HK1202271B - An implant - Google Patents

Description

Implant and method of manufacturing the same

Technical Field

The invention relates to an implant comprising at least two layers made of fibers and at least one layer of a biologically active material arranged between the at least two layers.

Background

Reinforced composites made using particulate fillers or reinforcing fibers are known. The prior art fiber reinforced composites provide high strength properties and by selecting the multiphase resin matrix of the composite, the processing characteristics of the composite can be significantly improved.

On the other hand, much development has been made in bioactive materials (i.e., bioactive ceramics and glasses and sol-gel treated silica). These materials can be used to achieve adhesion of, for example, bone to a biomaterial surface after contacting the material with tissue. An additional advantage of bioactive glass is its antimicrobial effect on microorganisms present, for example, in infected sinus bones. Document WO2004/049904 discloses bioactive absorbable scaffolds for tissue engineering. The scaffold is made of a bioactive glass mesh comprising interwoven bioactive glass fibers and may contain cultured cells such as fibroblasts and chondroblasts.

From a surgical point of view, individual replacement of bone, cartilage and soft tissue is not sufficient in tumor, trauma and tissue reconstruction surgery, despite the increasing progress in biomaterial research and its clinical application methods and tissue engineering. The need and indications for new material development stem from the disadvantages of using allografts. The risk of infectious diseases (HIV, creutzfeldt-jakob disease, etc.) is associated with allograft transplantation. Metals are not bioactive or osteoconductive, and their use can cause stress shielding and bone atrophy of adjacent bones. Metal implants also pose serious problems in Magnetic Resonance Imaging (MRI) when diagnosing patient disease. These major disadvantages are well documented in a large clinical series of studies.

There is therefore still a need for alternative implants for medical use.

Disclosure of Invention

The object of the present invention is to provide a biocompatible material which does not have the above-listed drawbacks, or at least minimizes these drawbacks. In particular, it is an object of the present invention to provide materials that can be used in medical, dental and surgical applications, such as bone grafting and fixation of broken bone fragments that can be used to repair bone defects.

Drawings

Fig. 1 schematically shows an implant according to a first embodiment.

Fig. 2 schematically shows an implant according to a second embodiment.

Fig. 3 schematically shows an implant according to a second embodiment from a different angle.

Fig. 4 schematically shows an implant according to a third embodiment.

Fig. 5 schematically shows an implant according to a fourth embodiment.

Fig. 6 schematically shows an implant according to a fourth embodiment from a different angle.

Fig. 7 schematically shows an implant according to a fifth embodiment.

Detailed Description

The invention relates to an implant comprising at least two layers made of fibers and at least one layer of a biologically active material arranged between the at least two layers.

A typical implant according to the present invention comprises at least two layers made of fibers and a bioactive material disposed between the at least two layers. At least one of said layers is at least mainly constituted by a mesh made of glass fibres having a diameter of 3-100 μm, and the mesh size is chosen such that the bioactive material is retained in the implant. Furthermore, the layers are embedded in a matrix made of a resin selected from the group consisting of polyester, epoxy, acrylate and mixtures thereof, and the layers are connected to each other along the contour of the implant. Further, the bioactive material is selected from the group consisting of bioactive glass, hydroxyapatite, tricalcium phosphate, and mixtures thereof.

The implant according to the invention thus utilizes capillary action, since at least one surface is at least predominantly composed of a mesh. In fact, the structure of the implant, thanks to the use of at least one mesh and a bioactive material, allows the capillary action to be enhanced, thus leading to an improved bone ingrowth, since the fluid can penetrate better into the interior of the implant than if both surfaces were made of tightly woven cloth or film. Furthermore, the openings of the mesh enable body fluid to penetrate from all directions of the implant, which means that fluid penetration is insensitive to the direction of blood flow from the artery.

