HK1164679B - A composite and its use - Google Patents

Description

Composite and use thereof

Technical Field

The present invention relates to a composite comprising a structural part, a porous part and at least two interconnecting parts arranged at a distance from each other and extending from the structural part to the porous part, thereby connecting them to each other, which composite can be used for bone and cartilage reconstruction and implants. The invention also relates to a method for manufacturing a composite comprising a structural part, a porous part and at least two interconnecting parts.

Background

The use of reinforced composites made of particulate fillers or reinforcing fibers has gained popularity in the dental and medical fields. Several fiber reinforced composites are known. Recent fiber reinforced composites produce high strength properties and by selecting a multiphase resin matrix for the composite, the processing characteristics of the composite can be significantly improved. These have been described, for example, in patent applications WO96/25911 and WO 99/45890.

On the other hand, many advances have been made in bioactive materials, i.e., bioactive ceramics and glasses, and sol-gel processed silicas. These materials can be used to achieve, for example, bone attachment to a biomaterial surface after contacting the material with tissue. An additional advantage of bioactive glass is its antibacterial effect on microorganisms present in, for example, the bone sinuses. These properties have been described in several articles and patent applications, such as WO96/21628 and zehnderet, JEndod2004 Apr; 30(4): 220-4.

Despite the increasing progress in biomaterial research and their methods of clinical application and tissue engineering, the replacement of bone, cartilage and soft tissue alone is not sufficient from a surgical point of view in tumor, trauma and tissue reconstruction surgery. The need and evidence for developing new materials arises from the deficiencies 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 leads to stress shielding phenomena and bone atrophy adjacent to the skeleton. Metal implants also cause serious problems in magnetic resonance imaging when diagnosing a patient's disease. These major disadvantages have been well documented in a number of clinics. On the other hand, stem cell based medical treatments are becoming the choice for treating tissue damage. In a large number of reconstructive cases, stem cell therapy requires the use of scaffolds with some porosity. Currently, stents are made of biodegradable polymers and no non-absorbable porous fiber-reinforced composite has been used in conjunction with regenerative therapy of stem cells and reconstructive therapy by fiber composite implants.

Document US2007/0061015 discloses biocompatible appliances for bone and tissue regeneration having a multilayer structure. The multilayer structure can be reinforced by adding strips to the outer surface of the appliance. In document US2004/0258732, the implant material is made by combining a porous article and a peg penetrating the porous article.

There are several different composites comprising bioactive materials and mimicking bone structure, for example, in patent applications WO2004/103319 and WO 2005/118744. A problem encountered with these materials is their insufficient mechanical strength. Another problem with these materials is the weak adhesion of the porous material (which is impregnated to a low degree by the matrix resin) to the load bearing material. Another problem is that: particles added to the material to enhance osteoconductivity tend to become loose and disappear from the material before the material is placed in the final position.

Objects and summary of the invention

It is an object of the present invention to provide a biocompatible material which does not have the above-mentioned disadvantages, or at least minimizes them. 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 for bone grafting. It is a further object of the present invention to provide materials and composites which have good mechanical properties and in which the additional particles can be used in a safe manner. Further, it is an object of the present invention to provide an implant structure which can be used as a scaffold for stem cell seeding.

The invention thus relates to a composite comprising a structural part, a porous part and at least two interconnecting parts which are arranged at a distance from each other and which extend from the structural part to the porous part, thereby connecting them to each other. In a typical composite of the invention, each interconnecting portion is in the form of a strip having a length, a width and a height, each of the width and height independently being less than 20% of the length of the strip, and at least one interconnecting portion is at least partially embedded in the structural and porous portions.

The invention also relates to the use of these composites in dental and medical applications. The invention also relates to a method of manufacturing a composite comprising a structural part, a porous part and at least two interconnecting parts.

Drawings

Figure 1 illustrates the testing of a complex according to a first embodiment of the invention.

Fig. 2a and 2b illustrate a composite according to a second embodiment of the invention.

Figure 3 illustrates a composite according to a third embodiment of the invention.

Fig. 4 illustrates an implant and its use according to a fourth embodiment of the invention.

Fig. 5 illustrates an implant and its use according to a fifth embodiment of the invention.

Fig. 6 illustrates an implant and its use according to a sixth embodiment of the invention.

Detailed Description

The invention is defined by the appended independent claims.

The invention relates to a composite comprising a structural part, a porous part and at least two interconnecting parts which are arranged at a distance from each other and which extend from the structural part to the porous part, thereby connecting them to each other. In a typical composite of the invention, each interconnecting portion is in the form of a strip having a length, a width and a height, each of the width and height independently being less than 20% of the length of the strip, and at least one interconnecting portion is at least partially embedded in the structural and porous portions.

