Replacement heart valve with reduced sutures

Abstract

A heart valve replacement device comprises: a stent having a first end, a second end, an outer surface and an inner surface, the inner surface defining an inner cavity; and a valve disposed within the inner cavity of the stent, the valve being formed from a single piece of tissue, the valve having an outer surface, an inner surface and a thickness between the outer surface and the inner surface, the valve comprising at least three leaflets, wherein the valve is attached to the stent with a minimum of sutures. The leaflets are formed as curved surfaces.

Description

[0001] This divisional application is a divisional application based on the Chinese patent application with application number 201880076903.4, application date September 12, 2018, and invention name “Replacement heart valve with reduced sutures”. Technical Field

[0002] The present disclosure relates to a novel and advantageous heart valve formed from a biological material. Background Art

[0003] The background description provided herein is to generally present the context of the present disclosure. To the extent described in this background section, the work of the presently named inventors and aspects of the description that may not constitute prior art at the time of filing are neither explicitly nor implicitly admitted to be prior art to the present invention.

[0004] When a patient has a condition such as a congenital heart defect or valvular heart disease, it may be necessary to replace a natural heart valve. A diseased heart valve may cause backflow (where the valve does not function correctly and blood flows in the direction opposite to the normal direction of flow), and / or stenosis (where the valve has narrowed in some cases due to calcification of the valve, such as some blockages of the valve of plaque or inflammation). The heart valve can be replaced by surgical repair, or the valve can be deployed relative to the natural heart valve by a transcatheter method. A transcatheter valve replacement device generally includes a tissue leaflet, which is attached to an expandable or self-expanding stent structure that is curled onto a catheter for deployment. The stent is advanced to the position of the problematic heart valve, where the stent expands or expands by a balloon or other device. Once located in the valve, the blood flow and muscle of the heart will cause the tissue leaflet to open and close. When manufacturing these transcatheter valve replacement devices, one of the most time-consuming and labor-intensive parts of the process is to firmly attach the leaflet to the stent. The leaflet is attached to the stent with hundreds of sutures, which are usually sutured by hand by skilled workers. Typically, each valve replacement device may have anywhere from 150 sutures to 300 sutures or more.In order to reduce the cost and time required to manufacture these devices, it is desirable to significantly reduce the number of sutures required to securely attach tissue to an expandable or self-expanding stent. Summary of the invention

[0005] The following presents a simplified summary of one or more embodiments of the present disclosure in order to provide a basic understanding of these embodiments. This summary is not an extensive overview of all contemplated embodiments, and is neither intended to identify key or important elements of all embodiments nor to delineate the scope of any or all embodiments.

[0006] In some embodiments, a heart valve replacement device of the present disclosure includes a stent having a first end, a second end, an outer surface and an inner surface, the inner surface defining an inner cavity; and a valve arranged in the inner cavity of the stent, the valve being formed by a single piece of tissue, the valve having an outer surface, an inner surface and a thickness between the outer surface and the inner surface, the valve comprising at least three leaflets, wherein the valve is attached to the stent with less than forty sutures. In some embodiments, the valve is attached to the stent with less than thirty sutures. In some embodiments, the valve is attached to the stent with less than twenty sutures. In some embodiments, the valve is attached to the stent with between three and twenty sutures. In some embodiments of the present disclosure, the valve has a main body portion connected to the leaflets. In at least one embodiment, the thickness of the main body portion is different from the thickness of the leaflets. In some embodiments, the valve has a cuff portion that can be connected to the main body portion of the valve. In at least one embodiment, the thickness of the cuff portion is different from the thickness of the main body portion. In at least one embodiment, the thickness of the cuff portion is different from the thickness of the leaflets. In at least one embodiment, the cuff portion can expand relative to the stent from a first position to a second position. The stent of the heart valve replacement device can have at least one attachment feature. In some embodiments, at least one suture connects the stent to the valve at an attachment feature.

[0007] In some embodiments of the present disclosure, a replacement heart valve comprises a plurality of leaflets; and a main body portion connected to the leaflets, wherein the main body portion and the leaflets are formed from a single piece of tissue material. The replacement heart valve may include a cuff portion connected to the main body portion. In some embodiments, the thickness of the leaflets may be different from the thickness of the cuff portion. In some embodiments, the thickness of the main body portion may be different from the thickness of the cuff portion. A heart valve according to claim 14, wherein the tissue material is artificial tissue. In some embodiments, the tissue material is a biological material. In some embodiments, the valve comprises an attachment point located on at least the main body portion of the heart valve.

