Non-fixed implant for craniotomy and method for manufacturing the same

Abstract

A non-fixed implant is proposed, which is made of raw materials including a biomaterial, a ceramic matrix composite with excellent osteoconductivity, and a polymer. The non-fixed implant can be precisely fixed to the gap between the skull and the bone flap and can be conveniently used. A method for manufacturing the non-fixed implant is also proposed. The non-fixed implant includes a flexible wedge that can be deformed to conform to the outer contour of the bone flap, and a plurality of wings connected to the upper or lower part of the flexible wedge and extending to both sides of the flexible wedge. The wings have a porous structure. The wings on one side will be located on the bone flap, while the wings on the other side will be located on the skull. The non-fixed implant has the following advantages: it can precisely fill the defect formed by craniotomy, has improved biocompatibility and osteointegration ability, and allows tissue invasion.

Description

Technical Field

[0001] The present invention relates to an implant for filling a gap between the skull bone and a bone flap generated by a craniotomy. More specifically, the present invention includes a 3D printed implant made of a single polymer or a composite material of a polymer and a ceramic compound, the ceramic compound having excellent osteoconductivity similar to natural bone, and a method for manufacturing the same.

[0002] The non-fixed implant for craniotomy of the present invention is manufactured by 3D printing technology, has structural flexibility, can be applied to a defective site, and can be precisely combined with the defect due to its wedge-shaped insert. Therefore, the non-fixed implant of the present invention has the advantage of not requiring an additional fixing device for fixing the implant.

[0003] Project Unique Number: P0008811

[0004] Government Agency: Ministry of Trade, Industry and Energy

[0005] Project Management Professional Institution: Korea Institute of Technology Advancement

[0006] Research Business Name: 3D Printing Medical Device Industry Technology Demonstration Project

[0007] Research Business Name: Demonstration of Custom 3D Printed Implants for Surgery Using Polymer-Based Biodegradable Materials

[0008] Contribution Rate: 1 / 1

[0009] Research Institution: TNR Biofab Co., Ltd.

[0010] Research Period: April 1, 2019 to December 31, 2022 Background Art

[0011] For neurosurgery through the skull, a craniotomy is performed to access the patient's brain. During this process, a gap, i.e., a bone defect, appears due to cutting during the surgical procedure. The gap between the bones causes a risk that the brain will be exposed through it, and thus cannot be safely protected. In addition, blood flow at the incision site may be blocked, leading to osteolysis. Furthermore, the skin depresses along the gap after surgery, causing aesthetic dissatisfaction to the patient.

[0012] To solve these problems, conventionally, there have been methods of filling the gap with a metal mesh or bone cement.

[0013] Surgeries using a metal mesh such as titanium (Ti) or a titanium alloy have the advantage of preventing some problems such as skin depression, but have some problems, for example, they cannot promote bone tissue healing and require additional fixation devices for fixing the metal mesh to the skull. Additionally, when radiotherapy for treatment is performed, due to the inherent properties of the metal mesh, the radiation cannot pass through the metal mesh, so this patent cannot receive effective radiotherapy. Furthermore, the scattering of radiation from the implanted metal may cause side effects such as necrosis of surrounding tissues and atrophy of the flap, which may lead to the exposure of the implant to the outside.

[0014] The bone reconstruction part that fills the cranial depression with bone cement, used as an alternative to conventional surgery, makes up for the disadvantages of conventional surgery using a metal mesh. However, the reconstruction technique using bone cement brings inconvenience to practitioners due to the long operation time for filling cranial gaps of arbitrary shapes, and there is still a problem that surrounding tissues may be damaged due to the exothermic reaction during the cement curing process. Summary of the Invention

[0015] Technical Problem

[0016] In order to effectively solve the problems that occur in the prior art, the present invention provides an implant using a biocompatible material and a ceramic-based composite material and a polymer with excellent osteoconductivity, wherein the implant is a three-dimensional non-fixed implant that can be conveniently used and is configured to be placed in a bone defect. The present invention also provides a method for manufacturing the implant.

[0017] In addition, the present invention provides a non-fixed implant manufactured by a 3D printer and a method for manufacturing the same. The implant is precisely placed in the defect generated by a craniotomy, has improved biocompatibility and bone-bonding ability, and allows tissue penetration.

[0018] Technical Solution

[0019] The non-fixed implant 10 for craniotomy according to an embodiment of the present invention is used to reattach the bone flap 2 removed from the skull 1 during a neurosurgical operation. The non-fixed implant 10 includes: a flexible wedge 100 that can be deformed to conform to the outer contour of the bone flap 2; and a plurality of wings 200 that are connected to the upper or lower part of the flexible wedge 100 and extend from both sides of the flexible wedge 100.