Different parts of the complex: the structural portion, the porous portion, and the interconnecting portion all form part of a composite. The present invention thus meets the above object, i.e. it provides a material useful for medical, dental and surgical applications, such as bone grafting, which has good mechanical properties, as shown in the experimental part below, and wherein additional particles can be used in a safe manner.

The porous part of the composite promotes the growth of new bone, cartilage, etc., and the structural part provides mechanical strength. The interconnecting members bond the two parts together and provide shear strength to the composite, while also increasing the compressive and tensile strength of the composite. Another advantage of the present invention is that it allows the manufacture of implant materials that closely resemble true bone, i.e. the use of allografts is avoided. On the other hand, the use of conventional metal implants is becoming increasingly undesirable due to the increase in magnetic resonance imaging. Thus, the present invention provides graft materials that are both safe (without the risk of contamination with allografts) and interfere with currently used imaging systems (like metals).

Another advantage of the invention and the use of the exchange connection in tape form is: the strip gives a better reinforcement than the plug. Furthermore, the use of a band allows for the use of capillary forces during healing, thereby enhancing blood flow into the implant and directing cell growth.

The porous portion of the composite enables embryonic, hematopoietic or mesenchymal stem cells to be seeded into the implant, reinforcing the attachment of the implant to bone or cartilage after being implanted into the body. Thus, the material of the invention allows the use of stem cells in regenerative medical treatment in combination with non-metallic fiber reinforced composites in regenerative medical treatment.

In the present application, curing is mentioned, which means polymerization and/or crosslinking. Reference to a matrix, which is understood to be the continuous phase of the composite, reference to an uncured matrix, denotes a matrix in its deformable state but capable of being cured (i.e. hardened to a substantially non-deformable state). The uncured matrix may already include some long chains but has not been substantially polymerized and/or crosslinked. By prepreg is meant a semi-finished product, i.e. a product that is not polymerized or only partially polymerized but still deformable. Polymerization, i.e., curing of the resin, produces a composite material.

The interconnecting parts are in the form of strips, such as strips, rods or cylinders. They may be straight or curved, for example, they may follow the shape of a blood vessel that will grow in the implant once it is placed in the patient. According to a preferred embodiment, the interconnecting parts are arranged such that blood vessels, in particular large blood vessels, will grow naturally between them, since blood vessels and bone will not normally grow through the interconnecting parts. More preferably, the outer surface of the implant is not covered with a material similar to the material of the interconnecting portions, as this would inhibit tissue ingrowth. Preferably, the outer surface is covered with a dense layer of material that has been perforated to allow bodily fluids to flow within the implant. Over time, this layer will degrade.

According to an embodiment of the invention, the width and height of the interconnecting section are each independently less than 15% of the length of the interconnecting section. Thus, the length is the largest dimension of the interconnecting section. In practice, the length of the interconnecting sections depends on the size of the implant that has been made.

According to one embodiment of the invention, the structural portion and the porous portion each comprise fibers and a matrix. According to another embodiment of the invention, the amount of fibres per volume of the structural part is greater than the amount of fibres per volume of the porous part. In addition, the basis mass per volume of the structural portion may be greater than the basis mass per volume of the porous portion.

Thus, the structural portion preferably has a higher density than the porous portion, and the fibers are impregnated by the resin forming the matrix to a higher degree than in the porous portion. The degree of partial impregnation may be 5 to 100%.

According to one embodiment, the interconnecting members are comprised of a matrix material (i.e., a polymer). According to another embodiment, the interconnecting portion further comprises a filler and a matrix. Thus, it may be made of a filled polymer, or it may also comprise reinforcing materials such as fibres and thus be made of a composite. Preferably there are more than two interconnecting sections spaced from each other. This spacing may be, for example, 1-100 mm. Suitable spacing between the interconnecting portions is from 0.5, 1, 3,6, 10, 15, 25, 30, 35, 40 or 50mm up to 3, 5, 10, 14, 15, 20, 30, 40, 55, 65, 80 or 100 mm. The spacing between two particular interconnecting sections need not be equal to the spacing between two other particular interconnecting sections, although the distribution of interconnecting sections may also be uniform and regular. The spacing of the interconnecting parts from each other is used to mimic the original bone and bone structure and has a significant impact on the capillary forces in the implant during healing.

The interconnecting portion extends from the porous portion to the structural portion and preferably has the same height (thickness) as the thickness of the composite, i.e. it extends over the entire thickness of the composite. The thickness of the composite may be, for example, from 0.05 to 5mm or more.

According to a preferred embodiment of the present invention, the matrix material of the structural part, the porous part and the interconnecting part is composed of different amounts of the same component, respectively. This enhances the binding between the moieties due to the same chemical structure of the matrix. Examples of which are given in the experimental section.

