Mesh enclosed tissue constructs

Abstract

A scaffold to form tissue membranes, comprising: at least one layer of mesh having a first side and a second side, the layer of mesh being either a woven wire metal mesh or a flat metal sheet that is acid-etched such that the layer of mesh includes a network of holes passing directly through the mesh from the first side to the second side; and at least one layer of cells at each side of the mesh enclosing the layer of mesh, such that the at least one layer of cells on the first side interacts with the at least one layer of cells on the second side through the network of holes to provide for structure integration.

What is claimed is: 
     
         1 . A scaffold to form tissue membranes, comprising:
 at least one layer of mesh having a first side and a second side, the layer of mesh being either a woven wire metal mesh or a flat metal sheet that is acid-etched such that the layer of mesh includes a network of holes passing directly through the mesh from the first side to the second side; and   at least one layer of cells at each side of the mesh enclosing the layer of mesh, such that the at least one layer of cells on the first side interacts with the at least one layer of cells on the second side through the network of holes to provide for structure integration.   
     
     
         2 . The scaffold of  claim 1 , wherein the mesh becomes biologically active when implanted in-vivo. 
     
     
         3 . The scaffold of  claim 1 , further comprising a frame attached to the layer of mesh with the at least one layer of cells at each side of the mesh, wherein the frame is formed of a biocompatible metal and is covered with a woven polyester cloth. 
     
     
         4 . The scaffold of  claim 1 , wherein the mesh and at least one layer of cells at each side of the mesh are formed as leaflets, such that the scaffold is operable as a tissue heart valve. 
     
     
         5 . The scaffold of  claim 4 , wherein the scaffold includes at least two leaflets. 
     
     
         6 . The scaffold of  claim 5 , further comprising a flexible frame having a saddle-shaped base with at least two upstanding posts, with the leaflets each having a peripheral free portion and a fixed portion, such that the peripheral free portion extends between the posts and the fixed portion is attached to the base. 
     
     
         7 . The scaffold of  claim 6 , further comprising a frame having a base with three upstanding posts, with the leaflets attached to the frame and between the posts. 
     
     
         8 . The scaffold of  claim 4 , further comprising a flexible frame having a saddle-shaped base with at least two upstanding posts, with the leaflets each having a peripheral free portion and a fixed portion, such that the peripheral free portion extends between the posts and the fixed portion is attached to the base. 
     
     
         9 . The scaffold of  claim 4 , further comprising a frame having a base with three upstanding posts, with the leaflets attached to the frame and between the posts, and wherein the frame is formed of a biocompatible metal and is covered with a woven polyester cloth. 
     
     
         10 . The scaffold of  claim 1 , wherein the layer of mesh is a tubular wire mesh, wherein the at least one layer of cells at each side of the mesh are formed around the mesh to completely or partially conceal the mesh therein, whereby the scaffold is formed in the shape of a vessel to operate as a vascular graft. 
     
     
         11 . The scaffold of  claim 1 , wherein the mesh has a shape of a heart valve leaflet. 
     
     
         12 . The scaffold of  claim 11 , wherein a plurality of leaflets are attached together to form a heart valve shape. 
     
     
         13 . The scaffold of  claim 1 , wherein the mesh is a Nitinol mesh with a thickness between approximately 25 and 76 microns. 
     
     
         14 . The scaffold of  claim 1 , wherein the at least one layer of cells is selected from the group consisting of smooth muscle cells, fibroblast/myofibroblast cells and vascular endothelial cells. 
     
     
         15 . A method for forming a scaffold according to  claim 1 , comprising:
 preparing a layer of mesh having a first side and a second side, the layer of mesh being either a woven wire metal mesh or a flat metal sheet that is acid-etched, such that the layer of mesh comprises a network of holes passing directly through the mesh from the first side to the second side, and   growing a biological matrix around the layer of mesh such that the biological matrix comprises at least one layer of cells at each side of the mesh enclosing the layer of mesh, such that the at least one layer of cells on the first side interacts with the at least one layer of cells on the second side through the network of holes to provide for structure integration.   
     
     
         16 . The method of  claim 15 , wherein the mesh is formed of stainless steel wires, and wherein said preparing the layer of mesh further comprises a preparation technique, or any combination thereof, selected from the group consisting of:
 polishing the layer of mesh;   acid washing the layer of mesh;   ultrasonic clean washing the layer of mesh; and   glow discharging the layer of mesh.   
     
     
         17 . The method of  claim 15 , wherein said preparing the layer of mesh comprises modifying the surface of the mesh by ion beam surface modification to provide a smooth surface and to ensure biocompatibility of the mesh and enhanced cell attachment to said mesh. 
     
     
         18 . The method of  claim 15 , wherein said growing a biological matrix around the layer of mesh comprises modifying the surface of the mesh with an additive to ensure tissue growth. 
     
     
         19 . The method of  claim 18 , wherein the additive is collagen, which applied to the layer of mesh to coat the layer of mesh to promote development of an interconnected pore network. 
     
     
         20 . The method of  claim 15 , wherein said growing a biological matrix around the layer of mesh comprises seeding the at least one layer of cells sequentially on each side of the layer of mesh. 
     
     
         21 . The method of  claim 20 , wherein the sequential seeding of cell layers further comprises adding cytokines, including TGF-β1 with each sequentially seeded layer. 
     
     
         22 . The method of  claim 20 , wherein, if more than one layer of cells is seeded on each side of the mesh, a time interval of approximately two weeks is provided between seeding of each of the different layers of cells. 
     
     
         23 . The method of  claim 15 , wherein the biological matrix is able to further grow and develop when implanted in vivo. 
     
     
         24 . The method of  claim 15 , wherein the biological matrix is grown around the layer of mesh in vitro. 
     
     
         25 . The method of  claim 15 , wherein the layer of mesh is a tubular wire mesh, wherein the at least one layer of cells at each side of the mesh are formed around the mesh to completely or partially conceal the mesh therein, whereby the scaffold is formed in the shape of a vessel to operate as a vascular graft. 
     
     
         26 . The method of  claim 15 , comprising cutting the mesh to the shape of a heart valve leaflet. 
     
     
         27 . The method of claim  35 , comprising attaching a plurality of leaflets together to form a heart valve shape. 
     
     
         28 . The method of  claim 15 , wherein the cells in the at least one layer of cells at each side of the mesh are selected from the group consisting of smooth muscle cells, fibroblast/myofibroblast cells, and vascular endothelial cells.