• 专利附录
  • 专利说明
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    • 专利摘要:
    IMPLANTS AND METHODS FOR USING IMPLANTS TO FILL HOLES IN BONE TISSUE Implants for filling a hole in a bone, eg a skull, comprise a single ceramic implant body, width D and thickness H, and a plurality of arms of anchorages that extend substantially laterally. The implants provide both filling the bone defect and fixing the bone flap. Methods for forming such implants employ molding techniques. Methods of using such implants to fill a hole between a bone flap and surrounding bone comprise attaching one or more anchor arms to the bone flap and one or more anchor arms to the surrounding bone.
    公开号:BR112014004089B1
    申请号:R112014004089-3
    申请日:2012-08-21
    公开日:2021-06-08
    发明作者:Bo QWARNSTROM；Thomas Engstrand；Jonas Aberg
    申请人:Ossdsign Ab；
    IPC主号:
    专利说明:

    Field of Invention
    [0001] The invention relates to surgical implants, methods to produce such implants, and methods to use such implants to fill holes in bone tissue.
    [0002] Background of the invention
    [0003] Craniotomy is a procedure during which a surgeon makes a bone flap and removes the flap temporarily to access the brain during surgery. The bone flap is formed by first drilling a plurality of, usually two to four, spaced apart holes through the patient's skull and then cutting through the bone between the holes using a saw. At the end of the procedure, the bone flap is replaced and reattached to the skull. However, the holes rarely heal and provide no protection for the underlying brain.
    [0004] Such holes that cannot heal can be filled using autographic, allographic or synthetic support materials. Support strategies involve the provision of metal meshes or porous ceramic materials. Current strategies using metal mesh do not induce tissue healing. The ceramics currently used are only used to provide osteoconductive support, but they will not provide fixation of the bone flap to the adjacent cranial bone. Most commonly, holes are left untreated. Invention Summary
    [0005] The present invention is directed to implants, methods of producing implants and methods of implanting an implant in a hole. The implants and methods overcome several disadvantages of prior art strategies and methods related to cranial holes.
    [0006] In one embodiment, the invention is directed to an implant for filling a hole in a bone characterized in that it comprises a single ceramic implant body of width D and thickness H, and a plurality of anchorage arms that extend substantially laterally.
    [0007] In another embodiment, the invention is directed to methods of forming an implant according to the invention, to fill a hole in a bone, characterized in that the method comprises the steps of molding a cement composition around of at least one anchor arm extending substantially laterally and subsequently allowing said cement composition to cure.
    [0008] In yet another embodiment, the invention is directed to methods of implanting an implant according to the invention in a hole between a bone flap and surrounding bone, the method comprising the steps of in a hole between a bone flap and surrounding bone , the method comprising the steps of 1) placing the implant body in the hole, and 2) attaching one or more anchor arms to the bone flap and the other one or more anchor arms to the surrounding bone.
    [0009] The implants and methods of the invention are advantageous in providing both a filling function to fill a hole and a fixation function, for fixation to the adjacent bone, i.e., to the skull. Additionally, the implant is easily attached to the adjacent bone structure during surgery. Such additional modalities and modalities, aspects and advantages of the implants and methods of the present invention will be more fully apparent in view of the following Detailed Description. Brief Description of Drawings
    [0010] The drawings will facilitate the understanding of the Detailed Description, in which:
    [0011] Figure 1 schematically shows a skull with a bone flap and holes;
    [0012] Figure 2 schematically shows an enlarged portion of the skull shown in Figure 1 with a hole capped with an implant according to an embodiment of the present invention;
    [0013] Figures 3a)-3c) schematically show the implant of Figure 2, in perspective views, plan and side, respectively;
    [0014] Figure 4 schematically shows an enlarged portion of the skull shown in Figure 1 with a hole capped with an implant according to a second embodiment of the present invention;
    [0015] Figure 5a)-5c) schematically show the implant of Figure 4, in perspective views, plan and side respectively;
    [0016] Figure 6 schematically shows an enlarged portion of the skull shown in Figure 1 with a hole capped with an implant according to a third embodiment of the present invention;
    [0017] Figure 7a)-7c) schematically show the implant of Figure 6, in perspective views, plan and side, respectively;
    [0018] Figures 8a) and 8b) schematically show a fourth modality of an implant according to the present invention,
    [0019] Figures 9a) and 9b) schematically show in plan view and in section along line A-A of Figure 9a), respectively, a mold used to produce an implant according to the present invention;
    [0020] Figure 9c) shows in section another modality of a mold and a wire for producing an implant according to the present invention;
    [0021] Figure 10 schematically shows an enlarged portion of the skull shown in Figure 1 with a hole capped with an implant according to another embodiment of the present invention;
    [0022] Figures 11a)-11c) schematically show the implant of Figure 10, in perspective, plan and side views, respectively;
    [0023] Figure 12 schematically shows an enlarged portion of the skull shown in Figure 1 with a hole capped with an implant according to yet another embodiment of the present invention;
    [0024] Figures 13a) and 13b) schematically show in plan view and in section along line A-A in Figure 13a), respectively, another embodiment of a mold used to produce an implant according to the present invention;
    [0025] Figure 13c) shows in section yet another modality of a mold and a plate for producing an implant according to the present invention; and
    [0026] Figures 14a) and 14b) show plan and side views, respectively, of one embodiment of a wire mesh as used in example 1.
    [0027] The drawings are non-limiting to the invention defined in the claims. Detailed Description of the Invention
    [0028] The present invention is directed to an implant (an implant is a type of medical device made to replace and act as a missing biological structure), alternatively referred to as a surgical implant and/or a biomedical implant. The implant comprises a single ceramic implant body of width D and thickness H, formed, for example, of a biomaterial tile element, and a plurality of substantially laterally extending anchor arms formed, for example, of wire or plates. The implant provides high and combined bone incorporation and better mechanical properties compared to prior art systems.