When the composite of the present invention is ready for use, at least a portion of at least one of the substrates may be in a partially uncured form to allow the composite to be shaped into a desired shape. It may also be shaped prior to the actual application of the composite, for example, on a model for reconstructing the defect to be treated.

The fibers may be any suitable fibers known per se, for example selected from the group consisting of: glass fibers, silica fibers, carbon/graphite fibers, ceramic fibers, aramid fibers, nylon fibers, polyethylene fibers, polytetrafluoroethylene fibers (e.g., Teflon @)Fibers), poly (p-phenylene-2, 6-benzobisoxazole) fibers, poly (2, 5-dihydroxy-1, 4-phenylenepyridobisimidazole) fibers, polyolefin fibers, fibers made from olefin copolymers, polyester fibers, polyamide fibers, and mixtures thereof. Poly (p-phenylene-2, 6-benzobisoxazole) fibers and poly (2, 5-dihydroxy-1, 4-phenylenepyridobisimidazole) fibers belong to the group known as rigid rod polymer fibers. It will be apparent to those skilled in the art that any other known fiber may be used in the present invention, provided that suitable adhesion between the fiber and the matrix can be achieved to achieve the desired mechanical properties. Preferably, glass fibers are used in dental applications. In applications where load bearing capacity is required, continuous biostable fibers are preferred.

According to one embodiment of the invention, the fibers are selected from the group consisting of: inert glass fibers, bioactive glass fibers, silica fibers, quartz fibers, ceramic fibers, carbon/graphite fibers, aramid fibers, ceramic fibers, poly (p-phenylene-2, 6-benzobisoxazole) fibers, poly (2, 5-dihydroxy-1, 4-phenylenepyridobisimidazole) fibers, polyolefin fibers, fibers made from olefin copolymers, polyester fibers, polyamide fibers, polyacrylic fibers, sol-gel treated silica fibers, collagen fibers, cellulosic fibers, modified cellulosic fibers, and mixtures thereof.

The fibers may be in the form of: continuous fibers, woven fibers, felted fibers, chopped fibers, and mixtures thereof, the fibers may be oriented in one direction, two directions, three directions, four directions, randomly, or mixtures thereof.

According to one embodiment, the fibers of the structural part are in the form of a fiber fabric or a unidirectional fiber yarn bundle. The fibers of the porous portion are in the form of, for example, chopped (short) randomly oriented fibers, a fiber fabric, or a three-dimensional fiber fabric.