The implant may have both of its outer surfaces made of mesh, or one of its surfaces made of film or tightly woven cloth. When the other surface is not made of mesh, it is usually on the outside once the implant is in place. The implant may also comprise more than two layers, such as three, four or five layers. According to one embodiment, the layer thickness is about 500-700 μm. The thickness of the implant depends, for example, on the thickness of the bone to be replaced. More typically, a maximum thickness of 10 millimeters is achieved with five layers. When several layers are used, the middle layer (i.e. the inner layer opposite the outermost layer) is preferably made of a mesh. According to a preferred embodiment, all layers are impregnated with resin, i.e. embedded in a matrix. The resins selected may be the same or different for each layer. Furthermore, when several layers are used, only the two outermost layers may be connected to each other along the implant contour, or all or part of the other layers (intermediate layers) may be connected to each other in a similar manner.

In this specification, curing refers to polymerization and/or crosslinking. By matrix is understood a continuous phase of the composition, uncured matrix referring to a matrix that is in its deformable state but that can be cured (i.e. hardened) to a substantially non-deformable state. The uncured matrix may already contain some long chains, but it has not been substantially polymerized and/or crosslinked. Prepreg refers to a semi-finished product, i.e. a product which has not polymerized or has only been partially polymerized, but is still deformable. Curing of the resin produces a composite material in which the cured resin constitutes the matrix.

The layer of the implant is at least mainly composed of mesh, meaning that at least 55% of the surface of the layer is made of mesh. Preferably at least 60, 65, 70, 75, 80, 85, 90 or 95% of the surface is made of mesh. As will be explained below, the layer may also contain regions where the layer is in another form than a web, such as a tightly woven cloth or continuous fibers. Typically these areas are used to cut or bend the implant. Most preferably the layer is made of mesh except for these areas. Sometimes, the contours of the layers may be made of continuous fibers. This can be used for example for the following implants: the implant is attached to the bone in a region where the bone (and thus the connection) is under significant stress. Thus, the continuous fibers enhance the contour of where the bone connection occurs.

According to one embodiment of the invention, the fibers are selected from inert glass fibers and bioactive glass fibers. According to another embodiment, the glass fibers are made of a glass composition of E-glass, S-glass, R-glass, C-glass or bioactive glass.

According to yet another embodiment, the diameter of the fibers is 4-25 μm. The diameter of the fibers may for example be from 3, 5, 6, 10, 15, 20, 25, 30, 40, 45, 50, 60, 70 or 80 μm up to 5, 6, 10, 15, 20, 25, 30, 40, 45, 50, 60, 70, 80, 90 or 100 μm. Nanoscale fibers, i.e., with cross-sectional diameters varying between 200 and 1000nm, may also be used.

The bioactive material can be in any form suitable for insertion between two layers consisting essentially of a mesh. It may, for example, be in the form of a monolith, or in the form of particles. A particle refers to an entity in which the largest dimension does not exceed five times the smallest dimension. It may thus also be in the form of chopped, short fibers. When particles are used, their size is smaller than the mesh size of the layer in order for the layer to be able to retain them inside the implant. The bioactive material may also be in the form of a monolith, or just two, three, or four large particles. Some possible particle sizes are 10-1000 μm. The particle size may be, for example, from 10, 20, 50, 100, 150, 200, 250, 300, 400, 500, 650, 700, or 800 μm up to 20, 50, 100, 150, 200, 250, 300, 400, 500, 650, 700, 800, 900, or 1000 μm.

The bioactive material may also be in the form of a fluid having a viscosity such that the mesh layer is impermeable to the fluid, that is, the implant may comprise such bioactive material in addition to those recited in the independent claims. The fluid may be a highly viscous fluid or a gel in fluid form. Colloidal refers to a substance that is microscopically uniformly dispersed throughout another substance. The bioactive material may also naturally be in several of these forms, such as a combination of particles in a fluid. Preferably, the bioactive material is a bioactive glass.

According to one embodiment, the mesh size is optimized by the weaving process of the web and the viscosity and amount of the impregnating resin of the web. According to one embodiment, the mesh size is preferably 1 to 5 microns smaller than the smallest diameter of the particles. The mesh size may be, for example, 9-999 μm. The mesh size may thus be, for example, from 1, 2, 3, 5, 7, 9, 10, 15, 20, 50, 100, 150, 200, 250, 300, 400, 500, 650, 700, 800 or 900 μm up to 2, 3, 5, 7, 9, 10, 15, 20, 50, 100, 150, 200, 250, 300, 400, 500, 650, 700, 800, 900, 950 or 1000 μm.

