Regenerative materials

Abstract

Methods of making tissue fillers are provided. In certain embodiments, the tissue is flake-like and has regenerative properties.

What is claimed is: 
     
         1 . A method of treatment, comprising:
 selecting an anatomical site; and   implanting a tissue filler into the anatomical site, the tissue filler comprising a group of small, irregularly sized and shaped tissue matrix flakes having a size distribution ranging from 0.2-5 mm in length, 0.2-3 mm in width, and 0.02-0.3 mm in thickness.   
     
     
         2 . The method of  claim 1 , wherein the group of tissue matrix flakes comprise fragments that have been cut from a collagen-containing tissue matrix. 
     
     
         3 . The method of  claim 2 , wherein the tissue matrix fragments comprise acellular tissue matrix. 
     
     
         4 . The method of  claim 3 , wherein the acellular tissue matrix comprises an acellular dermal matrix. 
     
     
         5 . The method of  claim 3 , wherein the acellular tissue matrix comprises an acellular porcine dermal matrix. 
     
     
         6 . The method of  claim 1 , wherein the size distribution of the tissue matrix flakes prevents undesirable migration of the flakes into areas surrounding the implantation site. 
     
     
         7 . The method of  claim 1 , wherein the tissue matrix flakes are created using a process comprising applying a cryoprotectant solution prior to freezing. 
     
     
         8 . The method of  claim 7 , wherein the cryoprotectant solution comprises at least one of a maltodextrin, sucrose, polyethylene glycol (PEG), or polyvinylpyrrolidone (PVP) solution, or a combination thereof. 
     
     
         9 . The method of  claim 8 , wherein the cryoprotectant solution comprises a maltodextrin solution. 
     
     
         10 . The method of  claim 9 , wherein the maltodextrin solution comprises 5-50% (w/v) maltodextrin. 
     
     
         11 . The method of  claim 9 , wherein the maltodextrin solution comprises 15-25% (w/v) maltodextrin. 
     
     
         12 . The method of  claim 1 , wherein the group of tissue matrix flakes have been sterilized by application of at least one of ethylene oxide, propylene oxide, gamma irradiation or e-beam irradiation. 
     
     
         13 . The method of  claim 1 , further comprising hydrating the tissue matrix flakes. 
     
     
         14 . The method of  claim 13 , further comprising hydrating the tissue matrix flakes in a solution comprising a bioactive substance. 
     
     
         15 . The method of  claim 14 , wherein the tissue matrix flakes are a carrier for controlled delivery of the bioactive substance. 
     
     
         16 . The method of  claim 14 , wherein the bioactive substance comprises at least one of: an antimicrobial agent, a cytokine, a growth factor, and adipose tissue. 
     
     
         17 . The method of  claim 1 , wherein the anatomical site is at least one of: a wound, a tissue void, a pressure ulcer, a diabetic foot ulcer, a periosteal bone defect, or a wrinkle. 
     
     
         18 . The method of  claim 1 , further comprising blending the tissue matrix flakes to form a slurry prior to implanting the tissue filler. 
     
     
         19 . The method of  claim 18 , wherein the flakes in the slurry are loosely intertwined and fibrillar.