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