Synthetic scaffolds and organ and tissue transplantation

Abstract

A synthetic scaffold for replacing at least a portion of an airway includes an airway mold, one or more structural ribs on the airway mold, and a non-structural wall. Each of the one or more structural ribs is formed from a first material and the non-structural wall is formed from a second material. The non-structural wall coats the airway mold and forms a conduit that incorporates the one or more structural ribs.

1 . A synthetic scaffold for replacing at least a portion of an airway, comprising:
 a generally tubular body having a length, an interior channel surface extending along the length, and an opposed exterior surface defined on a central support surface, the tubular member having;   one or more structural ribs contiguously connected to the tubular body, wherein each structural rib is formed from a polymeric material; and   a wall member formed from a polymeric material, wherein the wall member is connected to and extends from the one or more structural ribs.   
     
     
         2 . The synthetic scaffold of  claim 1 , wherein the tubular body includes a convex anterior section and a straight posterior section when viewed in cross section and wherein the rib is U-shaped and is coplanar with the convex section of the tubular body. 
     
     
         3 . The synthetic scaffold of  claim 2 , wherein each structural rib is about 0.5 cm thick and wherein the one or more structural ribs are separated by about 0.5 cm along the length of the tubular body. 
     
     
         4 . The synthetic scaffold of  claim 1  wherein the tubular body has a diameter of approximately 2-3 cm and is configured as a trachea. 
     
     
         5 . The synthetic scaffold of  claim 1  wherein the tubular body has a diameter of approximately 1 to 1.5 cm. 
     
     
         6 . The synthetic scaffold of  claim 1  wherein the tubular body is branched and includes at least one tracheal segment and at least one bronchial segment. 
     
     
         7 . The synthetic scaffold of  claim 1  wherein at least one of the interior channel surface and the opposed exterior surface of the tubular channel has a plurality of pores having an average pore diameter defined thereon. 
     
     
         8 . The synthetic scaffold of  claim 7  wherein the average pore size is 20-100 microns. 
     
     
         9 . The synthetic scaffold of  claim 7  wherein the average pore size is 20-40 microns. 
     
     
         10 . A method of seeding a synthetic airway scaffold, the method comprising incubating a synthetic airway scaffold in a rotating bioreactor in the presence of a cellular solution. 
     
     
         11 . The method of  claim 10 , wherein cells of the cellular solution are mesenchymal cells. 
     
     
         12 . The method of  claim 11  wherein the temperature of the incubating step is about 30° C. 
     
     
         13 . A method of preparing a seeded synthetic scaffold for transplantation, the method comprising adding one or more growth factors to the seeded scaffold. 
     
     
         14 . The method of  claim 13 , wherein a first growth factor is added to a structural rib of the synthetic scaffold or wherein the one or more growth factors is EPO and the EPO is added in an amount sufficient to prevent apoptosis. 
     
     
         15 . The method of  claim 13 , wherein the first growth factor promotes cartilage formation or wherein the first growth factor is TGF-B or wherein the first growth factor is injected into the structural rib or wherein a second growth factor is added to the wall of the synthetic scaffold or wherein the second growth factor promotes cell mobilization and proliferation or wherein the second growth factor is GCSF. 
     
     
         16 . The method of  claim 10 , wherein cells of the cellular solution are obtained from human bone marrow. 
     
     
         17 . The method of  claim 10 , wherein the incubating step lasts for 1-3 days. 
     
     
         18 . The method of  claim 17 , wherein the incubating step lasts for 2 days. 
     
     
         19 . The method of  claim 11 , further comprising adding epithelial cells. 
     
     
         20 . The method of  claim 16 , further comprising adding epithelial cells. 
     
     
         21 . The method of  claim 10 , wherein the incubating step proceeds at a temperature of between about 25° C. and 37° C. 
     
     
         22 . The method of  claim 11 , wherein the incubating step proceeds at a temperature of about 30° C. 
     