    [0029] For the purpose of the present disclosure, a wire anchoring arm comprises one or a plurality of wires. In a specific modality, the wire or wires are arranged in a configuration in which one or more wires intersect. In such arrangements, the crossing wires can be linked together, or they can be separated or untied. Within the context of the present description, the mesh comprises wire or wires arranged in a configuration in which at least two intersecting wires are connected at one, some, or all of their intersections. A biomaterial is any matter, surface, or construction that interacts with biological systems. The implant combines a plurality of high strength, optionally flexible, wire or flat anchor arms with at least one mosaic tile formed from a biomaterial. The invention can be employed as a replacement for bone removed by drilling during, for example, craniotomy. The biomedical implant can be composed of resorbable biomaterials and/or stable biomaterials, such as polymers, ceramics and metals. In one modality, the implant is either osteoconductive (ie, it can serve as a support on which bone cells can attach, migrate, and grow and divide) or osteoinductive (ie, it can serve to induce new bone formation), and has high mechanical strength. This is satisfied by an implant system that combines an anchoring system (eg one or more wires) with a solid biomaterial tile - the implant body. In a specific modality, the anchoring system is made of a biomaterial. This system has the beneficial effects of a mechanically strong anchoring system (eg a metallic wire) and a solid osteoconductive and/or osteoinductive implant (eg made of a ceramic material). The implant system can be easily attached to a skull in the operating room. The anchorage system can be attached to adjacent cranial bone and bone flap by screws. Alternatively, the anchorage system can use anchorage channels formed in the skull and/or bone flap, which are positioned to receive the wires. Combinations of bolts and anchor channels are also possible. The solid implant body, which is preferably molded onto the anchorage arms, i.e. wire or plates, during implant fabrication, is preferably composed of an osteoconductive and/or osteoinductive material, which facilitates bone incorporation into the implant system .
    [0030] Within the present disclosure, a plurality of anchor arms refers to two or more anchor arms. Implants can therefore have two, three, four, five, six, or more anchor arms. In a specific modality, the anchorage system comprises one or more wires that can be manipulated by the surgeon to match a crack in the skull. The implant body can also be flat or, preferably, it is concave to provide a better match to the curvature of a skull. In one embodiment of the present invention, a body of biomaterial is molded around the one or more wires or plates. In this way, a structure comprising a wire-supported implant body is formed.
    [0031] In another embodiment of the present invention, the wires extend outside the implant body and then re-enter the implant body, thus forming a closed loop that can be anchored in channels formed with a corresponding shape and dimensions appropriate to the bone.
    [0032] Non-limiting examples of metallic wire materials include polymers, shape memory alloys, Ti, Ti alloys (eg Ti6A14V, having a chemical composition of 6% aluminum, 4% vanadium, 0.25% (maximum) iron, 0.2% (maximum) oxygen, and the remainder titanium, and stainless steel. In the present description, the word "metallic wire" is intended to include filaments made of any material. of plate include titanium or polymer, including degradable polymer or non-degradable polymer. The biomaterial implant body is preferably moldable from the chemically bonded ceramic class of materials or a biopolymer, non-limiting examples include Ca salts, e.g. calcium sulfate, calcium phosphate, calcium silicate, calcium carbonate or combinations thereof. The materials are preferably molded onto anchor arms, i.e., wires or plates, using a water-miscible, non-aqueous liquid o, or using a mixture of water and a water-miscible, non-aqueous liquid, allowed to harden to form a mosaic implant in a bath containing water, or other moist environment, and subsequently the mosaic implant is released from of the mold. After packaging and sterilization, the implant is ready to use.
    [0033] A typical mold and fabrication process for an implant system according to an embodiment of the present invention involves the following steps: 1. Fabricate a positive implant model. 2. Fabricate a mold for the support. The mold is preferably produced from a polymer which is easy to demould after hardening, for example sodium alginate or polyether. A preferred molding material is silicone rubber due to its high biocompatibility and easy handling. The template is used to fabricate the mold by applying the mold material over the positive model and letting the mold material harden. Examples of suitable mold materials include: Silagoma, Silagoma light (DMG Dental) and Silupran 2450 (Wacker silicones). The first two are dental impression materials and the last one is used for temporary implants. 3. Place anchor arms, i.e. wire or plates, into the mold and fill the mold with a chemically bonded ceramic precursor powder mixed with a non-aqueous water miscible liquid and optionally water. 4. Allow the filled mold to harden in a humid or wet environment, preferably at temperatures between room temperature and 120°C. According to a modality, the material is solidified and hardened under an external pressure, for example, using mechanical pressure or similar. This produces a final product with a higher mechanical strength compared to a final product hardened in the absence of external pressure. 5. Demold the specimen and optionally allow the specimen to further harden in a humid or wet environment preferably at elevated temperatures, as described below. 6. Optionally soak the sample to remove any excess non-aqueous water miscible liquid. 7. Optionally final polish the sample. 8. Pack and sterilize using conventional sterilization methods and packaging solutions.
    [0034] The inventive implant provides both filling a bone defect with osteoconductive/inductive material and simultaneously fixing the bone flap with the anchorage system. In a specific embodiment of the invention, the ceramic tile that forms the body of the implant can be simply placed inside the defect and fixed with screws inserted into openings or links in the anchorage arms. In a more specific modality, two anchorage arms are attached to the bone flap and two anchorage arms are attached to the adjacent bone.
    [0035] Figure 1 schematically shows a side view of a skull 1 with three holes 3. The holes are connected by saw cuts 5, which, together with the holes, form a continuous cut line through the skull, thus freeing a bone flap 7 from the rest of the skull. The bone flap 7 can be elevated to allow access to the underlying tissue. When the bone flap 7 is replaced, it is desirable not only to fix it in place, but also to at least partially fill the holes 3.
    [0036] Figure 2 schematically shows an enlarged portion of the skull shown in Figure 1 with a hole 3 capped with an implant 11 according to the present invention. The implant 11 comprises a round tile 13 and a plurality of anchor arms 15 extending substantially laterally from the tile 13. Other implant tile body shapes are also conceivable, for example oval, triangular, square, rectangular, pentagonal, hexagonal, etc., however a circular shape is preferred as it can fit more closely with a circular hole that is typically formed during bone flap formation. Each arm 15 is accommodated in its own slit 17 formed in the skull. The arms are each held in their slots by retaining devices - shown by dashed lines, for example by plates 16 and screws 18 and/or fasteners and/or sutures 20 or any other retaining devices.
