Methods of making implantable collagen fiber
First Claim
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1. A method of processing an implantable collagen fiber, comprising:
- a) placing at least one synthetic elongate collagen fiber in a desired orientation in a tissue culture vessel;
b) seeding the at least one synthetic elongate collagen fiber with a plurality of cells while in the vessel; and
c) applying a strain and/or stress to the at least one synthetic elongate collagen fiber in the vessel and either;
(i) inducing the cells to differentiate into tendon or ligament fibroblasts or tendon or ligament phenotype cells;
(ii) forming an extracellular matrix of collagen, wherein the extracellular matrix comprises collagen in amount greater than other proteins;
or(iii) both inducing the cells to differentiate into tendon or ligament fibroblasts or tendon or ligament phenotype cells and forming an extracellular matrix, wherein the extracellular matrix comprises collagen in amount greater than other proteins,wherein the applying step comprises applying a first low offset strain and/or tensile load to the at least one synthetic elongate collagen fiber, then applying a cyclic strain and/or tensile load that varies between 2% to about 15% above the first low offset strain and/or tensile load.
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Abstract
The invention relates to implantable collagen devices made by seeding at least one elongate collagen construct, e.g., comprising at least one elongate synthetic collagen fiber with a plurality of cells and applying a strain and/or stress to the at least one elongate collagen fiber to induce the cells to differentiate into target phenotypes, e.g., tendon or ligament phenotype cells (and/or fibroblasts), typically with an extracellular matrix of collagen to organize into a tissue on the at least one collagen fiber.
76 Citations
24 Claims
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1. A method of processing an implantable collagen fiber, comprising:
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a) placing at least one synthetic elongate collagen fiber in a desired orientation in a tissue culture vessel; b) seeding the at least one synthetic elongate collagen fiber with a plurality of cells while in the vessel; and c) applying a strain and/or stress to the at least one synthetic elongate collagen fiber in the vessel and either; (i) inducing the cells to differentiate into tendon or ligament fibroblasts or tendon or ligament phenotype cells; (ii) forming an extracellular matrix of collagen, wherein the extracellular matrix comprises collagen in amount greater than other proteins;
or(iii) both inducing the cells to differentiate into tendon or ligament fibroblasts or tendon or ligament phenotype cells and forming an extracellular matrix, wherein the extracellular matrix comprises collagen in amount greater than other proteins, wherein the applying step comprises applying a first low offset strain and/or tensile load to the at least one synthetic elongate collagen fiber, then applying a cyclic strain and/or tensile load that varies between 2% to about 15% above the first low offset strain and/or tensile load. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
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21. A method of processing an implantable matrix, comprising:
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a) placing an implantable matrix of woven synthetic elongate collagen fibers in a container, wherein the implantable matrix of woven synthetic elongate collagen fibers has a tensile strength, stiffness, and dynamic flexibility that meets or exceeds that of a natural ligament or tendon that the implantable matrix is designed to mimic; b) seeding the implantable matrix with a plurality of cells; and c) mechanically applying a first low offset strain and/or tensile load to the implantable matrix, then a cyclic strain and/or tensile load that varies between 2% to about 15% above the first low offset strain and/or tensile load and either; (i) inducing the cells to differentiate into tendon or ligament fibroblasts or tendon or ligament phenotype cells; (ii) forming an extracellular matrix of collagen, wherein the extracellular matrix comprises collagen in amount greater than other proteins;
or(iii) both inducing the cells to differentiate into tendon or ligament fibroblasts or tendon or ligament phenotype cells and forming an extracellular matrix, wherein the extracellular matrix comprises collagen in amount greater than other proteins. - View Dependent Claims (22, 23, 24)
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Specification