[0020] The plurality of wings 200 may have a porous structure, wherein each wing 200 includes a first side wing 201 to be disposed on the bone flap 2 and a second side wing 202 to be disposed on the skull 1.

[0021] The flexible wedge 100 and the plurality of wings 200 are made of a material in which a polymer and a calcium phosphate compound are mixed at a weight ratio of 10:0 to 5:5, and are manufactured by 3D printing using an FDM 3D printer.

[0022] Each wing 200 has a porous structure with a lattice pattern. The porous structure includes: a first layer in which a plurality of lines extend in a first direction and have a width of 300 μm to 500 μm and a line spacing of 300 μm to 500 μm; and a second layer in which a plurality of lines extend in a second direction at an angle of 60° to 120° with respect to the first direction and have a width of 300 μm to 500 μm and a line spacing of 300 μm to 500 μm.

[0023] In addition, the flexible wedge 100 is composed of a plurality of stacked lines formed above or below the plurality of wings 200. The plurality of stacked lines are composed of alternately connected protrusions ("∩") and depressions ("U"). The plurality of stacked lines are formed such that an A-pattern line inclined at an acute angle with respect to the bottom surface and a B-pattern line inclined at an obtuse angle with respect to the bottom surface are stacked on each other.

[0024] In the flexible wedge 100, the width of its upper end is the same as the width of its lower end, but is greater than the width of its middle portion. This design enables the reliable fixation of the skull 1 and the bone flap 2.

[0025] One of the materials for 3D printing the flexible wedge 100 and the plurality of wings 200 can be a polymer selected from the group consisting of polyethylene, metallocene-PE (m-PE), polypropylene, polyisobutylene, poly-4-methylpentene-1, polybutadiene, polyisoprene, polycyclooctene, polystyrene, polymethylstyrene, polyvinylnaphthalene, styrene-butadiene (SB), styrene-butadiene-styrene (SBS), styrene-ethylene-butene-styrene (SEBS), styrene-ethylene-propylene-styrene, styrene-isoprene, styrene-isoprene-styrene (SIS), styrene-butadiene-acrylonitrile (ABS), styrene-acrylonitrile-acrylate (ASA), styrene-ethylene, polyvinyl chloride (PVC), polychlorobutene and polyvinylidene chloride (PVDC), polymethyl methacrylate (PMMA), butyl acrylate, lauryl acrylate, stearyl acetate, polyacrylonitrile, polyacrylamide, polyamide, polyimide, polyamideimide, polyetherimide, polyesterimide, poly(ether)ketone, polysulfone, polyethersulfone, polyarylsulfone, polyphenylene sulfide, polybenzimidazole, polyhydantoin, polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polypropylene (PP) terephthalate, polyethylene naphthylate, poly-1,4-dihydroxymethylcyclohexane terephthalate, polyhydroxybenzoate, polyhydroxynaphthalate, polylactide, polyglycolide, polycaprolactone, polyanhydride, polyamide, polyurethane, polyesteramide, polyorthoester, polydioxanone, polyacetal, polyketal, polycarbonate, polyorthocarbonate, polyphosphazene, polyhydroxybutyrate, polyhydroxyvalerate, polyalkylene oxalate, polyalkylene succinate, poly(malic acid), poly(amino acid), polyvinylpyrrolidone, polyethylene glycol, polyhydroxycellulose, chitin, chitosan, poly(L-lactic acid), poly(lactide-co-glycolide), poly(hydroxybutyrate-co-valerate), its copolymers and its terpolymers.

[0026] In addition, the calcium phosphate compound can include at least one selected from the group consisting of hydroxyapatite (HAP), carbonate apatite, tricalcium phosphate (TCP), calcium hydrogen phosphate, calcium dihydrogen phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, tricalcium phosphate, octacalcium phosphate and calcium pyrophosphate.

[0027] The material in which the polymer and the calcium phosphate compound are mixed can further include at least one natural polymer material selected from the group consisting of carboxymethyl cellulose, heparin sulfate, hyaluronic acid, collagen, dextran and alginate.

[0028] Materials comprising a polymer and a calcium phosphate compound or materials comprising a polymer, a calcium phosphate compound, and a natural polymer material may further comprise at least one selected from the group consisting of bone morphogenetic protein (BMP), epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor (TGFβ), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGE), insulin-like growth factor (IGF-1), thioredoxin (TRX), stem cell factor (SCF), hepatocyte growth factor (HGF), human growth hormone, and angiogenin.