    [0037] Figures 3a)-3c) schematically show the implant 11 of Figure 2, in perspective views, plan and side, respectively. Implant 11 has a circular body 13 of diameter D and height H. In one modality, D is larger than H. In specific modality, D is 8 to 20 mm, or 9 to 15 mm, or 10 to 14 mm. Additionally, in specific modalities, height H is from 1 to 10 mm, or from 2 to 8 mm, or from 3 to 6 mm. Any of these combinations of D and H are appropriate. Protruding substantially laterally, eg radially, from body 13 are anchor wires 15. Each wire protrudes distance P from body 13 and has a diameter T. In specific embodiments, the length of distance P is 2 to 15 mm, or 3 to 10 mm, or 4 to 8 mm. The diameter T of each wire is suitably less than 3 mm, more specifically less than 2 mm, or 1 mm or less. In this example of the first embodiment of the invention, four anchor wires 15 made from two lengths of wire are provided, which intersect within the tile, as shown by dotted lines in Figures 3a) and 3b). Instead of having crossing wires, it is conceivable to have two bent wires that do not cross, as shown by dashed lines in Figure 3b), or to use four wires (not shown), with each wire forming an anchor wire. Alternatively, the anchor wires can be replaced by flat plates with a height, for example, from 0.2 to 2 mm, a width, for example, from 2 to 6 mm, and a length, for example, from 5 to 15 mm. Each plate is provided with a through hole that allows an attachment screw to be inserted through the plate and screwed into the underlying bone. Examples of plate material are titanium or degradable polymer. Plates can be molded into the ceramic tile and extended outside the tile laterally on a plurality of sides.
    [0038] Figures 4 and 5a)-5c) schematically show a second embodiment of the present invention, in which each anchor wire 415 extending from the body 413 of the implant 411 is provided with a substantially circular anchor tile 419 at its distal end. Each anchor tile has a diameter d and a height h. In specific modalities, d is from 2 to 10 mm, or from 3 to 8 mm, or from 4 to 6 mm. In specific modalities, height h is from 0.5 to 6 mm, or from 1 to 5 mm, or from 1.5 to 4 mm. The anchor tile is intended to be positioned in an anchor chamber 421 formed at the end of each of the anchor slots 417. In one embodiment, d is less than D and h is less than H, in order to minimize the amount of material that must be removed to form anchor chambers. The anchoring arms and/or tiles are each retained in their slots by retaining devices - not shown - for example, through plates and screws and/or fasteners and/or sutures or any other fastening devices, wire currently overlaps both the main tile - retention channel and the distal tile - retention channel. The implant illustrated in this embodiment can be manufactured by a method as described above, with the option of allowing the anchor arms, i.e. the wires, to extend into an anchor tile mold cavity for forming the anchor tiles over the distal ends of the wires. Anchor tiles can be formed simultaneously with the body or in a separate molding step. In other embodiments, the anchor tiles are preformed and subsequently affixed to the anchor arm wires.
    [0039] Figures 6 and 7a)-5c) schematically show a third embodiment of the present invention, in which the anchor wire 615 of the implant 611 forms one or more closed loops 623 projecting from the body 613 of the implant. As can be seen in Figure 7b), a single anchor wire is formed into a figure-eight figure with its ends almost meeting in the center of the figure-eight figure. The implant body 613 is formed over these ends. Closed links extend distance E from body 613. In specific embodiments, E is 5 to 15 mm, or 6 to 12 mm, or 8 to 10 mm. The anchorage links are intended to be positioned in appropriately formed anchorage slots 617 which extend from a hole 603 and then return to the same hole. The arms are each retained in their slots by retaining devices - shown by dashed lines, for example, by plates 616 and screws 618 and/or fasteners and/or sutures 620 or any other fastening devices.
    [0040] Figures 8a) and 8b) schematically show a fourth embodiment of the present invention, in which the single anchor wire 815 of the implant 811, in addition to being curved into a flat figure of figure eight to form two closed loops 823 , is provided with at least one (in this example two) substantially circular anchor tile 819 at intermediate portions of the links. Each anchor tile has a diameter d and a height h. In specific modalities, d is from 2 to 10 mm, or from 3 to 8 mm, or from 4 to 6 mm. In specific modalities, height h is from 0.5 to 6 mm, or from 1 to 5 mm, or from 1.5 to 4 mm. Each anchor tile is intended to be positioned in an anchor chamber formed into a position properly located in an anchor slot (not shown). Alternatively, each anchoring tile can be provided with an opening to accept a screw that can be used in place of an anchoring slot or in addition to an anchoring slot to affix the anchoring tile to the underlying skull. The anchoring arms and/or tiles can also each be retained in their slots by retaining devices - not shown - for example, through plates and screws and/or fasteners and/or sutures or any other fastening devices.
    [0041] It is conceivable to form the loops from a plurality of wires with the ends of each wire embedded in the implant body 813 and the anchor tiles 819; however, the use of a single wire is preferred as it is easier to manipulate.
    [0042] It is of course possible to affix any anchoring devices according to the present invention directly to the bone flap and bone without forming anchorage channels - this can be achieved by securing the anchor wires or plates by appropriately placed screws that secure the anchor wires. anchoring or plates or tile between the underside of the screw and underlying bone or bone flap, or through the use of sutures or any other fixation devices.
    [0043] An implant in accordance with the above modalities of the present invention may be implanted in a patient by a method comprising the steps of: i) optionally forming one or more anchoring slits in the bone and/or bone flap surrounding a hole , and, if the implant comprises one or more anchor tiles or, forms one or more anchor chambers in the bone and/or bone flap, ii) if necessary, bend the anchor wires to match the orientations of the one or more slots of anchorage and any anchorage chambers, if anchorage slots or anchorage chambers are present, iii) place the implant body in the hole, iv) optionally, place the one or more anchor wires in the one or more anchorage slots, if present , and/or, if present, the one or more anchor tiles in the one or more anchor chambers, v) attach any anchor wires or plates that are not anchored in the anchor slots or anchor chambers, preferably by arrangement anchorage items, such as a screw or suture or similar, to the surrounding bone and bone flap.
    [0044] Thus, implants can be fixed to the bone and skull flap by anchoring devices provided and retained in anchorage slots or channels, or by screws passing through anchorage links or holes or by plates and screws and the like and by combinations of these methods.
