Microfabricated membranes and matrices

Abstract

The invention relates to microfabricated membranes and matrices that have a highly controlled and complex three-dimensional topography. The new microfabricated membranes and matrices can be prepared of man-made as well as natural materials, such as materials found in naturally occurring membranes, and thus can be made in the form of tissue substitutes or analogs, such as basal lamina, dermal, or skin analogs.

What is claimed is:  
     
         1 . A dermal analog comprising a polymeric matrix and a basal lamina analog fixed to a surface of the polymeric matrix, wherein the basal lamina analog comprises a microfabricated membrane comprising a sheet of conforming material that comprises a defined, three-dimensional topography, wherein the membrane is  1  to 50 microns thick, and the three-dimensional topography mimics a three-dimensional topography of a natural basal lamina.  
     
     
         2 . A dermal analog of  claim 1 , wherein the polymeric matrix comprises collagen.  
     
     
         3 . A dermal analog of  claim 1 , wherein the polymeric matrix comprises type I collagen and a glycosaminoglycan (GAG).  
     
     
         4 . A dermal analog of  claim 1 , wherein the polymeric matrix comprises hyaluronic acid.  
     
     
         5 . A tissue substitute comprising 
 a dermal analog of  claim 1 , and mammalian cells grown on and in the dermal analog.    
     
     
         6 . A tissue substitute of  claim 5 , wherein the mammalian cells are epithelial cells.  
     
     
         7 . A tissue substitute of  claim 5 , wherein the epithelial cells are keratinocytes, and the tissue substitute is a skin substitute.  
     
     
         8 . A tissue substitute of  claim 5 , wherein the mammalian cells are human cells.  
     
     
         9 . A tissue substitute of  claim 5 , wherein the mammalian cells are engineered to include a nucleic acid construct that encodes a heterologous polypeptide.  
     
     
         10 . A tissue substitute of  claim 5 , wherein the mammalian cells are engineered to include a nucleic acid construct that encodes a therapeutic protein, a growth factor, a wound healing factor, or a hormone.