Layered aligned polymer structures and methods of making same

• US 20030141618A1
• Filed: 11/27/2002
• Published: 07/31/2003
• Est. Priority Date: 11/30/2001
• Status: Active Grant

• Current Assignee: Cambridge Polymer Group, Inc.
• Original Assignee: Cambridge Polymer Group, Inc.
• Inventors: Ruberti, Jeffrey W., Braithwaite, Gavin J. C.
• Granted Patent: US 7,048,963 B2
• Time in Patent Office: Days
• US Class Current: 264/40.7
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: B29C 2037/90 Measuring, controlling or regulating
• CPC Class Codes: B29C 41/045 the axis being placed vertically, e.g. spin casting
• CPC Class Codes: B29C 41/22 Making multilayered or multicoloured articles
• CPC Class Codes: B29C 41/36 Feeding the material on to the mould, core or other substrate
• CPC Class Codes: B29C 41/52 Measuring, controlling or regulating
• CPC Class Codes: B29C 48/022 characterised by the choice of material
• CPC Class Codes: B29C 48/08 flexible, e.g. films
• CPC Class Codes: B29C 67/0003 Moulding articles between moving mould surfaces, e.g. turning surfaces
• CPC Class Codes: B29C 67/24 characterised by the choice of material
• CPC Class Codes: B29K 2089/00 Use of proteins, e.g. casein, gelatine or derivatives thereof, as moulding material
• CPC Class Codes: B29K 2995/005 Oriented
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin
• CPC Class Codes: D01D 5/18 by means of rotating spinnerets
• CPC Class Codes: D01D 5/38 Formation of filaments, threads, or the like during polymerisation
• CPC Class Codes: D01F 4/00 Monocomponent artificial filaments or the like of proteins; Manufacture thereof

Abstract

This invention includes a method of producing a thin, oriented layer of polymer material. The material is preferably produced by the method of introducing a shearing flow to a free surface in a predominantly monomeric solution of the self-assembling polymer sub-units, and inducing polymerization or growth of the monomer while in this shearing flow. The system for forming the oriented layer of material provides relative movement between a delivery system and the substrate on or over which the material is deposited. The rate of flow of the material from the delivery system and the relative velocity between the deposition surface and the material as it is delivered to the surface are controlled to properly orient the material at the desired thickness. These rates can be adjusted to vary the properties of the film in a controlled manner. Preferred embodiments include either angular or linear relative movement between the delivery system and the substrate.

Claims

1. A method of producing a thin film of oriented polymer structures, comprising the steps of:

controlling the flow of a polymer solution into a device having a substrate, the device generating a shear flow to induce alignment of polymer structures;

controlling a plurality of parameters during polymerization; and

generating a layer of oriented polymer.

2. The method of claim 1, wherein the polymer is a biopolymer such as collagen.

3. The method of claim 2, wherein the method further comprises the steps of:

mixing a solution of collagen with phosphate buffered saline solution;

adjusting the pH of the solution to 7.4±

0.2;

applying the solution at a controlled rate onto a substrate which generates a shearing flow;

causing preferential orientation of the gelling collagen fibrils; and

generating successive layers, each layer representing a portion of the component.

4. The method of claim 3, wherein the layers have a uniform, controllable thickness ranging from sub-micron to 100 microns.

5. The method of claim 2, wherein the collagen is either type I or type V collagen.

6. The method of claim 1, wherein the principle orientation of the aligned fibrils in a single layer alternates in each successive layer.

7. The method of claim 3, wherein the angle between the principle orientation of each layer is approximately in the range of 0 to 180 degrees.

8. The method of claim 1, wherein the solution properties, including temperature, concentration and surfactant composition are controlled.

9. The method of claim 1, wherein the shear flow is generated by spinning the substrate at a controlled rate in a range of approximately 50 to 50,000 Hz.

10. The method of claim 1, wherein the shear flow is generated by drawing the substrate out of the collagen solution.

11. The method of claim 1, wherein the atmosphere is controlled to a specified temperature and relative humidity.

12. The method of claim 1, wherein the solution conditions are modulated to control the polymerization kinetics and morphology.

13. The method of claim 1, wherein the use of shear flow aligns polymerizing polymer chains in a layer such that polymers are predominantly aligned parallel to each other.

14. The method of claim 1, further comprising angular rotation of the substrate providing shear flow and confinement to orient the polymerized polymers.

15. The method of claim 14, wherein an input flow rate, solution viscosity and substrate rotational velocity combine to produce a shear rate between 1 s⁻

1 and 500,000 s<sup>−

1</sup>.

16. The method of claim 14, wherein an input flow rate, solution viscosity and substrate rotational velocity combine to produce a shear rate preferably between the range 10 s⁻

1 and 10,000 s<sup>−

1</sup>.

17. The method of claim 1, wherein a second aligned polymer layer is produced on top of a first polymer layer by repeating the method.

18. The method of claim 17, wherein a rotating surface is moved to change a deposition direction on the substrate.

19. The method of claim 17, wherein the second layer comprises a different material than the first layer.

20. The method of claim 17, wherein the second layer is a promoter of at least one of cell adhesion and proliferation.

21. The method of claim 17, wherein an additional layer comprising collagen type IV and cell adhesion proteins such as, laminin, fibronectin and/or any integrin receptor is deposited between aligned polymer layers.

22. The method of claim 15, wherein a construct of a plurality aligned layers is used as a replacement or repair of the human stroma.

23. The method of claim 17, wherein the alignment of the polymers in a plane of second and subsequent layers is predominantly parallel with the alignment of the polymers in a plane of the layer in the first layers.

