Tissue engineering of three-dimensional vascularized using microfabricated polymer assembly technology
First Claim
3-1. The multilayer device of claim 1, wherein the material of the first layer is selected from the group consisting of silicon, glass, ceramics and polymeric materials.
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Abstract
The invention provides for the translating two-dimensional microfabrication technology into the third dimension. Two-dimensional templates are fabricated using high-resolution molding processes. These templates are then bonded to form three-dimensional scaffold structures with closed lumens. These scaffolds can be formed by layering techniques, to interconnect flat template sheets to build up a full, vascularized organ. Alternatively, such scaffolds can be formed by rolling or folding the templates to form thick three-dimensional constructs.
The scaffolds can serve as the template for cell adhesion and growth by cells that are added to the scaffolds through the vessels, holes or pores. A second set of cells, such as endothelial cells, can also be added to or seeded onto the scaffold. The second set of seeded cells form small-dimensioned blood vessels between and through the first set of seeded cells. Once the sets of cells have been added to or seeded onto the three-dimensional scaffold, this tissue-engineered organ is implanted into a recipient.
593 Citations
37 Claims
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3-1. The multilayer device of claim 1, wherein the material of the first layer is selected from the group consisting of silicon, glass, ceramics and polymeric materials.
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25. A method of making a multilayer device, comprising the steps of:
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(a) obtaining at least a first layer comprised of a material suitable for attachment and culturing of animal cells and having a pattern of channels therein, (i) wherein the channels are suitable for the attachment and culturing of animal cells within the channels, and (ii) wherein the channels are connected for the circulation of fluid through the layer; and
(b) obtaining at least a second layer for supporting animal cell growth wherein the second layer is comprised of a material suitable for attachment and culturing of animal cells; and
(c) joining or fastening together the first and second layers.
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27. A method of making a multilayer device, comprising the steps of:
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(a) obtaining a layer comprised of a material suitable for attachment and culturing of animal cells and having a pattern of channels therein, (i) wherein the channels are suitable for the attachment and culturing of animal cells within the channels, and (ii) wherein the channels are connected for the circulation of fluid through the layer; and
(b) folding or rolling the layer to form a multilayer device having channels.
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28. A method of making a multilayer device containing animal cells, comprising the steps of:
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(a) obtaining a multilayer device, comprising;
(i) at least a first layer comprised of a material suitable for attachment and culturing of animal cells and having a pattern of microchannels therein, (A) wherein the pattern of channels are suitable for the attachment and culturing of animal cells within the channels, and (B) wherein the pattern of channels are connected for the circulation of fluid through the layer; and
(ii) at least a second layer, wherein the second layer is comprised of a material suitable for attachment and culturing of animal cells, wherein the first and second layers are fastened together, and (b) adding, loading or seeding animal cells onto at least the first layer.
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32. A method of implanting a bioartificial organ into a recipient, comprising:
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(a) obtaining a multilayer device, comprising;
(i) at least a first layer comprised of a material suitable for attachment and culturing of animal cells and having a pattern of microchannels therein, (A) wherein the channels are suitable for the attachment and culturing of animal cells within the channels, and (B) wherein the channels are connected for the circulation of fluid through the layer; and
(ii) at least a second layer wherein the second layer is comprised of a material suitable for attachment and culturing of animal cells, the layers of the maultilayer device being fastened together;
the multilayer device comprising animal cells; and
(b) implanting the multilayer device comprising animal cells into the recipient, wherein the implanted multilayer device comprising animal cells is a bioartificial organ.
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33. An image reversal method for forming a scaffold having a material having a pattern of microchannels therein, comprising
(a) selecting a mold having a complex pattern of microchannels on the mold in a reverse image of the channels; - and
(b) replica molding the pattern from the mold to a material suitable for attachment and culturing of animal cells;
wherein the replica molding forms a scaffold having a complex pattern of microchannels therein. - View Dependent Claims (35, 36, 37)
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34. A multilayer device, comprising:
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(a) multiple layers of tissue;
(b) multiple layers of material suitable for attachment and growth of tissue and having a pattern of microchannels in the material;
(b) vasculature within the tissue or on the material; and
(c) connections for flow into and out of the vasculature.
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Specification