Extracellular matrix based gastroesophageal junction reinforcement device

Abstract

Provided are medical devices for implantation in patients having suffered the loss of or damage to at least part of their esophagus. The medical device connects the esophagus or remaining part thereof with the stomach to form a gastro-esophageal junction that promotes healing and encourages new host tissue growth while distributing the load and decreasing tension at the anastomotic site. The medical device comprises extracellular matrix shaped into a conformation that more closely approximates the geometry of the native gastro-esophageal junction than does direct attachment of the stomach to the shortened esophagus. Molds useful in manufacturing the medical device and methods of use of the device are also described herein.

1 . A device comprising one or more layers of extracellular matrix tissue and comprising: 
 a) a tubular esophageal portion having essentially a constant diameter; and    b) a tubular gastric portion attached to the esophageal portion at a junction having a diameter that increases from the junction to a distal tip of the gastric portion.    
   
   
       2 . The device of  claim 1 , wherein the diameter of the gastric portion increases in an essentially uniform manner from the junction to the distal tip of the gastric portion.  
   
   
       3 . The device of  claim 1 , wherein the gastric portion is modeled to conform with a portion of a patient's stomach.  
   
   
       4 . The device of  claim 3 , wherein the gastric portion is modeled to conform with a cardiac region of a stomach adjacent to a cardiac opening of the stomach.  
   
   
       5 . The device of  claim 1 , wherein 
 a) the esophageal portion has a length of between 1 to 30 cm and a diameter of between 0.5 to 5 cm; and    b) the gastric portion has a length of between 1 to 8 cm and the distal tip of the gastric portion has a diameter of between 1-12 cm.    
   
   
       6 . The device of  claim 5 , wherein 
 a) the esophageal portion has a length of about 3 cm and a diameter of about 2.3 cm; and    b) the gastric portion has a length of about 3-4 cm and a diameter of the distal tip of about 7 cm.    
   
   
       7 . The device of  claim 1 , wherein the extracellular matrix tissue is isolated from urinary bladder tissue.  
   
   
       8 . The device of  claim 7 , wherein the extracellular matrix tissue comprises epithelial basement membrane and subjacent tunica propria.  
   
   
       9 . The device of  claim 7 , wherein the extracellular matrix tissue comprises tunica submucosa.  
   
   
       10 . The device of  claim 7 , wherein the extracellular matrix tissue comprises epithelial basement membrane, subjacent tunica propria, and tunica submucosa.  
   
   
       11 . The device of  claim 7 , wherein the extracellular matrix tissue comprises tunica muscularis.  
   
   
       12 . The device of  claim 1 , wherein the extracellular matrix tissue is isolated from intestinal submucosa.  
   
   
       13 . The device of  claim 12 , wherein the extracellular matrix tissue is isolated from small intestinal submucosa.  
   
   
       14 . The device of  claim 1 , wherein the extracellular matrix tissue is isolated from dermis of skin.  
   
   
       15 . The device of  claim 1 , wherein the extracellular matrix tissue is isolated from the esophagus.  
   
   
       16 . The device of  claim 1 , comprising 2-10 layers of extracellular matrix tissue.  
   
   
       17 . The device of  claim 1 , seeded with cells.  
   
   
       18 . The device of  claim 17 , wherein the cells are human.  
   
   
       19 . The device of  claim 18 , wherein the cells are obtained from a patient into whom the device is to be implanted.  
   
   
       20 . The device of  claim 1 , contained within packaging material.  
   
   
       21 . The device of  claim 1 , wherein the device is sterilized.  
   
   
       22 . A mold for molding extracellular matrix tissue, comprising: 
 a) a tubular esophageal portion having essentially a constant diameter; and    b) a tubular gastric portion attached to the esophageal portion at a junction having a diameter that increases from the junction to a distal tip of the gastric portion.    
   
   
       23 . The mold of  claim 22 , wherein the diameter of the gastric portion increases in an essentially uniform manner from the point of connection to the esophageal portion to the distal tip of the gastric portion.  
   
