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WO2025088167A1 - Implant comprenant une pluralité de canaux - Google Patents

Implant comprenant une pluralité de canaux Download PDF

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Publication number
WO2025088167A1
WO2025088167A1 PCT/EP2024/080305 EP2024080305W WO2025088167A1 WO 2025088167 A1 WO2025088167 A1 WO 2025088167A1 EP 2024080305 W EP2024080305 W EP 2024080305W WO 2025088167 A1 WO2025088167 A1 WO 2025088167A1
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WO
WIPO (PCT)
Prior art keywords
implant
channels
main body
opening
main cavity
Prior art date
Application number
PCT/EP2024/080305
Other languages
English (en)
Inventor
Jacob Burkhard SPINNEN
Tilo Dehne
Andreas Engels
Simon ENBERGS
Michael Sittinger
Original Assignee
Charité - Universitätsmedizin Berlin
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Charité - Universitätsmedizin Berlin filed Critical Charité - Universitätsmedizin Berlin
Publication of WO2025088167A1 publication Critical patent/WO2025088167A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/28—Bones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • A61F2/30771—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/28—Bones
    • A61F2002/2817—Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30667—Features concerning an interaction with the environment or a particular use of the prosthesis
    • A61F2002/30677—Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30667—Features concerning an interaction with the environment or a particular use of the prosthesis
    • A61F2002/30677—Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
    • A61F2002/3068—Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body the pharmaceutical product being in a reservoir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • A61F2/30771—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves
    • A61F2002/30772—Apertures or holes, e.g. of circular cross section
    • A61F2002/30784—Plurality of holes

Definitions

  • Implant comprising a plurality of channels
  • the invention relates to an implant which may be used for defects, in particular segmental and critical bone defects. Furthermore, the invention relates to a kit comprising the implant, a regenerative medium and/or an instruction manual.
  • non-union fractures Continuity-disrupting bone defects caused by trauma, surgery or insufficiently healed fractures (so called non-union fractures) always require surgical treatment. The majority of these fractures are treated with the transplantation of autologous bone material in order to provide sufficient regenerative capacity or load-bearing stability.
  • Autologous bone material also known as autograft bone or autogenous bone, refers to bone tissue that is taken from a patient's own body and used for various medical purposes, such as bone grafting or reconstruction. This bone tissue is typically harvested from a different part of the patient's body, such as the iliac crest, scapula, fibula or other bones, and then transplanted to the area where it is needed.
  • Biologically active fluids and hydrogels can help promote processes of tissue integration, colonization and vascularization.
  • implants with combinations of solid and gel-like materials have already been developed and successfully used clinically as hybrid material structures.
  • the connection of very large, mechanically stable, open-pored structures that can be evenly filled with liquid materials represents a major challenge.
  • Bone replacement materials developed to date are based on mechanical stability and with the highest possible comparability with the biological structure (biomimetic) from bone tissue points of view.
  • cell-based implant based on Polylactide-co-glycolide (PLGA) and autologous bone cells for defect filling in oral, maxillofacial, and dental surgery, specifically in sinus lift procedures were developed until market approval stage.
  • PLGA Polylactide-co-glycolide
  • US 11 ,291 ,556 B2 discloses an interbody bone implant which can be described as a cage implant for interbody fusion of two vertebral bodies.
  • the implant is specifically designed to be used with larger amounts of autologous bone.
  • W02007003324A2 relates to artificial bone chips, methods for their production, and their use in surgery. They consist of bioresorbable or biocompatible scaffold structures made of fibrin or hydrogel, osteogenic cells, and factors - such as growth factors or osteogenic bioactive factors - that are shaped into interlocking geometric bodies.
  • W00159068A2 describes of a cell-free graft, comprising a cohesive, structure forming matrix with open porosity made from a biologically and pharmaceutically acceptable material and serum.
  • bone replacement materials are largely based on calcium phosphate materials and require functioning bone healing or an adequate microenvironment for bone development. Colonization of bone cells works best in biopolymers that are as soft as possible with the addition of osteogenic growth factors. The osteogenic potential is ensured for a wide variety of hydrogel-forming polymers such as collagen, gelatin, hyaluronic acid derivatives and alginates.