The matrix material may comprise a monomer selected from the group consisting of: methyl acrylate, ethyl acrylate, propyl acrylate, isopropyl acrylate, n-hexyl acrylate, styrene acrylate, allyl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, isopropyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, 2-ethylhexyl methacrylate, cyclohexyl methacrylate, isobornyl methacrylate, tetrahydrofurfuryl methacrylate, benzyl methacrylate, morpholinoethyl methacrylate, diurethane dimethacrylate, acetoacetoxyethyl methacrylate (AAEM), methacrylate-functionalized dendrimers, other methacrylated hyperbranched oligomers, hydroxymethyl methacrylate, hydroxymethyl acrylate, hydroxyethyl methacrylate, hydroxyethyl acrylate, propyl methacrylate, hydroxyethyl acrylate, isopropyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, 2-ethylhexyl methacrylate, cyclohexyl methacrylate, isobornyl methacrylate, tetrahydrofurfuryl methacrylate, benzyl methacrylate, morpholinyl ethyl methacrylate, urethanedimethacrylate, acetoacetoxyethyl methacrylate (AAEM), methacrylic acid-functionalized dendrimers, other methacrylated hyperbranched oligomers, Hydroxypropyl acrylate, tetrahydrofurfuryl methacrylate, tetrahydrofurfuryl acrylate, glycidyl methacrylate, glycidyl acrylate, triethylene glycol diacrylate, tetraethylene glycol dimethacrylate, tetraethylene glycol diacrylate, trimethylolethane trimethacrylate, trimethylolpropane trimethacrylate, pentaerythritol trimethacrylate, trimethylolethane triacrylate, trimethylolpropane triacrylate, pentaerythritol tetramethacrylate, pentaerythritol tetraacrylate, ethylene dimethacrylate, ethylene diacrylate, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate (TEGDMA), ethylene glycol diacrylate, diethylene glycol diacrylate, butanediol dimethacrylate, ethylene glycol diacrylate, propylene glycol diacrylate, Butanediol diacrylate, neopentyl glycol dimethacrylate, neopentyl glycol diacrylate, 1, 3-butanediol dimethacrylate, 1, 3-butanediol diacrylate, 1, 4-butanediol dimethacrylate, 1, 4-butanediol diacrylate, 1, 6-hexanediol dimethacrylate, 1, 6-hexanediol diacrylate, di-2-methacryloyloxyethyl-hexamethylene dicarbamate, di-2-methacryloyloxyethyl-trimethylhexamethylene dicarbamate, di-2-methacryloyloxyethyl-dimethylbenzene dicarbamate, di-2-methacryloyloxyethyl-dimethylcyclohexane dicarbamate, methylene-bis-2-methacryloyloxyethyl-4-cyclohexylmethyl-cyclohexane dicarbamate Carbamates, di-1-methyl-2-methacryloyloxyethyl-hexamethylene dicarbamate, di-1-methyl-2-methacryloyloxyethyl-trimethylhexamethylene dicarbamate, di-1-methyl-2-methacryloyloxyethyl-dimethylbenzene dicarbamate, di-1-methyl-2-methacryloyloxyethyl-dimethylcyclohexane dicarbamate, methylene-bis-1-methyl-2-methacryloyloxyethyl-4-cyclohexyl carbamate, di-1-chloromethyl-2-methacryloyloxyethyl-hexamethylene dicarbamate, bis-1-chloromethyl-2-methacryloyloxyethyl-hexamethylene dicarbamate, and mixtures thereof, Bis-1-chloromethyl-2-methacryloyloxyethyl-trimethylhexamethylene dicarbamate, bis-1-chloromethyl-2-methacryloyloxyethyl-dimethylbenzene dicarbamate, bis-1-chloromethyl-2-methacryloyloxyethyl-dimethylcyclohexane dicarbamate, methylene-bis-2-methacryloyloxyethyl-4-cyclohexylcarbamate, bis-1-methyl-2-methacryloyloxyethyl-hexamethylene dicarbamate, bis-1-methyl-2-methacryloyloxyethyl-trimethylhexamethylene dicarbamate, bis-1-methyl-2-methacryloyloxyethyl-dimethylbenzene dicarbamate Bis-1-methyl-2-methacryloyloxyethyl-dimethylcyclohexanedicarbamate, methylene-bis-1-methyl-2-methacryloyloxyethyl-4-cyclohexylcarbamate, bis-1-chloromethyl-2-methacryloyloxyethyl-trimethylhexamethylene dicarbamate, bis-1-chloromethyl-2-methacryloyloxyethyl-dimethylbenzenedicarbamate, bis-1-chloromethyl-2-methacryloyloxyethyl-dimethylcyclohexanedicarbamate, methylene-bis-1-chloromethyl-2-methacryloyloxyethyl-4-cyclohexylcarbamate, bis-methyl-ethyl-4-cyclohexylcarbamate, bis-methyl-2-methyl-ethyl-methyl-carbamate, bis-methyl-2-methacryloyloxyethyl-methyl-4-cyclohexyl carbamate, bis-, 2, 2-bis (4- (2-hydroxy-3-methacryloyloxy) phenyl) propane (bis GMA), 2 '-bis (4-methacryloyloxyphenyl) propane, 2' -bis (4-acryloyloxyphenyl) propane, 2 '-bis [4 (2-hydroxy-3-acryloyloxyphenyl) propane, 2' -bis (4-methacryloyloxyethoxyphenyl) propane, 2 '-bis (4-acryloyloxyethoxyphenyl) -propane, 2' -bis (4-methacryloyloxypropoxyphenyl) propane, 2 '-bis (4-acryloyloxy-propoxyphenyl) propane, 2' -bis (4-methacryloyloxydiethoxyphenyl) -propane, bis (4-methacryloyloxydiethoxyphenyl) propane, 2, 2 ' -bis (4-acryloyloxydiethoxyphenyl) propane, 2 ' -bis [3 (4-phenoxy) -2-hydroxypropane-1-methacrylate ] propane, 2 ' -bis [3 (4-phenoxy) -2-hydroxypropane-1-acrylate ] propane and mixtures thereof.

The matrix may also be composed of crosslinkable monomers or polymers such as: caprolactone, polycaprolactone, polylactic acid, polyhydroxyproline and other biopolymers, as well as polyamides, polyurethanes, polyethylene, polypropylene, other polyolefins, polyvinyl chloride, polyesters, polyethers, polyethylene glycol, polysaccharides, polyacrylonitrile, poly (methyl methacrylate), phenol-formaldehyde, melamine-formaldehyde and urea-formaldehyde. The matrix may of course also consist of a mixture of monomers and polymers.