[0008] In some embodiments, a method for manufacturing a heart valve replacement device includes forming a valve from a single piece of tissue material, the valve having a main body and at least three leaflets, wherein the at least three leaflets are connected to the main body; inserting the valve formed by the single piece of material into the lumen of a stent; and fixing the valve to the stent with less than forty sutures. In some embodiments, the valve is fixed to the stent with less than thirty sutures. In some embodiments, the valve is fixed to the stent with less than twenty sutures. In some embodiments, the valve is fixed to the stent with between three and twenty sutures. In some embodiments, the step of forming the valve includes inserting the single piece of tissue material into a mold. The mold may have a lower portion (primary mold) and an upper portion (secondary mold). In some embodiments, the mold has a locking member for locking the position of the upper portion relative to the lower portion. In some embodiments, a spacer is inserted between the single piece of tissue material and at least one of the upper portion and the lower portion. In some embodiments, a cross-linking treatment is applied to the single piece of tissue material when the single piece of tissue material is in the mold. In some embodiments, the tissue material may be an artificial tissue or a biological material. In some embodiments, the single piece of tissue material has different thicknesses from one end of the material to the other end. In some embodiments, the single piece of tissue material is cut from one end to the other end of the single piece of tissue material using a cutting device to change the thickness from one end to the other end of the single piece of tissue material.

[0009] Although multiple embodiments are disclosed, other embodiments of the present disclosure will become apparent to those skilled in the art from the following detailed description which shows and describes illustrative embodiments of the present invention. As will be appreciated, the various embodiments of the present invention are capable of modification in various obvious respects, all without departing from the spirit and scope of the present disclosure. Therefore, the drawings and detailed description are to be regarded as illustrative rather than restrictive. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] While the specification concludes with claims particularly pointing out and distinctly claiming the subject matter believed to form the various embodiments of the present disclosure, it is believed that the invention will be better understood from the following description taken in conjunction with the accompanying drawings, in which:

[0011] Figure 1 is a perspective view of a heart valve replacement device including a heart valve disposed relative to a stent structure according to one embodiment of the present disclosure.

[0012] Figure 2 yes Figure 1 A first side view of a heart valve replacement device.

[0013] Figure 3 yes Figure 1A second side view of a heart valve replacement device.

[0014] Figure 4 is from Figure 1 A view of the distal end of a heart valve replacement device.

[0015] Figure 5 is from Figure 1 A view showing the proximal end of a heart valve replacement device.

[0016] Figure 6 is a perspective view of a heart valve replacement device according to one embodiment of the present disclosure, the heart valve replacement device including a heart valve arranged relative to a stent structure.

[0017] Figure 7 is a perspective view of a heart valve according to one embodiment of the present disclosure.

[0018] Figure 8 yes Figure 7 Side view of the heart valve.

[0019] Fig. 9 is from Figure 7 A view of the distal end of a heart valve.

[0020] Fig.10 is from Figure 7 A view of the proximal end of a heart valve.

[0021] Fig.11 is a perspective view of a mold assembly for manufacturing a heart valve of the present disclosure according to one embodiment of the present disclosure, the mold assembly having a first mold portion and a second mold portion.

[0022] Fig.12 yes Fig.11 A top view of a first mold portion of a mold assembly.

[0023] Fig.13 yes Fig.11 A bottom view of the second mold portion of the mold assembly.

[0024] Fig.14 yes Fig.11 A top view of the second mold part.

[0025] Fig.15 is a schematic diagram of a cutting assembly for manufacturing a heart valve from biological material according to one embodiment of the present disclosure. Specific embodiments

[0026] The present disclosure relates to replacement heart valves for the mitral valve, tricuspid valve, aortic valve or pulmonary valve of the heart. In some cases, the replacement heart valve can be arranged within the native valve so that a portion of the replacement heart valve or a portion of the device (e.g., a stent attached to the replacement heart valve) is adjacent to the native heart valve.

[0027] In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of some embodiments. However, it will be appreciated by those of ordinary skill in the art that some embodiments may be practiced without these specific details. In other cases, well-known methods, processes, components, units and / or circuits are not described in detail to avoid obscuring the discussion.