According to a further embodiment, the two web layers are also connected to each other along at least one cutting line. The cutting line may for example consist of unidirectional continuous fibres.

The connection regions, i.e., the portions of the implant where the layers are connected together, may vary in width. The advantage of a large attachment area is that the implant can be cut smaller to fit the intended use, while still retaining functionality because the bioactive material remains in the implant.

The positioning of the attachment region is also important and may vary depending on the intended use. For example, the implant may be manufactured such that it has more than one portion (e.g., two, three, four, five, or six portions), each portion being separated from the other portion by a connection region (i.e., a cut line). The connecting regions between the parts can be used, for example, for easier bending of the implant or for cutting out one or more parts from the implant. Thus, a multi-functional implant can be made, whereby the user only has to determine how large a size is required immediately before implanting the implant. This is particularly important for emergency surgery and is believed to reduce costs as it will no longer be necessary to keep an inventory of different sized implants. The shelf life of these implants is believed to be about one year, which is naturally determined by the components used.

The profile of the implant, i.e. the connection zone along the profile, may also contain holes extending through both layers of the mesh to facilitate connection of the implant to be seated with, for example, bone screws. Similar holes may also be provided in the cutting line, if desired. Furthermore, when a large connection area along the contour of the implant is used, it can be equipped with a series of holes at different distances from the edge, so that the implant can be easily connected even when cut to smaller dimensions.

The implant may be uniform in its structure and material, or it may be composed of different materials and/or properties at different locations. It may, for example, vary one or more of the following: mesh size, matrix material, matrix mass, fiber material, fiber diameter, or bioactive material. This may result in different strengths, for example at different locations of the implant.

Preference is given toThe matrix material of (a) is an acrylate polymer. The matrix is formed when the resin is cured. According to one embodiment, the matrix resin is selected from substituted and unsubstituted dimethacrylates and methacrylates. Some particularly advantageous matrix materials (monomers) are methyl acrylate, methyl methacrylate, methacrylate-functionalized dendrimers, glycidyl dimethacrylate (bis-GMA), triethylene glycol dimethacrylate (TEGDMA) and polyurethane dimethacrylate (UDMA). The materials may be used as blends, and they may form Interpenetrating Polymer Networks (IPNs)_s). They may also be functionalized with bioactive molecules that allow for drug-like contact effects. Combinations of monomers and polymers are also suitable, including modifying the resin system with iodine-containing pendant antimicrobial groups, which provides additional benefits in terms of improving the radio-opacity of the resin system.

The viscosity of the resin is such that it does not block the mesh structure. Some examples of resin viscosity and mesh size are given below.

The implant may further comprise modifier particles. These modifier particles may, for example, be bioactive and, for example, improve the osteoconductivity of the implant. The particles may be in the form of particulate fillers or fibres. The weight fraction of these modifier particles in the implant may be, for example, 10-60 wt%, such as from 5, 10, 15, 20, 35 or 50 wt% up to 10, 15, 20, 35, 50, 55, 60 or 75 wt%.

According to one embodiment, the modifier particles are selected from the group consisting of bioactive ceramics, bioactive glass, silica gel, titanium gel, silica xerogel, silica aerogel, sodium silicate glass, titanium gel, bioactive glass ionomer, hydroxyapatite, Ca/P doped silica gel and mixtures thereof. Any combination of the materials mentioned can naturally also be used. When rapid mineralization is desired, it is preferred to provide the bioactive glass with sol-gel treated silica particles.

The implant according to the invention may also comprise additional particulate filler materials, such as metal oxides, ceramics, polymers and mixtures thereof. The metal oxide can be used, for example, as a radiation-or X-ray-opaque material or as a coloring material.

