Three-Dimensional Microfabricated Bioreactors with Embedded Capillary Network

A method of making a three-dimensional device, said method comprising:

• a. providing photocurable liquid composition having a top surface;
• b. providing a light source capable of curing at least a portion of said composition;
• c. illuminating said composition top surface with gray scale illumination, wherein said gray scale illumination is a pattern of light intensity or duration that generates a pattern of polymer having a spatially varying cross-linking density;
• and
• d. contacting said polymer with an etchant that selectively removes polymer having a lower cross-linking density;
• thereby making a three-dimensional device.

A method of producing a biological material, said method comprising:

• a. providing a vascularized bioreactor having a three-dimensional network of microvessels capable of fostering a cell population, wherein said network has
• i. a polymeric wall with a lumen-facing side and a cell-facing side, wherein at least a portion of said wall is permeable to said biological material and said wall has a permeability that varies with microvessel position;
• ii. an inlet port upstream of said network for introducing culture media to said network;
• iii. an outlet port downstream of said network for removing said culture media;
• b. obtaining an isolated cell population capable of producing said biological material or a precursor thereof;
• c. contacting said cell population to at least a portion of said outward-facing side of said network wall;
• d. culturing said cell population in said bioreactor by introducing a culture media to said inlet port to expose said network wall inward-facing side to said culture media;
• and
• e. collecting said culture media that has transited said microvessel network at said outlet port;
• wherein said cell population produces a biological material capable of diffusing from said cell population to said culture media via said network wall so that said collecting step collects at least a portion of said produced biological material, said biological material is a biofuel, pharmaceutical, drug, a prodrug, or any precursors thereof.

A vascularized bioreactor comprising:

• a. a three-dimensional network of microvessels having a wall made of a biocompatible polymer, wherein said wall has at least one parameter that varies with a longitudinal or a radial position within the network;
• b. an inlet port for introducing culture media to said network;
• and
• c. an exit port where culture media is removed from said network.