Fabrication of tissue lamina using microfabricated two-dimensional molds
First Claim
1. An apparatus capable of supplementing or replacing at least one organ function comprising multiple layers of tissue lamina stacked and fastened together,wherein each layer of tissue lamina comprises:
- (a) a first polymer scaffold configured with a plurality of branched microchannels and having endothelial cells seeded within the branched microchannels to form a vasculature system;
(b) a second polymer scaffold having parenchymal cells within the scaffold to form a parenchymal tissue; and
(c) a semi-permeable membrane disposed between the first and second polymer scaffolds, the semi-permeable membrane configured to allow exchange of oxygen, nutrients and waste between fluid circulating in the vasculature system of the first polymer scaffold and the parenchymal tissue present in the second polymer scaffold;
wherein the first polymer scaffold and the second polymer scaffold are fastened together about the semi-permeable membrane.
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Abstract
Methods and materials for making complex, living, vascularized tissues for organ and tissue replacement, especially complex and/or thick structures, such as liver tissue is provided. Tissue lamina is made in a system comprising an apparatus having (a) a first mold or polymer scaffold, a semi-permeable membrane, and a second mold or polymer scaffold, wherein the semi-permeable membrane is disposed between the first and second molds or polymer scaffolds, wherein the first and second molds or polymer scaffolds have means defining microchannels positioned toward the semi-permeable membrane, wherein the first and second molds or polymer scaffolds are fastened together; and (b) animal cells. Methods for producing complex, three-dimensional tissues or organs from tissue lamina are also provided.
104 Citations
49 Claims
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1. An apparatus capable of supplementing or replacing at least one organ function comprising multiple layers of tissue lamina stacked and fastened together,
wherein each layer of tissue lamina comprises: -
(a) a first polymer scaffold configured with a plurality of branched microchannels and having endothelial cells seeded within the branched microchannels to form a vasculature system; (b) a second polymer scaffold having parenchymal cells within the scaffold to form a parenchymal tissue; and (c) a semi-permeable membrane disposed between the first and second polymer scaffolds, the semi-permeable membrane configured to allow exchange of oxygen, nutrients and waste between fluid circulating in the vasculature system of the first polymer scaffold and the parenchymal tissue present in the second polymer scaffold; wherein the first polymer scaffold and the second polymer scaffold are fastened together about the semi-permeable membrane. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26)
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27. A method of making a tissue lamina comprising the steps of:
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(a) positioning a semi-permeable membrane between a first and second polymer scaffold, wherein the first polymer scaffold is configured with a plurality of branched microchannels and the second polymer scaffold is configured as a reservoir for holding parenchymal cells; (b) fastening the first and second polymer scaffolds together such that the semi-permeable membrane is disposed between the polymer scaffolds; (c) seeding endothelial cells into the branched microchannels of the first polymer scaffold; (d) seeding parenchymal cells into the reservoir of the second polymer scaffold; and (e) culturing the cell-seeded polymer scaffolds under conditions such that the endothelial cells form a vasculature system within the branched microchannels of the first polymer scaffold and the parenchymal cells form a parenchymal tissue in the second polymer scaffold. - View Dependent Claims (28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49)
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Specification