The implant may also comprise therapeutically active agents or cells such as stem cells, proteins such as growth factors and/or signal transduction molecules. Several types of cells, including hematopoietic bone marrow cells, fibroblasts, osteoblasts, regenerative cells, stem cells, such as embryonic stem cells, mesenchymal stem cells, or adipose stem cells, may be seeded into the implant. Embryonic stem cells may or may not be of human origin. The stem cells seeded to the implant can be cultured ex vivo in a bioreactor, in other parts of the body before the formed tissue is inserted into its final location, or directly at the location where regeneration and reconstitution processes are required. The implant may also contain additives that improve its processability, such as polymerization initiators. The material of the implant may be bioresorbable, biodegradable, biostable or a mixture of these.

The implant may also contain interconnections between layers that are rigid and substantially incompressible. These interconnecting portions thus ensure that the layers do not touch each other when the material is bent, since they should remain spaced apart. This thereby ensures that the properties of the implant with respect to capillary effect and bone ingrowth remain substantially intact.

The size and shape of the implant is selected according to the intended use. The diameter of the implant may be, for example, 10 to 350 millimeters. The shape may be any suitable shape, such as circular, oval, square, etc. The implant may also have a substantially symmetrical cross-section relative to the two layers, i.e. they are equally spaced along substantially the entire width of the implant. The implant may also have different shapes, as will be explained in more detail below in connection with the figures. The implant may thus have a substantially flat upper (or lower) surface and a protruding portion on the other surface. This form is particularly suitable for craniocerebral use to fill boreholes following surgical procedures.

The implant may be used for bone reconstruction after surgery for trauma, defects or disease. The reconstruction of the implant of the damaged or missing part of the skeleton is carried out by the following method: providing an immediate repair of the bone fragments with anatomical shape and adequate mechanical support while allowing blood and osteoblasts to penetrate from the adjacent tissue into the implant. This is often required in neurosurgery and repair of post-traumatic skull defects, in reconstruction of the bony infraorbital and jaw bones, but implants can also be used in orthopedic and spinal surgery, as well as for fixation of scattered bone fragments. When there is long bone weakened by disease, or when part of the cortical bone is missing, the implant can be used to reinforce the long bone and cover the opening where the cortical bone is missing. In tissue engineering applications, an implant manufactured in a desired form may be loaded with stem cells, or tissue formed in a bioreactor or adjacent tissue of a patient, before the implant is applied to a final location.

The implant is preferably manufactured as follows. A two-piece mold is made from a translucent mold material to provide the shape of both sides of the implant. Generally, the outer surface of the implant is made thicker and non-reticulated, while the inner surface to be in contact with the blood circulation of the damaged tissue is reticulated. The outer surface may also be made of a mesh material, in case the implant is preferably better penetrated by fluids and/or tissue. The fiber fabric for the outer surface is typically completely impregnated with the monomer resin system and the fiber fabric is placed into a mold. Bioactive glass particles are poured onto the inner surface of the outer surface layer thus formed. To make the reticulated inner surface of the implant, the reticulated fiber fabric is impregnated with the monomer resin. By varying the amount of monomer resin and its viscosity in the fibrous web, the size of the openings in the inner layer laminate can be varied. Some examples of suitable viscosities are as follows. The viscosity of the monomer resins glycidyl dimethacrylate and triethylene glycol dimethacrylate may vary from 550pa.s for pure glycidyl dimethacrylate to 50pa.s for triethylene glycol dimethacrylate. 50% of glycidyl dimethacrylate and triethylene glycol dimethacrylate 50% of the mixture may have a viscosity of 180pa.s and the resin may be used to impregnate a web having an opening size of 300 microns. By increasing the ratio of glycidyl dimethacrylate, the viscosity of the mixture is increased and larger openings of the web can be used to have a final mesh (opening) size of 300 microns. The viscosity is given at a temperature of 25 ℃.

The mesh fibers are placed over the outer laminate and bioactive granules of the implant, followed by closing the mold system. The initial polymerization of the monomer resin system is initiated by light through the translucent mold material. The photoinitiator and activator system in the monomer resin of the implant will polymerize first. The mold is opened, the initially polymerized implant is removed from the mold and curing is completed in vacuum and at elevated temperature, followed by polishing of the implant (rounding of contours, etc.).

