Composite scaffold for soft tissue repair, reconstruction and regeneration

文档序号：1909046 发布日期：2021-11-30 浏览：27次中文

阅读说明：本技术 用于软组织的修复、重建和再生的复合支架 (Composite scaffold for soft tissue repair, reconstruction and regeneration ) 是由 K·A·罗科 B·莫汉拉杰 J·奥特 J·本迪戈 J·E·科门达 M·T·阿伦森 A·J 于 2020-02-07 设计创作，主要内容包括：所公开的复合支架提供了在张力下基本上保持其三维形状的高度多孔且柔性的结构,并且首先通过支架机械性质,并且随后通过在所述支架被再吸收时新再生的功能组织提供了对修复或重建的机械加强。(The disclosed composite scaffold provides a highly porous and flexible structure that substantially retains its three-dimensional shape under tension, and provides mechanical reinforcement to repair or reconstruction, first through scaffold mechanical properties, and then through newly regenerated functional tissue as the scaffold is resorbed.)

1. A composite stent, comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate and collectively defining a void space; and

a structure supporting the microporous matrix;

wherein the surface area of the composite scaffold is between about 0.3m²G and 15.0m²Between/gram.

2. The composite stent of claim 1, wherein the surface area of the composite stent is between about 0.6m²G and 1.2m²Between/gram.

3. The composite stent of claim 1, wherein the surface area of the composite stent is between about 0.7m²G and 1.0m²Between/gram.

4. The composite stent of claim 1, wherein the void space has a volume of between about 3.0cm³G and 9.0cm³Between/gram.

5. A composite stent, comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate and collectively defining a void space having a measurable volume; and

a structure supporting the microporous matrix;

wherein the volume of the void space is between about 3.0cm³G and 9.0cm³Between/gram.

6. The composite stent of claim 5, wherein the volume of void space is between about 3.5cm³G and 7.0cm³Between/gram.

7. The method of claim 5A composite scaffold, wherein the volume of void space is between about 4.0cm³G and 5.0cm³Between/gram.

8. The composite stent of claim 5, wherein the surface area of the composite stent is between about 0.3m²G and 1.5m²Between/gram.

9. A composite stent, comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate and collectively defining a void space having a volume; and

a structure supporting the microporous matrix;

wherein the void space volume is between about 75% and 98% of the measurable volume of the composite scaffold.

10. The composite scaffold of claim 9, wherein the void space volume is between about 80% and 90% of the measurable volume of the composite scaffold.

11. The composite scaffold of claim 9, wherein the void space volume is between about 80% and 85% of the measurable volume of the composite scaffold.

12. The composite stent of claim 9, wherein the surface area of the composite stent is between about 0.3m²G and 1.5m²Between/gram.

13. A composite scaffold having a volume and a surface area and comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and

a structure supporting the microporous matrix;

wherein the composite scaffold has a permeability of between about 1200 and 3000 millidarcies.

14. The composite stent of claim 13, wherein the composite stent has a permeability of between about 1400 and 2600 millidarcies.

15. The composite scaffold of claim 13, wherein the permeability of the composite scaffold is between about 1500 and 2200 millidarcies.

16. The composite stent of claim 13, wherein the void space has a volume of between about 3.0cm³G and 9.0cm³Between/gram.

17. The composite stent of claim 13, wherein the surface area of the composite stent is between about 0.3m²G and 1.5m²Between/gram.

18. A composite stent, comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate and collectively defining a void space having a void space volume; and

a structure supporting the microporous matrix;

wherein the tortuosity of the plurality of interconnected pores is approximately between 1 μm/μm and 50 μm/μm, wherein the tortuosity defines a ratio of an actual flow path length to a linear distance between a first end and a second end of the microporous matrix.

19. The composite scaffold of claim 18, wherein the tortuosity of the plurality of interconnected pores is approximately between 5 μ ι η/μ ι η and 30 μ ι η/μ ι η.

20. The composite scaffold of claim 18, wherein the tortuosity of the plurality of interconnected pores is approximately between 6 and 20 μ ι η/μ ι η.

21. A composite scaffold occupying a measurable volume and comprising:

a microporous substrate having a plurality of interconnected pores collectively defining a void space having a surface area; and

a structure supporting the microporous matrix;

wherein the ratio of the void space surface area to the measurable volume is between about 5,000cm²/cm³And 16,000cm²/cm³In the meantime.

22. The composite scaffold of claim 21, wherein the ratio of the void space surface area to the measurable volume is between about 7,000cm²/cm³And 14,000cm²/cm³In the meantime.

23. The composite scaffold of claim 21, wherein the ratio of the void space surface area to the measurable volume is between about 9,000cm²/cm³And 12,000cm²/cm³In the meantime.

24. A composite stent, comprising:

a support structure defining an interior space; and

a microporous matrix disposed within the interior space of the support structure,

wherein the microporous matrix comprises a plurality of interconnected pores having a median pore size between about 10 μm and 100 μm.

25. The composite scaffold of claim 24, wherein the microporous matrix comprises a plurality of interconnected pores having a median pore size between about 12 μ ι η and 70 μ ι η.

26. The composite scaffold of claim 24, wherein the microporous matrix comprises a plurality of interconnected pores having a median pore size between about 20 μ ι η and 40 μ ι η.

27. A composite stent, comprising:

a support structure defining an interior space; and

a microporous matrix disposed within the interior space of the support structure, the microporous matrix having a plurality of interconnected pores that collectively define a void space;

wherein at least about 60% of the void spaces comprise pores having a size dimension of 10 μm or greater.

28. The composite stent of claim 27, wherein at least about 70% of the void spaces comprise pores having a size dimension of 10 μ ι η or greater.

29. The composite stent of claim 27, wherein at least about 80% of the void spaces comprise pores having a size dimension of 10 μ ι η or greater.

30. The composite stent of any one of the preceding claims 1-29, wherein the composite stent has a tensile elongation-to-break of between about 20% and 125%.

31. The composite stent of any one of the preceding claims 1-29, wherein the composite stent has an elongation at yield of between about 5% and 50%.

32. The composite stent of any one of the preceding claims 1-29, wherein the stiffness of the composite stent is approximately between 2.5N/mm and 25N/mm.

33. The composite stent of any one of the preceding claims 1-29, wherein the ultimate strain of the composite stent is approximately between 0.2 and 0.7.

34. The composite stent of any one of the preceding claims 1-29, wherein the ultimate strength of the composite stent is approximately between 2.5MPa and 30 MPa.

35. The composite stent of any one of the preceding claims 1-29, wherein the ultimate stress of the composite stent is approximately between 2.5MPa and 30 MPa.

36. The composite stent of any one of the preceding claims 1-29, wherein the composite stent has a modulus of approximately between 2.5MPa and 70MPa, wherein modulus defines the stress divided by strain of the cross-sectional area of the composite stent including the void space.

37. The composite scaffold of any of the preceding claims 1-29, wherein the composite scaffold has a modulus of approximately between 150MPa and 600MPa, where modulus defines the stress divided by strain of a bulk material comprising the composite scaffold that does not include the void space.

38. The composite stent of any one of the preceding claims 1-29, wherein the ultimate load displacement of the stent is approximately between 5mm and 50 mm.

39. The composite stent of any one of the preceding claims 1-29, wherein the yield displacement of the stent is approximately between 1mm and 8 mm.

40. The composite stent of any one of the preceding claims 1-29, wherein the yield force of the stent is approximately between 20N and 70N.

41. The composite stent of any one of the preceding claims 1-29, wherein the stiffness of the stent can be approximately between 2.5N/mm and 25N/mm.

42. The composite stent of any one of the preceding claims 1-29, wherein the ultimate strain of the composite stent is approximately between 20% and 70%.

43. The composite stent of any one of the preceding claims 1-29, wherein the stent has an ultimate load of approximately between 100N and 200N.

44. The composite scaffold of any one of claims 1-3 and 8, wherein the surface area of the composite scaffold is measured using mercury intrusion porosimetry.

45. The composite scaffold of claim 44, wherein the surface area of the composite scaffold comprises a surface area of pores approximately equal to or greater than 1 μm in size.

46. The composite stent of claim 18, wherein the void space has a volume of between about 3.0cm³G and 9.0cm³Between/gram.

47. The composite stent of claim 18, wherein the surface area of the composite stent is between about 0.3m²G and 1.5m²Between/gram.

48. The composite stent of claim 27, wherein the void space has a volume of between about 3.0cm³G and 9.0cm³Between/gram.

49. The composite stent of claim 27, wherein the surface area of the composite stent is between about 0.3m²G and 1.5m²Between/gram.

50. The composite stent of claim 27, wherein the surface area of the composite stent is between about 0.3m²G and 1.5m²Between/gram.

51. A composite scaffold occupying a measurable volume and comprising:

a microporous substrate having a plurality of interconnected pores collectively defining a void space having a surface area; and

a structure supporting the microporous matrix;

wherein the ratio of the void space surface area to the measurable volume is between about 5,000cm²/cm³And 16,000cm²/cm³In the meantime.

52. The composite scaffold of claim 51, wherein the ratio of the void space surface area to the measurable volume is between about 7,000cm²/cm³And 14,000cm²/cm³In the meantime.

53. The composite scaffold of claim 51, wherein the ratio of the void space surface area to the measurable volume is between about 9,000cm²/cm³And 12,000cm²/cm³In the meantime.

54. A composite stent, comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate and collectively defining a void space; and

a structure supporting the microporous matrix;

wherein the surface area of the composite scaffold is between about 0.3m²G and 15m²Between/gram.

55. The composite scaffold of any one of claim 54, wherein the surface area of the composite scaffold is measured using gas adsorption.

56. The composite scaffold of any one of claim 55, wherein the surface area of the composite scaffold is measured using krypton gas adsorption.

57. The composite scaffold of claim 54, wherein the surface area of the composite scaffold comprises a surface area of pores approximately equal to or less than 1 μm in size.

58. A composite stent, comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and

a structure supporting the microporous matrix;

the composite scaffold has a measurable dry weight value indicative of the weight of the composite scaffold in a substantially dry state and a measurable dry volume value indicative of the volume of the composite scaffold in a substantially dry state,

wherein an increase in the weight value of the composite scaffold of about 200% to 600% due to fluid absorption changes the dry volume value of the composite scaffold by about 0% to 10%.

59. The composite stent of claim 58, wherein an increase in the dry weight value of the composite stent of about 300% to 600% due to fluid absorption changes the dry volume value of the composite stent by about 2% to 7%.

60. The composite stent of claim 58, wherein an increase in the dry weight value of the composite stent of about 300% to 600% due to fluid absorption changes the dry volume value of the composite stent by about 4% to 6%.

61. The composite stent of claim 58, wherein an increase in the dry weight value of the composite stent of about 300% to 600% due to fluid absorption changes the dry length value of the composite stent by about 0% to 3%.

62. The composite stent of claim 58, wherein an increase in the dry weight value of the composite stent of about 300% to 600% due to fluid absorption changes the dry length value of the composite stent by about 0% to 2%.

63. A composite stent, comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and

a structure supporting the microporous matrix;

the composite support having a measurable dry weight value indicative of a weight of the composite support in a substantially dry state and a measurable dry length value indicative of a dimensional parameter of the composite support in a substantially dry state,

wherein an increase in the weight value of the composite scaffold of about 200% to 600% due to fluid absorption changes the dry length value of the composite scaffold by less than about 0% to 3%.

64. The composite stent of claim 63, wherein an increase in the dry weight value of the composite stent of about 300% to 600% due to fluid absorption changes the dry length value of the composite stent by about 0% to 2%.

65. The composite stent of claim 63, wherein an increase in the dry weight value of the composite stent of about 500% to 600% due to fluid absorption changes the dry length value of the composite stent by less than about 1%.

66. The composite scaffold of claim 63, wherein an increase in the dry weight value of the composite scaffold of about 300% to 600% due to fluid absorption changes the dry volume value of the composite scaffold by about 2% to 7%.

67. The composite scaffold of claim 63, wherein an increase in the dry weight value of the composite scaffold of about 300% to 600% due to fluid absorption changes the dry volume value of the composite scaffold by about 4% to 6%.

68. A composite stent, comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and

a structure supporting the microporous matrix;

the composite scaffold has a measurable dry weight value indicative of a weight of the composite scaffold in a substantially dry state and a measurable cross-sectional profile value indicative of a dimensional parameter of the composite scaffold in a substantially dry state,

wherein an increase in the weight value of the composite scaffold of about 300% to 600% due to fluid absorption changes the cross-sectional profile value of the composite scaffold by about 0% to 3%.

69. The composite stent of claim 68, wherein an increase in the dry weight value of the composite stent of about 300 to 600 percent due to fluid absorption changes the cross-sectional profile value of the composite stent by about 0 to 2 percent.

70. The composite stent of claim 68, wherein an increase in the dry weight value of the composite stent of about 500% to 600% due to fluid absorption changes the cross-sectional profile value of the composite stent by less than about 1%.

71. The composite stent of claim 68, wherein an increase in the dry weight value of the composite stent of about 300 to 600 percent due to fluid absorption increases the cross-sectional profile value of the composite stent by about 0 to 2 percent.

72. The composite stent of claim 68, wherein an increase in the dry weight value of the composite stent of about 500% to 600% due to fluid absorption increases the cross-sectional profile value of the composite stent by less than about 1%.

73. A composite stent, comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and

a structure supporting the microporous matrix;

wherein the composite scaffold has a minimum dimension that is a thickness dimension of about greater than or equal to 1mm, and

wherein the swelling curve of the composite scaffold is measurable by a change in measured wet thickness of the composite scaffold of less than or equal to 10% compared to measured dry thickness of the composite scaffold.

74. A composite stent, comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and

a structure supporting the microporous matrix;

the composite support has a measurable dry weight value representing the weight of the composite support in a substantially dry state,

wherein the microporous matrix comprises less than about 6% of the dry weight value of the composite scaffold.

75. A stent, comprising:

a three-dimensional support structure having a length dimension defined by first and second ends thereof and a thickness dimension perpendicular to the length dimension defined by first and second outer layers separated by a space, an

A plurality of spacer elements extending through the space and connecting the first outer layer and the second outer layer;

wherein the thickness dimension of the support structure varies by less than about 10% when the length dimension is elongated by about 5%.

76. A stent, comprising:

a three-dimensional support structure having a length dimension defined by a first end and a second end thereof and a cross-sectional area perpendicular to the length dimension defined at least in part by first and second outer layers separated by a space, an

A plurality of spacer elements extending through the space and connecting the first outer layer and the second outer layer;

wherein the change in cross-sectional area is less than about 35% when the length dimension is elongated about 13%.