[0029] As another embodiment of the present invention, a method for manufacturing an implant for filling a gap between a skull bone 1 and a bone flap 2 generated by a craniotomy is provided, the method comprising: mixing a polymer and a calcium phosphate compound in a weight ratio of 10:0 to 5:5 to prepare a composite material; using an FDM 3D printer and printing a plurality of wings 200 using the composite material; and using an FDM 3D printer and the composite material to form a plurality of stacked lines on the plurality of wings 200 to form a flexible wedge 100.

[0030] The plurality of wings 200 may have a porous structure, wherein a first side wing 201 of the wing 200 is disposed on the bone flap 2 and a second side wing 202 of the wing 200 is disposed on the skull bone 1.

[0031] The printing of the plurality of wings 200 may include: forming a first layer, wherein a plurality of lines extend in a first direction and have a width of 300 μm to 500 μm and a line spacing of 300 μm to 500 μm; and forming a second layer, wherein a plurality of lines extend in a second direction at an angle of 60° to 120° with respect to the first direction and have a width of 300 μm to 500 μm and a line spacing of 300 μm to 500 μm, wherein the formation of the first layer and the formation of the second layer are performed in sequence.

[0032] In the formation of the flexible wedge 100, the flexible wedge 100 may be formed of a plurality of lines stacked above or below the plurality of wings 200, wherein the plurality of stacked lines may include alternately connected protrusions (“∩”) and depressions (“U”), and the plurality of stacked lines may include A-pattern lines inclined at an acute angle with respect to the bottom surface and B-pattern lines inclined at an obtuse angle.

[0033] More preferably, the width of the upper end of the flexible wedge 100 is the same as the width of the lower end of the flexible wedge 100 and is greater than the width of the middle portion of the flexible wedge 100.

[0034] Beneficial effects

[0035] The non-fixed implant for craniotomy of the present invention is made of a material including a polymer such as polycaprolactone (PCL), and thus has a high elongation rate. Therefore, due to the high elongation rate of the non-fixed implant, the non-fixed implant can even be flexibly applied to the curved defect generated by craniotomy. In addition, since the non-fixed implant has a wedge-shaped insert to be inserted into the skull defect, the non-fixed implant can be fixed without using an additional fixing device after insertion. This means that the non-fixed implant has the ability to precisely bond to the defect.

[0036] In addition, the material of the non-fixed implant of the present invention may further include a ceramic compound, such as calcium phosphate. Therefore, the material of the non-fixed implant is crystallographically and chemically similar to the inorganic components constituting actual bone, and has the ability to directly bond to bone and excellent osteoconductivity.

[0037] In addition, when a biodegradable substance or a biodegradable polymer is used for the non-fixed implant, due to the property of being absorbed in the body, the non-fixed implant has a decomposition period of about 24 months, and thus no separate removal process is required. In addition, due to the unique porous structure, tissues can penetrate into the implant, and the implant can be replaced by new bone or absorbed into the body. Description of the Drawings

[0038] In Figure 1 , (a) and (b) are respectively a plan view and a three-dimensional view of the non-fixed implant for craniotomy of the present invention.

[0039] In Figure 2 , (a) and (b) are respectively cross-sectional views taken along directions I and II of Figure 1 .

[0040] Figure 3 is a schematic diagram showing an exemplary pattern of the wedge of the non-fixed implant for craniotomy of the present invention, in which pattern A and pattern B are alternately arranged.

[0041] Figure 4 is a schematic diagram showing the cross-sectional structure of the wedge of the non-fixed implant for craniotomy of the present invention.

[0042] Figure 5 is a photograph showing the flexibility of the non-fixed implant for craniotomy of the present invention.

[0043] Figure 6 is a photograph showing the states before and after reattaching the bone flap 2 to the skull 1 by using the non-fixed implant for craniotomy of the present invention.

[0044] [Description of the Reference Numerals in the Drawings]

[0045] 1: Skull

[0046] 2: Bone flap

[0047] 10: Non - fixed implant for craniotomy

[0048] 100: Flexible wedge

[0049] 200: Wings

[0050] 201: First wing

[0051] 202: Second wing Detailed implementation manners

[0052] Before describing the preferred embodiments of the present disclosure, it should be noted that the terms and words used in this specification and the appended claims should not be construed as limited to the conventional or dictionary meanings, but should be construed as meanings and concepts consistent with the technical idea of the present invention.

[0053] It will be further understood that when used in this specification, the terms "comprises" and / or "comprising" or "includes" and / or "including" or "has" and / or "having" specify the presence of the described features, regions, integers, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, regions, integers, steps, operations, elements, and / or components.

[0054] Thereafter, embodiments of the present disclosure will be described. However, the scope of the present disclosure is not limited to the preferred embodiments described below, and those skilled in the art can implement various modified forms of the content described herein without departing from the scope of the present disclosure.