[0028] Figure 1-5 One embodiment of a heart valve replacement device 100 is shown, which includes a stent 102 having a proximal end 104 and a distal end 106, and a valve 108 disposed within the lumen of the stent and connected to the stent 102 at a position distal to the proximal end 104. Although the application uses the terms "proximal" and "distal" in the same relative manner with respect to the devices shown in the figures, within the scope of the present invention, "proximal" and "distal" can be interchanged with "distal" and "proximal" in other embodiments. The stent 102 can have any configuration and can be expanded from a first position to an expanded position. As shown in FIG. Figure 1-5 As shown, the stent 102 is in an expanded position. The stent 102 can be self-expanding, balloon-expandable, or otherwise expandable from a first position to a second position. The stent 102 can have an outer surface 110 and an inner surface 112, wherein the inner surface 112 defines a lumen 114 on at least a portion of the stent. In at least one embodiment, the outer surface 110 can have a layer of a coating material. In at least one embodiment, the inner surface 112 can have a layer of a coating material to reduce friction with the valve 108. The stent 102 can have one or more attachment features 115 on the outer surface 110, the inner surface 112, or both, for connecting the valve 108 to the stent 102. In at least one embodiment, at least one of the attachment features 115 can have a radiopaque marker or coating for imaging purposes to help position the heart valve replacement device 100 within the vascular system.

[0029] The valve 108 can be attached to the stent 102 at one or more attachment features 115 using sutures or using other mechanical means. The valve 108 can also be attached to the stent 102 using an adhesive. The valve 108 can be attached to the stent 102 at the attachment features using an adhesive. The valve 108 can also be attached to the stent 102 by a polymer attachment layer. In some embodiments, the valve 108 can be attached using one or more of sutures, other mechanical attachment means, an adhesive, or a polymer attachment layer.

[0030] In some embodiments, valve 108 can be made of a single piece of tissue material. In some embodiments, the tissue material can be a biomaterial. In some embodiments, the tissue material can be a cross-linked collagen-based biomaterial, which includes a cell-free or cell-free tissue selected from the group consisting of heart tube tissue, heart tissue, heart valve, aortic root, aortic wall, aortic leaflet, pericardial tissue, connective tissue, dura mater, skin tissue, vascular tissue, cartilage, pericardium, ligament, tendon, blood vessel, umbilical cord tissue, bone tissue, fascia, and submucosal tissue and skin. In some embodiments, the tissue material is an implantable biomaterial, such as the biomaterial disclosed in the U.S. Patent No. 9,205,172 entitled "Implantable Biomaterial and Method of Producing Same" filed on December 21, 2005, which is incorporated herein by reference as a whole. In some embodiments, the tissue material can be an artificial tissue. In some embodiments, the artificial tissue can include a single-piece molded or shaped polymer. In some embodiments, the artificial tissue can include polytetrafluoroethylene, polyethylene terephthalate, other polymers and other polymer coatings.

[0031] The valve 108 can have a proximal end 116 and a distal end 118. The valve 108 can have an outer surface 122 and an inner surface 124, wherein the inner surface 124 defines an inner cavity 125. The valve 108 can have at least one leaflet 126. In some embodiments, the valve 108 includes at least three leaflets 126 connected to each other. In some embodiments, the valve 108 can include three leaflets 126. In some embodiments, the valve 108 can include two leaflets 126. In some embodiments, the valve 108 can include four leaflets 126. In some embodiments, the valve 108 can include more than four leaflets 126. The leaflets 126 can each form a cup-shaped concave portion 128. Therefore, the leaflets 126 are not flat pieces of tissue, but form a curved shape. Studies such as those disclosed in an article entitled "Flat or Curved Pericardial Aortic Valve Cusps: A Finite Element Study" published by Khee Hiang Lim, Johanes Candral, Joon Hock Yeo and Carlos MG Duran in Journal of Heart Valve, Vol. 13, No. 5 (September 2004), which is hereby incorporated by reference in its entirety, have shown that three-dimensional leaflet cusps similar to those shown herein have approximately 35% stress reduction compared to flat tissue sheets. The leaflets 126 are positioned adjacent to each other at commissures 130. The valve 108 may also include a main body portion 132 connected to at least the leaflets 126. In some embodiments, the main body portion 132 may be positioned distally relative to the leaflets. In at least one embodiment, the valve 108 may have an annular region 138 at the distal end 112. The annular region 136 may be connected to the main body portion 132. In some embodiments, the valve 108 can have a cuff portion 140 attached to the annular region 138. The cuff portion 140 can have an outer surface 142 and an inner surface 144. The cuff portion 140 can extend proximally on at least a portion of the main body portion 132. In some embodiments, the cuff portion 140 can be expandable to form a seal against natural tissue. In some embodiments, the valve 108 can further include a first edge 146 and a second edge 147, which form a seam 148 extending axially along the valve 108. In some embodiments, the seam 148 can be joined with some adhesives or other chemical processes. In some embodiments, the first edge 146 and the second edge 147 can be joined across the seam 148 by a suture.In some embodiments, the first edge 146 and the second edge 147 can be joined across the seam 148 by a first suture near the proximal end of the seam 148 and a second suture near the distal end of the seam 148. In some embodiments, the first edge 146 and the second edge 147 can be joined across the seam 148 by a first suture near the proximal end of the seam 148, a second suture near the distal end of the seam 148, and at least one suture between the first suture and the second suture. In other embodiments, the seam 148 can form a relatively small gap between the first edge 146 and the second edge 147 without compromising the performance of the valve. In some embodiments, the leaflet 126 can have a thickness between the outer surface 122 and the inner surface 124 that is less than the thickness of the main body region.