    [0045] One embodiment of a method of manufacturing a mosaic implant according to the present invention employs a mold 901 of thickness M. As shown in the plan view in Figure 9a) and Figure 9b), as a section along the line AA of Figure 9a), the mold comprises at least one cavity 903 of depth H and width D. Each cavity is shaped like an implant body. The cavity depth D and the resulting tile thickness are less than the mold depth M. Each cavity 903 has a closed bottom end 905 which is closed by floor 907 of mold 901 and is open at the opposite open end 909 to allow filling of cavity 903. Floor 907 does not need to be permanently affixed to the mold, but can, by For example, be a surface that the mold is in contact with during implant fabrication and that can be removed after demoulding to facilitate release of the implant from the mold. In one embodiment, each cavity, and thus each subsequently formed tile, is in the shape of a circle. However, it is conceivable that the cavity and the implant body, subsequently formed, could have another shape, such as a triangle, a square, a rectangle, a pentagon, a hexagon, etc. In this embodiment of a mold, the wall 911 of each cavity 903 is pierced by at least one narrow wire retaining channel 913 of width T and depth that is the same as T (which is used when the upper surface of the anchor wire must be flush with the upper surface of the implant body) or greater than T (which is used when the upper surface of the anchor wire is intended to lie below the upper surface of the implant body). It is also possible for the depth of the wire retention channels to be less than T, in which case the upper surface of the anchor wire will be above the upper surface of the implant body. Wire retention channels 913 are intended to receive, and retain, during the molding process, the wires used to form the implant anchorage arrangement. In this embodiment of the invention, each cavity is only crossed by a wire in the first direction and a wire in the substantially perpendicular direction. Other arrangements, such as two wires crossing at 120° or any other non-perpendicular angle, are also conceivable.
    [0046] In another embodiment of a mold 901', shown in Figure 9c), the wire retention channels are omitted and, instead, wire 916 can be bent so that portions 918 of the wire outside the cavity fall apart. lie on the upper mold surface and extend radially away from the mold cavity, an intermediate portion 920 projects downwardly into the mold cavity, and the remaining portion of wire 922 extends parallel to the upper mold surface. The intermediate and remaining portions of the wire are subsequently covered with cement. An implant made in this way will be able to be provided with its upper surface flush with the upper surface of the bone and/or skull flap, with only the exposed portions of the metallic wire(s) protruding above the surface of the bone and/or skull flap.
    [0047] Although the cavity has been shown with vertical walls 911, it is of course possible to have walls that slope so that the width through any section of the bottom closed end of each cavity is less than the width of the corresponding section of the cavity. open end of the cavity in order to form release slopes that help release the molded product from the mold. An implant in accordance with the present invention can be made by placing wires in the wire retention channels, filling the mold with cement, allowing the cement to cure, and then removing the implant thus formed from the mold.
    [0048] Other molding methods can be used to form a mosaic implant in accordance with the present invention. For example, one or more anchor wires may be placed on the exposed surface of a first mold half comprising one or more cavities of a depth less than D, separated by walls. The first mold half is provided with an excess amount of cementitious composition that not only fills the cavity and covers the wire(s), but also extends away from the exposed surface of the first mold half. A second mold half, which preferably has cavities of depth less than D, but which, together with the depth of the cavities of the first mold half, are equal to D, is provided. The cavities are arranged as a mirror image of the first mold half, and the second mold half is subsequently placed over the top of the wire and compressed towards the lower mold to allow molding of implant bodies around the wires. The excess amount of cement composition must be sufficient to fill the cavity in the second mold half and must be positioned to be able to fill the second mold half. Excess cement is removed after the mold halves have been joined and preferably before the cement sets. Cement hardening can be achieved by adding moisture through the holes, each hole being connected to each mold cavity within the mold. Such holes preferably are sized so that they are also suitable to allow excess cement to leave the mold.
    [0049] Figures 10 and 11a)-11c) schematically show another embodiment of the present invention, in which each anchor wire 1015 extending from the body 1013 of the implant 1011 is provided with a substantially circular anchorage link 1019 at its distal end. Each anchor link has a diameter d1 and a height h1. In specific modalities, d1 is from 2 to 10 mm, or from 3 to 8 mm, or from 4 to 6 mm. In specific modalities, the height h1 is the same as the anchor wire thickness and is from 0.1 to 2 mm, or from 0.25 to 1.25 mm, or from 0.3 to 0.8 mm. The anchorage linkage is intended to be positioned directly on the bone or bone flap and to be retained by a 1018 screw or similar passing through the 1019 linkage and into the underlying bone. The anchoring links may be closed, as shown, by links referenced 1019, or open, as shown by links referenced 1019'.
    [0050] Figure 12 schematically shows yet another embodiment of the present invention, similar to that of Figures 10 and 11a) to 11c), in which the anchor wires have been replaced by anchor plates 1215, which extend from the body 1213 of implant 1211. The plates have a height H1, which, in a specific modality, is 0.2 to 2 mm, and a width W1, which, in a specific modality, is 2 to 6 mm, and a length L1. , which, in a specific modality, is preferably 5 to 15 mm. Each plate is provided with a through hole that allows an attachment screw to be inserted through the plate and screwed into the underlying bone. Each plate is provided with an anchorage opening 1219 at its distal end, the opening being intended to receive a screw, suture or similar for fixation to the underlying bone.
    [0051] Preferably, the implant should have at least two anchor arms in the form of anchor wires and/or anchor plates, one anchor device being intended to be attached to the bone flap and the other for attachment to the surrounding bone. Increased implant stability is achieved by having three or more anchorage arms.
    [0052] Figures 13a) and 13b) schematically illustrate, respectively, a plan view and a section along line BB of Figure 13a) of a mold for use in the manufacture of a mosaic implant according to the embodiment of the invention shown in Figure 12. A mold 1301 of thickness M is used, which, as shown in Figures 13a) and 13b), comprises at least one cavity 1303 of depth H and width D. Each cavity is shaped like an implant body. The cavity depth H and the resulting tile thickness are less than the mold depth M. Each cavity 1303 has a closed bottom end 1305 which is closed by floor 1307 of mold 1301 and is open at the opposite open end 1309 to allow filling of cavity 1303. Floor 1307 need not be permanently affixed to the mold, but may, for example , be a surface that the mold is in contact with during implant fabrication and that can be removed after demoulding to facilitate release of the implant from the mold. In one embodiment, each cavity, and thus each subsequently formed tile, is in the shape of a circle. However, it is conceivable that the cavity and the subsequently formed implant body could have another shape, such as a triangle, a square, a rectangle, a pentagon, a hexagon, etc. Wall 1311 of each cavity 1303 is pierced by at least one narrow plate retention channel 1313 of width T and depth H2, which is greater than or the same as or less than the thickness of plate H1, depending on whether the top surface of the plate must be above, flush with, or below the top surface of the implant body. These plate retention channels 1313 are intended to receive and retain, during the molding process, the anchor plates used to form the implant anchoring arrangement. In another embodiment of a mold 130, shown in section in Figure 13c), the plate retaining channels are omitted and, instead, plates 1316 can be curved so that the portion 1318 of the plate outside the cavity is over the upper surface of the mold and extends radially away from the cavity, an intermediate portion 1320 projects downwardly into the mold cavity, and the remaining portion of plate 1322 extends parallel to the upper surface of the mold. The intermediate and remaining portions of the board are subsequently covered by cement, while the portion of the board outside the cavity is available for attachment to an underlying surface. An implant made in this way will be able to be provided with its upper surface flush with the upper surface of the bone flap and/or skull, with only the exposed portion of the plate(s) projecting above the surface of the bone flap and /or skull.