[0055] The non - fixed implant for craniotomy of the present invention is constructed in such a way as to precisely fix the defect generated by craniotomy. The non - fixed implant has improved biocompatibility and osseointegration ability and allows tissue penetration. The non - fixed implant is manufactured using an FDM 3D printer.

[0056] Reference Figure 1 and 2 , the non - fixed implant 10 for craniotomy according to an embodiment of the present invention is used to re - attach the bone flap 2 removed from the skull 1 during brain surgery. The non - fixed implant 10 includes: a flexible wedge 100 that can be deformed to conform to the external contour of the bone flap 2; and a plurality of wings 200 that are connected to the upper or lower part of the flexible wedge 100 and extend towards both sides of the flexible wedge 100.

[0057] The plurality of wings 200 may have a porous structure, wherein the first side wing 201 (or 202) of the wing 200 is disposed on the bone flap 2, and the second side wing 202 (or 201) of the wing 200 is disposed on the skull 1.

[0058] The flexible wedge 100 and the plurality of wings 200 are made of a mixed material in which a polymer and a calcium phosphate compound are mixed at a weight ratio of 10:0 to 5:5, and are manufactured by 3D printing using an FDM 3D printer.

[0059] As the calcium phosphate compound, β-tricalcium phosphate (β-TCP) is preferably used. The β-tricalcium phosphate (β-TCP) is pulverized with a mortar and sieved to have an average particle size of about 100 μm.

[0060] First, as Figure 1 shown in the plan view (a) and the perspective view (b), the wing 200 has a multi-layer structure in which a plurality of lines are arranged at regular intervals in each layer. That is, the wing 200 includes: a first layer in which a plurality of lines extend in a first direction and have a width of 300 μm to 500 μm and a line pitch of 300 μm to 500 μm; and a second layer in which a plurality of lines extend in a second direction at an angle of 60° to 120° with respect to the first direction and have a width of 300 μm to 500 μm and a line pitch of 300 μm to 500 μm.

[0061] The wing 200 is configured such that a basic unit composed of the first layer and the second layer stacked in sequence is repeatedly stacked one to five times.

[0062] For each layer, the line width and the line pitch may be the same. Alternatively, for each layer, the line width and the line pitch may vary within an appropriate range. When the constituent lines have a predetermined width and pitch for directional arrangement, the wing not only has good mechanical strength but also has sufficient elasticity and flexibility.

[0063] As Figure 1 shown, the wing 200 preferably has a polygonal shape such as a hexagonal shape, so the width of each wing 200 is the longest at its center, where the wedge 100 is vertically formed at its top. In addition, in the wing 200, the left side of the central portion and the right side of the central portion are preferably symmetric. Although each wing 200 preferably has a hexagonal shape, the shape of the wing 200 is not limited thereto.

[0064] The wedge 100 is vertically formed on the top of the central portion of the wing 200 by an FDM 3D printing process. Preferably, the wedge 100 is made of the same material as the wing 200. The wedge 100 formed to protrude from the top of the wing 200 is linear and has an inclination angle of 60° to 120° with respect to the horizontal direction (0°). The line pitch of the wedge 100 may be 2 mm to 3 mm (Figure 3 P), and the line spacing is uniform and continuous as if the line spacing were drawn in a single-line drawing manner (see Figure 3 ).

[0065] In this case, the height of one layer of the wedge 100 is 100 μm to 200 μm, and the total height of the wedge 100 is preferably 3 mm to 8 mm. When forming each layer of the wedge 100, the lateral flexibility can be adjusted by controlling the spacing between the lines ( Figure 3 P). In this case, preferably, as Figure 3 shown, the A pattern and the B pattern are provided alternately by layer. This arrangement can prevent the implant from bending only in one direction or prevent the implant from having unidirectional flexibility.

[0066] When the A pattern and the B pattern are stacked alternately, as Figure 3 shown, the A pattern and B pattern layers can alternate for each layer (e.g., A - B - A - B - A - B -...). Alternatively, as shown in Tables 1 to 3, the A pattern and the B pattern can alternate every two layers (e.g., A - A - B - B - A - A - B - B -...) or every three layers (e.g., A - A - A - B - B - B -...). In this case, a total of six or more layers can be stacked according to the stacking rule. As shown in Tables 1 to 3, the number of stacked layers is not necessarily limited to 6.

[0067] That is, the flexible wedge 100 is composed of multiple lines stacked above or below the central portion of the plurality of wings 200. Each of the multiple lines has a pattern in which protrusions (“∩”) and depressions (“U”) are alternately connected. Each of the multiple lines has an A pattern inclined at an acute angle with respect to the bottom surface or a B pattern inclined at an obtuse angle with respect to the bottom surface. When the inclination angle of the A pattern is 45° to 90° and the inclination angle of the B pattern is 135° to 90°, the sum of the inclination angles of the A pattern and the B pattern is preferably equal to 180° so that the A pattern and the B pattern are complementary to each other.

