Medical implant preform produced using an inside out flipping method

Abstract

A method of making a medical implant is provided by electrospinning a polymer solution to form a preform around a mandrel. The formed preform distinguishes an inner surface and an outer surface. The formed preform is removed from the mandrel and flipped inside-out resulting in the inner surface of the formed preform becoming the outer surface of the inside-out flipped preform, and the outer surface of the formed preform becoming the inner surface of the inside-out flipped preform. At least part of the inside-out flipped preform forms the medical implant such as e.g. an artificial heart valve, an artificial leaflet, an artificial graft, or an artificial vessel. The products made according to the method of this invention greatly improve the performance and durability of the medical implant.

Claims

1. A method of making a medical implant, comprising: (a) using a polymer solution to form a preform with a desired thickness around the surface of a mandrel, wherein the mandrel has a plurality of three-dimensional convex shapes, wherein the formed preform distinguishes an inner surface and an outer surface; (b) removing the formed preform from the mandrel; and (c) flipping the formed preform inside-out resulting in the inner surface of the formed preform becoming the outer surface of the inside-out flipped preform, and the outer surface of the formed preform becoming the inner surface of the inside-out flipped preform, wherein at least part of the inside-out flipped preform forms the medical implant with a plurality of three-dimensional concave shapes; (d) maintaining the concave shapes of the plurality of three-dimensional concave shapes as the medical implant.

2. The method as set forth in claim 1, wherein the step of forming the preform on the mandrel comprises electro-spinning the polymer solution on the mandrel.

3. The method as set forth in claim 1, wherein the medical implant is an artificial heart valve, an artificial leaflet, an artificial graft, or an artificial vessel.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIGS. 1A-B show according to an exemplary embodiment of the invention a normally open valve (FIG. 1A) and a normally closed valve (FIG. 1B). In this exemplary embodiment a trileaflet heart valve is formed by folding a tubular shape around a support frame with 3 upward posts.

(2) FIGS. 2A-B show according to an exemplary embodiment of the invention a definition of lobe diameter and/or inner diameter compared to outer diameter.

(3) FIGS. 3A-C show that reducing lobe diameter and/or inner diameter compared to outer diameter (as defined in FIGS. 2A-B), results in a thickness gradient along the circumference of the electrospun structure (FIG. 3A). If lobe diameter and/or inner diameter are further reduced compared to outer diameter, the mandrel shape becomes too concave, resulting in fiber bridging (FIG. 3C). These phenomena are known in the art as limitations of the electrospinning process.

(4) FIGS. 4A-B show according to an exemplary embodiment of the invention material distribution before (FIG. 4A) and after flipping inside out (FIG. 4B). Arrows in FIG. 4B indicate compression forces at the inner surface and stretch forces at the out surface. As a result of these forces, the material will have the tendency to bend inward after flipping inside out, which can be beneficial for example when creating a heart valve with a preference for the closed position.

(5) FIGS. 5A-B show according to an exemplary embodiment of the invention material distribution in a closed leaflet before (FIG. 5A) and after flipping inside out (FIG. 5B). Arrows indicate compression forces at the inner surface and stretch forces at the out surface. This indicates that a tubular preform that is flipped inside out has the tendency towards a closed valve configuration, compared to a tendency towards the open configuration for a tubular preform that is not flipped inside out.

(6) FIGS. 6A-B show according to a prior art example in FIG. 6A a mandrel which is used to create the preform shown in FIG. 6B (left). FIG. 6B (right) shows the fiber distribution thickness of the cross-section of the preform. This illustrates limitations known in the art on electrospinning of too concave surfaces, namely fiber bridging and thickness gradients.

(7) FIGS. 7A-C show according to an exemplary embodiment of the invention in FIG. 7A a mandrel which is used to create the preform shown in FIG. 7B (left). FIG. 7B (right) shows the preform once the preform shown in FIG. 7B (left) is flipped inside out. FIG. 7C (right) shows the fiber distribution thickness of the cross-section of the flipped preform (FIG. 7C (left). This way flipping inside out overcomes the problem of bridging, by avoiding spinning on a too concave surface.

(8) FIGS. 8A-B show according to an exemplary embodiment of the invention in FIG. 8A a mandrel which is used to create the preform shown in FIG. 8B (left). FIG. 8B (right) shows the preform once the preform shown in FIG. 8B (left) is flipped inside out. This illustrates that the circumferential profile can be varied along the length of the mandrel and the resulting preform.