77. A stent, comprising:

a three-dimensional support structure having a length dimension defined by first and second ends thereof and a width dimension perpendicular to the length dimension at least partially defined by first and second outer layers,

the first outer layer and the second outer layer are separated by a space and further define a thickness dimension perpendicular to the length dimension and the width dimension, an

A plurality of spacer elements extending through the space and connecting the first outer layer and the second outer layer,

wherein the change in the width dimension is less than about 5% when the length dimension is elongated by about 13%.

78. A scaffold structure, comprising:

a first outer layer and a second outer layer having a length dimension defined by respective first and second ends thereof and defining an interior space therebetween,

each of the first and second outer layers comprises a plurality of interconnected wales extending substantially parallel to a respective length dimension;

a plurality of spacer elements extending through the interior space substantially perpendicular to the respective length dimension and attached to each of the first and second outer layers proximate one of the plurality of wales, the plurality of spacer elements at least partially partitioning the interior space into a plurality of channels extending along the respective length dimensions of the first and second outer layers.

79. The scaffold structure of claim 78 wherein each of first and second outer layers has a corresponding number of wales, and wherein the plurality of spacer elements are attached to the corresponding wales of each of the first and second outer layers.

80. A scaffold structure according to claim 78 wherein the plurality of spacer elements comprise spacer yarns.

81. A scaffold structure according to claim 78 wherein the distance between spacer elements along wales of the first or second outer layer is between about 100 and 2500 μm.

82. The scaffold structure of claim 78 wherein the distance between wales in the first or second outer layer is between about 200 μm and 5000 μm.

83. The scaffold structure of claim 78 wherein the length of the plurality of spacer elements extending between the first and second outer layers is between about 100 μm and 5000 μm.

84. A scaffold structure according to claim 78 wherein the wales of one of the first and second outer layers comprise pillar stitches and axially laid-in yarns.

85. The scaffold structure of any one of the preceding claims 75-84 wherein the scaffold has a tensile elongation at break between about 20% and 125%.

86. The scaffold structure of any one of the preceding claims 75-84, wherein the scaffold has an elongation at yield of between about 5% and 50%.

87. A scaffold structure according to any one of preceding claims 75 to 84 in which the scaffold has a stiffness of approximately between 2.5 and 25N/mm.

88. The scaffold structure of any one of the preceding claims 75-84, wherein the scaffold has an ultimate strain of approximately between 20% and 70%.

89. The scaffold structure of any one of the preceding claims 75-84, wherein the scaffold has an ultimate stress of approximately between 2.5MPa and 30 MPa.

90. The scaffold structure of any one of the preceding claims 75-84, wherein the scaffold has a yield stress of approximately between 2.5MPa and 30 MPa.

91. The scaffold structure of any one of the preceding claims 75-84, wherein the scaffold has a modulus of approximately between 2.5MPa and 70MPa, where modulus defines the stress divided by strain for the scaffold's cross-sectional area including the void space.

92. The scaffold structure of any one of the preceding claims 75-84, wherein the scaffold has a modulus of approximately between 150MPa and 600MPa, where modulus defines the stress divided by strain of a bulk material comprising the scaffold that does not contain the void space.

93. A scaffold structure according to any one of preceding claims 75 to 84, in which the scaffold can have a stiffness of approximately between 2.5 and 250N/mm.

94. The scaffold structure of any one of the preceding claims 75-84, wherein the scaffold has an ultimate strain of approximately between 20% and 70%.

95. The stent structure of any of the preceding claims 75-84, wherein the tenacity of the stent is between about 0.07 and 1.10 grams-force/denier.

96. The stent of any one of the preceding claims 75-84, wherein the stent has a failure tenacity of approximately between 0.3 and 2 grams-force/denier.

97. The scaffold of any one of the preceding claims 75-84, wherein at least a portion of the scaffold is coated with a hydrophilic solution.

98. The stent of claim 97, wherein the hydrophilic solution comprises polyethylene glycol (PEG).

99. The stent of claim 97, wherein the stent comprises monofilament, multifilament or textured yarns, or any combination thereof, woven into a three-dimensional structure.

100. The stent of any one of the preceding claims 75-84, wherein the stent comprises any combination of bioabsorbable polymers, natural polymers, and/or additives.

101. The stent of claim 100, wherein the stent comprises any of a homopolymer, copolymer, or polymer blend of any of the following: polylactic acid, polyglycolic acid, polycaprolactone, polydioxanone, polyhydroxyalkanoates, polyanhydrides, poly (ortho esters), polyphosphazenes, poly (amino acids), polyalkylcyanoacrylates, polypropylene glycol fumarate, trimethylene carbonate, poly (glycerol sebacate), poly (gluconate), poly (ethylene glycol), poly (vinyl alcohol), and polyurethane, or any combination thereof.

102. A scaffold structure according to any one of preceding claims 75 to 84, in which the cross-sectional area of the composite scaffold can be approximately between 3mm²And 3000mm²Wherein the cross-sectional area defines an area of a two-dimensional shape of the stent at a point perpendicular to the length of the stent, and

wherein the cross-sectional area varies by less than about 10% at a percent elongation of 5%.

103. A stent, comprising:

a three-dimensional support structure having a first end thereof and

a length dimension defined by the second end and a thickness dimension perpendicular to the length dimension defined by the first and second outer layers separated by the space, an

A plurality of spacer elements extending through the space and connecting the first outer layer and the second outer layer;

wherein the ratio of the void space surface area to the measurable volume is between about 500cm²/cm³And 7,000cm²/cm³In the meantime.

104. A composite stent, comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and

a structure supporting the microporous matrix;

wherein the composite scaffold has a density of approximately between 0.05g/cc and 0.75g/cc, wherein the density is defined as the mass of the composite scaffold per unit volume.

105. The composite stent of claim 104, wherein the composite stent has a density approximately between 0.10g/cc and 0.50 g/cc.

106. The composite stent of claim 104, wherein the composite stent has a density approximately between 0.15g/cc and 0.25 g/cc.

107. A composite stent, comprising:

a three-dimensional support structure having a length dimension defined by a first end and a second end thereof and defined by a first outer layer and a second outer layer separated by an interior space,

a plurality of spacer elements extending through the space and connecting the first outer layer and the second outer layer;

a microporous matrix disposed in the interior space and having a plurality of interconnected pores collectively defining a void space between a first end and a second end of the support structure.

108. The composite stent of claim 107, wherein at least about 60% of the void spaces comprise pores having a size dimension of at least 10 μ ι η or greater.

109. The composite stent of claim 107, wherein the void space has a volume of between about 3.0cm³G and 9.0cm³Between/gram.

110. The composite stent of any one of the preceding claims 104 to 109, wherein a cross-sectional area of the composite stent can be approximately between 3mm²And 250mm²And is prepared from

Wherein the cross-sectional area varies by less than about 17% at a strain percentage of 13%.

111. The composite stent of claim 107, wherein the surface area of the composite stent is between about 0.3m²G and 1.5m²Between/gram.

112. A composite stent, comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate and collectively defining a void space; and

a structure supporting the microporous matrix;

the composite stent has a substantially rectangular cross-section defined by an outer side, and

wherein a plurality of the interconnected pores proximate one of the exterior sides has a largest dimension toward the one exterior side.

113. The composite stent of claim 112, wherein the plurality of the interconnected pores have a largest dimension oriented at about 45 ° to 135 ° relative to the one outer side.

114. The composite stent of claim 112, wherein the plurality of the interconnected pores have a largest dimension oriented at approximately 60 ° to 120 ° relative to the one outer side.

115. The composite stent of claim 112, wherein the plurality of the interconnected pores have a largest dimension that is oriented at approximately 75 ° to 105 ° relative to the one outer side.

116. The composite stent of any one of the preceding claims 104-112, wherein the composite stent has an ultimate strain of between about 0.2 and 1.25.

117. A composite stent, comprising:

a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate and collectively defining a void space; and

a structure supporting the microporous matrix;

wherein the volume of the void space is between about 3.0cm³G and 9.0cm³Between/gram.

118. The composite stent of claim 117, wherein the volume of void space is between about 3.5cm³G and 7.0cm³Between/gram.

119. The composite stent of claim 117, wherein the volume of void space is between about 4.0cm³G and 5.0cm³Between/gram.

120. The composite stent of any one of the preceding claims 104-112, wherein the composite stent has an ultimate stress of approximately between 2.5MPa and 30 MPa.

121. The composite stent of any one of the preceding claims 104-112, wherein the yield stress of the composite stent is approximately between 2.5MPa and 30 MPa.

122. The composite stent of any one of the preceding claims 104-112, wherein the modulus of the composite stent is approximately between 2.5MPa and 70MPa, wherein modulus is calculated using the cross-sectional area of the material comprising the composite stent and the void space.

123. The composite stent of any one of the preceding claims 104-112, wherein the modulus of the composite stent is approximately between 150MPa and 600MPa, wherein modulus is calculated using the cross-sectional area of the material comprising only the composite stent.

124. The composite scaffold of any one of the preceding claims 104-119, wherein the structure supporting the microporous matrix comprises a three-dimensional textile structure.

125. The composite scaffold of any one of the preceding claims 104-119, wherein the microporous matrix comprises any one of: a sponge, foam, or textured fiber or yarn, or any combination thereof.

126. The composite scaffold of claim 125, wherein the microporous matrix comprises any one of: a freeze-dried sponge, an open-cell extruded foam, a particulate leached sponge, or any combination thereof.

127. The composite scaffold of claim 125, wherein the microporous matrix comprises any of a sponge, foam, or texturized fiber or yarn, or any combination thereof, disposed within the scaffold by any of braiding, weaving, lyophilizing, particle leaching, open-cell extrusion, solvent casting, solid state foaming, and crosslinking.

128. The composite scaffold of any of preceding claims 104-119, wherein the microporous matrix comprises one of collagen and a hydrogel.

129. The composite scaffold of claims 104-119, wherein the scaffold comprises monofilament, multifilament or textured yarns, or any combination thereof, woven into a three-dimensional structure.

130. The composite stent of claims 104-119, wherein the stent comprises any combination of synthetic bioabsorbable polymers, natural polymers, and/or additives.

131. The composite stent of claim 130, wherein the stent comprises any of a homopolymer, copolymer, or polymer blend of any of the following: polylactic acid, polyglycolic acid, polycaprolactone, polydioxanone, polyhydroxyalkanoates, polyanhydrides, poly (ortho esters), polyphosphazenes, poly (amino acids), polyalkylcyanoacrylates, polypropylene glycol fumarate, trimethylene carbonate, poly (glycerol sebacate), poly (gluconate), poly (ethylene glycol), poly (vinyl alcohol), and polyurethane, or any combination thereof.

132. A composite scaffold occupying a measurable volume and comprising:

a microporous substrate having a plurality of interconnected pores collectively defining a void space having a surface area; and

a structure supporting the microporous matrix;

wherein the ratio of the void space surface area to the measurable volume is between about 5,000cm²/cm³And 16,000cm²/cm³In the meantime.

133. The composite scaffold of claim 132, wherein the ratio of the void space surface area to the measurable volume is between about 7,000cm²/cm³And 14,000cm²/cm³In the meantime.

134. The composite scaffold of claim 132, wherein the ratio of the void space surface area to the measurable volume is between about 9,000cm²/cm³And 12,000cm²/cm³In the meantime.

135. A method of repairing a ligament or tendon injury with a composite scaffold, the method comprising:

A) providing a composite stent, the composite stent comprising:

i) a first layer and a second layer spaced apart to define an interior space therebetween, and a plurality of spacer elements extending through the interior space and attached to the first layer and the second layer; and

ii) a microporous matrix disposed within the interior space, the microporous matrix having a plurality of interconnected pores, an

B) Pre-tensioning the composite scaffold along its length dimension;

C) attaching the composite scaffold to an allograft tendon or an autograft tendon or a damaged or torn ligament or tendon.

136. A method of manufacturing a composite stent, the method comprising:

A) constructing a three-dimensional support structure extending along a length dimension between first and second ends thereof and defining an interior surface within the support structure; and

B) forming a microporous matrix within the inner surface, the microporous matrix having a plurality of interconnected pores in fluid communication with the outer surface of the support structure,

wherein a plurality of the interconnected pores are oriented with respect to a dimensional characteristic of the support structure.

137. The method of claim 136, wherein the plurality of interconnected pores face radially inward from an outer surface of the support structure into the interior space.

138. The method of claim 136, wherein the plurality of interconnected pores are oriented toward the length dimension of the support structure.

139. The method of claim 136, wherein the support structure has an outer profile, and B) comprises:

B1) disposing the support structure in a solution-filled mold having a cross-sectional profile that at least partially mimics the outer profile of the support structure, an

B2) Changing the temperature of the mold to crystallize the solution in the interior space of the support structure.

140. The method of claim 136, further comprising:

C) at least partially covering the support structure with a hydrophilic substance.

141. The method of claim 136, wherein a) comprises:

A1) a braided stent comprising a first layer and a second layer spaced apart to define an interior space therebetween, but attached together by a plurality of spacer elements extending through the interior space.

142. The method of claim 140, wherein at least partially covering the three-dimensional support structure with a hydrophilic species is performed prior to disposing a microporous matrix in the interior space.

143. The method of claim 140, wherein the hydrophilic species at least partially comprises polyethylene glycol (PEG).

144. The method of claim 2, wherein the microporous matrix comprises one of collagen and a hydrogel.

145. The method of claim 136, wherein the support structure comprises a scaffold comprising any combination of synthetic bioabsorbable polymers, natural polymers, and/or additives.

146. The method of claim 145, wherein the scaffold comprises monofilament, multifilament, or multifilament and textured yarns, or any combination thereof, woven into a three-dimensional structure.

147. The method of claim 136, wherein the microporous matrix comprises any one of: a sponge, foam, or textured fiber or yarn, or any combination thereof.

148. The method of claim 136, wherein the microporous matrix comprises any one of: a freeze-dried sponge, an open-cell extruded foam, a particulate leached sponge, or any combination thereof.

149. The biomimetic scaffold of claim 136, wherein B) comprises forming a microporous matrix by any one of lyophilization, particle leaching, open-cell extrusion, solvent casting, solid state foaming, and cross-linking.

150. A composite stent, comprising:

a support structure having an outer contour defining an interior space and extending along a length dimension between first and second ends thereof;

a microporous matrix disposed within the interior space, the microporous matrix having a plurality of interconnected pores open to an exterior of the support structure;

wherein a plurality of the interconnected pores are oriented with respect to a dimensional characteristic of the support structure.

151. The composite stent of claim 150, wherein the plurality of interconnected pores face radially inward from an outer surface of the support structure into the interior space.

152. The composite scaffold of claim 150, wherein the plurality of interconnected pores are oriented toward the length dimension of the support structure.

