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1. WO2020160491 - EXTRUSION MICROFLUIDIQUE

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

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CLAIMS:

We claim:

1. A biopolymer fiber comprising a collagen, wherein the biopolymer fiber has one or more of the following characteristics:

an ultimate tensile strength of between about 1 MPa to about 1,700 MPa;

a modulus of elasticity of between about 10 MPa to about 20,000 MPa;

a strain at break of between about 2 percent and about 45 percent elongation; an average fiber diameter between about 10 pm and about 90 pm;

maintains its strength after soaking in DPBS at room temperature for at least about 1 hour; and

wherein the fiber exhibits an ordered, longitudinally oriented structure.

2. The biopolymer fiber of claim 1, wherein

the ultimate tensile strength is between about 1 MPa to about 800 MPa;

the modulus of elasticity is between about 10 MPa to about 7,500 MPa; and the average fiber diameter is between about 10 pm and about 30 pm.

3. The biopolymer fiber of claim 1, wherein

the ultimate tensile strength is between about 25 MPa to about 1,700 MPa;

the modulus of elasticity is between about 15,000 MPa to about 29,000 MPa; and a strain at break of between about 7 percent and about 20 percent elongation.

4. The biopolymer fiber of claim 1, wherein the collagen comprises clinical grade collagen, atelocollagen, telocollagen, recombinant collagen, or a blend thereof.

5. The biopolymer fiber of claim 1, wherein the collagen further comprises one or more bio-acceptable polymers.

6. The biopolymer fiber of claim 1, further maintaining a strength greater than about 60 MPa after 6 months in DBPS at room temperature or after implantation into a subject.

7. The biopolymer fiber of claim 1, wherein the fibers are cross-linked by a cross-linker comprising glyoxal, DL-Glyceraldehyde, or a combination thereof.

8. The biopolymer fiber of claim 1, further comprising adhered tenocytes and wherein the tenocytes retain at least about 75 % cell viability and at least about

95 % cell survival after about seven days incubation under conventional mammalian cell culture conditions of temperature, pH, and humidity.

9. The biopolymer fiber of claim 1, wherein the fiber has a cross section that is substantially circular, ovoid, square, rectangular, ribbon-like, triangular, or irregularly shaped.

10. A bundle of the biopolymer fibers of claim 1, the bundle comprising between 2 and about 10,000 fibers.

11. An implantable biopolymer scaffold for supporting repair of a soft tissue injury comprising the biopolymer fibers of any of claims 1 to 9 or the bundle of biopolymer fibers of claim 10.

12. A woven sheet-like support, a patch, or a brace comprising biopolymer fibers of any of claims 1 to 9.

13. A method for producing a biopolymer fiber comprising the steps of: dissolving collagen in an acid solution to form a collagen solution;

passing the collagen solution at a first speed through a first needle having a first diameter simultaneously with passing a formation buffer solution at a second speed through a second needle coaxially surrounding the first needle and having a second diameter greater than the first diameter to form a sheath around the collagen solution to form a coaxial flow,

wherein the second flow rate of the foundation buffer solution through the second needle is at least twice the first flow rate of the collagen solution through the first needle,

passing the coaxially-flowing collagen and formation buffer solution through a reaction zone comprising a fibril-forming bath for a time and at speeds sufficient to form a fiber,

dehydrating the collagen fiber at an extrusion speed, and

withdrawing the fiber onto a spool at a third speed greater than the extrusion speed sufficient to increase molecular alignment and reduce the diameter of the fiber.

14. A method for producing a biopolymer fiber comprising the steps of:

dissolving collagen in an acid solution to form a collagen solution;

passing the collagen solution at a first speed through a first needle having a first diameter into a formation buffer solution,

passing the collagen and formation buffer solution through a reaction zone comprising a fiber- forming bath for a time and at speeds sufficient to form a fiber, dehydrating the collagen fiber at an extrusion speed, and

withdrawing the fiber onto a spool at a speed of between about 2 times the extrusion speed and about 10 times the extrusion speed sufficient to increase molecular alignment and reduce the diameter of the fiber.

