Production of tissue engineered digits and limbs
First Claim
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1. A method of producing an artificial composite flexible digit construct permitting coordinated motion, comprising:
- providing a first biocompatible, biodegradable matrix, wherein the first matrix comprises a composite synthetic polymer and collagen matrix having a substantially uniform porous structure and a porosity greater than about 50% for cell accommodation, the composite further comprising about 25% to about 75% synthetic polymer to provide sufficient rigidity to provide structural support for bone tissue regeneration;
seeding the first matrix with an isolated population of cells selected from the group consisting of cartilage-forming cells, bone-forming cells and combinations thereof;
providing a second biocompatible matrix, wherein the second matrix comprises a flexible, collagen-containing matrix;
seeding the second matrix with an isolated population of muscle progenitor cells (MPCs);
preconditioning the seeded second matrix in a bioreactor that provides intermittent stretching of the MPC-seeded second matrix to promote unidirectional muscle fiber growth and orientation;
joining the first matrix to the second matrix; and
joining the second matrix to an additional matrix or a bone structure such that the second matrix produces a flexible linkage therebetween to produce the artificial composite flexible digit construct capable of coordinated motion.
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Abstract
The invention pertains to methods of producing artificial composite tissue constructs that permit coordinated motion. Biocompatable structural matrices having sufficient rigidity to provide structural support for cartilage-forming cells and bone-forming cells are used. Biocompatable flexible matrices seeded with muscle cells are joined to the structural matrices to produce artificial composite tissue constructs that are capable of coordinated motion.
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Citations
30 Claims
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1. A method of producing an artificial composite flexible digit construct permitting coordinated motion, comprising:
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providing a first biocompatible, biodegradable matrix, wherein the first matrix comprises a composite synthetic polymer and collagen matrix having a substantially uniform porous structure and a porosity greater than about 50% for cell accommodation, the composite further comprising about 25% to about 75% synthetic polymer to provide sufficient rigidity to provide structural support for bone tissue regeneration; seeding the first matrix with an isolated population of cells selected from the group consisting of cartilage-forming cells, bone-forming cells and combinations thereof; providing a second biocompatible matrix, wherein the second matrix comprises a flexible, collagen-containing matrix; seeding the second matrix with an isolated population of muscle progenitor cells (MPCs); preconditioning the seeded second matrix in a bioreactor that provides intermittent stretching of the MPC-seeded second matrix to promote unidirectional muscle fiber growth and orientation; joining the first matrix to the second matrix; and joining the second matrix to an additional matrix or a bone structure such that the second matrix produces a flexible linkage therebetween to produce the artificial composite flexible digit construct capable of coordinated motion. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 19, 23, 24)
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12. A method of producing an artificial composite flexible joint construct permitting coordinated motion, comprising:
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providing a first biocompatible, biodegradable matrix, wherein the first matrix comprises a composite synthetic polymer and collagen matrix having a substantially uniform porous structure and a porosity greater than about 50% for cell accommodation, the composite further comprising about 25% to about 75% synthetic polymer to provide sufficient rigidity to provide structural support for bone tissue regeneration; seeding the first matrix with an isolated population of cells selected from the group consisting of cartilage-forming cells, bone-forming cells and combinations thereof; providing a second biocompatible matrix, wherein the second matrix comprises a flexible, collagen-containing matrix; seeding the second matrix with an isolated population of muscle progenitor cells (MPCs); preconditioning the seeded second matrix in a bioreactor that provides intermittent stretching of the MPC-seeded second matrix to promote unidirectional muscle fiber growth and orientation; joining the first matrix to the second matrix; and joining the second matrix to an additional matrix or a bone structure, such that the second matrix produces a flexible linkage therebetween to produce the artificial composite flexible joint construct capable of coordinated motion, wherein at least one of the isolated populations of cells have been transformed to express a biological agent. - View Dependent Claims (13, 14, 15, 20, 25, 26)
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16. A method of producing an artificial composite flexible joint construct permitting coordinated motion, comprising:
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providing a first biocompatible, biodegradable matrix, wherein the first matrix comprises a composite synthetic polymer and collagen matrix having a substantially uniform porous structure and a porosity greater than about 50% for cell accommodation, the composite further comprising about 25% to about 75% synthetic polymer to provide sufficient rigidity to provide structural support for bone tissue regeneration; seeding the first matrix with an isolated population of osteoblasts and at least one population of cells selected from the group consisting of cartilage cells, chondrocytes and chondroblasts; providing a second biocompatible matrix, wherein the second matrix comprises a flexible, collagen-containing matrix; seeding the second matrix with an isolated population of muscle progenitor cells (MPCs); preconditioning the seeded second matrix in a bioreactor that provides intermittent stretching of the MPC-seeded second matrix to promote unidirectional muscle fiber growth and orientation; joining the first matrix to the second matrix; and joining the second matrix to an additional matrix or a bone structure, such that the second matrix produces a flexible linkage therebetween to produce the artificial composite flexible joint construct capable of coordinated motion. - View Dependent Claims (17, 21, 27, 28)
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18. A method of producing an artificial composite flexible joint construct permitting coordinated motion, comprising:
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providing a first biocompatible, biodegradable matrix, wherein the first matrix comprises a composite synthetic polymer and collagen matrix having a substantially uniform porous structure and a porosity greater than about 50% for cell accommodation, the composite further comprising about 25% to about 75% synthetic polymer to provide sufficient rigidity to provide structural support for bone tissue regeneration; seeding the first matrix with an isolated population of cells selected from the group consisting of cartilage-forming cells, bone-forming cells and combinations thereof; providing a second biocompatible matrix, wherein the second matrix comprises a flexible, collagen-containing matrix; seeding the second matrix with an isolated population of muscle progenitor cells (MPCs); preconditioning the seeded second matrix in a bioreactor that provides intermittent stretching of the MPC-seeded second matrix to promote unidirectional muscle fiber growth and orientation; joining the first matrix to the second matrix; and joining the second matrix to an additional matrix or a bone structure, such that the second matrix produces a flexible linkage therebetween to produce the artificial composite flexible joint construct capable of coordinated motion, wherein at least one of the first and second matrix further comprises at least one nanoparticle coupled to a releasable biological agent and incorporated within the matrix. - View Dependent Claims (22, 29, 30)
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Specification