153. The composite stent of claim 150, wherein the support structure has a cross-sectional outer profile that is substantially rectangular in shape.

154. The composite stent of claim 150, wherein the support structure has a cross-sectional outer profile that is substantially circular in shape.

Technical Field

The present disclosure relates to soft tissue repair and reconstruction, and more particularly, to a composite stent that may be used to stabilize soft tissue injuries or defects while promoting new tissue regeneration.

Background

Biological and synthetic scaffolds for tissue engineering applications and surgical repair and reconstruction are known, however, few provide the best combination of: sufficient porosity for cell ingrowth; sufficient biological matrix and surface area for cell migration and proliferation; sufficient interconnected void volume and size for meaningful extracellular matrix deposition and tissue regeneration; sufficient composite mechanical properties and mechanical load sharing with local tissue to promote functional tissue maturation while resisting collapse or compression under the mechanical load; and a sufficient bioresorption timeline to support tissue repair by complete healing while promoting regeneration of functional tissue.

Some stents, such as hernia meshes, have sufficient mechanical properties to perform surgical repair, but lack behavioral characteristics that are not optimally suited for healing and regeneration of knee, ankle, shoulder, elbow and hand soft tissues, as well as non-musculoskeletal soft tissues. Many such stents are made of permanent synthetic polymers that cause acute or chronic undesirable inflammation, pain or complications. In addition, many mesh scaffolds are essentially two-dimensional, in which the surface area for cell ingrowth is insufficient and the void volume for regeneration of the bulk tissue is insufficient, thus adversely affecting the regeneration of functional tissue. In contrast, most biological scaffolds for repair and reconstruction of soft tissue are derived from bulk tissue harvested and processed from allogeneic or xenogeneic sources, and typically heal slowly or incompletely due to any combination of bulk architecture, tissue source, and processing methods. Highly processed biomaterials such as collagen gels or sponges, reconstituted into a completely new architecture, can be produced with porosity suitable for tissue ingrowth, but lack adequate strength and collapse resistance for ligament or tendon repair.

Many commercially available stents constructed from fibers have suitable mechanical properties, but are not suitable for functional tissue regeneration due to architectural deficiencies resulting from existing manufacturing processes (e.g., braiding, weaving, braiding) and non-weaving methods (e.g., electrospinning, pneumatic spinning, melt blowing, etc.); this is because the fibers do not have sufficient space between the filaments and/or bundles (insufficient porosity or void volume or density-such as typical electrospun textiles), or the surface area, void volume and size for meaningful tissue regeneration is too small (such as typical flat warp knit textiles or knits, or bundles of fibers), or when sufficient void volume is created, the fibers are either discontinuous at a cell and biologically relevant scale, or collapse as the structure is tensioned.

Accordingly, there is a need for a scaffold and method for repairing or regenerating ligament tissue.

There is also a need for a composite scaffold, i.e. a scaffold that mimics the mechanical properties of natural tendons and ligaments.

There is a further need for a scaffold that provides sufficient porosity and interconnected void volume for cell infiltration and tissue ingrowth while substantially retaining its shape under load or tension.

There is still a further need for a scaffold that is bioabsorbable over a period of time, the scaffold supporting healing for several weeks or months while promoting regeneration of functional tissue capable of bearing mechanical loads after scaffold resorption.

There is also a need for a scaffold that minimizes the synthetic polymer density and maximizes the surface area to volume ratio of the scaffold, thereby limiting foreign body response and improving tissue regeneration.

There is also a need for a stent having an adjustable length, width and height for use in different procedures.

There is also a need for a bioabsorbable stent that regenerates tissue of sufficient strength and thickness after complete resorption of the stent material.

There is also a need for a scaffold that provides a second support matrix capable of promoting the growth of cells spaced apart from the scaffold to promote ingrowth of tendon or ligament tissue.

This stent still requires engineered regions of variable size, density, porosity, material composition, fiber type and surface properties to improve tissue regeneration and/or surgical manipulation and implantation.

Disclosure of Invention

A composite scaffold for ligament or tendon repair is disclosed that provides mechanical reinforcement to a repaired and healed tendon or ligament. In an embodiment, the composite scaffold includes a support structure defining a void volume. A porous material or hydrogel is disposed within the void volume of the support structure. The support structure reinforces and supports the porous material/hydrogel, increases the tensile strength of the stent, and resists compression when the stent is extended or subjected to an elongation force. The porous material/hydrogel has a porosity and void volume that allows for sufficient extracellular matrix deposition and regeneration of new functional tissue. In embodiments, the void volume is continuous or substantially continuous along the long axis of the stent, which allows cells to migrate completely within the device and allows new tissue to form in an orientation in the axial direction of the stent while being protected from significant collapse, compression, or over-expansion during mechanical loading or tensioning of the stent. Optionally, all or a portion of the scaffold may be hydrated with biological fluids such as blood, bone marrow aspirate, platelet rich plasma, autologous or allogeneic cells, etc., to modulate or direct the immune response and further promote and accelerate healing and tissue regeneration.

The disclosed composite scaffolds possess a large surface area for cell proliferation and migration, but also possess interconnected void spaces large enough to allow tissue ingrowth, extracellular matrix deposition and biomechanical remodeling of functional tissues. Further, the scaffold possesses the ability to maintain a highly porous structure under tension, e.g., resist collapse during surgical procedures and after implantation, thereby maintaining cell infiltration and new tissue ingrowth throughout the scaffold under physiological loading. Due to the complex mechanical properties of the device, these loads are shared mechanically between the device and the local tissue, i.e. preventing stress shielding of the proximal, prosthetic or natural tissue as well as the developing new tissue within the scaffold itself. Further, these complex mechanical properties promote mechano-biological signaling of cells within the scaffold to differentiate and form a load-bearing, oriented extracellular matrix and connective tissue. The disclosed composite stents may be fabricated using a variety of different textile and composite fabrication methods and are not limited to a single fabrication technique.

The disclosed composite scaffold provides a highly porous and flexible structure that substantially retains its three-dimensional shape under tension, and provides mechanical reinforcement to repair or reconstruction, first through scaffold mechanical properties, and then through newly regenerated functional tissue as the scaffold is resorbed.

The disclosed stents may have different regions with different mechanical properties to facilitate fixation or different tissue regeneration. In embodiments, the composite scaffold may be impregnated with cells, biological aspirates, or bioactive agents prior to implantation to create a biological "woundplast. In other embodiments, the biologically induced scaffold is seeded with cells of autologous, allogeneic or xenogeneic origin for a temporary pre-culture period to allow the cells to form a collagen-rich extracellular matrix within the scaffold. The scaffold may then be treated and/or decellularized to leave a fiber-reinforced tissue scaffold that may be subsequently implanted, or may be implanted "as is". The disclosed stent may be compatible with a variety of currently available fixation methods, such as sutures, suture anchors, tacks, staples, and the like.

The disclosed composite scaffold provides a mechanism for spacing tissue fibers from each other within the scaffold, thereby providing space for ingrowth into higher quality tissue that is not damaged by polymers or corresponding inflammation. The microporous matrix acts as a stabilizer that helps maintain such spaces and provides a larger surface for cell growth to allow tissue maturation while the primary fibers of the scaffold remain strong. If the microporous matrix is resorbed at a faster rate than the support structure, complete mass loss of the microporous matrix occurs, allowing tissue to be recovered and remodeled within the newly created volume in the body, while the primary support structure retains strength, allowing cells to invade first and then encapsulate the structure, and over time create functional tissue. Additionally, if a natural material is used to create a secondary matrix such as collagen, it may reduce scaffold inflammation and further promote cellular ingrowth into the scaffold without contact with any synthetic fibers comprising the support structure.

According to one aspect of the present disclosure, a composite scaffold includes a first matrix and an optional second matrix that may be integrally formed with one another to maximize the surface area to volume ratio of the scaffold while still maintaining mechanical and structural integrity. According to an embodiment, the first substrate may be implemented with a three-dimensional textile structure including a first support layer and a second support layer spaced apart to define an interior space or void therebetween. A plurality of spacer elements extend between the first and second support layers to hold the support layers apart. The first support layer and the second support layer may have different geometries, fibers, or material compositions. The first and second support layers and the spacing elements may be embodied as a three-dimensional textile formed from any combination of synthetic bioabsorbable polymers, natural polymers and/or additives, including a multi-layered braided or woven surface of multifilament fibers or monofilament fibers or any combination thereof. The second matrix is disposed within the void space between and proximate to the first support layer and the second support layer of the first support matrix. The second matrix may be implemented with a low density, high surface area material, including any of the following: a sponge, foam, felt, textured fibers or yarns, collagen or tissue-derived materials, or any combination thereof. The first and second matrices of the composite scaffold may have the same or different structure, composition and bioabsorbable properties to promote optimal regeneration of functional tissue.

In an embodiment, the composite scaffold may have a minimum thickness of about greater than or equal to 1 mm. The thickness of the stent may be uniform along its length or may vary in a repeating or non-repeating manner depending on the particular application for which the stent is to be used. In other embodiments, the length dimension of the disclosed composite stent may be between about 2mm to 1000mm, depending on the particular application for which the stent is to be used. The disclosed stents may be manufactured in different incremental lengths, or may be manufactured in lengths that may be cut or customized as needed or appropriate to the particular procedure by the practitioner.

According to one aspect of the present disclosure, a composite stent includes: a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate and collectively defining a void space; and a structure supporting the microporous matrix; wherein the surface area of the composite scaffold is between about 0.6m²G and 1.2m²Between/gram.

According to another aspect of the present disclosure, a composite stent includes: a microporous matrix having voids open to an outer surface of the microporous matrix and collectively defining a measurable volumeA plurality of interconnected pores of interstitial space; and a structure supporting the microporous matrix; wherein said volume of void space is between about 3.5cm³G and 7cm³Between/gram.

According to another aspect of the present disclosure, a composite stent includes: a microporous matrix having a plurality of interconnected pores open to an outer surface of the microporous matrix and collectively defining a void space having a measurable volume, and wherein the void space volume is between about 80% and 90% of the measurable volume of the biomimetic scaffold.

According to another aspect of the present disclosure, a composite stent includes: a microporous substrate having a plurality of interconnected pores open to an outer surface of the microporous substrate and collectively defining a void space having a measurable volume, wherein a tortuosity of the plurality of interconnected pores is approximately between 5 μm/μm and 45 μm/μm, wherein the tortuosity defines a ratio of an actual flow path length to a linear distance between a first end and a second end of the microporous substrate.

According to another aspect of the present disclosure, a composite stent includes: a support structure defining an interior space; and a microporous matrix disposed within the interior space of the support structure, wherein the microporous matrix comprises a plurality of interconnected pores having a median pore size between about 12 μ ι η and 50 μ ι η.

According to another aspect of the present disclosure, a composite stent includes: a support structure defining an interior space; and a microporous matrix disposed within the interior space of the support structure, the microporous matrix having a plurality of interconnected pores collectively defining a void space; wherein at least about 60% of the void spaces comprise pores having a size dimension of 10 μm or greater.

According to another aspect of the present disclosure, a composite stent includes: a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and a structure supporting the microporous matrix; the biomimetic scaffold has a measurable dry weight value representing a weight of the biomimetic scaffold in a substantially dry state and a measurable dry volume value representing a volume of the biomimetic scaffold in a substantially dry state, wherein an increase in the weight value of the biomimetic scaffold of about 200% to 600% due to fluid absorption changes the dry volume value of the biomimetic scaffold by about 0% to 10%.

According to another aspect of the present disclosure, a composite stent includes: a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and a structure supporting the microporous matrix; the composite scaffold has a measurable dry weight value indicative of a weight of the composite scaffold in a substantially dry state and a measurable dry length value indicative of a dimensional parameter of the composite scaffold in a substantially dry state, wherein an increase in the weight value of the composite scaffold by about 200% to 600% due to fluid absorption changes the dry length value of the composite scaffold by less than about 0% to 3%.

According to another aspect of the present disclosure, a composite stent includes: a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and a structure supporting the microporous matrix; the composite scaffold has a measurable dry weight value representing a weight of the composite scaffold in a substantially dry state and a measurable cross-sectional profile value representing a dimensional parameter of the composite scaffold in a substantially dry state, wherein an increase in the weight value of the composite scaffold by about 200% to 600% due to fluid absorption changes the cross-sectional profile value of the composite scaffold by about 0% to 10%.

According to another aspect of the present disclosure, a composite stent includes: a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and a structure supporting the microporous matrix; wherein the composite scaffold minimum dimension is a thickness dimension of about greater than or equal to 1mm, and wherein the composite scaffold swelling curve is measurable by a change in measured wet thickness of the composite scaffold of less than or equal to 10% compared to measured dry thickness of the composite scaffold.

According to another aspect of the present disclosure, a composite stent includes: a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and a structure supporting the microporous matrix; the composite scaffold has a measurable dry weight value representing the weight of the composite scaffold in a substantially dry state, wherein the microporous matrix comprises less than about 6% of the dry weight value of the composite scaffold.

According to another aspect of the present disclosure, a stent includes: a three-dimensional support structure having a length dimension extending between a first end and a second end of the support structure, the support structure comprising first and second outer layers spaced apart a distance therebetween defining a thickness dimension perpendicular to the length dimension, and a plurality of spacing elements connecting the first and second outer layers to maintain the spacing therebetween; wherein the thickness dimension of the support structure varies by less than about 35% when the length dimension is elongated by about 13%.

According to another aspect of the present disclosure, a stent includes: a three-dimensional support structure having a length dimension extending between a first end and a second end of the support structure and defining a cross-sectional area perpendicular to the length dimension, the support structure comprising first and second outer layers spaced apart to define an interior spatial volume therebetween, and a plurality of spacer elements extending through the interior spatial volume between the first and second layers and attached therebetween to hold the first and second layers apart; wherein the change in cross-sectional area is less than about 5% when the length dimension is elongated by about 13%.

According to another aspect of the present disclosure, a stent includes: a three-dimensional support structure having a length dimension extending between a first end and a second end of the support structure and defining a width dimension perpendicular to the length dimension, the support structure comprising first and second outer layers spaced apart a distance therebetween defining a thickness dimension perpendicular to the length dimension and the width dimension, and a plurality of spacer elements connecting the first and second outer layers to maintain the spacing therebetween; wherein the width dimension of the support structure varies by less than about 5% when the length dimension is elongated by about 13%.

According to another aspect of the present disclosure, a support structure includes: first and second outer layers having a length dimension defined by respective first and second ends thereof and defining an interior space therebetween, each of the first and second outer layers comprising a plurality of interconnected wales extending substantially parallel to the respective length dimension; a plurality of spacer elements extending through the interior space substantially perpendicular to the respective length dimension and attached to each of the first and second outer layers proximate one of the plurality of wales, the plurality of spacer elements at least partially partitioning the interior space into a plurality of channels extending along the respective length dimensions of the first and second outer layers.