15. The method of claim 13 or of claim 14, further comprising degassing the collagen solution before passing the collagen solution into the formation buffer solution.

16. A method for producing a biopolymer fiber comprising the steps of:

dissolving clinical-grade collagen in an acid solution to form a collagen solution; passing the collagen solution at a first volumetric flow rate through a first needle to yield a first speed simultaneously with passing a formation buffer solution at a second speed in a tube coaxially surrounding the first needle and forming a sheath around the collagen solution to form a coaxial flow,

wherein the speed of the foundation buffer solution is between about 2 times and about 20 times the first speed of the collagen solution through the first needle, passing the coaxially-flowing collagen and formation buffer solution through a reaction zone comprising a fibril-forming bath for a time and at speeds sufficient to form a fiber,

dehydrating the collagen fiber at an extrusion speed, and

withdrawing the fiber at a third speed greater than the extrusion speed sufficient to increase molecular alignment and reduce the diameter of the fiber.

17. The method of claim 16, further comprising collecting the fiber on a bar collector or a flat cylinder.

18. The method of claim 16, further comprising collecting the fiber on a grooved spool.

19. A method for producing a biopolymer fiber comprising the steps of: dissolving clinical-grade collagen in an acid solution to form a collagen solution; extruding the solution through a nozzle into a guide that passes the extruded solution into a flowing bath of formation buffer to form a fiber;

dehydrating the fiber formed in the formation buffer bath; and

collecting the fiber.

20. The method of claim 19, further comprising drying the dehydrated fiber by passing air over the fiber for a time sufficient to dry the fiber before collecting the fiber.

21. The method of claim 19, further comprising crosslinking the fibers with a cross-linker comprising glyoxal, DL-Glyceraldehyde, or a combination thereof, and drying the cross-linked fibers.

22. A method for producing a biopolymer fiber comprising the steps of:

dissolving clinical-grade collagen in an acid solution to form a collagen solution; passing the collagen solution at a first speed through a first needle having a first diameter into a formation buffer solution,

passing the collagen and formation buffer solution through a reaction zone comprising a fiber- forming bath for a time and at speeds sufficient to form a fiber, dehydrating the collagen fiber at an extrusion speed, and

withdrawing the fiber onto a spool at a speed of between about 2 times the extrusion speed and about 12 times the extrusion speed, in one or more stages, sufficient to increase molecular alignment and reduce the diameter of the fiber.

23. The method of claim 22, further comprising crosslinking the fibers with a cross-linker comprising glyoxal, DL-Glyceraldehyde, or a combination thereof, and drying the cross-linked fibers.

24. A biopolymer fiber produced by the method of any of claims 13 to 23.

25. An implantable biopolymer scaffold for supporting repair of a soft tissue injury comprising the biopolymer fibers of claim 24.

26. A method for supporting the repair of a soft tissue injury comprising the implantation of a biopolymer scaffold according to claim 25.

27. The method of claim 26, wherein the soft tissue is selected from the group comprising connective tissue, including ligament, tendon, enthesis, bone, muscle, myotendinous junction, skin; fascia; internal organs, and eyes.

28. A suture comprising the biopolymer fibers of claim 24.

29. The suture of claim 28 that is resorbable.

30. An internal brace comprising the biopolymer fibers of claim 24, wherein the brace, when implanted into a subject, supports, reinforces, augments, or shares the mechanical load of ligaments or tendons in joints, such as the anterior cruciate ligament, Achilles tendon, and rotator cuff.

31. An internal brace comprising the biopolymer fibers of claim 24, wherein the brace, when implanted into a subject, supports an injured joint by connecting from one bone to another bone, optionally to restore biomechanics and isometry to a level that is substantially comparable to those of a healthy native joint.