  • the present invention solves this problem by providing an implant comprising a main body, wherein a main cavity is formed in the main body.
  • the lumen of the main cavity is accessible via an inlet opening allowing for fluid communication between the lumen of the main cavity and the ambience of the main body.
  • a plurality of channels is formed in the main body, wherein each of the plurality of channels has a first opening facing the main cavity and a second opening facing the ambience of the main body and is configured to allow for fluid communication from the main cavity through the channel to the ambience of the main body, wherein the cross sectional area of the first opening of the at least one of the plurality of channels is larger than the cross sectional area of the second opening of the at least one of the plurality of channels; preferably the at least one of the plurality of channels has a tapered shape.
  • the term “implant” is understood as a scaffold manufactured to replace a missing biological structure, support a damaged biological structure, or enhance an existing biological structure.
  • the implant can be used with a regenerative medium.
  • the main cavity extends in the main body along a first direction X
  • the plurality of channels extend through the main body along a second direction Y and wherein the first direction X and second direction Y are different from each other in that an angle a between the first and second direction is selected from the range of 60° to 120°; more preferably a is selected from the range of 75° to 105°, even more preferably a is selected from 85° to 95° or is 90°.
  • the wall of the main cavity as well as the wall of the at least one, more than one or all of the plurality of channels may be formed of a continuous wall or may be formed of a discontinuous or broken wall.
  • the angle a between the first and second direction is 90°.
  • the main cavity penetrates said main body in a vertical direction and the plurality of channels penetrate said main body in a horizontal direction.
  • horizontal and vertical are terms used to describe the two fundamental directions, i.e. the first direction X and the second direction Y, within the main body of the implant. The emphasis lies in considering the relative orientations, where the horizontal and vertical directions are at right angles to each other, i.e. the angle a being 90°.
  • the main cavity penetrates said main body in a vertical direction thereby defining an axis corresponding the vertical direction.
  • the plurality of channels penetrate said main body in a horizontal direction, i.e. in a direction perpendicular to the vertical direction.
  • the main cavity is formed as an elongated central channel which penetrates said main body only partially in the first direction X.
  • the feature that the main cavity penetrates the main body only partially means that the channel comprises only a single main inlet opening through which the fluid can be introduced while the other end of the main cavity is closed in order to ensure that the fluid does not pass through the main body in the first direction X entirely but instead is directed to the plurality of channels which are preferably oriented in a horizontal direction, i.e. the second direction Y.
  • the regenerative medium can be immersed into the implant into the main cavity and is then directed to and evenly distributed in the plurality of channels extending outwardly, i.e. in the Y-direction from the main cavity.
  • the invention provides a mechanically stable structure that can be perfused with a viscous material through a fluidic microarchitecture without significantly reducing its mechanical loadbearing stability. This allows the fracture ends to be indirectly connected via a bioregenerative matrix, such as a hydrogel, while simultaneously ensuring the necessary load-bearing stability required for sufficient bone healing.
  • the diameter of at least one of the plurality of channels is constant along the second direction through the main body wherein at least one of the plurality of channels, preferably each of the plurality of channels, has a cylindrical shape.
  • the diameter of each of the plurality of channels is selected from the range of 0.1 mm to 2 mm, more preferably from the range of 0.1 mm to 1.75 mm more preferably the diameter is selected from the range of 0.2 mm to 1.75 mm.
  • the diameter is preferably determined by the viscosity of the liquid. For instance, if the viscosity is very low, a channel size of below 1 mm is preferred. In such a case with a smaller diameter, the liquid is then advantageously held by capillary forces. Therefore, the skilled person may advantageously adapt the diameter size of the channels to the viscosity of the medium. Preferably for a viscosity range of 1 to 40 mPa*s, the diameter of the channels is chosen not above 1 mm, preferably from 0.2 to 1 mm.
  • the diameter of at least one of the plurality of channels is constant along the second direction from the main cavity through the main body to the ambience so that an inner diameter at the first opening is essentially the same as an outer diameter at the second opening.