24. The method of claim 17, wherein the alignment of the polymers in a plane of a layer in a second and subsequent layers is predominantly orthogonal with the alignment of the polymers in the plane of a layer in the first layers.

25. The method of claim 17, wherein the alignment of the polymers in a plane of a layer in the second and subsequent layers does not have a defined angular relationship to the alignment of the polymers in a plane of a layer in the first layers.

26. The method of claim 1, wherein the end-associating biopolymer monomer is included in an aqueous solution.

27. The method of claim 26, wherein the biopolymer monomer is collagen.

28. The method of claim 26, wherein the biopolymer monomer is extracted or recombinant collagen.

29. The method of claim 26, wherein the collagen is Type I as the polymerizing medium.

30. The method of claim 26, wherein the collagen is Type I and Type V to assist in creation of heterotypic fibrils.

31. The method of claim 1, wherein the polymer solution is injected at a constant rate.

32. The method of claim 1, wherein the polymer solution is injected with a flow rate between 0.05-1000 ml/min.

33. The method of claim 1, wherein the material is preferably injected with a flow rate between of 0.1-100.0 ml/min.

34. The method of claim 1, further comprising a post-processing step including spinning off any effluent material from the substrate.

35. The method of claim 1, further comprising the substrate and a substrate holder being modified to minimize waste of polymerization solution.

36. The method of claim 1, wherein the solution is preferably composed of 8:

1;

1 ratio of collagen type I (3 mg/ml) to 10×

PBS to 0.1M NaOH with pH adjusted to 7.4.

37. The method of claim 1, wherein the viscosity of the solution is between 1 mPa.s and 100 Pa.s.

38. The method of claim 1, where the viscosity solution is preferably between 5 mPa.s and 1 Pa.s.

39. The method of claim 1, wherein the substrate comprises one of a flat surface or curved surface.

40. The method of claim 39, wherein the flat surface is optically smooth.

41. The method of claim 39, wherein preferably the flat surface has a surface roughness of approximately less than 10 microns.

42. The method of claim 39, wherein the substrate is a borosilicate glass disk.

43. The method of claim 1, wherein a surface of the substrate is treated to control adhesion of the polymer and wetting of the solution.

44. The method of claim 1, wherein a surface of the substrate is ultrasonicated in 10% micro90 (Brand) cleaner for a time duration.

45. The method of claim 1, wherein a surface of the substrate is plasma cleaned.

46. The method of claim 1, wherein a surface of the substrate is homogeneous.

47. The method of claim 1, wherein the substrate has a surface treatment that is heterogeneous.

48. The method of claim 1, wherein the substrate has a surface treatment that is patterned.

49. The method of claim 1, wherein a substrate is patterned to constrain the flow.

50. The method of claim 1, wherein a surface of the substrate and atmospheric conditions are modulated to control self-assembly.

51. The method of claim 50, wherein the atmospheric conditions include a temperature range of 30°

C.-45°

C. and humidity range of 80-100%.

52. The method of claim 51, wherein the preferred range is 35°

C.-42°

C. with 90-100%.

53. The method of claim 1, wherein a substrate of the rotation velocity is used to control layer thickness and final polymerized material morphology.

54. The method of claim 53, wherein a layer thickness is between 100 nm and 1 mm.

55. The method of claim 53, wherein layer thickness is preferably between 0.5 μ

m and 100 μ

m.

56. The method of claim 53, wherein the substrate rotational velocity is varied.

57. The method of claim 53, wherein the velocity is initially between 10 to 5,000 rpm.

58. The method of claim 53, wherein the velocity is preferably initially between 60 to 1,000 rpm.

59. The method of claim 53, wherein the velocity during polymerization is constant.

60. The method of claim 53, wherein the velocity during polymerization is varied.

61. The method of claim 53, wherein the velocity is in the range 100 to 50,000 rpm.

62. The method of claim 53, wherein the velocity is preferably in the range 500 to 10,000 rpm.

63. The method of claim 53, wherein the average velocity is in the range 100 to 50,000 rpm.

64. The method of claim 63, wherein the average velocity is preferably in the range 500 to 10,000 rpm.

65. The method of claim 1, wherein additives are injected with the polymer solution to control the polymerization process and final morphology of the layer.

66. The method of claim 65, wherein the additives are proteoglycans.

67. The method of claim 65, wherein the additives are at least one of chondroitin sulfate, dermatan sulfate and keratan sulfate proteoglycans.

68. The method of claim 65, wherein the proteoglycans are one of at least or a combination of decorin, lumican, biglycan, keratocan or syndican.

69. The method of claim 65, wherein the percent (by weight) of added proteoglycans is between 0.25 and 50.0.

70. The method of claim 65, wherein the percent by weight of added proteoglycans is between 0.5 and 10.

71. The method of claim 1, wherein a network of channels is used to guide the growth of the polymerizing polymers.

72. The method of claim 71, wherein the growing polymer is attached to a fixed point and extruded from a channel as it polymerizes.

73. The method of claim 71, wherein the growing polymer is attached to a moving plate pulled through a channel where conditions conducive to polymerization are maintained.

74. The method of claim 71, wherein conditions outside the channels are not conducive to polymerization.

75. The method of claim 71, where in said channel is part of an array of identical channels.

76. The method of claim 71 wherein said channel is treated to prevent adhesion of polymerizing material.

77. The method of claim 71, wherein said channels are manufactured using any standard microfabrication process.

78. The method of claim 71, wherein said channels are obtained from a self-assembled three dimensional network.

79. A system to align polymerizing polymer chains in a layer such that polymers are predominantly aligned parallel to each other, comprising:

an apparatus to generate shear flow;

a plurality of sensors to monitor a plurality of parameters; and

a processor to modulate a plurality of control parameters.