According to another aspect of the present disclosure, a composite scaffold having a measurable volume comprises: a microporous matrix having a plurality of interconnected pores open to an outer surface of the microporous matrix and collectively defining a void space, wherein a density of the composite scaffold is approximately between 0.05g/cc and 0.75g/cc, wherein the density is defined as a mass per unit volume of the composite scaffold.

According to another aspect of the present disclosure, a composite scaffold having a measurable volume comprises: a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and a structure supporting the microporous matrix; wherein a total surface area to volume ratio of the composite scaffold is approximately between 160,000:1 and 190,000:1, wherein the ratio defines a ratio of the surface area of the scaffold to the volume of the composite scaffold other than the void space.

According to another aspect of the present disclosure, a stent includes: a three-dimensional support structure extending along an axis between first and second ends of the support structure, the support structure comprising first and second layers spaced apart to define an interior spatial volume therebetween, and a plurality of spacer elements extending through and attached between the interior spatial volume between the first and second layers to hold the first and second layers apart and define a cross-section perpendicular to the axis; and a microporous matrix within the interior space and having a plurality of interconnected pores collectively defining a void space between a first end and a second end of the support structure; wherein at least about 60% of the void spaces comprise pores having a size dimension of at least 10 μm or greater; and wherein the volume of the void space is between about 3.0cm³G and 9.0cm³Between/gram.

According to another aspect of the present disclosure, a composite stent includes: a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate and collectively defining a void space; and a structure supporting the microporous matrix; the composite scaffold has a substantially rectangular cross-section defined by exterior sides, wherein a plurality of the interconnected pores open to one of the exterior sides and have a maximum dimension oriented relative to the one exterior side. In one embodiment, the plurality of the interconnecting apertures have a largest dimension oriented at about 45 ° to 135 ° relative to the one outer side.

According to another aspect of the present disclosure, a stent includes: a three-dimensional support structure having a length dimension defined by first and second ends thereof and a thickness dimension perpendicular to the length dimension defined by first and second outer layers separated by a space, and a plurality of spacer elements extending through the space and connecting the first and second outer layers; wherein the ratio of the surface area of the void space to the measurable volume is about 500cm²/cm³And 7,000cm²/cm³In the meantime.

According to another aspect of the present disclosure, a composite scaffold occupying a measurable volume comprises: a microporous substrate having a plurality of interconnected pores collectively defining a void space having a surface area; and a structure supporting the microporous matrix; wherein the ratio of the void space surface area to the measurable volume is between about 5,000cm²/cm³And 16,000cm²/cm³In the meantime.

According to another aspect of the present disclosure, a method of repairing a ligament or tendon injury with a composite scaffold includes: A) providing a composite stent, the composite stent comprising: i) a first layer and a second layer spaced apart to define an interior space therebetween, and a plurality of spacer elements extending through the interior space and attached to the first layer and the second layer; and ii) a microporous matrix disposed within the interior space, the microporous matrix having a plurality of interconnected pores; and B) pre-tensioning the composite scaffold along its length dimension; C) attaching the composite scaffold to an allograft or autograft tendon or a damaged or torn ligament or tendon.

According to another aspect of the present disclosure, a method of manufacturing a composite stent includes: A) constructing a three-dimensional support structure extending along a length dimension thereof between a first end and a second end and defining an interior surface within the support structure; and B) forming a microporous matrix within the inner surface, the microporous matrix having a plurality of interconnected pores in fluid communication with the outer surface of the support structure, wherein a plurality of the interconnected pores are oriented with respect to a dimensional characteristic of the support structure. In an embodiment, the plurality of interconnected pores face radially inward from an outer surface of the support structure into the interior space. In an embodiment, the plurality of interconnected pores are oriented toward the length dimension of the support structure.

According to another aspect of the present disclosure, a composite stent includes: a support structure having an outer contour defining an interior space and extending along a length dimension between first and second ends thereof; a microporous matrix disposed within the interior space, the microporous matrix having a plurality of interconnected pores open to an exterior of the support structure; wherein a plurality of the interconnected pores are oriented with respect to a dimensional characteristic of the support structure.

According to another aspect of the present disclosure, a composite stent includes: a microporous substrate having a multiplicity of interconnected pores open to an outer surface of the microporous substrate that collectively define a void space; and a structure supporting the microporous matrix; the composite scaffold has a measurable dry weight value representing the weight of the composite scaffold in a substantially dry state, wherein the microporous matrix comprises less than about 6% of the dry weight value of the composite scaffold.

In embodiments, the second support matrix (e.g., a sponge) degrades about two to twelve times faster than the first support matrix based on mass loss or molecular weight loss. The composite scaffold may have a degradation curve that: greater than or equal to 50% strength retention for at least about two weeks after implantation and 100% mass loss for about six months to twelve months or more after implantation.

In embodiments, a higher density or mass of the supporting matrix provides the primary structure and bulk structure of the disclosed scaffold as compared to a more porous matrix disposed in the supporting matrix. More specifically, the first and second support matrices have different density or mass components relative to each other. In one embodiment, the measurable mass or density of the first support structure (e.g., textile) is greater than or equal to one time the mass or density of the second support matrix (e.g., sponge).

In disclosed embodiments, the pore structure of the microporous matrix is designed to promote cell attachment, proliferation, and ingrowth throughout the scaffold dimensions. In embodiments, the face of the device, the second matrix or pore structure may be architecturally engineered to promote cell migration in a certain direction or to promote the formation of aligned tissue such as connective tissue. In other embodiments, the surfaces of the device may differ from each other in physical or chemical properties to reflect use in a particular anatomical location, i.e., one side promotes integration with bone and the other side promotes integration of tendons; or one side to promote abdominal wall regeneration and the other side to prevent visceral adhesions.

In embodiments, the composite scaffolds disclosed herein provide a significantly higher surface area to volume ratio to promote faster and greater amounts of cellular infiltration and tissue ingrowth within the composite scaffold as compared to existing commercially available devices. More specifically, the ratio of the surface area of the fibers to the volume of the device, calculated using the scaffold denier, polymer density and size, is greater than 10 times, based primarily on the first support matrix (e.g., textile).

In embodiments, the stent may have ends that narrow and transition to a suture-like size, or be modified, such as sutured or knotted, to attach to the ends of conventional sutures used in the procedures described herein. In other embodiments, the first support matrix (e.g., textile) has ends or edges modified to be heat set or embroidered or impregnated with other materials to facilitate better handling, better integration with existing tissue, and further reduce dimensional distortion of the stent under pressure, tension, or shear forces. In other embodiments, a monofilament or multifilament suture of any material may be threaded longitudinally through the stent and exit from both ends and attached or secured to the stent.

In other embodiments, selected sections of the scaffold may be repeated randomly or at a fixed frequency to increase or decrease the density of the scaffold by increasing or decreasing the density of the textile, for example by changing the textile pattern of the first support matrix. In still other embodiments, such repeating regions may be selected to alter the surface finish of the stent by altering the smoothness or roughness of the outer surface of the stent in order to improve acceptance of the stent after implantation.

In one embodiment, the composite scaffold includes only a single three-dimensional support matrix, which may be the same as or different from the first support matrix or the second support matrix described herein, and may have any of the characteristics of the composite scaffold described herein.

Also disclosed is a method of treating damage to a ligament or tendon in which a scaffold is attached to an allograft or autograft tendon and used to replace the damaged ligament or tendon, or is used to reinforce the damaged or torn ligament or tendon. The use method can comprise the following steps: preparing the scaffold with a solution to improve its performance; pre-tensioning the stent; and/or fixing the distal femur; and independently tensioning and securing the tendon and graft in the tibial tunnel.

In use, the composite stent may be used for a wide range of medical procedures, including reinforced suture repair, stand-alone repair or reconstruction, or reconstruction using tissue grafts and for fixation purposes. The use of the composite scaffold to augment repair or reconstruction may be applicable to the knee, ankle, shoulder, hip, elbow, foot and hand as well as non-musculoskeletal soft tissues.

According to another aspect of the present disclosure, the graft preparation station provides a surface and fixation mechanism that allows independent tensioning of tissue (e.g., tendons or ligaments) and composite scaffolds prior to or during an implantation procedure.

According to another aspect of the present disclosure, the fixation device allows tissue (e.g., tendon or ligament) and composite scaffold to be attached to each other, thereby avoiding the need for cross-suturing. Such devices may include clips with legs that pass through the graft and tendon.

Drawings

The various features and advantages of this invention may be more readily understood by reference to the following detailed description taken in conjunction with the accompanying drawings, in which like reference numerals identify like structural elements, and in which:

FIG. 1A is a conceptual diagram of a composite stent according to the present disclosure;

fig. 1B is a photograph of a composite stent according to the present disclosure;

fig. 1C is a photograph of a composite stent according to the present disclosure;

FIG. 2A is a conceptual diagram of a weave pattern that may be used for an outer layer of a composite stent according to the present disclosure;

FIG. 2B is a conceptual diagram of an alternative weave pattern that may be used for the outer layer of a composite stent according to the present disclosure;

fig. 2C is a conceptual diagram of a yarn assembly pattern including the outer layer of fig. 2A-B according to the present disclosure;

FIG. 2D is a conceptual diagram of a perspective view of a textile pattern of a pair of composite stents usable in an ACL and rotator cuff procedure according to the present disclosure;

FIG. 3A is a photograph of a plan view of a composite stent according to the present disclosure having at least one outer layer made according to the pattern of FIG. 2A;

FIG. 3B is a photograph of a side view of the composite scaffold of FIG. 3A;

fig. 4A is an SEM photograph of a plan view of a composite stent having at least one outer layer made according to the pattern of fig. 2A according to the present disclosure;

FIG. 4B is an SEM photograph of a side view of the composite scaffold of FIG. 4A;

FIG. 4C is an SEM photograph of a perspective cross-sectional view of the composite scaffold of FIG. 4A as seen along axis 4A-4A in FIG. 4A;

FIG. 5A is a perspective view of a mold that may be used to manufacture a composite stent according to the present disclosure;

5B-C are top and side plan views, respectively, of another mold that may be used to fabricate a composite stent according to the present disclosure;

fig. 5D illustrates, in graphical form, the relationship of temperature, time, and pressure during a lyophilization process in accordance with the present disclosure;

6A-6C are SEM photographs of sagittal cross-sectional views of the microporous matrix of the composite scaffold of FIG. 1C taken along line A-A according to the present disclosure;

FIG. 6D is an SEM photograph of a coronal cross-sectional view of the microporous matrix of the composite scaffold of FIG. 1C taken along line B-B according to the present disclosure;

FIG. 6E is an SEM photograph of a transverse cross-sectional view of the microporous matrix of the composite scaffold of FIG. 1C taken along line B-B according to the present disclosure;

FIG. 6F is an SEM photograph of a sagittal cross-sectional view of the microporous matrix of the composite scaffold of FIG. 1C taken along line A-A according to the present disclosure;

FIG. 6G is an SEM photograph of a coronal cross-sectional view of the microporous matrix of the composite scaffold of FIG. 1C taken along line B-B according to the present disclosure;

FIG. 6H is an SEM photograph of a transverse cross-sectional view of the microporous matrix of the composite scaffold of FIG. 1C taken along line B-B according to the present disclosure;

FIG. 6I is an SEM photograph of a sagittal cross-sectional view of the microporous matrix of the composite scaffold of FIG. 1C taken along line A-A according to the present disclosure;

FIG. 7A is an SEM photograph of a typical microporous matrix attached to a fibrous support structure of a composite matrix according to the present disclosure;

FIG. 7B is an SEM photograph of a typical microporous matrix attached to a fibrous support structure of a composite matrix according to the present disclosure;

fig. 7C is an SEM photograph of the outer surface of a typical microporous matrix of a composite scaffold according to the present disclosure;

FIG. 8 graphically illustrates test data defining cumulative total pore surface area versus pore diameter, in accordance with the present disclosure;

figure 9 graphically illustrates the cumulative total pore volume versus pore diameter for several composite scaffold samples and textile-only support structures according to the present disclosure;

figure 10 illustrates in graphical form the relationship of several composite stent samples according to the present disclosure and a textile-only support structure composite stent versus mercury pressure;

FIG. 11 graphically illustrates pore size distribution versus log differential volume, in accordance with the present disclosure;

fig. 12 graphically illustrates the load versus extension relationship for both individual tendons and tendons reinforced with a composite scaffold according to the present disclosure;

FIG. 13A is a cross-sectional microscopic view of the composite scaffold of FIG. 1C, demonstrating the relationship of a porous matrix to a supporting matrix, according to the present disclosure;

fig. 13B is a cross-sectional microscopic view of the composite scaffold of fig. 1C hydrated with blood, and demonstrating how red blood cells completely infiltrate the collagen sponge porous matrix, according to the present disclosure;

fig. 14 is a photograph of a composite scaffold for MPFL repair or reconstruction attached to a portion of a human cadaver according to the present disclosure;

figure 15 conceptually illustrates a through image of a circular textile structure at various stages of manufacture, in accordance with the present disclosure;

figure 16 conceptually illustrates how the disclosed composite material according to the present disclosure can be used to enhance ACL repair, stabilization, or reconstruction; and is

FIG. 17 graphically illustrates pore size distribution versus percent porosity, as measured according to the present disclosure.

Detailed Description

Embodiments of the systems and methods will now be described in detail with reference to the drawings, in which like reference numerals designate identical or corresponding elements in each of the several views. Throughout this specification, the phrase "in an embodiment" and variations of this phrase are generally understood to mean that a particular feature, structure, system, or method described comprises at least one iteration of the disclosed techniques. Such phrases are not to be construed or interpreted to mean that the particular feature, structure, system, or method described is the best or only manner in which an embodiment may be practiced. Rather, such phrases should be understood to mean examples of ways in which the described technology may be implemented, but not necessarily the only way to do so. Further, words such as "top," "bottom," "side," "lower," and "upper" are used in an orientation, and references on particular axes in three-dimensional space, are used merely to help describe the position of components relative to each other. Words not indicating orientation are used to describe absolute orientation, i.e. "upper" portions must always be at the top.

Referring to fig. 1A-6D, the composite scaffold 10 includes a first three-dimensional supporting matrix and a second matrix integrally formed with each other to form the composite scaffold 10, the first matrix and the second matrix maximizing the surface area to volume ratio and the surface area to weight ratio of the scaffold. Referring to fig. 1A, in an embodiment, the first substrate may be implemented with a support structure 5 including a first outer layer 12 and a second outer layer 14 spaced apart to define an interior void space 16 therebetween. A plurality of spacer elements 18 extend between the first outer layer 12 and the second outer layer 14 to maintain separation of the layers. In embodiments, each of the layers 12, 14 and the spacing element 18 may be implemented as a three-dimensional textile structure each having a different geometry, fiber or material composition. For example, any of the outer layers 12, 14 and the spacing element 16 may be implemented with a textile of multifilament fibers and/or monofilament fibers. The support layers 12 and 14 may be embodied as a substantially planar three-dimensional textile including a multi-layer woven surface, and the spacing elements 16 may be embodied with interconnecting yarns in a "Z" direction perpendicular to the plane of the layers 12 and 14 to provide support against collapse.