[0068] [Table 1]

[0069]

[0070] [Table 2]

[0071]

[0072] [Table 3]

[0073]

[0074] Figure 2 In (b) of, the longitudinal direction of the wedge 100 protruding from the central portion of the wing 200 is shown ( Figure 1a vertical cross-section obtained by cutting in the direction I), and Figure 2 in (a) of FIG. shows a vertical cross-section obtained by cutting in the direction (i.e., the Figure 1 direction II) along the longest width of the wing 200 including the width of the wedge 100.

[0075] As Figure 2 shown in (a) of FIG., preferably, the width of the upper end of the flexible wedge 100 is equal to the width of the lower end of the flexible wedge 100 and is greater than the width of the middle portion of the wedge 100.

[0076] During craniotomy, the wedge 100 is inserted into the gap between the bone flap 2 and the skull 1. Therefore, when the widths of the upper end and the lower end are greater than the width of the middle portion, once the wedge 100 is inserted, the wedge can be stably fixed.

[0077] Figure 4 Schematically shows the cross-sectional structure of the wedge and the wing of the non-fixed implant 10 for craniotomy of the present invention having Figure 2 the shape shown in (a) of FIG. As described above, the width of the first layer of the wedge is the same as the width of the last layer of the wedge (see Figure 4 , A), and the width is preferably 3 mm to 10 mm. In addition, the middle portion of the wedge (see Figure 4 , B) is relatively narrow, and the width of the middle portion is preferably 2 mm to 9 mm.

[0078] The non-fixed implant for craniotomy having such a structure is made of a composite material in which a polymer and a calcium phosphate compound are mixed at a weight ratio of 10:0 to 5:5.

[0079] The polymers used in the present invention include one or more selected from the group consisting of polyethylene, metallocene-PE (m-PE), polypropylene, polyisobutylene, poly-4-methylpentene-1, polybutadiene, polyisoprene, polycyclooctene, polystyrene, polymethylstyrene, polyvinylnaphthalene, styrene-butadiene (SB), styrene-butadiene-styrene (SBS), styrene-ethylene-butene-styrene (SEBS), styrene-ethylene-propylene-styrene, styrene-isoprene, styrene-isoprene-styrene (SIS), styrene-butadiene-acrylonitrile (ABS), styrene-acrylonitrile-acrylate (ASA), styrene-ethylene, polyvinyl chloride (PVC), polychlorobutene and polyvinylidene chloride (PVDC), polymethyl methacrylate (PMMA), butyl acrylate, lauryl acrylate, stearyl acetate, polyacrylonitrile, polyacrylamide, polyamide, polyimide, polyamideimide, polyetherimide, polyesterimide, poly(ether)ketone, polysulfone, polyethersulfone, polyarylsulfone, polyphenylene sulfide, polybenzimidazole, polyhydantoin, polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polypropylene (PP) terephthalate, polyethylene naphthalate, poly-1,4-dihydroxymethylcyclohexane terephthalate, polyhydroxybenzoate, polyhydroxynaphthalate, polylactide, polyglycolide, polycaprolactone, polyanhydride, polyamide, polyurethane, polyesteramide, polyorthoester, polydioxanone, polyacetal, polyketal, polycarbonate, polyorthocarbonate, polyphosphazene, polyhydroxybutyrate, polyhydroxyvalerate, polyalkylene oxalate, polyalkylene succinate, poly(malic acid), poly(amino acid), polyvinylpyrrolidone, polyethylene glycol, polyhydroxycellulose, chitin, chitosan, poly(L-lactic acid), poly(lactide-co-glycolide), poly(hydroxybutyrate-co-valerate), their copolymers and their terpolymers. However, the polymers useful in the present invention are not limited thereto.

[0080] In addition, calcium phosphate compounds are inorganic components similar to natural bone. As the calcium phosphate compound, any calcium phosphate can be used without particular limitation as long as it can assist bone growth by conduction.

[0081] For example, at least one selected from the group consisting of hydroxyapatite (HAP), carbonated apatite, tricalcium phosphate (TCP), calcium hydrogen phosphate, monocalcium phosphate, dicalcium phosphate, calcium dihydrogen phosphate, tricalcium phosphate, octacalcium phosphate and calcium pyrophosphate can be used.

[0082] Optionally, in addition to the polymer and the calcium phosphate compound, at least one or more natural polymer materials may be further included, such as carboxymethyl cellulose, heparin sulfate, hyaluronic acid, collagen, dextran or alginate. Preferably, the natural polymer material may be included in an amount of 100 parts by weight or less per 100 parts by weight of the polymer.