    [0053] An implant in accordance with embodiments of the present invention can be implanted in a patient by a method comprising the steps of: 1) placing the implant body in the hole, and 2) securing the anchorage arms, for example wires or plates, preferably by screws and/or sutures or the like, to the surrounding bone and bone flap.
    [0054] An implant according to the present invention can be implanted in a patient by another method comprising the steps of: 1) affixing the implant by at least one screw to the bone flap before the bone flap is positioned in the cutout in the skull in order to avoid placing pressure on the adjacent brain while said screw is being attached to the bone flap, 2) place the implant body in the hole, and 3) secure the anchor wires or plates, preferably by screws and/or sutures or similar, to the surrounding bone and bone flap.
    [0055] In all embodiments of the present invention, depending on the composition of the cement, the hardening of the cement can be carried out at a reduced temperature, or normal or high, and in a humid or wet environment. The mold can be made of any dimensionally stable material that does not negatively react with cement or mesh/wires. If the mold material is permeable to water, it can assist the cement to harden.
    [0056] Various biomaterial cement molding systems can be used to form the implant tile body. In specific embodiments, one of the following three options relates to molding: 1. Use of (a) a Ca salt precursor powder composition, and (b) water-miscible, non-aqueous liquid. In this case, hardening needs to be carried out in a damp environment in order to start hardening. 2. Use of (a) a Ca salt precursor powder composition, and (b) a mixture of water and a water-miscible, non-aqueous liquid. Hardening will start automatically, but for the final hardening a moist environment is required. 3. Use of (a) a Ca salt precursor powder composition, and (b) a water-based liquid. Hardening is started during mixing. It is not necessary to perform hardening in a wet environment, but hardening could be in a wet environment.
    [0057] Methods 1 and 2 are preferred because they provide a longer working time before the material hardens. This provides a longer working time before the material hardens to handle the cement and to clear excess cement after tile formation. However, too much water in the method 2 mix can prevent the cement from setting and the amount of water in the water/non-aqueous water-miscible liquid mix should not be more than 50% by weight. The Ca salt precursor composition may comprise one or more Ca salts selected from the group consisting of anhydrous dicalcium phosphate, dicalcium phosphate dihydrate, octacalcium phosphate, α-tricalcium phosphate, e-tricalcium phosphate, amorphous calcium phosphate , calcium deficient hydroxyapatite, non-stoichiometric hydroxyapatite, tetracalcium phosphate monohydrate and monocalcium phosphate (MCPM), anhydrous monocalcium phosphate, phosphoric acid, pyrophosphoric acid, calcium sulfate (alpha or beta, preferably alpha) or calcium silicate (tricalcium silicate, dicalcium silicate or monocalcium silicate), calcium carbonate (aranonite, vaterite, calcite or amorphous) or combinations thereof.
    [0058] In a specific embodiment of the invention, a water-miscible, non-aqueous liquid can be used in the preparation of a cement slurry for supply to the mold. Possible liquids include glycerin and related liquids, compounds and derivatives (substances derived from non-aqueous water-miscible substances), substitutes (substances in which part of the mechanical structure has been replaced by another chemical structure), and the like. The purpose of the water-miscible non-aqueous liquid is to provide a longer working time during tile molding compared to using water alone, because if the material starts to harden too early, then it is impossible to precisely obtain the mosaic format.
    [0059] Certain alcohols may also be suitable for use as such a liquid. In a specific embodiment, the liquid is selected from glycerine, propylene glycol, poly(propylene glycol), poly(ethylene glycol) and combinations thereof. The composition may also include agents which facilitate rapid diffusion of water into the paste in situ, for example non-ionic surfactants such as polysorbates. The amount of surfactant is suitably from 0.01 to 5% by weight of the powder composition, or more especially from 0.1 to 1% by weight.
    [0060] In an alternative embodiment of the present invention, the precursor powder composition is chosen to obtain setting time above approximately 30 minutes and the liquid can then be water-based or water-containing. In this case, the liquid can be pure water. In some formulations, salts can be dissolved in the liquid to obtain faster or slower setting, for example, citric acid, H3C6H5O7, disodium pyrophosphate, Na2H2P207, sulfuric acid, H2SO4, phosphoric acid, H3PO4, or similar. Hardening can then be carried out in a dry environment.
    [0061] The compositions may also include pore-forming substances to provide a macroporous end product to facilitate rapid resorption and tissue growth. Pores provide a good foundation for bone cells to grow inside them. The pore-forming substance can include sugars and fast-absorbing agents. The amount of pore-forming substance is suitably from 5 and 30% by weight of the powder composition.
    [0062] The compositions may also include a non-toxic gelling agent to improve cohesion and wash resistance. The gelling agent may include collagen, gum, gelatin, alginate, cellulose, polyacrylic acid (eg PAA, PAMA), neutral polyacrylic acid (eg Na-PAA acid, Na-PAMA), hydroxypropylmethyl cellulose (HPMC), hydroxymethyl cellulose (HMC) and carboxymethyl cellulose (CMC), and combinations thereof. In specific embodiments, the amount of gelling agent can be from 0.1% by weight to 10% by weight of the powder composition, more specifically from 0.1% by weight to 2% by weight.
    [0063] In all of the cement compositions selected above, the ratio of precursor powder to liquid should preferably be within the range of 1 and 10, as this provides optimal results. In specific embodiments, the ratio is from 3 to 5. The average grain size of the precursor powder is preferably below 100 micrometers, and more preferably below 30 micrometers, when measured in the volumetric grain size mode. Smaller grain sizes provide higher mechanical strength than larger grain sizes. However, in an embodiment of the invention containing porous granules, the granule size may be larger, but is preferably still below about 500 micrometers. Normally, granules do not participate in the paste hardening reaction. They are added as ballast to the material and the presence of pores provides a better biological response to the material. Preferably, at least some of the pores in a granule should be large enough for cells to enter the granule, typically above at least 10 microns. Inevitably there will also be smaller pores in the granules, but they are of lesser importance for cell integration.