The support structure 5 is intended to provide mechanical support and resistance to compression for the new tissue in growth, so that the area intended to form the new tissue is maintained during patient movement and activity. As such, the support structure 5 provides tensile strength in its long axis and stiffness in the "z-direction" to resist compression.

In an embodiment, the support structure 5 may be formed of any one of the following and may optionally be coated with an anti-adhesive material: 30-150 denier multifilament fibers, 30-150 denier monofilament fibers, or 30-150 denier composite yarns, or any combination thereof, such as a combination of multifilament fibers and monofilament fibers. The rough edges of the stent 10 may be sealed or secured using methods including, but not limited to, heat setting or embroidery. I like her small fishing rod. In one embodiment, the support structure 5 is made of 75 denier 30 filament poly L-lactic acid (PLLA) having a polymer density of 1.25 g/cc. The yarns may be braided over twisted fiber yarns to provide higher stiffness yarns for use as lay-in yarns as described below.

In an embodiment, one or both of the outer layers 12 and 14 of the support structure 5 may be implemented by a warp knit open pillar stitch 22 using double yarns as illustrated in fig. 2A and 2C, resulting in the textile layer illustrated in fig. 3A. As can be seen from fig. 2A and 3A, the outer layer comprises a series of wales connected by a single weft inserted yarn 26 and having two 0 ° straight inserted yarns 24 inserted in a columnar structure on both sides, as illustrated in fig. 2A. The pattern of the first outer layer 12 and the second outer layer 14 may be the same or different. In an embodiment, the outer layers 12 and 14 may have the same number of wales, with the spacing elements 16 connecting similar corresponding wales in each of the layers 12 and 14. In embodiments, the outer layers 12 and 14 may have a different number of wales, with the spacing elements 16 connecting the wales in each of the layers 12 and 14.

As used herein, a wale is a "column of loops" that lines longitudinally into the fabric. Each wale may be a single fiber or a double fiber that serves to increase strength, but therefore also increases bulk. Increasing the number of wales or yarns per wale will increase the ultimate tensile strength of the fabric. By adjusting the number of wales, the width of the fabric can be varied, which allows the same textile design to be applied to: narrow applications, such as for ACL enhancement, e.g., 5mm wide; medium width applications, such as for rotator cuff, e.g. 23mm wide; very wide applications, such as for hernias, for example 200mm wide. A method of increasing ultimate tensile strength, resistance to elongation, and initial stiffness can be achieved by adding 0 ° straight laid-in yarns on the technical face of the fabric. These laid-in yarns are incorporated in each wale in a linear fashion.

The Machine used to make the support 10 is a Karl meyer Double Needle Bar Warp Knitting Machine (Karl major Needle Bar Warp Knitting Machine). These machines are computer controlled and allow many parameters to be modified to effect changes to the properties of the textile. The key variables include the number of wales, the number of yarns per wale, the addition of an inlay yarn to a wale, the inlay yarn design, and the number of yarns per inlay yarn. The ability of the fabric to stretch under tensile loading may be affected by, for example, knitting every two wales together rather than every three wales together.

Referring to fig. 3B and 4B, the spacing element 16 may be implemented with a plurality of yarns in the "Z" direction perpendicular to the plane of the layers 12 and 14, which connect the layers 12 and 14 and provide support to prevent collapse. In an embodiment, each of the layers 12 and 14 may have the same number of wales, and the spacing element 16 may connect corresponding wales in each of the layers 12 and 14. In other embodiments, the spacing elements 16 may diagonally cross between different wales of the layers 12 and 14. The spacing element 16 may comprise yarns which may be monofilament, multifilament or multifilament and/or textured.

One or both of the layers 12 and 14 may be implemented using the textile pattern illustrated in fig. 2B. Other textile patterns suitable for layers 12 and 14 may include Full Tricot, and Tricot, Single Atlas, Single side (Jersey), reversed bottom side (reverse Jersey), milan interlock, Milano (Milano), tri-flat (half Milano), and the like. Variations in the warp knit surface design may be used to adjust the size, density, and mechanical properties of layers 12 and 14 including any of the following: surface design, number of wales, number of yarns per wale, addition of inlay yarns to wales, inlay yarn design, number of yarns per inlay yarn, lengthening or decreasing quality (machine parameters) or lengthening or decreasing gap (machine parameters).

An alternative method for warp Knitting is to produce a knitted 3D spacer fabric using a V-bed Knitting machine, such as a Whole Garment Knitting machine (wheel yarn Knitting machine), or using a double rapier loom or multiple slit looms (fly-shot loom).

The addition of a drawstring between the cell phone panels (knotted panels) disperses tension and holds the panels together during the manufacturing process until the drawstring is removed without tearing or jamming. These drawstrings may be mechanically removed or may dissolve away during scrubbing.

In an illustrative embodiment, support structure number five, implemented with a three-dimensional textile, may have physical parameters as illustrated in fig. 1 below.

	Textile only
		Surface area (m)²/g)	0.2315
Quality (g)	0.0684
		Sample SA (m)²)	0.0158
Skeleton density (g/cc)	1.24
		Skeleton volume (cm)³)	0.0552
SA:Vol(cm²:cm³)	2871

A stent having the above-described physical values and defining a void space between the first and second outer layers 12, 14, respectively, through which the plurality of spacing elements 18 extend may be calculated to have a length of between about 500cm²/cm³And 7,000cm²/cm³The measurable void space surface area to volume ratio therebetween.

After manufacture, the scaffold textile may be scrubbed to clean it and remove any finish that may have been used. The scrubbing process may comprise the use of a mixture of water, solvent and aqueous solvent. The fabric may be laundered with or without restraint. The fabric may also be treated with an agent to modify its surface properties, for example to change its hydrophilicity. Various agents may be used for this purpose, including polyethylene glycol. The surface may also be treated by agents such as fibrin to improve cell adhesion. When a portion of the scaffold is intended to be placed in contact with a bone region, the surface of the fibers may be coated with calcium phosphate, hydroxyapatite or bioactive glass or growth factors such as bone morphogenic proteins and demineralized bone matrix.

In embodiments, the composite stent 10, or any portion thereof comprising the layers 12 and 14 or the spacing element 16, may include any combination of synthetic bioabsorbable polymers, natural polymers, and/or additives. Synthetic bioabsorbable polymers suitable for use as part of a composite scaffold may comprise homopolymers, copolymers or polymer blends of any of the following: polylactic acid, polyglycolic acid, polycaprolactone, polydioxanone, polyhydroxyalkanoates, polyanhydrides, poly (ortho esters), polyphosphazenes, poly (amino acids), polyalkylcyanoacrylate, poly (propylene glycol fumarate, trimethylene carbonate, poly (glycerol sebacate), poly (gluconate), poly (ethylene glycol), poly (vinyl alcohol), and polyurethane, or any combination thereof natural polymers suitable for use as part of a composite scaffold may comprise silk, collagen, chitosan, hyaluronic acid, alginate, and amniotic membrane derived matrices.

Size of composite stent

In embodiments, the thickness of the composite stent 10 (i.e., the vertical height dimension of the stent relative to the greater length and width dimensions) may be between about.5 mm and 5mm, and even more preferably between about 1mm and 3 mm. Even more preferably, the minimum thickness of the stent may be about greater than or equal to 1 mm. In embodiments, the thickness of the stent 10 may be uniform along its length or may vary in a repeating or non-repeating manner, depending on the particular application for which the stent is to be used.

In embodiments, the width dimension of the disclosed composite stent 10 may be between about 2mm to 1000mm, depending on the particular application for which the stent is to be used. In embodiments, the width of the disclosed stent may be uniform or may vary in a repeating or non-repeating manner, depending on the particular application for which the stent is to be used. For example, the stent 10 may have ends that narrow within the width of the stent and transition in size to a suture-like size, or ends that are modified to attach to conventional sutures used in the procedures described herein.

In embodiments, the length dimension of the disclosed composite stent may be between about 2mm to 1000mm, and even more preferably greater than or equal to about 10 inches, again depending on the particular application for which the stent is to be used. In embodiments, the disclosed stents may be manufactured in different incremental lengths, or may be manufactured in lengths that may be cut or customized by the practitioner as desired. Fig. 4B is an SEM photograph of a side view of a composite stent 10, which may have a length dimension and be formed from a pair of outer layers 12 and 14 separated by a plurality of spacing elements 18. The photograph of FIG. 4B was taken with a Philips/FEI XL30 ESEM Scanning Electron Microscope (SEM) with a 1mm scale legend shown on the image and the distance between the spacer yarns along the length dimension axis represented by reference lines 1-23. Table 1 shows each reference line and its corresponding distance value in microns and the average distance. As can be seen from table 1, the average distance between the spacer yarns along the length dimension axis is between about 200 μm and 300 μm.

TABLE 1

Fig. 4C is an SEM photograph of a perspective cross-sectional view of the composite stent of fig. 4A. The photograph of FIG. 4C is taken with an SEM in which a 1mm scale legend is shown on the image and the distance between the spacer yarns along the width axis perpendicular to the length dimension axis is represented by reference lines 1-17. Table 2 shows each reference line and its corresponding distance value in microns and the average distance. As can be seen from table 2, the average distance along the width axis between the spacer yarns is between about 300 μm and 400 μm (along the axis);

TABLE 2

In the disclosed composite stent 10, the respective distances between the spacer elements 18 (e.g., spacer yarns) create a series of substantially parallel, similarly sized channels that extend through the gap between the outer layers 12, 14. As described herein, these channels provide spaces within the interior of the support structure in which the microporous matrix 15 may be formed. Importantly, these channels are formed along the axis of the device so that there is a continuous channel between the two ends of the stent. When replaced by new tissue, the new tissue is substantial along the axis of the device and therefore may bear weight, and therefore is functional tissue.

Support structure additive

Composite stents 10 made from any of the above materials may be combined with additives to enhance various properties of the stent, including promoting regeneration of cell growth. Such additives suitable for use as part of a composite scaffold may comprise biologicals, including seeded cells, biological aspirates, and bioactive agents. Seeded cells suitable for use as part of a composite scaffold may comprise adipose-derived stem cells, mesenchymal stem cells, and induced pluripotent stem cells, or any combination thereof. A biological aspirate suitable for use as part of a composite scaffold may comprise whole blood, platelet rich plasma, and bone marrow aspirate concentrate, or any combination thereof.

Bioactive agents suitable for use as part of the composite scaffold 10 may comprise growth factors, extracellular matrix molecules and peptides, therapeutic agents and osteoinductive or osteoconductive agents, or any combination thereof, and may be added to the support structure 5 either before or after formation of the microporous matrix 15.

Growth factors suitable for use as part of a composite scaffold may comprise transforming growth factor-beta superfamily (e.g., transforming growth factor-beta, bone morphogenic protein), insulin-derived growth factors, platelet-derived growth factors, epidermal growth factors, interleukin 1 receptor antagonists, fibroblast growth factors, and vascular endothelial growth factors, or any combination thereof.

Extracellular matrix molecules and peptides suitable for use as part of a composite scaffold may comprise tenascin-C, hyaluronic acid, glycosaminoglycans (e.g., chondroitin sulfate, dermatan sulfate, and heparan sulfate), fibrin, thrombin, leucine-rich small peptides (e.g., decorin and biglycan), fibronectin, elastin, and arginine-glycine-aspartic acid (RGD) peptides, or any combination thereof.

Therapeutic agents suitable for use as part of a composite stent may comprise non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., aspirin (aspirin), ibuprofen (ibuprofen), indomethacin (indomethacin), nabumetone (nabumetone), naproxen (naproxen), and diclofenac (diclofenac)), steroidal anti-inflammatory drugs (e.g., cortisone (cortisone) and hydrocortisone (hydrocortisone)), antibiotics or antimicrobial agents, or any combination thereof.

Osteoinductive or osteoconductive agents suitable for use as part of a composite scaffold may comprise tricalcium phosphate, hydroxyapatite and bioactive glass or any combination thereof.

Microporous matrix

An optional microporous matrix 15 may be formed within the interior void space 16 of the composite scaffold 10. The microporous matrix 15 is supported and held by the support structure 5 and provides support for the colonization and proliferation of cells. The microporous matrix 15 is resorbable or degradable and is designed to be rapidly replaced by new tissue. Microporous matrices made from the materials described herein do not have useful mechanical strength properties themselves, whether in terms of tensile strength or compression resistance.

In an embodiment, a method of manufacturing a composite stent is disclosed, the method comprising: constructing a three-dimensional support structure extending along a length dimension between first and second ends thereof and defining an interior surface within the support structure; and forming a microporous matrix within the interior surface having a plurality of interconnected pores 60 in fluid communication with the exterior surface of the support structure. The microporous matrix is formed such that the plurality of interconnected pores 60 are oriented with respect to the dimensional characteristics of the support structure. For example, those pores proximate to the outer surface of the composite matrix may be oriented substantially perpendicularly or extend radially inward relative to the proximate outer surface of the support structure. Additionally, other apertures of the plurality of interconnected apertures 60 may be oriented toward the length dimension of the support structure in a manner that mimics the orientation of the spacing elements 18 (e.g., spacing yarns) separating the outer layer 12 from the outer layer 14.

In embodiments, the microporous matrix 15 may be implemented with a high surface area material, such as any of the following: a sponge, foam, or textured fiber or yarn, or any combination thereof. The method for making the microporous matrix 15 may include any of the following: freeze-drying, particle leaching, open-cell extrusion, solvent casting, solid state foaming, and crosslinking. In one embodiment, the sponge/foam that may be used as the microporous matrix may include any of the following: freeze-dried sponges, open-cell extruded foams, and particle leached sponges, or any combination thereof.

