Enhanced heart valve leaflets

Abstract

A heart valve with reinforced leaflets is provided. The free edge and / or ventral region of the leaflet has circumferentially aligned bands of aligned electrospun fibers with non-aligned fibers. The aligned and / or non-aligned fibers are configured to be bioabsorbable polymer fibers that can be replaced with newly formed tissue over time. A method for fabricating such heart valve leaflets is provided, which involves simultaneously electrospinning using two electrospinning sources to form separate or intermixed layers of aligned and non-aligned fibers.

Description

Technical Field

[0001] The present invention relates to a heart valve for repair.

Background Art

[0002] Since natural heart valves have a highly organized three-layer structure, they can cope with the forces applied to the heart valves and can open and close appropriately with sufficient thinness and flexibility. Natural heart valves consist of three different layers, each layer having its own structural and functional characteristics and having a favorable arrangement of tissue fibers beneficial to the performance of the heart valve.

[0003] Single-layer prosthetic heart valves or repair heart valves that replace natural heart valves are usually made from pericardium and have limitations in long-term durability. On the other hand, the scaffolds of heart valves cannot fully mimic the mechanical properties of natural donor scaffolds. In current durability tests of valve designs, the leaflets tend to mainly break in the radial direction. Therefore, there is a need for a new scaffold material that has higher durability while maintaining the desired necessary mobility. Reinforcing materials with different strengths in different regions / directions need to be arranged in the new scaffold. The present invention provides an electrospinning method specialized for heart valves to address at least some of the problems.

Summary of the Invention

Means for Solving the Problems

[0004] In one embodiment, the present invention relates to a method of electrospinning a heart valve leaflet. Aligned fibers are electrospun on a mandrel using a first source. The aligned fibers are configured to be biodegradable polymer fibers. Non-aligned fibers are electrospun on the mandrel using a second source. The second source is electrospun simultaneously with the first source, and these non-aligned fibers are configured to be biodegradable polymer fibers. The electrospinning of the aligned fibers is at the mandrel differentBy electrospinning a patch or region, a band aligned circumferentially with the heart valve leaflets is generated. different Aligned and unaligned fibers in a patch or area different Electrospinned as layers or mixed patterns. The circumferentially aligned bands are located on or near the free edge of the heart valve leaflet. joint from joint Bands may be provided up to or aligned circumferentially, and are used to reinforce the abdominal region of the heart valve leaflets.

[0005] In other embodiments, the present invention relates to a heart valve comprising at least one valve leaflet. The free edge of the valve leaflet comprises, or is essentially composed of, a circumferentially aligned band of aligned electrospun fibers having unaligned fibers. The aligned fibers are configured to be bioabsorbable polymer fibers, and the unaligned fibers are configured to be bioabsorbable polymer fibers, and the aligned and unaligned fibers of the free edge are different They are either layered or mixed together.

[0006] In yet another embodiment, the present invention relates to a heart valve comprising at least one valve leaflet. The abdominal region of the valve leaflet comprises, or is essentially composed of, a circumferentially aligned band of aligned electrospun fibers having unaligned fibers. The aligned fibers are configured to be bioabsorbable polymer fibers, and the unaligned fibers are configured to be bioabsorbable polymer fibers, with the aligned and unaligned fibers of the free edge being different It is either layered or mixed together.

[0007] In the embodiment, the bioabsorbable polymer fibers of the aligned fibers may be supramolecular bioabsorbable polymer fibers, and / or the bioabsorbable polymer fibers of the unaligned fibers may be supramolecular bioabsorbable polymer fibers.

