue filler.