Dendrimers with 5 to 35 functional groups (or more) such as methacrylate or acrylate groups may also be used. The multiple functionality forms a highly crosslinked matrix and reduces creep of the polymer over long term use. The functionality of the dendrimer can be varied to accommodate the attachment of drug molecules to the dendrimer-based implant for allowing slow release of the drug locally from the dendrimer-based implant. Examples of suitable dendrimers are given in, for example, US5,834,118 (incorporated herein by reference). The dendritic polymer may in particular be a star-shaped or hyperbranched methacrylated polyester.

According to one embodiment of the invention, the substrate can be made from the following monomer system: mono-, di-, or multifunctional acrylates, epoxies, dendrimers, hyperbranched reactive polymers, combinations thereof, and the like. For example, the matrix may be selected from the group consisting of: mono-, di-and multifunctional acrylates, mono-, di-and multifunctional methacrylates, epoxy resins, star-and-radial methacrylated polyesters, hyperbranched methacrylated polyesters and mixtures thereof. Alternatively, polymers of polymethacrylic acid, polyvinyl chloride, polyetherketone, polylactic acid, -caprolactone, combinations thereof, or the like may be used. Combinations of monomers and polymers may also be suitably employed. Currently, in dental applications, it is preferred to use a combination of dimethacrylate and polymethylmethacrylate as the matrix because it forms a gel-like matrix prior to polymerization. The matrix may be dense or contain pores and holes in the structure, depending on the clinical need. When considering bone ingrowth, the optimal pore size for intraosseous applications is 100 to 500 microns, but alternatively the composite may also comprise holes up to 5mm in diameter.

According to an embodiment of the invention, the matrix material is selected from the group consisting of: triethylene glycol dimethacrylate, 2-bis (4- (2-hydroxy-3-methacryloyloxy) phenyl) propane, polymethyl methacrylate, methyl methacrylate, hydroxyethyl methacrylate, urethane dimethacrylate, star-and-star-shaped methacrylated polyester, hyperbranched methacrylated polyester, polyvinyl chloride, polyetherketone, polylactic acid, -caprolactone, poly-OH-proline and mixtures thereof.

The composite of the present invention may further comprise modifier particles. These modifier particles may be, for example, bioactive and, for example, enhance the osteoconductivity of the composite. The particles may be in the form of particulate fillers or fibres. The weight fraction of these modifier particles in the composite may be, for example, 10-60 wt-%, such as from 5, 10, 15, 20, 35, or 50 wt-% 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 glasses, silica gels, titanium gels, silica xerogels, silica aerogels, sodium silica glasses, titanium gels, bioactive glass ionomers, hydroxyapatite, Ca/P-doped silica gels, and mixtures thereof. Of course any combination of the materials described may also be used. When rapid mineralization is desired, it is preferred to have the bioactive glass with sol-gel treated silica particles on the porous portion of the composite.

The composites of the present invention may further comprise particulate filler materials such as inert glasses, bioactive glasses, metal oxides, ceramics, polymers, and mixtures thereof. For example, metal oxides can be used as radiation or X-ray shielding materials or as coloring materials. For example, the composite may be prepared such that it is not necessary to coat it with additional materials to prepare the final outer surface of the finished device.

The complex may also include a therapeutically active agent or cell, such as a stem cell. Several cells can be seeded into the complex, including hematopoietic bone marrow cells, fibroblasts, osteoblasts, regenerative cells, stem cells (e.g., embryonic stem cells, mesenchymal stem cells, or adipose stem cells). Embryonic stem cells may or may not be of human origin. The stem cells seeded into the complex may be cultured in vitro in a bioreactor, cultured in other parts of the body before the resulting tissue is implanted in its final location, or cultured directly at the location where regeneration and reconstitution are required. The compound may also contain additives to enhance its processability, such as polymerization initiators. The composite material may be bioresorbable, biodegradable, biostable or a mixture of these materials.

Due to the dense part of the composite, the bond strength of the composite may vary from e.g. 5 to 500 Mpa. Thus, the strength is significantly higher than known biomaterials with porous parts.

The invention further relates to the use of the composites of the invention in dental and medical applications. Such uses are for example supports for replacement of bones or fractures. The above embodiments and details relating to the composites are also applicable to the use of the invention.

The compounds of the invention may also include other moieties as required for their further use as described below.

According to an embodiment of the invention, at the location of the interconnecting part, the composite further comprises a dental implant or a peg for a dental implant provided on the structural part. This has the advantage that when the jaw is reconstructed, the teeth can be located wherever they are needed, not just where the original bone is retained. With prior art materials, the material typically does not have sufficient strength to withstand the bite force. Dental implants can be made from titanium, ceramic materials, or polymer composites.