[0008] In the embodiment, aligned bioabsorbable polymer fibers form a porous network that allows cell invasion, and the porous network containing the invaded cells is replaceable over time with newly formed tissue, and / or unaligned fibers form a porous network that allows cell invasion, and the porous network containing the invaded cells is replaceable over time with newly formed tissue. [Brief explanation of the drawing]

[0009] [Figure 1] This is an external view of an enforcement ring for aligned fibers, which spins random fibers simultaneously to create an intertwined pattern, according to an exemplary embodiment of the present invention. [Figure 2] This is a cross-sectional view showing a matrix of randomly arranged fibers and alternating fibers according to an exemplary embodiment of the present invention. [Figure 3] An exemplary embodiment of the present invention describes a method of electrospinning to form a heart valve using two sources simultaneously, one source for aligned fibers and the other source for unaligned fibers. [Modes for carrying out the invention]

[0010] Embodiments of the present invention relate to a method for manufacturing reinforced heart valve leaflets. In one example, the present invention includes the following method: To form heart valves that enable endogenous tissue repair (ETR), aligned and unaligned fibers are spun simultaneously. By spinning them simultaneously, it becomes possible to create a microstructure that enables ETR and improves integrity and adhesion. • Electrospinning is performed simultaneously using two sources: one source that generates a straight jet and the other source that generates random fibers (Figure 3). The advantage of the straight jet is that the deposition location can be controlled more precisely. The advantages of performing electrospinning simultaneously using two sources are (i) improved adhesion between aligned and random structures, and (ii) improved porosity by avoiding excessive density in the aligned regions. The straight jet can also be achieved by certain melt extrusion processes (e.g., electrospinning without a voltage difference). • Creation of specific areas of the heart valve that are reinforced by fibers, made possible by precise control of the straight jet. For example, along the free edge of the heart valve. joint from joint A circumferentially aligned band extending to the other. In other examples, joint from joint A combination of bands / bundles that extend (along the entire edge) and are aligned circumferentially in a curved manner. In yet another example, bands / bundles aligned circumferentially in the ventral region of the valve leaflet. In one embodiment, a supramolecular polymer is used in this method.

[0011] Artificially fabricated electrospan heart valves have at least one layer of aligned fibers and at least one layer of randomly oriented fibers. This approach makes it possible to fabricate heart valves with mechanical properties that more closely match the mechanical properties of natural donor scaffolds in terms of rigidity and strength.

[0012] In one embodiment, highly directional aligned fibers are produced, which are mixed with more randomly oriented "normal" electrospun fibers. different It does not form layers. As a result, aligned and unaligned fibers are directly bound to and intertwined with each other, forming the tissue of the heart valve leaflets.

[0013] In other embodiments, aligned fibers differentGenerated in the area, and as a result, strengthens the tissue of the heart valve. Thereby, it may be alternately arranged with the misaligned fibers different A patch or band-like structure is obtained.

[0014] In yet other embodiments, the aligned fibers are manufactured simultaneously with the misaligned fibers, resulting in a stronger interaction and adhesion between the aligned and misaligned fibers, which helps prevent delamination and can provide a more optimal distribution of local porosity (for cell attachment and ETR).

[0015] In yet other embodiments, the aligned fibers are manufactured in the form of a straight jet, thereby enabling a more controlled volume.

[0016] In yet another embodiment, the straight jet for manufacturing the aligned fibers is manufactured through a melt extrusion process, an electrospinning process, or a winding process.

[0017] In yet other embodiments, the aligned fibers form a circumferentially aligned band that extends along the free edge of the heart valve leaflet joint from joint to

[0018] In yet other embodiments, the aligned fibers joint from joint to

[0019] form a set of curved circumferentially aligned bands / bundles that extend along the entire edge.

[0020] In yet other embodiments, to optimize the balance between the durability and flexibility of the valve leaflet, the aligned fibers are deposited on the valve leaflet in the form of a band or bundle.

[0021] In yet other embodiments, the aligned fibers may contain either an absorbent material or a non-absorbent material.

[0022] In yet another embodiment, the aligned fibers may be suture wires made from, for example, ultra-high molecular weight polyethylene (UHMWPE).

[0023] Spinning the fibers more circumferentially increases the durability of these heart valves. The aligned fibers may be locally defined or dispersed. Since increased circumferential forces on the valve leaflets can cause leaflet damage, alignment in a preferred direction may be performed. For example, circumferential reinforcement is preferred. The area of ​​aligned fibers may be locally defined, dispersed over the entire area, aligned in a preferred direction, and / or dispersed as patches or along the entire scaffold. This approach strengthens the valve leaflets, resulting in improved durability. They may be reinforced with aligned fibers in various ways, such as (bioabsorbable) wires, locally aligned fibers, or bands.