     
         23 . The method of  claim 16 , wherein the incubating step proceeds at a temperature of about 30° C. 
     
     
         24 . The method of  claim 17 , wherein the incubating step proceeds at a temperature of about 30° C. 
     
     
         25 . The method of  claim 18 , wherein the incubating step proceeds at a temperature of about 30° C. 
     
     
         26 . The method of claim 19 , wherein the incubating step proceeds at a temperature of about 30° C. 
     
     
         27 . The method of  claim 20 , wherein the incubating step proceeds at a temperature of about 30° C. 
     
     
         28 . The method of  claim 11 , wherein the incubating step proceeds at a temperature of about 35° C. 
     
     
         29 . The method of  claim 16 , wherein the incubating step occurs at a temperature of about 35° C. 
     
     
         30 . The method of  claim 17 , wherein the incubating step occurs at a temperature of about 35° C. 
     
     
         31 . The method of  claim 18 , wherein the incubating step proceeds at a temperature of about 35° C. 
     
     
         32 . The method of  claim 19 , wherein the incubating step proceeds at a temperature of about 35° C. 
     
     
         33 . The method of  claim 20 , wherein the incubating step proceeds at a temperature of about 35° C. 
     
     
         34 . The method of  claim 11  wherein the synthetic airway scaffold is composed of a polymeric material. 
     
     
         35 . The method of  claim 34  wherein the polymeric material is at least one of the following: polylactic acid, polyglycolic acid, polycaprolactone. 
     
     
         36 . The method of  claim 34  wherein the polymeric material is a polysaccahride material such as chitosan or glycosaminoglycans. 
     
     
         37 . The method of  claim 36  wherein the polysaccharide material includes hyaluronic acid in combination with cross linking agents. 
     
     
         38 . The method of  claim 34  wherein the polymeric material includes tissue extracts. 
     
     
         39 . The synthetic scaffold of  claim 7  wherein the average pore size is less than 10 microns. 
     
     
         40 . The synthetic scaffold of  claim 7  wherein the average pore size is less than 100 nm. 
     
     
         41 . The synthetic scaffold of  claim 8  further comprising cellular material adhering to at least one of the interior channel wherein at least one of the interior channel surface and the exterior channel surface, wherein the cellular material includes at least one of mesenchymal cells epithelial cells, chondrocytes, endothelial progenitor cells. 
     
     
         42 . The synthetic scaffold of  claim 1  wherein the polymeric material is selected from the group consisting of polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), collagen, fibrin, and polysaccharidic materials such as chitosan or glycosaminoglycans (GAGs) including hyaluronic acid possibly in combination with cross linking agents such as glutaraldehyde or carbodiimide. 
     
     
         43 . A synthetic scaffold for replacing at least a portion of an airway, comprising:
 a generally tubular body having a length, an interior channel surface extending along the length, and an opposed exterior surface defined on a central support surface, wherein the central support surface is composed of a polymeric material, wherein at least one of the interior channel surface and/or the exterior channel surface has a plurality of pores having a pore diameter defined therein;   a cellular material adhering to at least one of the interior channel surface or the exterior channel surface, wherein the cellular material includes at least one of mesenchymal cells, epithelial cells, chondrocytes, or endothelial progenitor cells.   
     
     
         44 . The synthetic scaffold of  claim 43  wherein the average pore size is 20-100 microns. 
     
     
         45 . The synthetic scaffold of  claim 43  wherein the average pore size is 20-40 microns. 
     
     
         46 . The synthetic scaffold of  claim 43  wherein the average pore size is less than 100 nm. 
     
     
         47 . The synthetic scaffold of  claim 43  wherein the polymeric material is selected from the group consisting of polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), collagen, fibrin, and polysaccharidic materials such as chitosan or glycosaminoglycans (GAGs) including hyaluronic acid possibly in combination with cross linking agents such as glutaraldehyde or carbodiimide.