The compounds of the invention may also be used to make implants for example for auditory ossicles or veins. Some applications of composites in contact with soft tissue are stents, catheters and prostheses to ensure the opening of a constricted cavity. Thus, the invention also relates to a prefabricated support consisting essentially of the material according to the invention. The preformed stent may be used, for example, in blood vessels, internal organs, esophagus, gastrointestinal tract, lymphatic vessels, urethra, respiratory tract, and nervous system.

Thus, the materials of the present invention can be used to fabricate any kind of device, and the fabrication method will be apparent to those skilled in the art. The size of the device may range from microns (e.g., for small auditory bone implants) to large tissue pieces. Thus, the material of the present invention can be used to make "spare parts" such as ears, nose and eyes.

In addition, the material can be used for manufacturing nose or soft facial tissues, knee or shoulder prostheses. Some examples of applications are as load bearing structural biomaterials, for replacement and repair of tissue, bone and skeleton, for maintenance of soft and cartilaginous tissue in a desired form, or for cell and tissue engineering and testing. As structural biomaterials, the composites can also be used for long bone replacement, root canal posts for independently formed teeth, dental implants, spinal, pelvic replacement, and reconstruction of other bone parts such as repair and replacement of ossicles. The composite may also be used as a replacement material for tissue invaded by a tumor, for example. In orthopaedic surgery, the composite may be used to hold soft or cartilaginous tissue in a position where the composite gives the best and desired support to the tissue, taking into account the aesthetics and beauty of the human body. The complexes of the invention may be used in humans and animals.

When different other moieties are attached to the composite of the invention, thereby forming an implant, the attachment is preferably made at the location of the interconnecting moieties. Attachment can be by mechanical bonding, using an adhesive such as silane, or by polymerization (e.g., by interpenetrating polymer networks, IPNs).

Thus, the invention also relates to an implant comprising a composite according to the invention. The implant may further comprise stem cells, therapeutically active agents, and the like.

The invention also relates to a method of manufacturing a composite comprising a structural part, a porous part and at least two interconnecting parts. In this method, the following steps are performed:

a) the structural part is manufactured and shaped into the desired final shape of the composite, and at least partially cured,

b) forming interconnecting portions, and placing them on the structural portions at a distance from each other,

c) fabricating a porous portion and shaping to a shape corresponding to the structural portion and at least partially curing, an

d) The porous portion is pressed against the structural portion on the same side as the interconnecting portion.

The method may further comprise a step e) between steps b) and d) (i.e. between steps b) and c) or between steps c) and d), wherein between the interconnecting parts, modifier particles are provided on the structural parts.

The method may further comprise a final curing step f).

In step b), the interconnecting parts may be formed as a mono-oriented composite material already in the form of a tape, or for example by injecting a paste comprising the components of the interconnecting parts.

Thus, the material can be used to make a custom-made form of the implant for the patient's anatomical needs on a rapid prototyping model, or the implant can be made in a standard form that will be used for the average treatment case.

In the manufacture of custom and standard composite implants, prepregs for the structural part are formed and initially polymerized on a rapid prototype of the reconstruction region by self-polymerization, photo-polymerization, thermal polymerization, ultrasonic or microwave polymerization. The interconnecting elements in the form of a non-polymeric paste are placed on the surface of the structural part that is desired to be covered by the porous composite, i.e. to be filled with tissue over time. A prepreg of porous material is placed over the interconnect element and pressed against the structural portion. Particles of bioactive glass or the like are sprinkled on the structural part before the porous prepreg is placed on the structural part. The interconnecting members and the porous composite prepreg are simultaneously polymerized by self-polymerization, photo-polymerization, thermal polymerization, ultrasonic or microwave polymerization. The composite is post-polymerized at a temperature that allows for an optimal degree of monomer conversion, i.e., at a temperature near the glass transition temperature of the polymer matrix. The composite implant is then preferably packaged and sterilized by heat, steam, hydrogen peroxide, supercritical carbon dioxide, or by radiation. These products typically have a shelf life of about one year.

The above specific embodiments and details relating to the composites and uses also apply to the implants and methods of the invention.

Detailed description of the drawings

Figure 1 illustrates the testing of a complex according to a first embodiment of the invention. This test is described in more detail in the experimental section.

Fig. 2a and 2b illustrate a composite according to a second embodiment of the invention. In this embodiment, as shown in fig. 2a viewed from above, the structural part 1, the bioactive particle 2 and the porous layer 3 are connected to each other with a longitudinal rectangular strip 10. In these figures, the length L, height H and width W of the belt 10 are also shown.

Figure 3 illustrates a composite according to a third embodiment of the invention. In this embodiment, two porous sections 3 and 6 are provided on the structural section 1. The bioactive particles 2 and 5 are disposed at two interfaces and all of these portions are interconnected by an interconnecting portion 4 in the form of a band.