[0032] The valve 108 can be arranged relative to the stent 102 such that the outer surface 122 of at least a portion of the valve 108 abuts the inner surface 112 of the stent 102. Figure 3 As shown, valve 108 can be attached to stent 102 with sutures 150. Sutures 150 can be used to connect cuff portion 140 to one of body portion 132 or stent 102. Sutures 150 can be used to connect body portion 133 to stent 102. Sutures 150 can be used to connect commissures 130 to stent 102. In at least one embodiment, sutures 150 can be used to connect commissures 130 to stent 102 at attachment points 115. In some embodiments, at least outer surface 122 of body portion 132 abuts inner surface 112 of stent 102. In some embodiments, in the first position, inner surface 144 at cuff portion 140 abuts outer surface 110 of stent 102. In some embodiments, in the first position, inner surface 144 at cuff portion 140 abuts outer surface 110 of stent 102. In some embodiments, in the first position, inner surface 144 at cuff portion 140 abuts outer surface 110 of stent 102. Figure 1-5 In the second expanded position shown, the inner surface 144 of the cuff portion 140 abuts the outer surface 110 of the stent 102. In some embodiments, when deployed in a native valve, and due to fluid flow of blood in the valve or blood pressure in the vessel, the cuff portion 140 can expand or move away from the outer surface 110 of the stent 102 to form a seal against the native heart structure.

[0033] At least in part because the valve is formed from a single piece of material, the valve can be attached to the stent with minimal sutures. Figure 6An embodiment of a heart valve replacement device 600 is shown in which a valve 608 is attached to a stent 602 with only fifteen sutures 650. The valve 608 is attached to the stent 602 at least at an attachment feature 615. In some embodiments, the attachment feature 615 can be aligned with the commissure 630 between the leaflets 626 of the valve 608. The valve 608 can be attached at the attachment feature 615 using a first set of sutures 650a. In at least one embodiment, the first set of sutures 650a includes three sutures 650. The valve 608 can be further attached with a second set of sutures 650b at or near the end of the stent. In some embodiments, the sutures of the second set of sutures 650b can connect the cuff portion 640 of the valve 608 to the stent 602. In some embodiments, the sutures of the second set of sutures 650b can connect the cuff portion 640 to the main body portion 632 overlapped by the cuff portion 640. In at least one embodiment, the second set of sutures 650b can be a continuous set of sutures that cross the circumference of the valve 608 on the outer surface 622 of the valve near the distal end of the stent. In at least one embodiment, the second set of sutures 650b can be a continuous set of sutures that cross the circumference of the valve at the edge 655 at the distal end 606 of the stent 602. In at least one embodiment, the second set of sutures 650b includes nine sutures 650. In at least one embodiment, the valve 608 can be attached with a third set of sutures 650c. The third set of sutures 650c can be axially positioned between the first set of sutures 650a and the second set of sutures 650b. The third set of sutures 650c can connect the main body 632 to the stent 602. The third set of sutures 650c can include three sutures 650. In some embodiments, the third set of sutures 650c can each be axially aligned with the first set of sutures 650a. In some embodiments, the third set of sutures 650c can each be radially offset and distally positioned from the sutures of the first set of sutures 650a. In at least one embodiment, at least one suture in the third set of sutures 650c can connect tissue on both sides of the seam 648 of the valve 602. Other suture arrangements are also contemplated by the present invention.

