Method for Engineering Three-Dimensional Synthetic Vascular Networks Through Mechanical Micromachining and Mutable Polymer Micromolding

Abstract

The present invention relates generally to a method that is used to create three-dimensional synthetic vascular networks. Micromachining and molding techniques are used to create a template in a shape that mimics a biological network. Cellular material can be seeded around the template or a space created by the template and grown into an engineered tissue-construct.

What is claimed is: 
     
         1 . An artificial vascularized structure comprising:
 a cavity embedded in a growth medium, wherein the cavity is formed by the following process:   forming a micromold having a microchannel with a circular cross-section;   flowing a template material into the microchannel,
 wherein the micromold has a dissolution rate that prevents dissolution of the micromold during flowing the template material; 
   causing the template material to solidify in the microchannel;   dissolving the micromold, leaving a template having a shape of the microchannel;   embedding the template in a growth medium;   solidifying the growth medium;   liquefying and then removing the template material, leaving the cavity in the growth medium in the shape of the template; and   perfusing the cavity with cellular material.   
     
     
         2 . The artificial vascularized structure of  claim 1 , wherein forming a micromold comprises:
 milling a groove on a substrate, wherein the groove forms a pattern that mimics a biologic structure;   transferring the pattern from the substrate to a first mold;   transferring the pattern from the substrate to a second mold, wherein the second mold is a mirror image of the first mold; and   joining the first mold and second mold together.   
     
     
         3 . The artificial vascularized structure of  claim 1 , wherein the cellular material is selected from the group consisting of endothelial cells and neural cells. 
     
     
         4 . The artificial vascularized structure of  claim 1 , wherein the growth medium is a collagen gel seeded with a second cellular material. 
     
     
         5 . The artificial vascularized structure of  claim 1 , wherein the template material is a gelatin solution. 
     
     
         6 . An engineered-tissue scaffold, comprising:
 a growth medium having a cavity with an interior surface,
 wherein the cavity has a circular cross-section and approximates a shape of a fabricated vascular-mimetic template, 
 wherein the growth medium is seeded with a first cellular material, 
 wherein the interior surface of the cavity is seeded with a second cellular material. 
   
     
     
         7 . The scaffold of  claim 6 , wherein the growth medium is a collagen gel. 
     
     
         8 . The scaffold of  claim 6 , wherein the second cellular material is endothelial cells.