(9) FIGS. 9A-B show according to an exemplary embodiment of the invention in FIG. 9A a mandrel which is used to create the preform shown in FIG. 9B (left). FIG. 9B (right) shows the preform once the preform shown in FIG. 9B (left) is flipped inside out.

(10) FIGS. 10A-C show according to an exemplary embodiment of the invention in FIG. 10A a mandrel which is used to create the preform shown in FIG. 10B (left). FIG. 10B (right) shows the preform once the preform shown in FIG. 10B (left) is flipped inside out. FIG. 10C shows a cross-section view before flipping (left) and after flipping (right).

(11) FIGS. 11A-C show according to an exemplary embodiment of the invention in FIG. 11A a mandrel which is used to create the preform shown in FIG. 11B (left). FIG. 11B (right) shows the preform once the preform shown in FIG. 11B (left) is flipped inside out. FIG. 11C shows a cross-section view before flipping (left) and after flipping (right).

(12) FIGS. 12A-C show according to an exemplary embodiment of the invention in FIG. 12A a mandrel which is used to create the preform shown in FIG. 12B (left). FIG. 12B (right) shows the preform once the preform shown in FIG. 12B (left) is flipped inside out. FIG. 12C shows a cross-section view before flipping (left) and after flipping (right).

DETAILED DESCRIPTION

(13) Fiber Alignment

(14) In one embodiment, the present invention is a method of producing a preform that enables creating a normally closed valve (e.g. heart valve) using a cylindrical mandrel. First, a cylindrical preform of a desired diameter is produced on a cylindrical mandrel for example by electrospinning Second, the formed preform is then turned inside out, by flipping the preform inside out, once the preform is removed from the mandrel. This will then result in having a preform with its original inner surface now on the outside. This method does not require any further post-processing steps, such as annealing or a dedicated suture technique as will be explained below.

(15) Preferential Inwards Bending

(16) The method of flipping inside-out a formed preform changes the distribution of the material within the preform, which creates forces within the preform (FIGS. 4A-B). The inside surface (which after flipping has become the outer surface) is stretched to conform to the desired outer diameter of the preform, while the outside surface (which after flipping has become the inner surface) is compressed to conform to the inner diameter of the preform. These forces combine to create a bending moment. Due to this bending moment, the preform preferentially bends inwards.

(17) The occurring strains are dependent on the ratio between the inner and the outer diameter of the preform. The actual forces that occur are a function of the Young's modulus and the occurring strains.

(18) The inner and outer strain ε.sub.i and ε.sub.o respectively, can be defined as a function of the inner and outer radii R.sub.i and R.sub.o by defining the change in circumferential length resulting from flipping inside out.

(19) ${\mathrm{.Math.}}_i=\frac{2\pi R_o-2\pi R_i}{2\pi R_o}=1-\frac{R_i}{R_o}{\mathrm{.Math.}}_o=\frac{2\pi R_i-2\pi R_o}{2\pi R_i}=1-\frac{R_o}{R_i}$

(20) As an example, for a tube with an inner diameter R.sub.i of 10 mm and a wall thickness of 1 mm, the other diameter R.sub.o is 11 mm. After flipping inside out the inner layer (now outer layer) feels a residual tensile strain of ˜9%, while the outer layer (now inner layer) feels a residual compressive strain of 10%. This creates an inward bending momentum in the material, which in one of the exemplary embodiments results in a heart valve scaffold with a tendency towards the closed position.

(21) Reduction in Local Strains

(22) For a valve made from a cylindrical preform, the preform undergoes a relatively large deformation when closing. These large deformations in the belly area of the leaflet create large strains in the material. In case of the inside-out preform, the deformations in the closed position are significantly reduced (FIGS. 5A-B). The neutral position of the preform is much more similar to the closed position, compared to the preform without flipping inside out. The highest loads are applied to a heart valve in its closed position. By reducing the strains in the closed position, the durability of the leaflet is increased. FIG. 5B shows a one-third section of a cylindrical preform that forms one leaflet of a heart valve. Arrows in FIG. 5B indicate compression forces at the inner surface and stretch forces at the outer surface.

(23) Concave Geometries

(24) In another embodiment, the present invention is a method of electro-spinning of a desired shape for a preform on a mandrel whereby the mandrel has the opposite or inverse shape of the finally desired shape of the preform.