[0034] Figure 7-10An embodiment of valve 700 is shown, which can be formed into a cylindrical structure before inserting a stent structure or other structures for deployment to a natural valve, rather than being formed into a flat tissue sheet before inserting a stent structure. In some embodiments, the tissue material can be an artificial tissue. In some embodiments, the tissue material can be a biomaterial. In some embodiments, the tissue material can be a cross-linked collagen-based biomaterial, which includes a cell-free or cell-free tissue selected from the group consisting of heart tube tissue, heart tissue, heart valve, aortic root, aortic wall, aortic leaflet, pericardial tissue, connective tissue, dura mater, skin tissue, vascular tissue, cartilage, pericardium, ligament, tendon, blood vessel, umbilical cord tissue, bone tissue, fascia, and submucosal tissue and skin. In some embodiments, the tissue material is an implantable biomaterial, such as the biomaterial disclosed in U.S. Patent No. 9,205,172, entitled "Implantable Biomaterial and Method of Producing Same", filed on December 21, 2005, which is incorporated herein by reference in its entirety. The valve 700 has a proximal end 702 and a distal end 704. The valve 700 can have an outer surface 706 and an inner surface 710, wherein the inner surface 710 defines an inner cavity 712. In some embodiments, the valve 700 includes a main body portion 714 and at least three leaflets 716 connected to the main body portion 714. In some embodiments, the valve 700 can include three leaflets 716. In some embodiments, the valve 700 can include four leaflets 716. In some embodiments, the valve 700 can include more than four leaflets 716. The leaflets 716 can have a curved portion 718. The curved portion 718 can form a cup-shaped concave portion. The leaflets 716 are positioned adjacent to each other at the commissure 720. In at least one embodiment, the valve 108, the main body portion 714 can have an annular region 722 at the distal end 704. In some embodiments, the valve 700 can have a cuff portion 724 attached to the annular region 722. The cuff portion 724 can have an outer surface 726 and an inner surface 728. The cuff portion 724 can extend proximally over at least a portion of the body portion 714. In some embodiments, the cuff portion 724 can be expandable to form a seal against native tissue.

[0035] In some embodiments, methods for making a valve of the present disclosure may include inserting a sheet of tissue into a mold to form leaflets and a cuff, and then, in some embodiments, forming the molded tissue into a torus. Figure 11-14One embodiment of a mold 1100 is shown. The mold can include an upper portion 1120 and a lower portion 1122. The upper portion 1120 and the lower portion 1122 can be separate components or can be connected to each other. In at least one embodiment, the upper portion 1120 and the lower portion 1122 can be formed as a clamshell structure, so that the upper portion 1120 and the lower portion 1122 are pivotably connected to each other at at least one hinge point. Fig.11 The mold in the closed position is shown. In at least one embodiment, the upper part 1120 and the lower part 1122 can be fixedly connected to each other in the closed position by a locking device 1123. In one embodiment, the locking device 1123 can include a first hole 1124 in the upper part 1120 and a second hole 1126 in the upper part 1120, and a first hole 1128 in the lower part 1122 and a second hole 1130 in the lower part 1122, and the first hole 1128 and the second hole 1130 can be aligned with the first hole 1124 and the second hole 1126. Bolts can be inserted into the first holes 1124, 1128 and the second holes 1128, 1138 and tightened with nuts. The locking device 1123 can also include a clamp that pushes the upper part 1120 and the lower part 1122 together. The present invention also contemplates other devices for locking the upper part 1120 in a position in the closed position relative to the lower part 1122. When locking device 1123 is engaged, a desired pressure may be applied to any tissue positioned within the mold.