[0024] The aligned fibers may differ in diameter, material, or other properties. If necessary, the aligned fiber polymer may differ from the unaligned fiber polymer. The aligned fiber polymer may be selected to be more or less bioabsorbent, if necessary.

[0025] The use of bioabsorbable wires improves the circumferential strength of a particular area. These wires are absorbed over time, like the rest of the heart valve, but provide support to prevent tearing during the initial ETR. The aligned wires may be sutured through the leaflet junction or attached by other means. Circumferentially aligned bands supporting the leaflets similarly prevent rupture. Alternatively, aligned edges or rims may be added on or within the scaffold during or after manufacturing, for example, by electrospinning directly on the scaffold.

[0026] In some examples, aligned fibers and unaligned fibers may be woven together and / or bonded together.

[0027] The method shown in Figure 3 employs a second polymer source used to apply aligned fibers during manufacturing, in addition to unaligned fibers produced by a first polymer source. These aligned fibers may be electrospinned using another power source or drawn from continuous droplets supplied by a pump. This allows for very precise alignment in the deposition area. This method makes it possible to perform spinning in a specific direction on a target with a complex shape for fabricating heart valves.

[0028] The electrospan materials referenced herein may include a ureidopyrimidinone (UPy) quadruple bond motif (pioneer Sijbesma (1997), Science 278, 1601-1604) and a polymer backbone selected from the group including, for example, biodegradable polyesters, polyurethanes, polycarbonates, poly(orthoesters), polyphosphates, polyanhydrides, polyphosphazenes, polyhydroxyalkanoates, polyvinyl alcohols, and polypropylene fumarates. Examples of polyesters include polycaprolactone, poly(L-lactide), poly(DL-lactide), poly(valerolactone), polyglycolides, polydioxanones, and their copolyesters. Examples of polycarbonates include poly(trimethylene carbonate), poly(dimethyltrimethylene carbonate), and poly(hexamethylene carbonate).

[0029] Similar results can be obtained with non-supramolecular polymers by carefully selecting their properties and processing the materials to ensure the required surface properties. These polymers may include biodegradable or non-biodegradable polyesters, polyurethanes, polycarbonates, poly(orthoesters), polyphosphates, polyanhydrides, polyphosphazenes, polyhydroxyalkanoates, polyvinyl alcohols, polypropylene fumarates, etc. Examples of polyesters include polycaprolactone, poly(L-lactide), poly(DL-lactide), poly(valerolactone), polyglycolides, polydioxanones, and their copolyesters. Examples of polycarbonates include poly(trimethylene carbonate), poly(dimethyltrimethylene carbonate), and poly(hexamethylene carbonate).

Claims

1. A method of electrospinning the heart valve leaflets, (a) Using a first source, the step of electrospinning aligned fibers of bioabsorbable polymer fibers onto a mandrel, (b) The step of electrospinning unaligned fibers of bioabsorbable polymer fibers onto the mandrel using a second source simultaneously with the first source, The electrospinning of the aligned fibers generates bands aligned circumferentially to the heart valve leaflets by electrospinning different regions on the mandrel, and the aligned and unaligned fibers in the different regions are electrospinned into either different layers or mixed patterns. A method wherein the circumferentially aligned bands extend from commissure to commissure near the free edge of the heart valve leaflet or in the vicinity of the free edge.

2. The method according to claim 1, wherein the bioabsorbable polymer fibers of the aligned fibers are configured to be supramolecular bioabsorbable polymer fibers, and / or the bioabsorbable polymer fibers of the unaligned fibers are configured to be supramolecular bioabsorbable polymer fibers.

3. The method according to claim 1, wherein the bioabsorbable polymer fibers of the aligned fibers form a porous network that enables cell invasion, and the porous network containing the invaded cells is replaced over time by newly formed tissue, and / or the bioabsorbable polymer fibers of the unaligned fibers form the porous network that enables cell invasion, and the porous network containing the invaded cells is replaced over time by newly formed tissue.

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