  • the diameter of each of the plurality of channels is constant along the second direction Y from the main cavity through the main body to the ambience in such a way that an inner diameter at the first opening is the same as the outer diameter at the second opening.
  • the plurality of channels have an inner diameter and an outer diameter wherein the inner diameter is the same as the outer diameter.
  • the inner diameter (DI) is the diameter of the channels at the main cavity.
  • the outer diameter (DO) is the diameter of the channels at the outer periphery of the main body, i.e. the ambiance of the main body.
  • the embodiment with a constant diameter Due to its high wall thickness and low-volume channels, the embodiment with a constant diameter possesses high mechanical durability. Nevertheless, although the initial design exhibits satisfactory mechanical characteristics, it may fail to promote an equitable dispersion of fluid throughout the structure, requiring either a substantial volume of filling material or resulting in areas remaining unfilled.
  • cross sectional area of the first opening of the at least one of the plurality of channels is larger than the cross sectional area of the second opening of the at least one, more than one or all of the plurality of channels; preferably the at least one, more than one or all of the plurality of channels has a tapered shape.
  • the term “tapered” means that the cross sectional area at the first opening is larger than the cross sectional area at the second opening.
  • the cross sectional area i.e. the cross-sectional area perpendicular to an axis extending in the second direction Y
  • the first opening and the second opening may have a cross- sectional shape in a plane perpendicular to the second direction which is regular or irregular.
  • the cross sectional shape of the first opening may be the same or different than the cross sectional shape of the second opening, provided that the cross sectional area of the first opening is larger than the cross sectional shape of the second opening.
  • the cross sectional shape of the first and/or the second opening may be round, oval, or polygonal.
  • the minimum diameter of the cross sectional area of the at least one of the plurality of channels decreases along the second direction Y from the main cavity through the main body to the ambience so that an inner diameter (e.g. the minimum diameter of the cross sectional area) at the first opening is larger than an outer diameter (e.g. the minimum diameter of the cross sectional area) at the second opening; preferably the diameter of each of the plurality of channels decreases along the second direction from the main cavity through the main body to the ambience so that an inner diameter (DI) at the first opening is larger than an outer diameter (DO) at the second opening (wherein the inner and outer diameter is preferably calculated as minimum inner diameter of the cross sectional area of the corresponding first and/or second opening).
  • DI inner diameter
  • DO outer diameter
  • At least one of the plurality of channels preferably has a conical shape; more preferably more than one or all of the plurality of channels have a conical shape.
  • a "conical shape” in the context of the invention refers to a three-dimensional geometric shape that resembles a cone.
  • a cone is a solid object with a flat, circular or oval base and a curved surface that tapers to a point called the apex or vertex. The base and the apex are connected by a curved side, which is often called the lateral surface. Cones can vary in size and proportions, but they all share this fundamental conical shape.
  • the at least one, more than one or all the channels of the plurality of channels preferably have a conical shape, wherein at least one, more than one or each of the cones have an apex having a diameter corresponding to the outer diameter (DO) of the channel and a base having a diameter corresponding to the inner diameter (DI) of the channel.
  • the implant is described wherein the inner diameter (DI) of the at least one, more than one or each of the plurality of channels ranges from 1.25 mm to 4.0 mm; and the outer diameter (DO) of the at least one, more than one or each of the plurality of channels ranges from 0.2 mm to 3.0 mm.
  • the implant is described wherein the inner diameter ranges from 1.25 mm to 2.55 mm; and the outer diameter ranges from 0.3 mm to 0.9 mm.
  • the implant is described wherein the inner diameter ranges from 1.5 mm to 3.5 mm; and the outer diameter ranges from 0.25 mm to 0.75 mm.
  • the implant is described wherein the inner diameter ranges from 1.3 mm to 1.5 mm; and the outer diameter ranges from 0.3 mm to 0.6 mm. According to a particularly preferred embodiment, the implant is described wherein the inner diameter is about 1.45 mm and the outer diameter is about 0.5 mm.
  • the diameter is preferably determined by the viscosity of the liquid. For instance, if the viscosity is very low, smaller values for diameters are preferred, wherein the liquid is then advantageously held by capillary forces. Therefore, the skilled person may advantageously adapt the diameter size of the channels to the viscosity of the medium.