Some embodiments of the invention will be explained in more detail in the drawings, which should not be construed as limiting the claims. Neither should the reference signs be construed as limiting the claims.

Detailed description of the drawings

In the following, the same reference numerals are used for the same or similar components in different embodiments and/or figures.

Fig. 1 schematically shows an implant according to a first embodiment. In this embodiment, the implant consists of two layers, a first upper layer 1 and a second lower layer 2 made of a fibrous web. The layers are connected to each other along the contour 3 of the implant and the bioactive granules 4 are arranged between the two layers. The profile 3 also contains holes 5 extending through the layers 1 and 2 to facilitate the attachment of the implant in place with, for example, bone screws.

Fig. 2 schematically shows an implant according to a second embodiment. In this embodiment, the implant is an orbital plate consisting of two layers, a first upper layer 1 and a second lower layer 2 made primarily of an open-celled woven fiber-reinforced composite mesh. The layers also have cutting lines 6 made of unidirectional long fibres 7. The layers are connected to each other along the contour 3 of the implant and along the cutting line 6. The bioactive particles 4 are disposed between the two layers. Fig. 3 schematically shows an implant according to a second embodiment from a different angle, i.e. perpendicular to the layers. In this figure it can be seen that the cutting line 6 consists of a continuous unidirectional fibre 7, said unidirectional fibre 7 extending from one end of the implant to the other. The figure also shows how the mesh size of the layers is smaller than the size of the particles 4. The figure also shows the width of the connecting zone along the profile 3.

Fig. 4 schematically shows an implant according to a third embodiment. In this embodiment, the cutting lines 6 are made of the same material as the rest of the layers and are formed by simply connecting the layers to each other.

Fig. 5 schematically shows an implant according to a fourth embodiment. In this embodiment, the implant is a fixation peg for a bone flap after a craniotomy. The connection region 3 is in this embodiment rather large in order to enable a good connection of the implant to the bone. The connection region 3 also has two holes 8, 8' for fixing screws, shown in this figure as half holes. The first, upper layer 1 is in this embodiment substantially flat, and the second, lower layer 2 constitutes an extension 9 below the first layer 1. The extension 9 is substantially the same size and shape as the bore in the skull. These extensions also contain bioactive particles 4 to enhance bone ingrowth.

Fig. 6 schematically shows an implant according to a fourth embodiment from a different angle, the two holes 8, 8' for the fixation screws being clearly visible.

Fig. 7 schematically shows an implant according to a fifth embodiment. In this embodiment, the implant is a covering plate for a bone defect of a long bone. The implant also contains interconnecting portions 10 which ensure that the layers do not contact each other in the areas where they should remain spaced apart when the material is bent, in order to allow better bone ingrowth.

Claims (8)

1. An implant comprising at least two layers made of fibers and a bioactive material disposed between the at least two layers, wherein

At least one of said layers is at least mainly formed by a web,

-is made of glass fibres having a diameter of 3-100 μm and wherein

-selecting a mesh size such that the bioactive material is retained in the implant,

said layer being embedded in a matrix made of a resin selected from the group consisting of substituted and unsubstituted dimethacrylates and methacrylates,

the layers are connected to each other along the contour of the implant,

characterized in that the bioactive material is in the form of particles and is selected from the group consisting of bioactive glass, hydroxyapatite, tricalcium phosphate and mixtures thereof.

2. The implant of claim 1, wherein the glass fibers are made of a glass composition of S-glass, E-glass, or bioactive glass.

3. An implant as claimed in claim 1 or 2, characterised in that the fibres have a diameter of 4-25 μm.

4. The implant of claim 1, wherein the bioactive material has a particle size of 10-1000 μ ι η.

5. The implant of claim 1, further comprising a bioactive material in the form of a fluid having a viscosity such that the layer of mesh is impermeable to the fluid.

6. An implant as claimed in claim 1, characterised in that the mesh size is 9-990 μm.

7. The implant of claim 1, wherein the two layers of mesh are further connected to each other along at least one cut line.

8. The implant of claim 7, wherein said cut line is comprised of unidirectional continuous fibers.