Fig. 4 illustrates an implant and its use according to a fourth embodiment of the invention. This figure shows a facial view of a maxillofacial implant 11, said maxillofacial implant 11 comprising an interconnection band 12 continuous along the direction of the facial vascular arteries 13. The cross-sectional view along line a-a shows the structure of the implant, i.e., the interconnecting band 12 is embedded in the porous layer 14 of the implant, thereby connecting them to each other and holding them together. The porous layer also provides space 15 for bioactive particles (not shown for clarity reasons) and for bone and blood vessel ingrowth. The surface of the implant is constituted by a surface layer 16.

Fig. 5 illustrates an implant and its use according to a fifth embodiment of the invention. This figure shows a sagittal view of a cranioplasty implant 17 replacing part of the parietal bone after brain surgery. The cross-sectional view along line B-B shows the structure of the implant, i.e. the interconnecting band 12, the space for bone ingrowth 15 and the porous layer 14. The implant also includes an outer surface layer 16.

Fig. 6 illustrates an implant and its use according to a sixth embodiment of the invention. The figure shows the mandible (osmandibularis) with a reconstruction implant 18, which reconstruction implant 18 has a dental implant 19 anchored to the interconnecting band 12 of the implant. The cross section along line C-C shows how the roots 20 of the dental implant 19 are anchored to the interconnecting band in order to withstand the shear forces exerted on the dental implant by chewing.

Test section

Some of the composites of the invention were made and their strength tests are described below.

Example 1

Using a woven E-glass fabric (120 g/m)²) A two-layer composite was prepared, the woven E-fiberglass fabric was impregnated with a monomer resin mixture of dual GMA-TEGDMA (70: 30 wt-%) including a photoinitiator-activator system. Four layers of resin impregnated fibers are used to obtain a dense load bearing laminate for composites. The glass fiber-resin ratio is 65 wt-% to 35 wt-%. The final thickness of the structural part (dense laminate with four layers of fibre fabric) was 1 mm. The laminate is photopolymerized into the shape of the outer surface of the composite.

The porous portion of the composite is made of E-glass fiber fluff with randomly oriented fibers. The fiber fluff was impregnated with a monomer resin mixture of bis-GMA-TEGDMA (40: 60 wt-%) including a photoinitiator-activator system. The low degree of resin impregnation of the pile results in interconnecting pores (interconnecting pores) in this section. The glass fiber-resin ratio of the porous portion of the composite was 76 wt-% to 24 wt-%. The thickness of the porous portion was 3 mm.

The structural part is joined to the porous part by interconnecting strips made of a composite resin comprising bis-GMA-TEGDMA (40: 60 wt-%) containing a photoinitiator-activator system and a particulate filler of silica having an average particle size of 1 μm and a weight ratio of 65% of the resin weight. This composite resin is in the form of a paste and has the viscosity of a typical paste. The paste was poured onto the structural part to obtain an interactive connecting tape 10mm long, 2mm wide and 1mm high. The distance between the interconnecting strips was 10 mm.

A bioactive modifier consisting of bioactive glass particles is sprinkled on the surface of the structured portion over the space between the interconnecting strips. The particle size of the bioactive glass is 0.5 to 0.8 mm. The porous section is placed on the structural section and on the interconnecting tape. The bioactive particulate is retained between the layers. The porous portion is pressed against the structural portion such that the interconnecting strips penetrate the porous layer. The pressing process stretches the interconnecting strips to achieve the above-mentioned final dimensions. The interconnecting tape and porous layer portion are then photopolymerized to attach it to the structural portion. The total weight fraction of bioactive glass in the composite was 26%.

Example 2

Bilayer composites with and without interconnecting strips between the structural and porous portions, as prepared in example 1, were tested to demonstrate the effect of the interconnecting strips on the shear resistance of the composites. The structural moiety is bonded to the acrylic block from the outer surface of the composite. The other surfaces have porous portions attached to the structural members only by photopolymerization of the resin matrix of the porous portions, or by using the interconnecting tape described in example 1. The test apparatus is shown in fig. 1.

In fig. 1, reference numeral 1 shows a structural portion, 7 shows an acrylic block, 3 shows a porous portion, 4 shows an interconnecting band, 8 shows dental gypsum (i.e., plaster of paris), and 9 shows the direction of shear force.

The porous section was filled with plaster of paris to simulate the situation of bone growth into interconnecting pores (interconnectivepores). After the plaster of paris is set, a shear force is applied to the porous portion and the plaster of paris. The force required to loosen the porous portion from the structural portion is used as an indicator of the shear resistance of the bilayer composite.