    [0064] In another embodiment of a method of manufacturing an implant according to the present invention, in a molding step, a non-aqueous, hydraulic cement composition comprising a non-aqueous mixture of (a) a powder composition of calcium phosphate forming Brushita or Monetita, and (b) a non-aqueous, water-miscible liquid is cast over the wire mesh and allowed to harden in a wet to wet environment.
    [0065] In another embodiment of a method of manufacturing an implant according to the present invention, in a molding step, a non-aqueous, hydraulic cement composition comprising a non-aqueous mixture of (a) a powder composition non-hydrated comprising porous granules of e-tricalcium phosphate (β-TCP) and at least one additional calcium phosphate powder, and (b) non-aqueous water miscible liquid, is cast over the wire mesh and allowed to harden into a humid to wet environment. In more specific embodiments, the non-aqueous hydraulic cement composition comprises a non-hydrated powder composition comprising porous powder and/or granules of e-tricalcium phosphate (β-TCP) and at least one additional calcium phosphate powder comprising mono -monocalcium phosphate hydrate (MCPM) or anhydrous monocalcium phosphate (MCPA).
    [0066] In other specific embodiments, the hydraulic cement composition, non-aqueous, is a Monetite-forming composition. Non-limiting examples of such compositions comprise a non-hydrated powder composition comprising porous powder and/or granules of e-tricalcium phosphate (β-TCP) and at least one additional calcium phosphate powder comprising monocalcium phosphate monohydrate (MCPM ) or anhydrous monocalcium phosphate (MCPA) in the molar ratio of B-TCP:MCPA or B-TCP:MCPM of 40:60 to 75:25, or more especially, 50:50 - 70:30. A specific example of a suitable Monetite-forming composition includes a 1:1 molar ratio of e-tricalcium phosphate (eg with grain size in the range of 0.1 to 100 micrometers) and monocalcium phosphate monohydrate (MCPM), or a 1:1 molar ratio of e-tricalcium phosphate (eg, with grain size in the range of 0.1 to 100 micrometers) and anhydrous monocalcium phosphate (MCPA). The grain size of MCMP or MCPA can have a greater spread than e-tricalcium phosphate, and preferably is in the range of 1 to 800 micrometers. In a specific modality, the ratio between powder and liquid is in the range of 3 to 5, and in the more specific modality, the ratio is from 3.5 to 4.5.
    [0067] An Example of a wet environment is a water bath. An example of a humid environment is a chamber where the relative humidity is 100%. Optionally, the hardening of the cement material can be carried out at a reduced, or normal or elevated temperature, combined with a humid environment, ie a relative humidity greater than 50%, or a wet environment.
    [0068] In an alternative embodiment, the precursor powder composition is basic (apatitic) and comprises (a) a basic calcium phosphate component comprising porous granules of β-TCP and calcium tetra phosphate (TTCP) and/or phosphate of amorphous calcium, and (b) an acidic phosphate, non-limiting examples of which include monocalcium phosphate monohydrate (MCPM), anhydrous monocalcium phosphate, phosphoric acid, pyrophosphoric acid or combinations thereof. The components of the apatitic precursor powder compositions are chosen such that (i) the pH of the cement paste during hardening is greater than 6; and (ii) the end product of the hardening reaction comprises amorphous calcium phosphate hydrate, hydroxyapatite, ion substituted hydroxyapatite, or combinations thereof.
    [0069] Once the cement has hardened, the cement and wire construction can be removed from the mold, any remaining unwanted cement, eg cement that has set on the wires, is removed and the implant packaged and sterilized.
    [0070] Optionally, the cement and wire construction of the implant system of the present invention could be exposed to pressure during hardening, for example, by pressing an inverse mold against the cement in order to obtain a stronger end product.
    [0071] The implant system can be attached to the host tissue through sutures and/or plates and screws and/or fasteners or any other fixation devices.
    [0072] The implant system can be used in tissue replacements (bone and soft tissue replacement) and in veterinary medicine. For soft tissue replacement, the implant structure is preferably composed of polymeric materials, preferably resorbable polymers. For hard tissue replacement, the implant system is preferably composed of metal wires and ceramic solids, preferably metal wires and resorbable ceramics. In the case where the patient is still growing, it is appropriate to use resorbable materials for the wires and/or mosaic tiles. Suitable resorbable polymers are polydioxanone, poly-L-lactic acid, and polyglycolic acid.
    [0073] The implant system can also optionally be combined with an injectable biomaterial or drug delivery vehicle that guides tissue growth into the interstices between the bone and the implant.
    [0074] Non-limiting modalities of the present implants and methods are provided in the following Examples. Example 1
    [0075] An implant was fabricated by filling calcium phosphate cement into a mold, having a diameter of 11 mm and a depth of 3 mm. The side walls of the mold were angled by 6°. A grade 4 titanium mesh, as shown in Figures 14a) and 14b), was placed in the mold after being bent so that the full circle was placed 1.5 mm high and the anchorage arms rested on the part. top of the mold. The cement precursor powder consisted of an equimolar ratio of mono-calcium phosphate monohydrate and beta tri-calcium phosphate. Glycerin was added to the powder at a powder-to-liquid ratio of 4 g/mL. After the cement mixture was injected into the mold and the mold was immersed in 37°C water for 4 hours. Then, the hardened implant was removed from the mold and placed in water at 20°C for 24 hours with a water change after 4 hours. The implant was subsequently sterilized using an autoclave (121°, 20 min.).
    [0076] X-ray diffraction was used to analyze the phase composition of the cement after hardening and sterilization. Results showed that the cement consisted of 97% Monetite and 3% unreacted beta-tricalcium phosphate.
    [0077] The implant was placed within a 12 mm hole in a 3 mm thick solid rigid polyurethane foam sheet (Sawbones) representing burr holes in a skull using standardized titanium surgical screws. The implant fitted well into the hole and did not break during fixation. In position, the implant could support a weight of 455 g without breaking. Example 2
    [0078] An implant was fabricated by filling calcium phosphate cement into a mold, diameter 13 mm and depth 5 mm. The side walls of the mold were inclined by 12°. A grade 4 titanium mesh was placed in the mold. The cement precursor powder consisted of an equimolar ratio of mono-calcium phosphate monohydrate and beta tri-calcium phosphate. Glycerin was added to the powder at a powder-to-liquid ratio of 3.5 g/mL. After the cement mixture was injected into the mold and the mold was immersed in 60°C water for 2 hours. Then, the hardened implant was removed from the mold and placed in water for 24 hours with a water change after 4 hours. The implant was subsequently dried at 180°C for 1 hour.