   
       24 . The mold of  claim 22 , wherein 
 a) the esophageal portion has a length of between 1 to 30 cm and a diameter of between 0.5 to 5 cm; and    b) the gastric portion has a length of between 1 to 8 cm and the distal tip of the gastric portion has a diameter of between 1-12 cm.    
   
   
       25 . The mold of  claim 24 , wherein 
 a) the esophageal portion has a length of about 3 cm and a diameter of about 2.3 cm; and    b) the gastric portion has a length of about 3-4 cm and a diameter of the distal tip of about 7 cm.    
   
   
       26 . The mold of  claim 22 , wherein the mold is made of one or more water-permeable materials.  
   
   
       27 . The mold of  claim 22 , wherein the gastric portion is modeled to conform with a portion of a stomach.  
   
   
       28 . The mold of  claim 22 , wherein the gastric portion is modeled to conform with a cardiac region of a stomach adjacent to a cardiac opening of the stomach.  
   
   
       29 . The mold of  claim 22 , wherein the esophageal portion is detachable from the gastric portion.  
   
   
       30 . The mold of  claim 22 , wherein the mold is collapsible.  
   
   
       31 . A method of reinforcing an anastomotic site in a patient comprising implanting a device between a portion of the patient's esophagus and stomach, the device comprising one or more layers of extracellular matrix tissue and comprising: 
 a) a tubular esophageal portion having essentially a constant diameter; and    b) a tubular gastric portion attached to the esophageal portion at a junction having a diameter that increases from the junction to a distal tip of the gastric portion.    
   
   
       32 . The method of  claim 31 , wherein the device is attached externally to the patient's remaining esophagus and stomach.  
   
   
       33 . The method of  claim 31 , wherein the device is attached internally to the patient's remaining esophagus and stomach.  
   
   
       34 . The method of  claim 33 , in which endomucosa is removed from the patient's esophagus and/or stomach where the device is implanted.  
   
   
       35 . The method of  claim 31 , wherein the patient has or previously has had Barrett's disease, esophageal cancer or trauma to the esophagus.  
   
   
       36 . The method of  claim 31 , wherein the diameter of the gastric portion increases in an essentially uniform manner from the junction to the distal tip of the gastric portion.  
   
   
       37 . The method of  claim 31 , wherein the gastric portion is modeled to conform with a portion of a patient's stomach.  
   
   
       38 . The method of  claim 37 , wherein the gastric portion is modeled to conform with a cardiac region of a stomach adjacent to a cardiac opening of the stomach.  
   
   
       39 . The method of  claim 31 , wherein 
 a) the esophageal portion has a length of between 1 to 30 cm and a diameter of between 0.5 to 5 cm; and    b) the gastric portion has a length of between 1 to 8 cm and the distal tip of the gastric portion has a diameter of between 1-12 cm.    
   
   
       40 . The method of  claim 39 , wherein 
 a) the esophageal portion has a length of about 3 cm and a diameter of about 2.3 cm; and    b) the gastric portion has a length of about 3-4 cm and a diameter of the distal tip of about 7 cm.    
   
   
       41 . The method of  claim 31 , wherein the extracellular matrix tissue is isolated from urinary bladder tissue.  
   
   
       42 . The method of  claim 41 , wherein the extracellular matrix tissue comprises epithelial basement membrane and subjacent tunica propria.  
   
   
       43 . The method of  claim 41 , wherein the extracellular matrix tissue comprises tunica submucosa.  
   
   
       44 . The method of  claim 41 , wherein the extracellular matrix tissue comprises epithelial basement membrane, subjacent tunica propria, and tunica submucosa.  
   
   
       45 . The method of  claim 41 , wherein the extracellular matrix tissue comprises tunica muscularis.  
   
   
       46 . The method of  claim 31 , wherein the extracellular matrix tissue is isolated from intestinal submucosa.  
   
   
       47 . The method of  claim 46 , wherein the extracellular matrix tissue is isolated from small intestinal submucosa.  
   
   
       48 . The method of  claim 31 , wherein the extracellular matrix tissue is isolated from dermis of skin.  
   
   
       49 . The method of  claim 31 , wherein the extracellular matrix tissue is isolated from the esophagus.  
   
   
       50 . The method of  claim 31 , wherein the device comprises 2-10 layers of extracellular matrix tissue.