  • the implant is described wherein the main body has at least an C n symmetry element.
  • An C n axis is a symmetry element that represents rotational symmetry. Specifically, it represents a rotation of 360 degrees divided by "n" equal parts. Each part of the rotation is called a "n-fold rotation” or "C n rotation.”
  • a C2 axis represents a two-fold rotation, which is a 180-degree rotation.
  • a C3 axis represents a three-fold rotation, which is a 120-degree rotation.
  • a C4 axis represents a four-fold rotation, which is a 90- degree rotation.
  • a C n axis describes a rotational symmetry by the specified angle, i.e.
  • the main cavity penetrates said main body in a first direction X which is defined along the C n axis and the plurality of channels penetrate said main body in a second direction Y which is defined along an axis having an angle a with the C n axis.
  • the implant is described wherein the main body has a cylindrical shape.
  • the main cavity penetrates said main body in a first direction X which is defined along the rotational axis of the cylindrically shaped main body and the plurality of channels penetrate said main body in a second direction Y which is defined along the second axis Y.
  • the cylindrically formed main body possess an C ⁇ (C infinity) axis representing an infinite rotational symmetry.
  • C ⁇ C infinity
  • the implant is described wherein the main cavity has a diameter of 2 to 4 mm.
  • the implant is described wherein the density of channels is in a range of 1 to 300 channels per cm 2 , preferably of 3 to 200 channels per cm 2 , more preferably of 3 to 100 channels per cm 2 .
  • the plurality of channels are arranged in a regular pattern along an axis extending in the first direction X.
  • the plurality of channels may be arranged in the main body in an irregular pattern along an axis extending in the first direction X.
  • the main body of the implant of the present invention may have a shape which is adapted to the site of administration in the body.
  • the shape of the main body is dependent from the specific application for which said implant is designed and, thus, for the implant of the present invention, the main body can have any shape suitable for the planned application and, thus, is not limited to a particular geometric shape.
  • the main body of the implant of the present invention can have e.g. a conical shape or a cylindric shape or any combination thereof.
  • the main body has a cylindrical shape and the plurality of channels are arranged in a circumferential direction and in a vertical direction of the main body, corresponding the first direction X, at a surface at the outer ambience of the main body.
  • a cylinder which forms the basis for the cylindrical shape of the above embodiment is a three- dimensional geometric object characterized by two parallel, congruent circular bases connected by a curved surface.
  • the term "congruent" means that the two bases have the same size and shape.
  • the curved surface which is often referred to as the lateral surface or the lateral surface area, connects the bases along their perimeters.
  • the curved surface of the cylinder wraps around the space between the two bases, forming a tube-like shape.
  • the curved surface is also referred to as circumferential area.
  • the circumferential direction refers to the circular path around the circumferential area of the cylinder.
  • the line segment that connects the centers of the two circular bases is called the axis of the cylinder.
  • the axis corresponds to the first direction X.
  • the implant is described wherein the main body comprises an inlet opening which is placed on top of the main body and wherein the main cavity penetrates the inlet opening.
  • the described implant primarily comprises a main body, a main cavity, and a plurality of channels, and its purpose is to provide support and treatment for bone fractures and for segmental and critical bone defects.
  • the inlet opening is incorporated into the design for serving a specific function within the implant's application.
  • the implant design includes a mechanism for the delivery of medications or therapeutic agents to the fracture site, with the inlet opening being part of this mechanism. It might allow for the introduction of fluids or substances into the implant to aid in the healing process.
  • a regenerative medium can be immersed into the implant through the inlet opening.
  • the inlet opening described above can fully integrated into the main body in such a way that it forms a single piece. Alternatively, the inlet opening can be separated from the main body and attached to it.
  • the implant is described wherein the inlet opening has a smaller diameter than an average diameter of the main cavity.
  • the regenerative medium can be immersed into the implant through the inlet opening. The regenerative medium will then be channeled through the inlet opening which has a smaller diameter into the main cavity. From there the fluid will be directed through the plurality of channels extending outwardly, i.e. along the second direction, from the main cavity.