[0036] The lower portion 1122 of the mold 1100 is Fig.12 As shown in FIG. 1 , the lower portion 1122 includes at least one leaflet region 1134, a commissure region 1136 between adjacent leaflet regions 1134, and a main body region 1138 connected to the commissure region 1136 and the leaflet region 1134. Fig.12As shown, the lower portion 1122 has three lobule regions 1134. In some embodiments, the lower portion 1122 can have two lobule regions 1174. In some embodiments, the lower portion 1122 can have four lobule regions 1134. In some embodiments, the lower portion 1122 can have more than four lobule regions 1134. In at least one embodiment, the lobule regions 1134 can include a protrusion forming feature. The lobule region 1134 can include at least one protrusion forming section 1135 and a recessed region 1137. At least one protrusion forming section 1135 can have a curved outer surface 1140, a first curved edge 1142 at a first end 1144, and a second curved edge 1146 adjacent to the adjacent commissure region 1136 and extending from the first end 1144 to the second end 1148. The first curved edge 1142 can form a parabola. The first curved edge 1142 and the second curved edge 1146 can intersect at a point 1150. As shown in FIG. Fig.12 As shown, the leaflet region 1134 has two projection-forming sections 1135. The first curved edge 1142 of the first projection-forming section intersects the first curved edge 1142 of the second projection-forming section at a point 1152. The point 1152 can be positioned above the recessed region 1137. The first curved edges 1142 each form a parabola. The second curved edge 1146 of the first projection-forming section 1135 intersects the second curved edge 1146 of the second projection-forming section 1135 at a point 1144. The second curved edge 1146 of the first projection-forming section 1135 and the second curved edge 1146 of the second projection-forming section 1135 can form a parabola. In some embodiments, the shape of the leaflet region 1134 can be similar to the leaflet template described in the disclosure of U.S. Patent No. 6,491,511, entitled "Mold to Form Stent-Less Replacement Heart Valves from Biological Membranes," filed on October 14, 1999, which is incorporated herein by reference. The body region 1138 can be connected to the commissure region 1136. The body region 1138 can be generally flat and extend outwardly from the lower portion 1122. In some embodiments, the lower portion 1122 has locking flanges 1160, 1162 extending outwardly on either side of the leaflet region 1134, wherein the first hole 1128 and the second hole 1130 are in each corresponding locking flange 1160, 1162.

[0037] The upper portion 1120 of the mold 1100 is Figure 13-14 As shown in FIG. 1 , the upper portion 1120 includes at least one leaflet region 1174 and a commissure region 1176 between adjacent leaflet regions 1174. Fig.13As shown, the upper portion 1120 has three lobule regions 1174. In some embodiments, the upper portion 1120 can have two lobule regions 1174. In some embodiments, the upper portion 1120 can have four lobule regions 1174. In some embodiments, the upper portion 1120 can have more than four lobule regions 1174. In at least one embodiment, the lobule regions 1174 can have concave forming features that cooperate with corresponding convex forming features on the lobule region 1134 of the lower portion 1122. The lobule region 1174 can include at least one concave forming section 1178 and a second section 1179. When in the closed position, the at least one concave forming section 1178 of the upper portion 1120 cooperates with the at least one convex forming section 1136 of the lower portion 1122. At least one concave forming section 1178 can have a curvilinear surface 1180, a first curvilinear edge 1182 at a first end 1184, and a second curvilinear edge 1186 that abuts the adjacent joining area 1178 and extends from the first end 1184 to the second end 1188. In some embodiments, when the mold is in a closed position, the second end 1148 of the lower portion 1148 is aligned with the second end 1188 of the upper portion. The first curvilinear edge 1182 can form a parabola. The first curvilinear edge 1182 and the second curvilinear edge 1186 can intersect at a point 1190. The first curvilinear edge 1182 of the first concave forming section intersects the first curvilinear edge 1182 of the second concave forming section at a point 1192. The point 1192 can be located adjacent to the second section 1179. The first curvilinear edges 1182 each form a parabola. The second curvilinear edge 1186 of the first concave forming section intersects the second curvilinear edge 1186 of the second concave forming section at a point 1194. The second curved edge 1186 of the first concave forming section and the second curved edge 1186 of the second concave forming section can form a parabola. In some embodiments, the shape of the leaflet region 1174 can be similar to the leaflet template described in the disclosure of U.S. Patent No. 6,491,511, entitled "Mold to Form Stent-Less Replacement Heart Valves from Biological Membranes", filed on October 14, 1999, which is incorporated herein by reference. In some other embodiments, the main body region can be connected to the commissure region 1176 and the leaflet region 1174. The main body region can be connected to the commissure region 1176. The main body region 1138 can be substantially flat and extend outward from the commissure region 1176. When in the closed position, the main body region can overlap at least a portion of the main body region of the lower portion 1122. The main body region of the upper portion 1120 can be relatively shorter than the main body region of the lower portion.The edges of the main body region of the upper portion 1120 can determine the edges of the annular region of the formed valve. In some embodiments, the upper portion 1120 has locking flanges 1196, 1198 extending outwardly on either side of the leaflet region 1174, wherein the first hole 1124 and the second hole 1126 are located in each corresponding locking flange 1196, 1198. The upper portion 1120 can also have a plurality of channels 1199 adjacent to the second end 1188.