    [0079] X-ray diffraction was used to analyze the phase composition of the cement after hardening. Results showed that the cement consisted of 98% Monetite and 2% unreacted beta-tricalcium phosphate.
    [0080] The implant was placed into a 14 mm hole in a 3 mm thick solid rigid polyurethane foam sheet (Sawbones) representing burr holes in a skull using standardized titanium surgical screws. The implant fitted well into the hole and did not break during fixation. In position, the implant could support a weight of 455 g without breaking. Example 3
    [0081] An implant was fabricated by filling calcium phosphate cement into a mold, having a diameter of 11 mm and a depth of 3 mm. The side walls of the mold were angled by 6°. A grade 2 titanium mesh was placed in the mold. The cement precursor powder consisted of an equimolar ratio of mono-calcium phosphate monohydrate and beta tri-calcium phosphate with an addition of 2% w/w calcium pyrophosphate. Water was added to the powder at a powder-to-liquid ratio of 3.2 g/mL. After mixing, the cement was injected into the mold and the mold was immersed in water at 37°C for 4 hours. After removal from the mold, the implant was sterilized using an autoclave (121°C for 20 min.).
    [0082] X-ray diffraction was used to analyze the phase composition of the cement after hardening. Results showed that the cement consisted of 96% Monetite and 4% unreacted beta-tricalcium phosphate.
    [0083] The implant was placed into a 12 mm hole in a 3 mm thick solid rigid polyurethane foam sheet (Sawbones) representing burr holes in a skull using standardized titanium surgical screws. The implant fitted well into the hole and did not break during fixation. In position, the implant could support a weight of 455 g without breaking. Example 4
    [0084] An implant was fabricated by filling calcium phosphate cement into a mold, having a diameter of 11 mm and a depth of 3 mm. The side walls of the mold were angled by 6°. A grade 4 titanium mesh was placed in the mold. The cement precursor powder consisted of alpha-calcium sulfate hemihydrate mixed with water at a powder-to-liquid ratio of 3.3 g/mL. After mixing, the cement was injected into the mold and allowed to harden in air for 4 hours.
    [0085] X-ray diffraction was used to analyze the phase composition of the cement after hardening. Results showed that the cement consisted of 100% calcium sulfate dihydrate.
    [0086] The implant was placed into a 12 mm hole in a 3 mm thick solid rigid polyurethane foam sheet (Sawbones) representing burr holes in a skull using standardized titanium surgical screws. The implant fitted well into the hole and did not break during fixation. In position, the implant could support a weight of 455 g without breaking. Example 5
    [0087] An implant was fabricated by filling calcium phosphate cement into a mold, having a diameter of 11 mm and a depth of 3 mm. The side walls of the mold were angled by 6°. A grade 4 titanium mesh was placed in the mold. The cement precursor powder consisted of an equimolar ratio of mono-calcium phosphate monohydrate and beta tri-calcium phosphate. Glycerin was added to the powder at a powder-to-liquid ratio of 4 g/mL. After mixing, the cement was injected into the mold and the mold was immersed in water at 37°C for 4 hours. Then the hardened implant was removed from the mold and placed in water at 20°C for 24 hours with a water change after 4 hours. The implant was subsequently dried at 60°C for 3 hours.
    [0088] X-ray diffraction was used to analyze the phase composition of the cement after hardening. Results showed that the cement consisted of 97% Monetite and 3% unreacted beta-tricalcium phosphate.
    [0089] The implant was placed into a 12 mm hole in a 3 mm thick solid rigid polyurethane foam sheet (Sawbones) representing burr holes in a skull using standardized titanium surgical screws. The implant fitted well into the hole and did not break during fixation. In position, the implant could support a weight of 455 g without breaking. Example 6
    [0090] An implant was fabricated by filling calcium phosphate cement in a mold, with a diameter of 11 mm and depth of 3 mm. The side walls of the mold were angled by 6°. A grade 4 titanium mesh was placed in the mold. The cement precursor powder consisted of a mixture of monocalcium phosphate monohydrate and beta calcium triphosphate in the weight ratio 52/48. Glycerin with 10% water content was added to the powder at a powder-to-liquid ratio of 3.5 g/mL. After the cement mixture was injected into the mold and the mold was immersed in 37°C water for 24 hours. There, after the hardened implant had been removed from the mold and placed in water for 24 hours. The implant was subsequently sterilized using an autoclave (121°C, 20 min.).
    [0091] X-ray diffraction was used to analyze the phase composition of the cement after hardening and sterilization. Results showed that the cement consisted of 100% Monetite.
    [0092] The implant was placed within a 12 mm hole in a 3 mm thick solid rigid polyurethane foam sheet (Sawbones) representing burr holes in a skull using standardized titanium surgical screws. The implant fitted well into the hole and did not break during fixation. In position, the implant could support a weight of 455 g without breaking. Example 7
    [0093] An implant was fabricated by filling calcium phosphate cement into a mold, having a diameter of 11 mm and a depth of 3 mm. The side walls of the mold were angled by 6°. A grade 4 titanium mesh was placed in the mold. The cement precursor powder consisted of a mixture of monocalcium phosphate monohydrate and calcium beta triphosphate in a molar ratio of 40/60 (MCPM/beta TCP). Water was added to the powder at a powder-to-liquid ratio of 3.5 g/mL. After the mixture the cement has been injected into the mold and allowed to harden at room temperature. The implant was subsequently sterilized using an autoclave (121°C, 20 min.).
    [0094] X-ray diffraction was used to analyze the phase composition of the cement after hardening and sterilization. Results showed that the cement consisted predominantly of Monetite after sterilization with brushita traces.
    [0095] The implant was placed into a 12 mm hole in a 3 mm thick solid rigid polyurethane foam sheet (Sawbones) representing burr holes in a skull using standardized titanium surgical screws. The implant fitted well into the hole and did not break during fixation. In position, the implant could support a weight of 455 g without breaking. Example 8
    [0096] An implant was fabricated by filling calcium phosphate cement in a mold, with a diameter of 11 mm and depth of 3 mm. The side walls of the mold were angled by 6°. A grade 4 titanium mesh was placed in the mold. The cement precursor powder consisted of alpha-tricalcium phosphate and the liquid phase consisted of an aqueous solution of 2.5% by weight of Na2HPO4. A powder-to-liquid ratio of 2.5 g/mL was employed. After mixing, the cement was injected into the mold and the cement hardened for 24 hours before removal from the mold. The implant was subsequently sterilized using an autoclave (121°C, 20 min.).