Suitable materials for implementing the micropores 15 are collagens, including bovine type 1 collagen. Other materials that may be used for the porous matrix 15, instead of or in addition to collagen, include hydrogels based on polyethylene glycol (PEG), Polycaprolactone (PCL), or poly (glycolide-co-caprolactone) (PGCL), or combinations thereof. The collagen solution may be infiltrated into the support structure 5 with the help of a mould for holding the scaffold. The secondary stent material may also coat the outer surface of the support structure 5 in an encapsulated manner. The mold with the textile and collagen solution can be placed into a shelf lyophilizer, also referred to as a freeze dryer, which uses temperature controlled shelves to freeze the contents of the mold to very cold temperatures, e.g., as low as-55C, which creates a crystalline structure in the collagen solution, forming a matrix of interconnected pores in the collagen structure occupying the interior void space 16 of the support structure 5. A vacuum is drawn in the freeze dryer chamber and the shelf temperature is gradually raised to provide energy to the frozen solvent, thereby allowing the sublimation process to occur. The sublimed solvent was collected in a separate condenser and completely removed from the inflammation. After a certain period of warming and vacuum, a highly porous, low density collagen matrix is formed within the textile.

During this process, the porosity of the collagen in the microporous matrix 5 can be affected in a number of ways. The volume porosity can be increased or decreased by decreasing or increasing the weight percent of the collagen solution, respectively. The size of the pores can be adjusted by varying the freezing rate in the mold. Increasing the freezing rate decreases the average size, and decreasing the freezing rate increases the average size.

Since the total surface area of the pores is related to the pore size, e.g., a larger number of small pores will have a larger surface area than a smaller number of large pores, increasing the freezing rate will decrease the average pore size, thereby increasing the total surface area, while decreasing the freezing rate will increase the average size, thereby decreasing the total surface area of the microporous matrix. Fig. 5C is a graph showing the relationship of temperature, pressure and time during the lyophilization process.

Variations in the mold material (including Delrin), aluminum, stainless steel or other materials) transfer heat in different ways and may produce different microporous matrix structures by altering the crystallization of the collagen solution as it freezes. For example, molds made of the thermoplastic delrin used for precision part manufacturing transfer heat more slowly, resulting in larger pore sizes in the collagen solution. In contrast, molds formed of aluminum transfer heat very quickly, thereby producing a microporous matrix with relatively small pore sizes. Molds made of stainless steel transfer heat more slowly than aluminum and produce pores that are larger than those produced with aluminum molds, but smaller than those produced with delrin molds.

In addition, adjusting the mold thickness between the bottom surface of the mold and the bottom of the cavity has a similar effect of increasing or decreasing the rate of heat transfer, which can result in different microporous matrix structures. In an embodiment, or the mold shown in fig. 5A and 5B is made of stainless steel and has the cavity dimensions listed in table 2 below, where a 5 x 260mm dimension post refers to the mold 50 illustrated in fig. 5A and a 23 x 30mm dimension post refers to the mold 57 illustrated in fig. 5B. The die 50 defines a plurality of rectangular cavities 52 and has a clamp 54 with pins 55 securable at its ends. The mould 57 contains a rectangular cavity 59 and an array of throwing holes 53.

TABLE 2

	5×260mm	23×30mm
			Width of cavity	5.21	23.20
Length of cavity	260.00	30.20
			Depth of cavity	4.09	8.00
Distance from bottom of cavity to bottom of mould	4.70	4.70

The mold illustrated in fig. 5A utilizes end clips made of delrin that can be secured to the main mold body and can be used to hold the textile support during the lyophilization process.

In the illustrative embodiment, the cavity 52 of the mold 50 has a substantially rectangular cross-sectional shape. Other cross-sectional shapes may be used to maximize contact between surface regions of the support structure 5 during the process of forming the microporous matrix therein. In particular, scaffolds having any of a D-shape, U-shape, O-shape, or C-shape may be used during lyophilization to maximize the surface area of the scaffold shape and further facilitate the orientation of the pores within the microporous matrix during the lyophilization process. In particular, for support structures 5 having a cylindrical or tubular shape, tubular molds, whether oriented horizontally or vertically, may be used during the lyophilization process.

Alignment of the pores with respect to the scaffold dimensions can be created by contact with the mold surface. As shown in the cross-sectional SEM photographs of fig. 6D-E, 6G-H, it can be seen that the pores within the microporous matrix 15 are formed proximate to the mold surface, perpendicular to the plane of contact with the mold. In an embodiment, applicants have found that the apertures may be oriented at 45 ° to 135 ° proximally with respect to a plane of contact with the die. In an embodiment, for a mold similar to that shown in fig. 5A, a large number of pores would be oriented perpendicular to the contact surface with the mold interior toward the center of the support structure 5. Such orientation further promotes faster ingrowth of cells into the composite scaffold 10.

Alternative mold designs utilize cavities similar to those above, but add a securely formed and air tight top cover. Similar to injection molding, vacuum or pressure or other means may be used to fill the mold with the collagen solution from one end and release entrapped gas at the other end, thereby facilitating further alignment of the collagen fibers during the injection process.

A further alternative mold design uses cavities that place the textile on its sides such that the face of the textile is perpendicular to the bottom surface of the mold. Additional alternative mold designs may use cavities having a "U" shaped cross-sectional profile or another shape that will result in a finished stent having a shape more suitable for a particular type of implant.

There are various manufacturing methods that may be used to create a microporous matrix within the void spaces of a textile support structure, including salt leaching, gas extrusion, and other methods that use high pressure or vacuum, as well as gases.

The resorption and mechanical properties of the microporous matrix can be further modified by crosslinking. In general, the materials used for crosslinking are potentially cytotoxic, so it would be very beneficial to be able to use lower levels. A benefit of the disclosed procedure is that the use of the support structure 5 allows the microporous matrix 15 to take advantage of low levels of cross-linking. The 3D textile filled with the dry, highly porous and low density collagen microporous matrix is removed from the mold cavity and placed on a permeable shelf such as a wire rack in a sealed chamber. The formaldehyde and ethanol solution was poured into the tray and the tray was placed under the shelf of the rack and the door was sealed. The tray fully encompasses the basic dimensions of the chamber (L x W) and the vapors from the solution are used to crosslink the collagen within the 3D textile. After a set time, the trays are removed and the product is moved to an aeration chamber where clean dry air or alternatively another gas such as nitrogen is pumped through and out of the chamber, effectively terminating the crosslinking process. Crosslinking of collagen can be increased by increasing the time in the chamber, increasing the concentration of formaldehyde in the ethanol solution, or reducing aeration. Also, cross-linking can be reduced by reducing the time in the chamber, reducing the concentration of formaldehyde in the ethanol solution.

Alternatively, a chemical crosslinking agent may be added to the collagen solution. These reagents may include, but are not limited to, aldehydes at various concentrations, such as glutaraldehyde, genipin (genipin), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC), and EDC/N-hydroxysuccinimide (EDC/NHS). An additional alternative crosslinking mode may be in the form of photochemically activated crosslinking, which may involve the use of UV or visible light to trigger the crosslinking process with or without a crosslinking initiator.

Mechanical Properties of composite stents

The mechanical properties of the composite stent 10 disclosed herein make the composite stent optimal for use in a wide range of medical procedures, including enhanced suture repair, stand-alone repair or reconstruction, or reconstruction using tissue grafts and for fixation purposes. Composite scaffolds 10 made according to the description herein and examples 1, 2 and 3 were tensile tested using a Mark-10 tensile tester at a crosshead speed of 20 mm/min, with the results listed in table 3.

TABLE 3

An advantage of the composite stent 10, and in particular the support structure 5, as disclosed herein is its ability to resist compression when elongated. In an embodiment, as can be seen from the values in table 3 above, the width, height and cross-sectional area of the three-dimensional textile comprising the support structure 5 resist compression under a considerable force. In particular, for a film having a thickness of about 9.92mm²A cross-sectional area, a thickness (height) of about 2.17mm and a width of about 4.57mm, the extension of the support structure 5 along its length axis due to a force of 35N extends the length dimension of the support structure 5 by about 13%. In an embodiment, the thickness dimension of the support structure varies by less than about 31% when the length dimension is elongated by about 13%. In an embodiment, the change in cross-sectional area is less than about 35% when the length dimension is elongated about 13%. In an embodiment, the change in the width dimension of the support structure is less than about 5% when the length dimension is elongated by about 13%.

In embodiments, a length of support structure 5 implemented with a three-dimensional textile scaffold as disclosed herein may have an ultimate load at a length dimension elongation percentage of between about 30% and 125%. In an embodiment, the stent may yield when the percent elongation of the length dimension is between about 5% and 15%. In an embodiment, the stent may have a tenacity of between about 0.073 and 1.102 g-force/denier. In an embodiment, the stiffness of the stent may be approximately between 2.5N/mm and 25N/mm, where stiffness defines the degree to which the stent resists deformation in response to an applied force. In an embodiment, the strain to failure of the stent may be approximately between 20% and 70%. In an embodiment, the stent may have a failure toughness of between about 0.3 and 2 grams-force/denier.

In an illustrative embodiment, the ultimate load displacement of a support structure 5 implemented with a three-dimensional textile scaffold having a width of 5mm, a length of 40mm, and a thickness of about 1mm, or as disclosed herein, may be between about 5mm and 50mm, wherein the ultimate load displacement defines the change in displacement at a load applied to the biomimetic scaffold above which the biomimetic scaffold will fail. Such tests were conducted using a 40mm gauge length and according to standards set forth by the American Society for Testing and Materials (ASTM). In the illustrated embodiment, the yield displacement of the scaffold may be approximately between 1mm and 8mm, where the yield displacement defines the change in displacement at which the biomimetic scaffold begins to deform. In the illustrated embodiment, the yield force of the scaffold may be approximately between 20N and 70N, where the yield force defines the force at which the biomimetic scaffold begins to deform. In the illustrated embodiment, the stiffness of the stent may be approximately between 2.5N/mm and 25N/mm, where stiffness defines the degree to which the biomimetic stent resists deformation in response to an applied force. In an illustrative embodiment, the ultimate strain of the stent may be approximately between 20% and 70%, where ultimate strain defines the deformation of the biomimetic stent due to stress. In the illustrated embodiment, the ultimate load of the stent may be approximately between 100N and 200N, where ultimate load is defined as the amount of load applied to the biomimetic stent beyond which the stent fails. In illustrative embodiments, the ultimate strength of the stent may be approximately between 2.5MPa and 20MPa, where ultimate strength is defined as the ability of the biomimetic stent to withstand a load that tends to elongate the biomimetic stent. In an illustrative embodiment, the ultimate stress of the stent may be approximately between 2.5MPa and 20MPa, where ultimate stress is defined as the maximum stress that the structure can withstand, beyond which the structure fails. In the illustrated embodiment, the modulus of the scaffold may be approximately between 2.5MPa and 70MPa, where the modulus defines a measure of the stiffness of the biomimetic scaffold having void spaces. In an illustrative embodiment, the modulus of the scaffold may be approximately between 150MPa and 600MPa, where the modulus defines a measure of the stiffness of a biomimetic scaffold without void spaces, where the modulus is calculated using the cross-sectional area of a material comprising only the composite scaffold.

According to embodiments, the staggered degradation rate of the composite scaffolds disclosed herein by the scaffold assembly provides greater support for a greater amount of regenerated tissue. More specifically, the first support matrix 5 and the second support matrix 15 of the stent 10 have different degradation rates. In one embodiment, the second support matrix 15 (e.g., a sponge) degrades 2 to 12 times faster than the first support structure 5 based on mass loss or molecular weight loss. For example, a sponge comprising a second support matrix may have a mass loss 3 months to 6 months after implementation, while a textile fabric comprising a first support matrix may have a mass loss 12 months after implantation. Such differences in degradation rates enable the bulk of tissue ingrowth promoted by the internal voids of the stent 10 to continue to be supported by the textile fabric for longer periods of time. As indicated, the parameter of material degradation can be measured by mass loss or molecular weight loss. In one embodiment, the composite scaffold may have a degradation curve that: greater than or equal to 50% strength retention for at least about four weeks after implantation and 100% mass loss for about six months to twelve months after implantation.

According to embodiments, the composite stents disclosed herein may have features that enhance usability and better performance once implanted. In embodiments, the stent 10 may have ends that narrow and transition to a suture-like size, or be modified, such as sutured or knotted, to attach to the ends of conventional sutures used in the procedures described herein. In an embodiment, the support structure 5 (e.g., a textile) has ends or edges modified to be heat set or embroidered or impregnated with other materials to facilitate better handling, better integration with existing tissue, and further reduce dimensional distortion of the stent 10 under pressure, tension, or shear forces. In embodiments, selected sections of the stent 10 may be repeated randomly or at a fixed speed to increase or decrease the density of the stent by increasing or decreasing the density of the textile, for example by changing the textile pattern of the first support structure 5. In embodiments, such repeating regions may be selected to alter the surface finish of the stent by altering the lyophilization, smoothness, or roughness parameters of the stent's outer surface in order to improve stent acceptance post-implantation.

In embodiments, the spacer element 18 may be located only in a portion of the interior space 16 of the stent 10, such as a hollow lumen, as illustrated in fig. X. In other embodiments, the spacer elements 18 may have any regular or irregular repeating pattern of placement in the interior space 16 between the layers 12, 14 of the stent 10. In other embodiments, the spacing element 18 itself may be implemented with a textile or tissue-derived material, such as felt, or as otherwise described herein.

According to an embodiment, the composite scaffold may also be seeded with cells for a temporary pre-incubation period to allow the cells to form a collagen-rich extracellular matrix on the sponge and textile component. The scaffold may then optionally be decellularized to leave a matrix template with native extracellular matrix proteins on the textile structure, and subsequently implanted to repair tendons or ligaments in vivo.

Characteristics of scaffold pores

Multiple samples of composite stents fabricated according to examples one and two and the process described herein were tested to determine various behavioral characteristics as described below. The microporous matrix in each sample composite scaffold has a plurality of interconnected pores that open to the microporous matrix and the outer surface of the composite scaffold. Various properties of the pores within the microporous matrix and, correspondingly, within the composite scaffold can be measured by Mercury Intrusion Porosimetry (MIP) or gas adsorption. Mercury is a non-wetting liquid that does not actively fill the porous structure. However, by applying pressure, using MIPs, mercury can be forced into the pores of the microporous matrix, with higher pressure allowing mercury to enter into smaller pores. By accurately monitoring the volume of mercury while gradually increasing the applied pressure, the pore size (diameter) and pore volume can be accurately measured. Pore size and volume measurements can generally be used to determine various properties of microporous matrices and composite scaffolds.