  • the implants according to the embodiments can for example be manufactured by using Fused layer modeling/manufacturing (FLM).
  • FLM is a popular 3D printing technology that is used to create three-dimensional objects layer by layer.
  • the FLM may comprise the following steps: Material Feed: A thermoplastic filament is fed into a heated nozzle.
  • Heating and Extrusion The nozzle melts the filament, making it malleable.
  • Layer-by- Layer Printing Material is extruded layer by layer, following a computer-generated design.
  • Filaments used in the implant according to the invention, in particular in the human body need to meet specific biocompatibility and safety criteria to ensure they are suitable for medical applications.
  • the filaments used for implants should be made from biocompatible materials, in that they do not licit an adverse immune response or toxicity when in contact with bodily tissues or fluids.
  • biocompatible materials include medical-grade metals (such as titanium or stainless, steel), non-degradable polymers (such as PEEK or ABS), biodegradable polymers (such as PTMC, PCL, PLA, PGA, PLGA or AA), or ceramic materials (such as hydroxyapatite, tricalcium phosphate or zirconium dioxide).
  • medical-grade metals such as titanium or stainless, steel
  • non-degradable polymers such as PEEK or ABS
  • biodegradable polymers such as PTMC, PCL, PLA, PGA, PLGA or AA
  • ceramic materials such as hydroxyapatite, tricalcium phosphate or zirconium dioxide.
  • Implant filaments should be able to withstand sterilization processes like autoclaving or ethylene oxide gas sterilization to ensure they are free from harmful microorganisms before implantation.
  • the filament material should possess suitable mechanical properties, such as strength, flexibility, and durability, to meet the specific requirements of the implant.
  • the mechanical properties will depend on the type of implant and its intended function.
  • Particularly preferred materials comprise Polylactic Acid (PLA).
  • PLA Polylactic Acid
  • PLA offers several advantages when used in implants. One of its primary benefits is its biocompatibility. PLA is well-tolerated by the human body, and it does not typically trigger an immune response or adverse reactions. This property is crucial for medical implants because it ensures that the material does not cause harm or complications when placed inside the body.
  • PLA has biodegradability. PLA implants gradually break down over time into non-toxic byproducts, which are absorbed or metabolized by the body. This feature is particularly useful for implants that serve a temporary purpose, such as those used in tissue regeneration. As the implant degrades, it gives way to natural tissue growth, reducing the need for additional surgeries to remove it.
  • PLA is also a versatile material. It can be molded into various shapes and sizes to match the specific requirements of different implant applications. This flexibility allows for customization and precision in implant design.
  • the invention relates to an implant for the treatment of bone defects, in particular by enabling a better fracture healing process.
  • the implant can be preferably used for the treatment of bone defects
  • the implant can be applied in a number of cases where a mechanically stable scaffold needs to be combined with additional regenerative potential.
  • the implant is described for the treatment of one or more of the following:
  • the force applied to the bone causes injury to the periosteum, cortex, and bone marrow, resulting in hematoma formation within the fracture gap.
  • Inflammatory Phase Within the fracture hematoma, pluripotent mesenchymal stem cells differentiate into osteoblasts, fibroblasts, and chondroblasts. Cytokines and growth factors secreted into the hematoma are crucial for controlling cell infiltration, angiogenesis, and cell differentiation. Immune cells invade the hematoma, triggering local inflammation and facilitating the migration of additional cells through subsequent capillary leakage.
  • Granulation Phase A network of fibrin and collagen forms within the fracture hematoma. This is gradually replaced by granulation tissue containing fibroblasts, more collagen, and capillaries (soft callus). This process typically occurs around 4 to 6 weeks after the fracture. Osteoclasts break down non-perfused bone tissue, while osteoblasts build new bone under the periosteum.
  • Callus Maturation Phase In this phase, the formed callus undergoes mineralization and becomes woven bone.
  • the initial structure is influenced by the invading capillaries and gradually orients itself along the axis of mechanical stress.
  • the duration of the callus maturation phase is approximately 3 to 4 months, after which the bone can withstand physiological loads again.
  • Modeling and Remodeling Woven bone is transformed into lamellar bone.
