FIBER-ASSEMBLED TISSUE CONSTRUCTS
The present invention relates to a fiber-assembled tissue construct comprising at least one sinusoid unit, the unit comprising at least two polymeric fibers arranged in a sinusoid structure and fused together, each of said fibers comprising a porous matrix supporting biological components encapsulated in the fiber, wherein the biological components are patterned in three-dimensions within the construct.
1 . A fiber-assembled tissue construct comprising at least one sinusoid unit, the unit comprising at least two polymeric fibers arranged in a sinusoid structure by rotating the fibers about a central axis and fusing the fibers together, each of said fibers comprising a porous matrix supporting biological components encapsulated in the fiber, wherein the biological components are patterned in three-dimensions within the construct.
2 . The fiber-assembled tissue construct of claim 1 , wherein at least one of said biological components is an encapsulated cell.
3 . The fiber-assembled tissue construct of claim 1 , wherein at least one of said polymeric fibers is a multi-component fiber, said multi-component fiber comprising at least two spatially defined internal domains.
4 . The fiber-assembled tissue construct of claim 3 , wherein said multi-component fiber comprises a first internal domain and a second internal domain, said first internal domain comprising at least one component that is absent in the second internal domain.
5 . The fiber-assembled tissue construct of claim 1 , wherein the sinusoid structure comprises a first polymeric fiber and a second polymeric fiber, said first polymeric fiber comprising at least one component that is absent in the second polymeric fiber.
6 . The fiber-assembled tissue construct of claim 4 , wherein said at least one component is a specific type of cell, biologic or chemical component.
7 . The fiber-assembled tissue construct of claim 1 , wherein the unit comprises at least one central fiber.
8 . The fiber-assembled tissue construct of claim 7 , wherein the unit comprises a central fiber wrapped by a plurality of outer fibers.
9 . The fiber-assembled tissue construct of claim 1 , wherein at least one of said polymeric fibers comprises a biological or chemical component selected from the group consisting of extracellular matrix proteins, cytoskeletal proteins, cell adhesion proteins, hormones, growth factors, angiogenic factors, amino acids, nucleic acids, galactose ligands, drugs, and mixtures thereof.
10 . The fiber-assembled tissue construct of claim 1 , wherein said sinusoid structure comprises a central fiber, and said central fiber comprises one or more of encapsulated endothelial cells, encapsulated epithelial cells or encapsulated neurons.
11 . The fiber-assembled tissue construct of claim 1 wherein the sinusoid structure comprises a central fiber and an outer fiber wrapped around said central fiber, said central fiber comprising encapsulated endothelial cells and said outer fiber comprising encapsulated hepatocytes.
12 . The fiber-assembled tissue construct of claim 1 , wherein the sinusoid structure comprises a central fiber and an outer fiber wrapped around said central fiber, said central fiber comprising encapsulated epithelial cells and said outer fiber comprising encapsulated fibroblasts.
13 . The fiber-assembled tissue construct of claim 1 , wherein the sinusoid structure comprises a central fiber and an outer fiber wrapped around said central fiber, said central fiber comprising encapsulated neurons and said outer fiber comprising encapsulated Schwann cells and/or encapsulated oligodendrocytes.
14 . A method for producing a three-dimensional fiber-assembled tissue construct comprising at least one sinusoid unit, the method comprising the steps of:
(a) dispensing at least two polyionic solutions in separate locations on a first template;
(b) drawing a separate nascent polymeric fiber from each of said polyionic solutions, wherein a first end of each of said nascent fibers remains attached to the first template and a second end of each of said nascent fibers remains attached to an opposing second template;
(c) rotating either or both templates to contact each of said fibers at a common fusion point; and
(d) fusing contacting fibers together to provide a sinusoid unit, wherein said fusing comprises:
(i) applying a fusing reagent to the fusion point and upwardly drawing each of said fibres such that the reagent travels downwardly along contacting fibers; or
(ii) continuing rotation of either or both templates causing fusion by compressive force.
15 . The method of claim 14 comprising the additional step of fusing two or more sinusoid units together.
16 . The method of claim 15 , wherein said fusing two or more sinusoid units is performed by spooling sinusoid units and fusing them together with a fusing reagent.
17 . The method of claim 14 , wherein the fusing reagent is selected from the group consisting of polyanionic polymers, polycationic polymers, multivalent cations, multivalent anions, or mixtures thereof.
18 . The method of claim 14 , wherein at least one of said polymeric fibers is a multi-component fiber, said multi-component fiber comprising at least two spatially defined internal domains.
19 . The method of claim 14 , wherein the sinusoid unit comprises at least one central fiber and at least one outer fiber wrapped around the central fiber.
20 . The method of claim 14 , wherein at least one of said polymeric fibers comprises a cell.
21 - 32 . (canceled)