[0038] In some embodiments, the mold can be formed of metal, polymer, or ceramic material. In some embodiments, the mold can be printed using additive manufacturing so that the mold can be created individually for a patient and a valve formed for that patient.

[0039] In at least one embodiment, the tissue piece can be inserted into the mold 1100 between the lower part 1122 and the upper part 1124. Then, the locking device 1123 can be engaged so that the lower part 1122 and the upper part 1124 are fixed in the closed position. In at least one embodiment, wherein the tissue piece is formed by a biomaterial, a cross-linking solution glutaraldehyde can be applied to the tissue piece to promote the cross-linking of the tissue. In some embodiments, the cross-linking solution comprises glutaraldehyde. In some embodiments, the cross-linking solution can be injected into the tissue, and in other embodiments, the cross-linking solution can be soaked, impregnated or penetrated into the tissue. In some embodiments, glutaraldehyde can be injected into the tissue, and in other embodiments, the glutaraldehyde can be soaked, impregnated or penetrated into the tissue. In at least one embodiment, the mold 1100 in which the tissue piece is inserted into the mold is immersed in the cross-linking solution, and the cross-linking solution can include glutaraldehyde. In at least one embodiment, when the tissue is partially cross-linked, the upper part 1124 can be removed from the mold 1100, and once the tissue is completely cross-linked, the tissue can be removed from the mold 1100. In at least one embodiment, upper portion 1124 is removed from mold 1100 while mold 1100 remains immersed in the cross-linking solution or glutaraldehyde. In at least one embodiment, a spacer or spacer layer can be inserted between lower portion 1122 and one of upper portions 1124 before glutaraldehyde is applied to the tissue piece.

[0040] In some embodiments, the valve can be made of a single piece of material having different thicknesses. In some embodiments, a method for making a tissue sheet for a valve can include using Fig.15The cutting system 1500 shown. The cutting system 1500 can have a first tissue retainer 1502 and a second tissue retainer 1504, which apply tension to a tissue sheet 1505 held by and between the two tissue retainers 1502, 1504. In at least one embodiment, one of the first tissue retainer 1502 and the second tissue retainer 1504 can be driven by a servo motor to move the tissue in a first direction. In at least one embodiment, each of the first tissue retainer 1502 and the second tissue retainer 1504 is driven by a servo motor. In this embodiment, the servo motor of the first tissue retainer 1502 moves synchronously with the servo motor of the second tissue retainer to maintain a predetermined constant tension in the tissue sheet 1505. In at least one embodiment, the second tissue retainer 1504 can be positioned perpendicular to the first tissue retainer 1502. Roller 1506 can be positioned between the first tissue retainer 1502 and the second tissue retainer 1504. In some embodiments, the cutting system 1500 may have a roller 1506 driven by a motor, which moves the tissue from the first tissue retainer to the second tissue retainer. The roller 1506 may be aligned with the first tissue retainer 1502 in a first direction and aligned with the second tissue retainer 1504 in a second direction. In at least one embodiment, the roller 1506 positions the tissue relative to the cutting blade 1508. The cutting system 1500 may have a blade 1508 operably connected to a motor drive shaft, which can controllably move the blade toward the roller 1506 (and therefore toward the tissue) or away from the blade according to the desired thickness of the tissue. In at least one embodiment, the blade 1508 is connected to a servo motor driving a ball screw to maintain precise distance accuracy. An operator or computer instruction can guide the user to move the blade toward or away from the tissue, thereby causing the tissue to have a desired and variable thickness along the sheet. In at least one embodiment, the blade is an oscillating blade that can oscillate at a high frequency, such as a frequency of up to 3,500 cycles per minute. In some embodiments, as the tissue moves past the blade 1508, the undesirable tissue 1510 falls off the remaining tissue connected to the second tissue holder 1504, thereby essentially dividing the tissue into two parts. Then, the desired tissue that remains connected to the tissue holders 1502, 1504 can be cut into pieces for insertion into a mold and then forming a valve. In other embodiments, as the tissue moves past the blade 1508, the desired tissue 1510 used to form a valve falls off the remaining tissue connected to the second tissue holder 1504.