[0083] Optionally, in addition to the polymer and the calcium phosphate compound, at least one selected from the following may be further included preferably in an amount of 1.0 part by weight or less per 100 parts by weight of the polymer: bone morphogenetic protein (BMP), epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor (TGFβ), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEG), insulin-like growth factor (IGF-1), thioredoxin (TRX), stem cell factor (SCF), hepatocyte growth factor (HGF), human growth hormone and angiogenin.

[0084] Figure 5 Photographs of the non-fixed implant 10 for craniotomy of one embodiment of the present invention when a physical force is applied to bend the implant in various ways are shown to study the constituent components of the implant and to examine the flexibility as a structural feature of the wings and wedges of the implant.

[0085] When a physical force is applied, it is confirmed that the implant bends flexibly without breaking. This confirmation shows that even if a craniotomy incision with various curvatures is made, the implant can be fixed to the skull 1 and the bone flap 2 while filling the gap between the skull 1 and the bone flap 2 (where the wing may be provided with holes to receive screws for fixing the implant to the skull and the bone flap).

[0086] In the case of the existing implant, the central portion of the wedge corresponding to the implant of the present invention has a straight rod-like structure. Therefore, when the implant has sufficient mechanical strength, the bendable angle of the existing implant is limited (i.e., when the mechanical strength is satisfactory, the bendable angle is insufficient). In the case of the implant of the present invention, as Figure 1 can be seen from Tables 1 to 3, both the mechanical strength and the flexibility can be maximized due to the wedge-shaped central portion which is a feature of the present invention. For example, as Figure 5 shown in (b) of

[0087] As another embodiment of the present invention, a method of manufacturing a non-fixed implant 10 for craniotomy is provided. The method includes: mixing a polymer and a calcium phosphate compound in a weight ratio of 10:0 to 5:5 to prepare a composite material; printing a plurality of wings 200 using an FDM 3D printer and the prepared composite material; and stacking a plurality of lines using an FDM 3D printer and the composite material to form a flexible wedge 100 on the plurality of wings 200.

[0088] The plurality of wings 200 have a porous structure. One side of the wing 201 is disposed on the bone flap 2, while the other side of the wing 202 is disposed on the skull 1. The wings 201 and 202 may be provided with holes to receive screws for fixing the non-fixed implant to the skull and the bone flap during craniotomy.

[0089] In order to produce the implant of the present invention by 3D printing using an FDM 3D printer and a composite material in which a polymer and a calcium phosphate compound are mixed, first, the polymer is introduced into a mixing container, then melted at 160 °C ± 20 °C for 40 minutes, and then the calcium phosphate is weighed and mixed with the melted polymer. In order to uniformly blend, the mixture is stirred at a speed of about 1200 rpm for 2 minutes. The stirring for 2 minutes is repeated about six times in total.

[0090] The composite material produced in this way is placed in a cylinder of a 3D printer and ejected through a nozzle of 500 μm. In this case, the ejection temperature is maintained at 120 °C, and the pneumatic pressure for ejection is maintained at 500 kPa. The printing speed of each layer is different, but the printing speed of each layer is controlled within a range of 700 mm / min to 1000 mm / min.

[0091] Figure 6 A photograph of the non-fixed implant 10 produced in the above manner is shown. In Figure 6 In it, (a) is a photograph taken before implantation, and (b) is a photograph taken after implantation. It can be seen that the non-fixed implant 10 for craniotomy of the present invention is disposed between the skull 1 and the flap 2 to fix the skull 1 and the flap 2.

[0092] The present disclosure is not limited to the above specific embodiments and descriptions, and those skilled in the art can make various changes and modifications thereto without departing from the scope of the present disclosure defined in the appended claims. Additionally, such changes may fall within the protection scope of the present disclosure.

[0093] Industrial Applicability

[0094] The present invention aims to provide an implant by using a ceramic composite material, a biomaterial, and a polymer with good osteoconductivity. Specifically, the present invention provides a non-fixed implant that is three-dimensionally designed to be precisely inserted into the gap and can be conveniently used. The implant is a 3D-printed implant that can be precisely bonded to the defect created by craniotomy, has improved biocompatibility and bone-bonding ability, and allows tissue invasion. In addition, the present invention provides a method for manufacturing such an implant.

[0095] The non-fixed implant for craniotomy of the present invention is made of a material including a polymer such as polycaprolactone (PCL), and thus has a high elongation rate. Therefore, due to the high elongation rate of the non-fixed implant, the non-fixed implant can even be flexibly applied to the curved defect created by craniotomy. In addition, since the non-fixed implant has a wedge-shaped insert to be inserted into the skull defect, the non-fixed implant can be fixed without using an additional fixing device after insertion. This means that the non-fixed implant has the ability to be precisely bonded to the defect, and thus has industrial applicability.