The shear force exhibited was 431N loading force for the sample without the cross-link tape and 879N for the sample with the cross-link tape. These values demonstrate that: the interconnecting strips are compressed by the stress, and the porous sections are firmly attached to the structural sections, i.e., the dense laminate, by the interconnecting strips.

In this specification, unless the context requires otherwise, the terms "comprising", "including" and "comprising" mean "including", "including" and "containing", respectively. That is, while the invention has been described or defined as including particular features, various embodiments of the same invention may also include other features. Furthermore, the reference signs shall not be construed as limiting the claims.

Claims (18)

1. A biocompatible composite, comprising:

a structural part (1),

a porous portion (3,6,14), and

at least two interconnecting sections (4,10,12) arranged at a distance from each other and extending from the structural section (1) towards the porous sections (3,6,14) thereby connecting them to each other,

the method is characterized in that:

each of said interconnecting sections (4,10,12) being made of a polymer, a filled polymer or a composite comprising a polymeric matrix material, a filler and a reinforcing material and being in the form of a tape having a length, a width and a height, each of said width and height being independently less than 20% of the length of the tape,

at least one of said interconnecting parts (4,10,12) being at least partially embedded in said structural part (1) and said porous part (3,6,14), and

the structural part (1) and the porous part (3,6,14) each comprise fibres and a matrix.

2. The compound of claim 1, wherein: the width and height of the interconnecting sections (4,10,12) are each independently less than 15% of the length of the interconnecting section.

3. The compound of claim 1, wherein: the amount of fibres per volume of the structural part (1) is greater than the amount of fibres per volume of the porous part (3,6, 14).

4. The compound of any preceding claim, wherein: the amount of matrix per volume of the structural part (1) is greater than the amount of matrix per volume of the porous part (3,6, 14).

5. The compound of claim 1, wherein: the fibres of the structural part (1) are in the form of a fibre fabric or a unidirectional fibre yarn bundle.

6. The compound of claim 1, wherein: the fibers of the porous portion (3,6,14) are in a form selected from the group consisting of: chopped randomly oriented fibers or fiber fabrics.

7. The compound of claim 1, wherein: the fibres of the porous part (3,6,14) are in the form of a three-dimensional fibre fabric.

8. The compound of claim 1, wherein: the interconnecting portion (4,10,12) comprises a matrix.

9. The compound of claim 8, wherein: the interconnecting part (4,10,12) further comprises a filler.

10. The compound of claim 1, wherein: it further comprises modifier particles (2, 5).

11. The compound of claim 10, wherein: the modifier particles (2,5) increase the osteoconductivity of the composite.

12. The compound of claim 10 or 11, wherein: the modifier particles (2,5) are selected from the group consisting of: bioactive ceramics, bioactive glass, silica gel, titanium gel, sodium silica glass, bioactive glass ionomers, hydroxyapatite, Ca/P-doped silica gel, and mixtures thereof.

13. The compound of claim 10 or 11, wherein: the modifier particles (2,5) are selected from the group consisting of: silica xerogels, silica aerogels, Ca/P-doped silica gels, and mixtures thereof.

14. The compound of claim 1, wherein: the matrix material of the structural part (1), the porous part (3,6,14) and the interconnecting part (4,10,12) is composed of different amounts of the same component, respectively.

15. The compound of claim 1, wherein: it further comprises a finished dental implant provided on said interconnection portion (4,10, 12).

16. An implant comprising the composite as claimed in any one of claims 1 to 15.

17. The implant of claim 16, wherein: it further comprises stem cells.

18. Method for manufacturing a composite comprising a structural part (1), a porous part (3,6,14) and at least two interconnecting parts (4,10,12), comprising the steps of:

a) the structural part (1) is manufactured and shaped into the desired final shape of the composite, and at least partially cured,

b) forming interconnecting portions (4,10,12) and being placed on said structural portions at a distance from each other,

c) manufacturing a porous part (3,6,14) and shaping it to correspond to the shape of the structural part (1) and at least partially curing, and

d) -pressing the porous parts (3,6,14) against the structural part (1) on the same side as the interconnecting parts (4,10,12) so that the interconnecting parts (4,10,12) extend from the structural part (1) towards the porous parts (3,6,14), thereby connecting them to each other,

the method is characterized in that:

each of said interconnecting sections (4,10,12) being made of a polymer, a filled polymer or a composite comprising a polymeric matrix material, a filler and a reinforcing material and being in the form of a tape having a length, a width and a height, each of said width and height being independently less than 20% of the length of the tape,

at least one of said interconnecting parts (4,10,12) being at least partially embedded in said structural part (1) and said porous part (3,6,14), and

the structural part (1) and the porous part (3,6,14) each comprise fibres and a matrix.