[0041] As used herein, the term "substantially" or "generally" refers to the complete or almost complete degree or grade of an action, characteristic, property, state, structure, project or result. For example, an object that is "substantially" or "generally" closed will mean that the object is completely closed or almost completely closed. The degree of the precise allowable deviation from absolute completeness may depend on the specific context in some cases. However, in general, approaching completion will have substantially the same overall result as obtaining absolute and complete completion. When used in a negative sense, the use of "substantially" or "generally" is equally applicable to referring to a complete or almost complete lack of action, characteristic, property, state, structure, project or result. For example, an element, combination, embodiment or composition that is "substantially free of" or "generally free of" a component or element can actually still include such items, as long as it generally has no measurable effect.

[0042] As used herein, any reference to "one embodiment" or "an embodiment" means that a particular element, feature, structure, or characteristic described in conjunction with the embodiment is included in at least one embodiment. The phrase "in one embodiment" appearing in various places in the specification does not necessarily all refer to the same embodiment.

[0043] As used herein, the terms "comprises," "includes," "has," or any other variations thereof are intended to encompass non-exclusive inclusions. For example, a process, method, article, or device that includes a series of elements is not necessarily limited to those elements, but may include other elements that are not explicitly listed or inherent to such a process, method, article, or device. In addition, unless explicitly stated to the contrary, "or" refers to an inclusive or rather than an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist).

[0044] In addition, "a" or "an" is used to describe the elements and components of the embodiments herein. This is done only for convenience and to give a general description. The description should be understood to include one or at least one, and the singular also includes the plural, unless otherwise clearly indicated.

[0045] Additionally, the drawings depict the preferred embodiments for purposes of illustration only. One skilled in the art will readily recognize from the discussion herein that alternative embodiments of the structures and methods shown herein may be employed without departing from the principles described herein.

[0046] After reading this disclosure, those skilled in the art will appreciate additional alternative structural and functional designs for the devices described herein. Thus, although specific embodiments and applications have been shown and described, it should be understood that the disclosed embodiments are not limited to the precise configurations and components disclosed herein. Various modifications, changes and variations that will be apparent to those skilled in the art may be made to the arrangement, operation and details of the methods and apparatus disclosed herein without departing from the spirit and scope defined in the appended claims.

[0047] Although the systems and methods described herein have been described with reference to some exemplary embodiments, these embodiments are not limiting and are not necessarily mutually exclusive, and it is contemplated that specific features of various embodiments may be omitted or combined for use with features of other embodiments while remaining within the scope of the invention. Any feature of any embodiment described herein may be used in any embodiment and may be used with any feature of any other embodiment.

Claims

1. A heart valve replacement device, comprising: a stent having a first end, a second end, an outer surface, and an inner surface, the inner surface defining a lumen; as well as A one-piece valve disposed within the lumen of the stent and attached to the stent, the one-piece valve being a unitary structure formed from a single sheet of cross-linked, acellular, collagen-based biomaterial, the one-piece valve having an outer surface, an inner surface defining a lumen of the one-piece valve, and a thickness between the outer surface of the one-piece valve and the inner surface of the one-piece valve, the one-piece valve having a valve proximal end and a valve distal end, the one-piece valve comprising: three molded leaflets at the proximal end of the valve, the three molded leaflets formed from the biomaterial, each molded leaflet having a portion formed into a curved three-dimensional shape having a concave profile, each molded leaflet having a thickness; molded commissures formed between adjacent molded leaflets, the molded commissures formed from the biomaterial; and a body portion formed from the biomaterial, the body portion being positioned distally relative to the molded leaflets and extending distally from the molded leaflets and from the molded commissures to the distal end of the valve, the body portion having a thickness, wherein the body portion, the molded commissures and the molded leaflets are integrally formed from a single sheet of the biomaterial, the one-piece valve having a first edge extending from the proximal end of the valve to the distal end of the valve, and a second edge extending from the proximal end of the valve to the distal end of the valve opposite the first edge, the first edge and the second edge forming a seam extending axially from the proximal end of the valve to the distal end of the valve, The one-piece valve is constructed of a single layer, and the molded commissures are connected to the stent by sutures.

2. The heart valve replacement device according to claim 1, wherein: The thickness of the main body portion is different from the thickness of the molded leaflets.

3. The heart valve replacement device according to claim 1, wherein: The body portion of the one-piece valve forms a cuff at the distal end of the valve.

4. The heart valve replacement device according to claim 3, wherein: The cuff is expandable relative to the stent from a first position to a second position.

5. The heart valve replacement device according to claim 1, wherein: The bracket has at least one attachment feature.

6. The heart valve replacement device according to claim 5, wherein: At least one suture attaches the stent to the one-piece valve at an attachment feature.

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