Flexible tissue matrix and methods for joint repair
First Claim
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1. A composition for supporting repair of biological tissues comprising:
- total polymers comprising caprolactone polymer molecules and at least one additional polyester polymer other than a caprolactone polymer which is not copolymerized with caprolactone polymer, wherein the total polymers are entangled with polysaccharide polymer molecules by a dual solvent emulsion process to form a dry flexible matrix, and at least one biologically active agent, said composition being formed by the steps consisting of;
a. dissolving the total polymers in an organic solvent;
b. dissolving the polysaccharide in an aqueous solvent;
c. combining the total polymers in the organic solvent with the polysaccharide in the aqueous solvent;
d. blending the total polymers in the organic solvent with the polysaccharide in the aqueous solvent to form the dual solvent emulsion;
e. removing the organic solvent and aqueous solvent from the emulsion to form a flexible matrix comprising the total polymer molecules entangled with polysaccharide polymer molecules; and
f. adding the at least one biologically active agent to the composition at any of steps (c) or (d),wherein the weight ratio of the polyester polymer to the caprolactone polymer ranges from about 1;
1 to about 4;
1 and wherein the composition maintains the flexibility when cooled to at least about room temperature.
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Abstract
Compositions and methods for repair of tissue defects are disclosed. The compositions are prepared by entangling high molecular weight polycaprolactone polymer molecules with a polysaccharide such as hyaluronic acid by a dual solvent emulsion process to produce a porous flexible matrix which supports cell and tissue growth in vivo and ex vivo.
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Citations
62 Claims
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1. A composition for supporting repair of biological tissues comprising:
- total polymers comprising caprolactone polymer molecules and at least one additional polyester polymer other than a caprolactone polymer which is not copolymerized with caprolactone polymer, wherein the total polymers are entangled with polysaccharide polymer molecules by a dual solvent emulsion process to form a dry flexible matrix, and at least one biologically active agent, said composition being formed by the steps consisting of;
a. dissolving the total polymers in an organic solvent; b. dissolving the polysaccharide in an aqueous solvent; c. combining the total polymers in the organic solvent with the polysaccharide in the aqueous solvent; d. blending the total polymers in the organic solvent with the polysaccharide in the aqueous solvent to form the dual solvent emulsion; e. removing the organic solvent and aqueous solvent from the emulsion to form a flexible matrix comprising the total polymer molecules entangled with polysaccharide polymer molecules; and f. adding the at least one biologically active agent to the composition at any of steps (c) or (d), wherein the weight ratio of the polyester polymer to the caprolactone polymer ranges from about 1;
1 to about 4;
1 and wherein the composition maintains the flexibility when cooled to at least about room temperature. - 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, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 54, 55, 56, 57, 58, 59, 60, 61, 62)
- total polymers comprising caprolactone polymer molecules and at least one additional polyester polymer other than a caprolactone polymer which is not copolymerized with caprolactone polymer, wherein the total polymers are entangled with polysaccharide polymer molecules by a dual solvent emulsion process to form a dry flexible matrix, and at least one biologically active agent, said composition being formed by the steps consisting of;
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50. A composition for supporting repair of a tissue defect in a subject, comprising:
- hyaluronic acid (HA) polymer molecules and a polymer mixture comprising poly (L-lactide-co-caprolactone) (PLCL) molecules and PLGA molecules, wherein the PLGA molecules are not copolymerized with the PLCL molecules, and wherein the PLCL, HA and PLGA molecules are entangled together by a dual solvent emulsion process and combined with at least one biologically active agent to form a dry flexible matrix, said composition being formed by the steps consisting of;
a. dissolving the polymer mixture in an organic solvent; b. dissolving the HA molecules in an aqueous solvent; c. combining the polymer mixture in the organic solvent with the HA molecules in the aqueous solvent; d. blending the polymer mixture in the organic solvent with the HA molecules in the aqueous solvent to form the dual solvent emulsion; e. removing the organic solvent and aqueous solvent from the emulsion to form a flexible matrix comprising the polymer mixture molecules entangled with the HA molecules; and f. adding the at least one biologically active agent to the composition at any of steps (c) or (d); wherein the flexible matrix has a flexibility at a room temperature, wherein the room temperature flexibility is maintained when the flexible matrix is cooled to a temperature of less than about 20°