Surface area

Important characteristics of the disclosed composite scaffold are the following ratios: stent surface area per unit weight of stent. Due to the large number of interconnected pores within the microporous matrix supported by the 3D textile support structure, the disclosed composite scaffold has a large surface area on which cell migration and subsequent new tissue development can occur. Using MIP, rather than just geometry and image quantification, the total surface area of the interconnected pores and the exterior of the composite scaffold can be measured more accurately. The surface area can be calculated from the known diameter of the pores measured by MIP using the following formula assuming that the pores are spheres:

A＝4πr²

thus, the surface area parameter is expressed in terms of square meters per gram (m)²/g) is the amount measured in units, i.e., the composite scaffold surface area per unit weight of the composite scaffold region. Fig. 8 is a graph 80 of test data showing cumulative total pore surface area versus pore size measured in microns for several composite scaffold samples and samples comprising only 3D textiles comprising support structures 5. In the sample of fig. 8, the 3D textile support structure 5, either alone or filled with a microporous matrix 15, comprises PLLA fibers. All samples were generated according to the methods described herein and examples 1 and 2. In embodiments, the surface area per unit weight of the disclosed composite scaffold may be between about 0.3m²G and 1.5m²Between/gram. The surface area per unit weight of the disclosed composite scaffold may be between about 0.6m²G and 1.2m²Between/gram. The surface area per unit weight of the disclosed composite scaffold may be between about 0.71m²G and 1.0m²Between/gram.

The total surface area of the interconnected pores and the exterior of the composite scaffold can also be more accurately measured using gas adsorption, such as krypton, rather than merely geometric dimensions and image quantification. The table below shows two samples having a width of 5mm and a length of 40 mm. Such as by krypton adsorption for particles smaller than diameterThe surface area of the composite scaffold, measured as pores of 1 μm, was between about 0.3m²G and 15m²Between/gram.

Sample (I)	BET SA(m²/g)
		5mm	0.5826
5mm	0.5558

Total pore volume

Another important characteristic of composite scaffolds is high void space volume, due in part to the number, size, orientation and interconnectivity of the pores that collectively define the void space within the microporous matrix. Such a high total pore volume promotes more rapid blood absorption, cell migration and subsequent new tissue development. The total volume of pores that collectively form the void space within the microporous matrix can be measured directly using the MIP by monitoring the change in mercury volume during the MIP process. As such, the pore volume parameter of the composite scaffold represents the total cumulative void volume of the composite scaffold per unit weight, e.g., cm³(ii) in terms of/g. Fig. 9 is a graph 90 showing the cumulative total pore volume, which can be measured in cubic centimeters per gram, versus pore size, measured in micrometers, for several composite scaffold samples and textile support structures only. In the sample of fig. 9, the textile support structure, whether alone or filled with a microporous matrix, includes PLLA fibers. All samples were generated according to the methods described herein. In embodiments, the total pore volume of the disclosed composite scaffold may be between about 3.0cm³G and 9.0cm³Between/gram. The volume of the disclosed composite scaffold may be between about 3.5cm³G and 7.0cm³Between/gram. The total pore volume of the disclosed composite scaffold may be between about 4.0cm³G and 5.0cm³Between/gram.

Porosity of the material

Another important characteristic of the composite scaffold is porosity, which is a measure of the volume of void space within the microporous matrix as a percentage of the measurable volume of the composite scaffold itself. Such calculations may be done using measurements taken during MIP. During the MIP process, the mass of each sample is known, and by monitoring the mercury volume, the occupied volume of the sample is also known. At the lowest pressure applied during MIP, there should be no mercury filling into the scaffold, so the bulk density of the composite scaffold can be calculated. At the higher pressures applied during MIP, the composite scaffold should be almost completely filled with mercury. Thus, the scaffold skeleton density can be calculated as follows:

porosity ═ 100 x 1- (density at low pressure/density at high pressure)

In this way, the measurable volume of the composite scaffold is calculated not by geometry, but by relative density. Fig. 10 is a graph 100 of composite stent density in grams per cubic centimeter versus mercury pressure measured in pounds per square inch absolute (i.e., measured in microns in vacuum) for several composite stent samples and textile-only support structures. In the sample of fig. 10, the textile support structure, whether alone or filled with a microporous matrix, includes PLLA fibers. All samples were generated according to the methods described herein. In embodiments, the porosity of the disclosed composite scaffold may be between about 75% to 98%. In embodiments, the porosity of the disclosed composite scaffold may be between about 80% to 90%. In embodiments, the porosity of the disclosed composite scaffold may be between about 80% to 85%.

Permeability rate of penetration

Another important characteristic of composite scaffolds is the permeability of the microporous matrix, which promotes faster absorption of fluids, particularly blood, both during and after implantation to accelerate the process of cell migration and subsequent new tissue development. The microporous structure (e.g., collagen) within the textile support structure facilitates the formation of a more uniform and well-defined pore structure as compared to collagen sponge alone, wherein the permeability is about 200% of the permeability of the collagen sponge itself. This is due at least in part to the more uniform and well-defined structure of the interconnected pores. Reproducible permeability values can be calculated from Mercury Intrusion Porosimetry (MIP) data using the Katz-Thompson equation (Katz-Thompson equation) listed below:

wherein:

k (mD): air permeability

Pt (psia): hg begins to flowBy passingPressure at void

D_c(μm): diameter (D) corresponding to Pt_c＝180/Pt)

D_max(μm): diameter at maximum hydraulic conductivity

Hydraulic conductivity: measurement of the ease of fluid flow through porous materials

Porosity from MIP data (minus inaccessible void space in the fiber)

S(D_max): size D_maxAnd a greater fraction of connected pore space/at D_maxFraction of total porosity of underfill

How to calculate permeability using the above described katz-thompson equation is illustrated in the following publications: goa and Hu entitled "estimating permeability using median low throat radius obtained from Mercury intrusion early growth" (2013, a report on geophysics and engineering (J.Geophysics. Eng.). In this way, reproducible permeability values can be calculated from the data collected during MIP. In embodiments, the permeability of the disclosed composite scaffold may be between about 1200 and 3000 millidarcies. In embodiments, the porosity of the disclosed composite scaffold may be between about 1400 and 2600 millidarcies. In embodiments, the porosity of the disclosed composite scaffold may be between about 1600 and 2000 millidarcies.

Total surface area/scaffold volume

Another important characteristic of composite scaffolds is the total surface area/scaffold volume ratio. The surface area of each given sample can be determined by MIP. The skeletal density may be calculated as explained above with reference to the porosity parameter. Surface area in square meters per unit weight of sample (m)²In/g) is reported in units and can be converted to cubic meters by multiplying by the sample mass. The scaffold volume is equal to the sample mass divided by the scaffold density. In embodiments, the ratio of void space surface area to scaffold volume of the disclosed composite scaffolds may be between about 5,000cm²/cm³And 16,000cm²/cm³In the meantime. In embodiments, the ratio of void space surface area to scaffold volume of the disclosed composite scaffolds may be between about 7,000cm²/cm³And 14,000cm²/cm³In the meantime. In embodiments, the ratio of void space surface area to scaffold volume of the disclosed composite scaffolds may be between about 9,000cm²/cm³And 12,000cm²/cm³In the meantime.

Pore size

Another important characteristic of the composite scaffold is the median pore size, measured in microns, of the interconnected pores within the void spaces of the microporous matrix 15. The pores of the microporous matrix must be large enough to allow cellular infiltration, while not being so large as to slow cellular proliferation and the formation of new tissue prior to resorption of the microporous matrix after implantation. According to the present disclosure, several pores of a given diameter are effectively measured by tracking the volume of indentation at a given pressure during MIP. Thus, both median pore size and pore size distribution are reported. Figure 12 is a graph 120 graphically illustrating pore size distribution measured in microns versus log differential volume measured in cubic centimeters per gram. In an embodiment, the microporous substrate may have a plurality of interconnected pores having a median pore size between about 10 μm and 70 μm. In an embodiment, the microporous substrate may have a plurality of interconnected pores having a median pore size between about 12 μm and 50 μm. In an embodiment, the microporous substrate may have a plurality of interconnected pores having a median pore size between about 20 μm and 35 μm.

Another important characteristic of the composite scaffold is the pore size distribution within the void space of the composite scaffold microporous matrix measured in microns. The cumulative pore volume can be determined by MIP. The fraction of contribution of pores of a certain size to void space may be calculated as the cumulative void space at a given pore size divided by the total void space. Figure 12 also shows the pore size distribution within the void spaces of the microporous matrix. As can be seen from fig. 12, a majority of the total void space within the microporous matrix includes pores having a size parameter greater than 10 μm. In an embodiment, the microporous matrix has a plurality of interconnected pores that collectively define a void space, wherein at least about 99% of the void space comprises pores having a size dimension of 10 μm or greater. In an embodiment, the microporous matrix has a plurality of interconnected pores that collectively define a void space, wherein at least about 95% of the void space comprises pores having a size dimension of 10 μm or greater. In an embodiment, the microporous matrix has a plurality of interconnected pores that collectively define a void space, wherein at least about 80% of the void space comprises pores having a size dimension of 10 μm or greater.

Swelling and absorption

According to embodiments, the composite scaffolds disclosed herein provide a measurably high absorption capacity (e.g., capable of absorbing aqueous media) or wicking to facilitate more rapid and greater uptake of biological fluids and/or cells within the scaffold. Specifically, the absorption capacity of a composite stent can be measured by the following formula:

absorption% (% sample wet mass-sample dry mass)/sample dry mass 100

In an embodiment, the disclosed composite scaffold has a measurable dry weight value representing the weight of the scaffold in a substantially dry state and a measurable dry volume value representing the volume of the scaffold in a substantially dry state, wherein an increase in the weight value of the scaffold by about 200% to 600% due to fluid absorption changes the dry volume value of the scaffold by about 0% to 10%. The percent change in volume of the composite scaffold can be measured by the following equation:

volume change% (% sample wet volume-sample dry volume)/sample dry volume 100

According to embodiments, the composite scaffolds disclosed herein provide a reduced swelling curve, e.g., resistance to dimensional changes with increased absorption of fluid. Specifically, the percent change in swelling of the composite scaffold can be measured by the following equation:

percent swelling ═ 100 (sample wet mass-sample dry mass)/(sample wet mass) ·

In an embodiment, the disclosed composite scaffold has a measurable dry weight value indicative of the weight of the composite scaffold in a substantially dry state and a measurable dry length value indicative of a dimensional parameter of the composite scaffold in a substantially dry state, wherein an increase in the weight value of the composite scaffold by about 200% to 600% due to fluid absorption changes the dry length value of the composite scaffold by less than about 0% to 3%. The percent change in length of the composite scaffold can be measured by the following equation:

length change [% sample wet length-sample dry length ]/[ sample dry length ] 100

In an embodiment, the disclosed composite scaffold has a measurable dry weight value representing the weight of the composite scaffold in a substantially dry state and a measurable cross-sectional profile value representing a dimensional parameter of the composite scaffold in a substantially dry state, wherein an increase in the weight value of the composite scaffold by about 200% to 600% due to fluid absorption changes the cross-sectional profile value of the composite scaffold by about 0% to 10%. The percent change in the cross-sectional profile value of the composite scaffold can be measured by the following equation:

percent change in cross-sectional profile [ (% wet width of sample [ ] wet height of sample [ (% dry width of sample [ ] dry height of sample) ]/(% dry width of sample [ ] dry height of sample [ ] 100 [ ]

Other related forms are as follows:

wet density [% wet weight of sample/wet volume of sample)/(dry weight of sample/dry volume of sample ] } 100

Thickness change [% of sample wet height-sample dry height ]/[ 100 ] of sample dry height

Wet weight% (% wet weight of sample/dry weight of sample) (% 100)

Filling sample volume% (sample wet mass-sample dry mass)/(sample dry volume)

Throughout the manufacturing process, the composite scaffold devices were weighed to obtain the mass of individual textiles, coated with PEG 400, and added with collagen solution and then lyophilized. The mass of collagen microporous matrix in each device can be calculated as follows:

quality of_Collagen-mass_{Support frame}-mass_{Textile product}+PEG 400

The% dry weight of collagen compared to the entire composite scaffold device can then be calculated:

class bracket density

Another important characteristic of composite scaffolds is scaffold density. According to embodiments, for the composite scaffolds disclosed herein, a higher density or mass of supporting matrix provides the primary structure and bulk structure of the disclosed scaffold as compared to a more porous matrix disposed in the supporting matrix. More specifically, the first support matrix 5 and the second support matrix 15 of the stent 10 have different density or mass compositions relative to each other. In one embodiment, the first support structure 5 (e.g., a textile) has a measurable mass or density that is greater than or equal to one times the mass or density of the second support matrix 15 (e.g., a sponge), and more preferably, 2 to 5 times the mass or density of the second support matrix 15. In embodiments, the maximum scaffold density of the disclosed composite scaffold can be less than 0.5g/cm³And specifically between about 0.05g/cm³And 0.3g/cm³In the meantime.

Manufacturing method

The method for manufacturing the composite stent according to the present disclosure is as follows. Composite scaffolds made of three-dimensional PLLA textile filled with a highly porous collagen matrix 5mm wide, 3mm high and 260mm long for ACL repair or reinforcement were fabricated as follows. According to the described warp knitting technique, a three-dimensional (3D) textile including a support structure is manufactured using the double column pattern shown in fig. 2A. The top and bottom layers of the resulting structure each had 6 wales. The corresponding wale top layer and wale bottom layer are interconnected by a series of braided spacer yarns that extend in the Z-direction (e.g., perpendicular to the X-Y plane of the outer layers 12 and 14) through the void spaces and interconnect the layers 12 and 14. The 3D textile was received as a continuous length textile 5mm wide and 3mm high and subjected to ultrasonic scrubbing (e.g., washing) in DI and IPA solution to remove particles and yarn spin finish. Multiple washes were used with the solution being changed between washes. The temperature of the wash solution may be room temperature, or up to 40C. The 3D textile is then air dried and cut to length.

An alternative method of preparing 3-D textiles prior to coating with hydrophilic solutions involves wrapping a continuous length of textile around a frame (also known as a tenter frame or a stitch frame) without overlap at moderate tension. The wrapped frame is then immersed in a solution of distilled water and isopropyl alcohol and washed with ultrasound or in a shaking bath for agitation. Multiple washes may be used with the solution being changed between washes. The temperature of the wash solution may be room temperature, or up to 40C. The 3D textile was then air dried under tension on a rack. The textile is then cut to length on a rack while under tension, resulting in a uniform length. By utilizing the sewing frame, washing under tension, and drying under tension, the textile is heat set, thereby reducing wrinkles, holding the top and bottom surfaces of the textile in an opposed and taut weave configuration, thus resulting in a final textile with less elongation under load.

The 3D textile that was scrubbed and cut to length is then immersed in a solution of polyethylene glycol (PEG) and ethanol to increase hydrophilicity. The concentration of PEG in ethanol was specifically controlled to produce a controlled weight percentage of PEG on the 3D textile. The 3D textile is then air dried. An alternative method of preparing 3-D textiles prior to coating with hydrophilic solutions involves immersing the 3D textiles in PEG and ethanol solutions after scouring, but before cutting to length. A further alternative method involves immersing the 3D textile wrapped on the frame in a PEG and ethanol solution after scrubbing, but before cutting. In the steps mentioned above, various combinations of each alternative may be utilized to achieve the same result.