    [0097] X-ray diffraction was used to analyze the phase composition of the cement after hardening and sterilization. Results showed that the cement consisted of 95% calcium deficient hydroxyapatite and 5% alpha-TCP.
    [0098] The implant was placed into a 12 mm hole in a 3 mm thick solid rigid polyurethane foam sheet (Sawbones) representing burr holes in a skull using standardized titanium surgical screws. The implant fitted well into the hole and did not break during fixation. In position, the implant could support a weight of 455 g without breaking.
    [0099] Although the invention has been illustrated with examples in which an implant according to the present invention is used to fill a hole between a bone flap and the surrounding bone, such implants are evidently suitable for filling any type of hole when the size and the shape of the implant are adapted to the size of the hole to be filled.
    [0100] The invention is not limited to the embodiments shown, which may be freely varied within the scope of the following claims. In particular, the features of the various modalities and examples described can be freely combined with each other to obtain additional modalities, which are all considered part of the scope of the present application.
    权利要求:
    Claims (17)
    [0001]
    1. Implant (11, 411, 611, 1011) for filling a hole in a bone comprising a single solid molded ceramic tile implant body (13, 413, 613, 1013) having a width D and a thickness H, at that D is greater than H, characterized in that the implant comprises a plurality of wire anchor arms (15, 415, 615, 1015) molded in, and extending substantially laterally from the ceramic implant body molded, wherein the implant body has an exposed upper ceramic surface and an exposed lower ceramic surface, and wherein the molded ceramic implant body has been molded around the wire anchor arms to provide a wire supported implant body .
    [0002]
    2. Implant (11, 411, 611, 1011), according to claim 1, characterized in that at least one of said wire anchoring arms (15, 415, 615, 1015) that extend laterally forms a link (623, 823) outside said implant body (13, 413, 613, 1013).
    [0003]
    3. Implant (11, 411, 611, 1011) according to claim 1, characterized in that at least one of said laterally extending wire anchor arms (15, 415, 615, 1015) is provided with an anchorage loop (1019) at its distal end.
    [0004]
    4. Implant (11, 411, 611, 1011) according to claim 3, characterized in that each of said laterally extending wire anchor arms (15, 415, 615, 1015) is provided with a anchoring loop (1019) at its distal end.
    [0005]
    5. Implant (11, 411, 611, 1011) according to claim 1, characterized in that at least one anchoring arm (15, 415, 615, 1015) is provided with an anchoring tile (419) of diameter of height h.
    [0006]
    6. Implant (11, 411, 611, 1011), according to claim 1, characterized in that the width D is between 8 and 20 mm.
    [0007]
    7. Implant (11, 411, 611, 1011), according to claim 1, characterized in that the thickness H is between 1 and 10 mm.
    [0008]
    8. Implant (11, 411, 611, 1011) according to claim 1, characterized in that it further comprises at least one anchoring arm in the form of a plate (1215) having an anchoring opening at its distal end .
    [0009]
    9. Implant (11, 411, 611, 1011), according to claim 1, characterized in that the width D is between 9 and 15 mm.
    [0010]
    10. Implant (11, 411, 611, 1011), according to claim 1, characterized in that the width D is between 10 and 14 mm.
    [0011]
    11. Implant (11, 411, 611, 1011), according to claim 1, characterized in that the thickness H is between 2 and 8 mm.
    [0012]
    12. Implant (11, 411, 611, 1011), according to claim 1, characterized in that the thickness H is between 3 and 6 mm.
    [0013]
    13. Implant (11, 411, 611, 1011), according to claim 1, characterized in that the implant body (13, 413, 613, 1013) comprises Monetite cement.
    [0014]
    14. Implant (11, 411, 611, 1011), according to claim 1, characterized in that the implant body (13, 413, 613, 1013) comprises Monetite cement formed from (a) and -tricalcium phosphate, and (b) either monocalcium phosphate monohydrate or anhydrous monocalcium phosphate, or a mixture thereof.
    [0015]
    15. Implant (11, 411, 611, 1011), according to claim 14, characterized in that the implant body (13, 413, 613, 1013) comprises Monetite cement formed at a ratio of 1:1 of (a) and (b).
    [0016]
    16. Implant (11, 411, 611, 1011), according to claim 14, characterized in that the implant body (13, 413, 613, 1013) comprises Monetite cement formed from (a) e-tricalcium phosphate having a grain size in a range of 0.1 to 100 micrometers, and (b) or monocalcium phosphate monohydrate or anhydrous monocalcium phosphate, or a mixture thereof, in which the grain size of (b) it has a spread of from 1 to 800 micrometers.
    [0017]
    17. Implant (11, 411, 611, 1011) according to claim 1, characterized in that said implant body (13, 413, 613, 1013) has a circular shape.
    类似技术:
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    同族专利:
    公开号 | 公开日
    AU2012298164A1|2014-04-03|
    JP6097294B2|2017-03-15|
    EP2747684A2|2014-07-02|
    WO2013027175A2|2013-02-28|
    AU2012298164B2|2017-08-03|
    WO2013027175A3|2013-04-25|
    HK1198625A1|2015-05-22|
    BR112014004089A2|2017-03-21|
    KR101957543B1|2019-03-12|
    CN103857351A|2014-06-11|
    EP2747684B1|2016-09-28|
    JP2014524328A|2014-09-22|
    KR20140079380A|2014-06-26|
    US20130053900A1|2013-02-28|
    ES2608873T3|2017-04-17|
    CN103857351B|2017-05-24|
    US9463046B2|2016-10-11|
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    法律状态:
    2018-12-11| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2019-10-29| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2020-12-01| B07A| Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]|
    2021-04-13| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-06-08| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 21/08/2012, OBSERVADAS AS CONDICOES LEGAIS. |
    2021-10-26| B25G| Requested change of headquarter approved|Owner name: OSSDSIGN AB (SE) |
    优先权:
    申请号 | 申请日 | 专利标题
    US13/214,441|US9463046B2|2011-08-22|2011-08-22|Implants and methods for using such implants to fill holes in bone tissue|
    US13/214,441|2011-08-22|
    PCT/IB2012/054228|WO2013027175A2|2011-08-22|2012-08-21|Implants and methods of using the implants to fill holes in bone tissue|
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