Claims

1. A non-fixed implant for filling the gap between the skull bone (1) and the bone flap (2) generated by craniotomy, the implant comprising: A flexible wedge (100) deformable to conform to the outer contour of the bone flap (2); And A plurality of wings (200) connected to the upper or lower part of the flexible wedge (100) and extending to both sides of the flexible wedge (100), Wherein the plurality of wings (200) have a porous structure, wherein a first side wing (201) of the plurality of wings (200) is to be disposed on the bone flap (2), and a second side wing (202) of the plurality of wings is to be disposed on the skull bone (1), The flexible wedge (100) includes a plurality of stacked lines disposed above or below the plurality of wings (200), The plurality of stacked lines have a structure in which protrusions and depressions are alternately connected, including A-pattern lines inclined at an acute angle to the bottom surface and B-pattern lines inclined at an obtuse angle to the bottom surface.

2. The implant according to claim 1, wherein the flexible wedge (100) and the plurality of wings (200) are made of a mixed material in which a polymer and a calcium phosphate compound are mixed in a weight ratio of 10:0 to 5:5, and are manufactured by 3D printing using an FDM 3D printer.

3. The implant according to claim 1, wherein the plurality of wings (200) have a porous structure with a lattice pattern, and the plurality of wings (200) have a multi-layer structure, wherein a plurality of lines are arranged at intervals in each layer, and the plurality of wings include: A first layer, wherein the plurality of lines extend in a first direction and have a width of 300 μm to 500 μm and a line spacing of 300 μm to 500 μm; And A second layer, wherein the plurality of lines extend in a second direction having an angle of 60° to 120° with respect to the first direction and have a width of 300 μm to 500 μm and a line spacing of 300 μm to 500 μm.

4. The implant according to claim 1, wherein in the flexible wedge (100), the width of its upper end is equal to the width of its lower end, but greater than the width of its middle part.

5. The implant according to claim 2, wherein the polymer comprises one or more selected from the group consisting of polyethylene, polypropylene, polyisobutylene, poly-4-methylpentene-1, polybutadiene, polyisoprene, polycyclooctene, polystyrene, polyvinylnaphthalene, styrene-butadiene (SB), styrene-butadiene-styrene (SBS), styrene-ethylene-butene-styrene (SEBS), styrene-ethylene-propylene-styrene, styrene-isoprene, styrene-isoprene-styrene (SIS), styrene-butadiene-acrylonitrile (ABS), styrene-acrylonitrile-acrylate (ASA), styrene-ethylene, polyvinyl chloride (PVC), polychlorobutene and polyvinylidene chloride (PVDC), polymethyl methacrylate (PMMA), butyl acrylate, lauryl acrylate, stearyl acetate, polyacrylonitrile, polyacrylamide, polyamide, polyimide, polyamideimide, polyetherimide, polyesterimide, poly(ether)ketone, polysulfone, polyethersulfone, polyarylsulfone, polyphenylene sulfide, polybenzimidazole, polyhydantoin, polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polypropylene (PP) terephthalate, polyethylene naphthalate, poly-1,4-dihydroxymethylcyclohexane terephthalate, polyhydroxybenzoate, polyhydroxynaphthalate, polylactide, polyglycolide, polycaprolactone, polyanhydride, polyamide, polyurethane, polyamide-ester, polyorthoester, polydioxanone, polyacetal, polyketal, polycarbonate, polyorthocarbonate, polyphosphazene, polyhydroxybutyrate, polyhydroxyvalerate, polyalkylene oxalate, polyalkylene succinate, poly(malic acid), poly(amino acid), polyvinyl pyrrolidone, polyethylene glycol, polyhydroxycellulose, chitin, chitosan, poly(lactide-co-glycolide), poly(hydroxybutyrate-co-valerate), copolymers thereof and terpolymers thereof.

6. The implant according to claim 2, wherein the calcium phosphate compound comprises at least one selected from the group consisting of hydroxyapatite (HAP), carbonate apatite, tricalcium phosphate (TCP), calcium hydrogen phosphate, monocalcium phosphate, calcium dihydrogen phosphate, octacalcium phosphate and calcium pyrophosphate.

7. The implant according to claim 2, wherein the hybrid material in which the polymer and the calcium phosphate compound are mixed further comprises at least one natural polymer material selected from the group consisting of carboxymethyl cellulose, heparin sulfate, hyaluronic acid, collagen, dextran and alginate.

8. The implant according to claim 2, wherein the mixed material of the polymer and the calcium phosphate compound further comprises at least one selected from the group consisting of epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor (TGFβ), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGE), insulin-like growth factor (IGF-1), thioredoxin (TRX), stem cell factor (SCF), hepatocyte growth factor (HGF), human growth hormone, and angiogenin.