Next, a 0.6 wt% collagen solution was prepared using low molarity acetic acid, and powdered type 1 bovine collagen was blended and vacuum-treated to remove entrapped air bubbles. Various low molarity acids such as hydrochloric acid may be used to prepare the collagen solution. Additionally, alternative methods may remove entrapped air bubbles, for example, by spinning the solution in a centrifuge.

Different weight percentages of collagen solution may be used. Increasing the weight percent of collagen increases the amount of collagen in the matrix. Reducing the weight percentage of collagen reduces the amount of collagen in the matrix. These changes, when used with the lyophilization process described herein, will affect the final collagen matrix density, structural properties, and porosity.

A stainless steel mold 57 shown in fig. 5B was used to direct the filling of the collagen solution into the 3D textile and freeze-dried by the next step to produce the collagen sponge matrix structure. The cavity of the mould is filled with a small amount of collagen solution. The 3D textile piece is then placed into the mold with the 3D textile face parallel to the bottom of the cavity and clamps are used on each end to secure the 3D textile and prevent movement. These clamps add benefits by creating a flat area at each end without the porous collagen matrix for product handling and suture attachment in the next step lyophilization.

Then, additional collagen solution is filled into the cavity with the textile, thereby completely immersing the textile in the collagen solution. The mold with the textile and collagen solution is then vacuum treated to remove the remaining air within the 3D textile so as to completely fill the textile with the solution. The mold with the textile and collagen solution was placed into a shelf lyophilizer and the temperature was reduced to-55C over a period of about 2 hours. The textile filled with the dry, highly porous and low density collagen matrix is removed from the mold cavity and placed on a wire rack in a sealed chamber. The formaldehyde and ethanol solution was poured into the tray and the tray was placed under the shelf of the product and the chamber door was sealed. The steam from the solution crosslinks the collagen within the textile. After about 2 hours, the trays were removed and the product was moved to an aerated chamber where clean, dry air was pumped through and out of the chamber, effectively terminating the crosslinking process. After a period of warming and vacuum, a highly porous, low density collagen matrix was formed within the 3D textile.

A 23mm wide, 3mm high and 30mm long composite scaffold made of three-dimensional PLLA textile filled with a highly porous collagen matrix for rotator cuff repair or reinforcement was fabricated as follows. Composite scaffolds made of three-dimensional PLLA textile filled with a highly porous collagen matrix of 5mm width, 3mm height and 260mm length were fabricated for ACL repair or reinforcement as described below. According to the described warp knitting technique, a three-dimensional (3D) textile including a support structure is manufactured using the double column pattern shown in fig. 2A. The top and bottom layers of the resulting structure each had approximately 25 wales. The respective wale top layer and wale bottom layer are interconnected by a series of braided spacer yarns extending in the Z-direction through the void spaces and interconnecting the layers.

The 3D textile was received as a continuous length textile 5mm wide and 3mm high and subjected to ultrasonic scrubbing (e.g., washing) in DI and IPA solution to remove particles and yarn spin finish. Multiple washes were used with the solution being changed between washes. The temperature of the wash solution may be room temperature, or up to 40C. The 3D textile is then air dried and cut to length. The 3D textile that was scrubbed and cut to length is then immersed in a solution of PEG and ethanol to increase hydrophilicity. The concentration of PEG in ethanol was specifically controlled to produce a controlled weight percentage of PEG on the 3D textile. The 3D textile is then air dried.

Next, a 0.6 wt% collagen solution was prepared using low molarity acetic acid, and powdered type 1 bovine collagen was blended and vacuum-treated to remove entrapped air bubbles.

The stainless steel mold shown in fig. 5B was used to direct the filling of the collagen solution into the 3D textile and freeze-dried by the next step to produce the collagen sponge matrix structure. The cavity of the mould is filled with a small amount of collagen solution. The 3D textile piece is then placed into the mold with the 3D textile face parallel to the bottom of the cavity and clamps are used on each end to secure the 3D textile and prevent movement. These clamps add benefits by creating a flat area at each end without the porous collagen matrix for product handling and suture attachment in the next step lyophilization.

Then, additional collagen solution is filled into the cavity with the textile, thereby completely immersing the textile in the collagen solution. The mold with the textile and collagen solution is then vacuum treated to remove the remaining air within the 3D textile so as to completely fill the textile with the solution. The mold with the textile and collagen solution was placed into a shelf lyophilizer and the temperature was reduced to-55C over a 2 hour period. A vacuum is drawn in the freeze dryer chamber and the shelf temperature is gradually raised to provide energy to the frozen solvent, thereby allowing the sublimation process to occur. The sublimed solvent was collected in a separate condenser and completely removed from the inflammation. After a period of warming and vacuum, a highly porous, low density collagen matrix was formed within the 3D textile.

The mold design may allow the entire scaffold to be encapsulated in a collagen gel, which may have the benefit of protecting the body from the textile scaffold components by a more bio-maternal biocompatible collagen gel.

Medical procedure

The composite stents described herein may be used in a wide range of medical procedures, including reinforced suture repair, stand-alone repair or reconstruction, or reconstruction using tissue grafts and for fixation purposes. The use of the composite scaffold to augment repair or reconstruction may be applicable to the knee, ankle, shoulder, elbow and hand as well as non-musculoskeletal soft tissues. The knee may comprise any one of ACL (anterior cruciate ligament), PCL (posterior cruciate ligament), LCL (lateral collateral ligament), MCL (medical collateral ligament), MPFL (medial patellofemoral ligament), ALL (anterior lateral ligament), and posterolateral angle injury (fibular collateral ligament, popliteal tendon, popliteal fibular ligament). The ankle may comprise any one of ATFL (anterior fibular ligament) and CFL (calcaneofibular ligament). The shoulder and elbow may include any one of trochanteric cuffs (supraspinatus, infraspinatus, infrascapular muscle, and teres minor tendon), acromioclavicular ligament, UCL (ulnar collateral ligament), and flexor tendon. The non-musculoskeletal soft tissue may comprise any one of the breast, abdominal wall and pelvic floor. The composite stents described herein may be used to secure permanent and resorbable materials, including sutures, suture anchors, tacks, and staples.

The physical dimensions and biomechanical properties of the composite stents disclosed herein are optimized for use in a wide range of medical procedures, including enhanced suture repair, stand-alone repair or reconstruction, or reconstruction using tissue grafts and for fixation purposes. The use of the composite scaffold to augment repair or reconstruction may be applicable to the knee, ankle, shoulder, elbow and hand as well as non-musculoskeletal soft tissues. Such physical properties are significantly different from those of commercially available products such as hernia meshes and orthopedic sutures, and are more amenable to the procedures described above. For example, orthopedic suture tape exists in the form of a three-dimensional solid and is measurable, being in fact two-dimensional for all intents and purposes related to surgery, with little value for regenerating the volume of tissue necessary to enhance or mimic the properties of a tendon or ligament. For surgical meshes and patches composed of bioabsorbable materials that have a wide range of applications and can be considered as stents, the resulting tissue plane formed after complete resorption of the material can be very thin and weak; this is due to the lack of sufficient void volume for thickness and/or appropriate pore size for cell ingrowth within the scaffold. Thus, there is a clear need to create tissue scaffolds of sufficient thickness to regenerate thicker and stronger tissue planes after polymer degradation.

In an exemplary embodiment, fig. 12 and table 4 below demonstrate, by several samples, the relationship of the tendon itself to the tendon reinforced by the disclosed composite scaffold, which is consistently stronger and able to withstand greater forces at similar extensions than the tendon alone.

TABLE 4

Another alternative form of the disclosed composite stent is to utilize tubular spacers, whether warp or weft knitted, which can be used as "sheaths" over autografts, allografts, or repaired tendons or ligaments. One method of producing the tubular spacer is to take a flat spacer fabric and then attach the opposing edges by sewing, heat sealing or other means to create a tube, as illustrated in fig. 18. Alternatively, a custom-made circular knitting machine may be used to knit the tubular spacer fabric without connecting seams. Another alternative method of manufacturing the tubular spacer is to weave the structure by a method of 3D circular woven preforms, the method and structure being shown in fig. 14.

An alternative method of manufacturing a textile component as a structure for accommodating a porous matrix is to 3D print the structure with an elastic or inelastic material and then fill the structure with the porous matrix.

Alternatively, both the structure and the substrate may be 3D printed from one or more materials, either as separate but combined entities, or as a single entity that provides strength, porosity, and resistance to compression.

In an embodiment, a stent includes a composite structure having a textile outer covering for providing strength and a 3D printed internal support structure for providing compression resistance. Such stents may be rectangular or tubular in shape. Braiding can be used as a cost-effective method of producing tubular structures. By braiding on the 3D printed internal support structure insert, continuous space is provided for tissue ingrowth. Polymer fibers may be provided that are longitudinally braided into an outer braided structure to further adjust the tensile properties of the stent.

Examples of the invention

EXAMPLE 1 textile support manufacture

A 75 denier 30 filament poly L-lactic acid (PLLA) yarn was produced for use in making the scaffold fabric. Warp beams were produced for use in the production of fabrics by a Karl Meier Double Needle bed Machine (Karl Mayer Double Needle Bar Machine). A 5mm wide fabric having 6 wales across its width and a 23mm wide fabric having 27 wales across it were produced, i.e., using a No. 22 needle bed. The two surface layers were separated in the Z direction by spacer yarns to make a 2mm thick fabric. The fabric was scrubbed in an ultrasonic bath with a mixture of deionized water and isopropyl alcohol and dried.

EXAMPLE 2 ACL enhancement/repair device fabrication

A 0.6% collagen solution (by weight) was prepared using low molarity acetic acid and powdered bovine collagen type 1. This solution was blended and treated under vacuum to remove entrapped air bubbles. The cavity of the stainless steel mold was filled with a small amount of collagen solution as shown in figure 5A. The textile support from example 1 (a 26cm long and 5mm wide sample) was placed into the mold with the textile face parallel to the bottom of the cavity and clamps were used at each end to hold the textile and prevent movement. Additional collagen solution is filled into the cavity with the textile, thereby completely submerging the textile in the collagen solution. The mould with the textile and collagen solution is vacuum treated to remove the remaining air inside the textile in order to completely fill the textile with said solution.

The mold was then placed in a SP Scientific advance Plus Lyophilizer (SP Scientific advance Plus Lyophilizer) and the sample was lyophilized, the lyophilization process decreasing the Lyophilizer interior from room temperature to-55C over a period of 2 hours. The textile filled with the dry, highly porous and low density collagen matrix is removed from the mold cavity and placed on a wire rack in a sealed chamber. The formaldehyde and ethanol solution was poured into the tray and the tray was placed under the shelf of the product and the chamber door was sealed. The steam from the solution crosslinks the collagen within the textile. After 2 hours, the trays were removed and the product was moved to an aerated chamber where clean, dry air was pumped through and out of the chamber, effectively terminating the crosslinking process. The final device is suitable for ACL enhancement or repair.

EXAMPLE 3 manufacture of a rotator cuff Reinforcement/repair device

A mould suitable for holding 23mm wide fabric was used to impregnate a 50mm x 23mm piece of fabric from example 1, following the method of example 2, but using the mould of figure 5B. The final device is suitable for rotator cuff reinforcement or repair.

EXAMPLE 4 production of matrix Material

Example 5 demonstration of tendon Reinforcement

The deep flexor tendons of pigs were obtained from a local slaughterhouse. The composite stent device from example 1 was doubled over on the tissue and cross-sutured at one end with #2 sutures. A tensile tester was used to simulate the graft preparation station. The cross-stitched ends were secured in the upper jaw of the tensile tester. Pretensioning is achieved by loading both ends of the composite stent to the appropriate force and securing the lower jaw. The construct was cycled to 3.75mm extension and back to zero. The performance data is shown in table 3 below and demonstrates the ability of the composite stent to be pre-tensioned to control the reinforcement provided by the stent.

TABLE 4

While the size of the composite stents described herein may vary depending on the intended application, it is contemplated that the stents may have a length of up to 1000mm and a width of 3mm to 1000mm to accommodate different soft tissue sizes and applications. Further, at the ends of the stent, the width may taper to the suture width.

The present disclosure will be more fully understood from the following description, which should be read in conjunction with the accompanying drawings. In the present specification, like numbers refer to like elements throughout the various embodiments of the disclosure. The skilled artisan will readily appreciate that the methods, apparatus, and systems described herein are merely exemplary and that changes may be made without departing from the spirit and scope of the present disclosure. The terms "comprises," "comprising," and/or their respective plural forms are open-ended and encompass a listed moiety and may encompass additional moieties not listed. The term "and/or" is open-ended and includes one or more of the listed components and combinations of the listed components.

In various places throughout this specification, numerical values are disclosed in groups or ranges. It is specifically intended that the specification includes each individual subcombination of the members of such groups and ranges, as well as any combination of the various endpoints of such groups or ranges. For example, integers in the range of 0 to 40 are specifically intended to disclose 0, 1, 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, and 40 individually, and integers in the range of 1 to 20 are specifically intended to disclose 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20 individually. Real numbers are intended to have similar inclusiveness, including values up to at least three decimal places.

The foregoing description has been presented for purposes of illustration. It is not exhaustive and is not limited to the precise form or embodiment disclosed. Modifications and adaptations will be apparent to those skilled in the art upon consideration of the specification and practice of the disclosed embodiments.

As used herein, the indefinite article "a" or "an" means "one or more. "similarly, unless the use of plural terms is clear in a given context, it does not necessarily mean plural. Unless expressly stated otherwise, words such as "and" or "mean" and/or ". Further, since numerous modifications and changes will readily occur to those skilled in the art upon studying the disclosure, it is not desired to limit the disclosure to the exact construction and operation shown and described, and accordingly all suitable modifications and equivalents may be resorted to, falling within the scope of the disclosure.

While several embodiments of the disclosure have been illustrated in the accompanying drawings, it is not intended that the disclosure be limited to those embodiments, but is intended to be as broad in scope as the art will allow and that the specification be read likewise. Any combination of the above embodiments is also contemplated and is within the scope of the appended claims. Moreover, although illustrative embodiments have been described herein, the scope of any and all embodiments includes equivalent elements, modifications, omissions, combinations (e.g., of aspects across various embodiments), adaptations and/or alterations as would be appreciated by those in the art based on the present disclosure. The limitations in the claims are to be interpreted broadly based on the language employed in the claims and not limited to examples described in the present application. The examples should be construed as non-exclusive. Further, the steps of the disclosed methods may be modified in any manner, including by reordering steps and/or inserting or deleting steps. Accordingly, the specification and examples are to be considered as illustrative only, with a true scope and spirit being indicated by the following claims and their full scope of equivalents.

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