C., and wherein the HA polymer molecules have a total HA weight, and wherein the PLGA molecules not copolymerized with the PLCL molecules, together with the PLCL molecules have a total polymer weight, wherein the ratio of the total polymer weight to the total HA weight in the composition is from about 1;
1 to about 4;
1.- View Dependent Claims (51)
- hyaluronic acid (HA) polymer molecules and a polymer mixture comprising poly (L-lactide-co-caprolactone) (PLCL) molecules and PLGA molecules, wherein the PLGA molecules are not copolymerized with the PLCL molecules, and wherein the PLCL, HA and PLGA molecules are entangled together by a dual solvent emulsion process and combined with at least one biologically active agent to form a dry flexible matrix, said composition being formed by the steps consisting of;
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52. A composition for supporting repair of biological tissues comprising:
- total polymers comprising caprolactone polymer molecules and at least one additional polyester polymer other than a caprolactone polymer which is not copolymerized with caprolactone polymer, wherein the total polymers are entangled with polysaccharide polymer molecules by a dual solvent emulsion process to form a dry flexible matrix, and at least one biologically active agent, said composition being formed by the steps consisting essentially of;
a. dissolving the total polymers in an organic solvent; b. dissolving the polysaccharide in an aqueous solvent; c. combining the total polymers in the organic solvent with the polysaccharide in the aqueous solvent; d. blending the total polymers in the organic solvent with the polysaccharide in the aqueous solvent to form the dual solvent emulsion; e. removing the organic solvent and aqueous solvent from the emulsion to form a flexible matrix comprising the total polymer molecules entangled with polysaccharide polymer molecules; and f. adding the at least one biologically active agent to the composition at any of steps (c) or (d), wherein the weight ratio of the polyester polymer to the caprolactone polymer ranges from about 1;
1 to about 4;
1 and wherein the composition maintains the flexibility when cooled to at least about room temperature.
- total polymers comprising caprolactone polymer molecules and at least one additional polyester polymer other than a caprolactone polymer which is not copolymerized with caprolactone polymer, wherein the total polymers are entangled with polysaccharide polymer molecules by a dual solvent emulsion process to form a dry flexible matrix, and at least one biologically active agent, said composition being formed by the steps consisting essentially of;
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53. A composition for supporting repair of a tissue defect in a subject, comprising:
- hyaluronic acid (HA) polymer molecules and a polymer mixture comprising poly (L-lactide-co-caprolactone) (PLCL) molecules and PLGA molecules, wherein the PLGA molecules are not copolymerized with the PLCL molecules, and wherein the PLCL, HA and PLGA molecules are entangled together by a dual solvent emulsion process and combined with at least one biologically active agent to form a dry flexible matrix, said composition being formed by the steps consisting essentially of;
a. dissolving the polymer mixture in an organic solvent; b. dissolving the HA molecules in an aqueous solvent; c. combining the polymer mixture in the organic solvent with the HA molecules in the aqueous solvent; d. blending the polymer mixture in the organic solvent with the HA molecules in the aqueous solvent to form the dual solvent emulsion; e. removing the organic solvent and aqueous solvent from the emulsion to form a flexible matrix comprising the polymer mixture molecules entangled with the HA molecules; and f. adding the at least one biologically active agent to the composition at any of steps (c) or (d); wherein the flexible matrix has a flexibility at a room temperature, wherein the room temperature flexibility is maintained when the flexible matrix is cooled to a temperature of less than about 20°
C., and wherein the HA polymer molecules have a total HA weight, and wherein the PLGA molecules not copolymerized with the PLCL molecules, together with the PLCL molecules have a total polymer weight, wherein the ratio of the total polymer weight to the total HA weight in the composition is from about 1;
1 to about 4;
1.
- hyaluronic acid (HA) polymer molecules and a polymer mixture comprising poly (L-lactide-co-caprolactone) (PLCL) molecules and PLGA molecules, wherein the PLGA molecules are not copolymerized with the PLCL molecules, and wherein the PLCL, HA and PLGA molecules are entangled together by a dual solvent emulsion process and combined with at least one biologically active agent to form a dry flexible matrix, said composition being formed by the steps consisting essentially of;
Specification