(25) First, a preform of a desired diameter is produced on the mandrel using electro-spinning Second, the formed preform is then turned inside out, by flipping the preform inside out, once the preform is removed from the mandrel. This will then result in having a preform with its original inner surface now on the outside, and the mandrel shape reversed/flipped as well. This method does not require any further post-processing steps, such as annealing or a dedicated suture technique as will be explained below. Furthermore, this process allows the manufacturing of complex shapes via electro-spinning, which would be challenging by definition with processes known in the art without any compromise neither on product quality nor on electro-spinning process.

(26) In particular, electrospinning of a preform that has at least one area with a concave shape is performed on a mandrel that has the inverse shape with the corresponding convex shape area. The method according to this invention allows the manufacturing of such complex shapes with at least one concave area via electro-spinning with very limited compromise on the product quality.

(27) Within the method of this invention conventional spinning methods can be used and microstructures can still be created as well.

(28) As a person skilled in the art would appreciate, the method of this invention could be applied to various applications and various types of complex shapes as long as the mandrel can provide the mirror image of the desired shape of the preform. Generally speaking a three-dimensionally shaped area desired in a preform is established by using a mandrel having the inverse of that three-dimensionally shaped area and once the preform is created on that mandrel and then flipped inside out the desired preform with the three-dimensionally shaped area is then created. One example according to the method is the production of artificial heart valves. Another example according to the method is the production of artificial grafts or vessels.

Example 1

State-of-Art

(29) A preform with a geometry that distinguishes a number of concave surfaces is desired. In a state-of-art example the outer geometry of the mandrel (FIG. 6A) would match the desired inside geometry of the preform. A preform produced on this mandrel would exhibit a number of problems associated with electrospinning on complex geometries. Spinning on this mandrel would yield a preform similar to be one as shown in FIG. 6B (left). The preform would have a varying thickness distribution and show areas with bridging, where the preform will no longer be attached to the mandrel (FIG. 6B, right).

(30) Flipping Inside Out

(31) To produce the same desired preform using the method of this invention, a mandrel with the inverse geometry is used (FIG. 7A). The mandrel distinguishes essentially convex surfaces, resulting in significantly less problems during the electrospinning process; a complex shape with mainly convex shapes and only very limited concave areas. In this embodiment, the target is uniformly formed along the whole length.

(32) The three leaflets are produced by electro-spinning on this specially formed target mandrel (FIG. 7A). Subsequently the produced tubular preform (FIG. 7B, left) having convex extension areas is carefully flipped inside-out (FIG. 7B, right). This results in a complementary “tubular preform having concave extension areas (FIG. 7B, right). The resulting preform will exhibit a much more uniform thickness distribution as shown in FIG. 7C compared to the preform produces according to the state of art example as shown in FIGS. 6A-B.

(33) Finally, the concave shape having three leaflets can for example be fixed or sutured to a covered frame. As an advantage the final tube area to be used for the design of the leaflets can be cut at any place since there is no difference along the length of the mandrel. In addition, several leaflets can be produced in one electrospinning step on the mandrel next to each other.

Example 2

(34) In the example of FIGS. 8A-B, the mandrel shown in FIG. 8A distinguishes a complex shape with mainly convex shapes and only very limited concave areas. In this example the mandrel and resulting preform are not uniformly formed along the whole length as shown, but shows a variation of the shape along its axis. FIG. 8B (left) is the preform that is formed using the mandrel (FIG. 8A). FIG. 8B (right) is the preform after the preform in FIG. 8B (left) is flipped inside-out. These tubular preforms could be advantageous in cases where the second end should stay open, e.g. for the production of transcatheter valves.

Example 3

(35) In the example of FIGS. 9A-B, the mandrel shown in FIG. 9A distinguishes a complex shape with mainly convex shapes and only very limited concave areas. In this example, the mandrel and the resulting preform distinguishes a complex shape with mainly convex shapes and only very local concave areas. In this example, the mandrel has local lobes attached to the cylindrical base. These lobed sections have mainly convex shapes and only very limited concave areas. FIG. 9B (left) is the preform that is formed using the mandrel (FIG. 9A). FIG. 9B (right) is the preform after the preform in FIG. 9B (left) is flipped inside-out. The resulting tubular preforms and the final preform (after flipping inside-out) could be advantageous in cases where a section of the preform has to conform to a specific shape, e.g. the indented section can be used to form the leaflets of a heart valve.

Additional Examples

(36) The method of the invention is applicable for targets with two or more lobes. As shown in FIGS. 9A-B, 10A-B (two lobes) and 11A-B (four lobes) creating a preform with multiple lobes can be applied for transcatheter applications. The lobes create preferential folding lines which allow for a more predictable behaviour of the preform while being crimped.