9. A method of manufacturing a non-fixed implant (10) for filling a gap between a skull bone (1) and a bone flap (2) caused by a craniotomy, the method comprising: Mixing a polymer and a calcium phosphate compound in a weight ratio of 10:0 to 5:5 to prepare a material; Printing a plurality of wings (200) using an FDM 3D printer and the material; And Stacking a plurality of lines on the plurality of wings (200) using an FDM 3D printer and the material to form a flexible wedge (100), wherein the plurality of wings (200) have a porous structure, wherein a first side wing (201) of the plurality of wings (200) is to be disposed on the bone flap (2), and a second side wing (202) of the plurality of wings is to be disposed on the skull bone (1), forming the flexible wedge (100) such that the flexible wedge (100) includes a plurality of stacked lines disposed above or below the plurality of wings (200), the plurality of stacked lines having a structure in which protrusions and depressions are alternately connected, including A-pattern lines inclined at an acute angle to the bottom surface and B-pattern lines inclined at an obtuse angle to the bottom surface.

10. The method according to claim 9, wherein the printing of the plurality of wings (200) comprises: forming a first layer, wherein a plurality of lines extend in a first direction and have a width of 300 μm to 500 μm and a line spacing of 300 μm to 500 μm; and forming a second layer, wherein a plurality of lines extend in a second direction having an angle of 60° to 120° with respect to the first direction and have a width of 300 μm to 500 μm and a line spacing of 300 μm to 500 μm, wherein the formation of the first layer and the formation of the second layer are sequentially performed at least twice.

11. The method according to claim 9, wherein in the flexible wedge (100), the width of the upper end thereof is equal to the width of the lower end thereof, but greater than the width of the middle portion thereof.

12. The method according to claim 9, wherein the polymer comprises one or more selected from the group consisting of polyethylene, polypropylene, polyisobutene, poly-4-methylpentene-1, polybutadiene, polyisoprene, polycyclooctene, polystyrene, polyvinylnaphthalene, styrene-butadiene (SB), styrene-butadiene-styrene (SBS), styrene-ethylene-butene-styrene (SEBS), styrene-ethylene-propylene-styrene, styrene-isoprene, styrene-isoprene-styrene (SIS), styrene-butadiene-acrylonitrile (ABS), styrene-acrylonitrile-acrylate (ASA), styrene-ethylene, polyvinyl chloride (PVC), polychlorobutene and polyvinylidene chloride (PVDC), polymethyl methacrylate (PMMA), butyl acrylate, lauryl acrylate, stearyl acetate, polyacrylonitrile, polyacrylamide, polyamide, polyimide, polyamideimide, polyetherimide, polyesterimide, poly(ether)ketone, polysulfone, polyethersulfone, polyarylsulfone, polyphenylene sulfide, polybenzimidazole, polyhydantoin, polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polypropylene (PP) terephthalate, polyethylene naphthalate, poly-1,4-dihydroxymethylcyclohexane terephthalate, polyhydroxybenzoate, polyhydroxynaphthalate, polylactide, polyglycolide, polycaprolactone, polyanhydride, polyamide, polyurethane, polyesteramide, polyorthoester, polydioxanone, polyacetal, polyketal, polycarbonate, polyorthocarbonate, polyphosphazene, polyhydroxybutyrate, polyhydroxyvalerate, polyalkylene oxalate, polyalkylene succinate, poly(malic acid), poly(amino acid), polyvinyl pyrrolidone, polyethylene glycol, polyhydroxy cellulose, chitin, chitosan, poly(lactide-co-glycolide), poly(hydroxybutyrate-co-valerate), their copolymers and their terpolymers.

13. The method according to claim 9, wherein the calcium phosphate compound comprises at least one selected from the group consisting of hydroxyapatite (HAP), carbonate apatite, tricalcium phosphate (TCP), calcium hydrogen phosphate, calcium monophosphate, calcium dihydrogen phosphate, octacalcium phosphate and calcium pyrophosphate.

14. The method according to claim 9, wherein the mixed material of the polymer and the calcium phosphate compound further comprises at least one natural polymer material selected from the group consisting of carboxymethyl cellulose, heparin sulfate, hyaluronic acid, collagen, dextran and alginate.

15. The method according to claim 9, wherein the mixed material of the polymer and the calcium phosphate compound further comprises at least one selected from the group consisting of epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor (TGFβ), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGE), insulin-like growth factor (IGF-1), thioredoxin (TRX), stem cell factor (SCF), hepatocyte growth factor (HGF), human growth hormone, and angiogenin.

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