  • the restoration of the original bone structure involves the regular nutritive supply of the bone through Haversian and Volkmann's canal systems.
  • the complete restoration of the original bone structure, including the formation of a medullary cavity, is the further process of remodeling and is typically completed within 6 to 24 months in the case of a normal healing process.
  • a crucial aspect of fracture healing is the presence of a sufficient fracture hematoma, which contains the necessary mesenchymal and leukocytic cells as well as the essential anabolic stimuli.
  • the bone defect is too large, i.e. usually >1.5 cm, for a hematoma to form within the defect area, or for biological reasons, the biological stimuli within the fracture gap are insufficient to achieve bone consolidation even after repositioning. In both scenarios, it would be necessary to introduce an adequately loadbearing, pro-regenerative matrix into the fracture gap.
  • the inventive implants derive their regenerative ability from the filled soft matrix instead of just the material and properties of the hard component.
  • the main cavity and at least one of the plurality of channels comprise a regenerative medium; preferably the main cavity and each of the plurality of channels comprise a regenerative medium.
  • the regenerative medium comprises or consists of a hydrogel.
  • the invention relates to a kit comprising an implant as described above and at least one, more than one or all components for forming a regenerative medium, preferably a hydrogel; and/or an optional instruction manual with detailed instructions on how to form the regenerative medium and how to infuse the regenerative medium into the main cavity and the plurality of channels of the implant.
  • the basis of this kit-of-parts is a range of scaffolds with different basic shapes, load-bearing capacities, and volumes, which are individually sterilized and requested by the surgeon based on the intraoperative defect assessment. All corresponding scaffolds are connected to the filling mechanism to add a soft matrix to the scaffold intraoperatively. It is a central point of the product concept that there are sufficient different fits for bone defects in different bone regions and manifestations.
  • Hydrogel-forming polymers such as collagen, gelatin, hyaluronic acid derivatives, and alginates, are materials that have the ability to absorb and retain water, forming gel-like structures. These polymers are commonly used in various biomedical and pharmaceutical applications due to their unique properties. Here's a brief explanation of each of these polymers:
  • Collagen is a natural protein found in connective tissues, including skin, bones, and tendons. It is a widely used hydrogel-forming polymer in tissue engineering and regenerative medicine because of its biocompatibility. Collagen hydrogels can provide a supportive matrix for cells to grow and repair damaged tissues.
  • Gelatin is derived from collagen and is another biocompatible polymer. It is often used in pharmaceuticals, food, and medical applications. Gelatin hydrogels can be employed for drug delivery systems, wound dressings, and tissue engineering.
  • Hyaluronic acid and its derivatives, is a naturally occurring polysaccharide found in the body, especially in joints and skin. Its derivatives are used to create hydrogels with excellent water retention properties.
  • Hyaluronic acid-based hydrogels are used in ophthalmology, dermatology, and as a component in dermal fillers.
  • Alginates are derived from brown seaweed and are known for their biocompatibility and low toxicity. They are commonly used in the pharmaceutical and food industries. In the context of hydrogels, alginates are often used for drug delivery systems, wound dressings, and tissue engineering scaffolds.
  • hydrogel-forming polymers are chosen based on their specific characteristics and intended applications. They can be engineered to have various properties, such as different degrees of stiffness, porosity, and degradation rates, making them versatile materials for a wide range of medical and biotechnological purposes.
  • a functionalized hydrogel is supplied in lyophilized form with the necessary liquid for resuspension.
  • the hydrogel has been functionalized in that it has been modified or treated in some way to have specific properties or functions, which could include properties like biocompatibility, controlled drug release, or tissue regeneration capabilities, depending on the specific intended use.
  • the hydrogel has been lyophilized.
  • lyophilized means that the hydrogel is processed through lyophilization.
  • the hydrogel is first frozen and then subjected to a vacuum environment. In the vacuum, the frozen water content is converted directly from ice to vapor without passing through a liquid phase, effectively removing the moisture. The result is a dry, powder-like substance that can be easily stored without degradation.
  • the decision of choosing the implant and a suitable medium by the surgeon is taken either preoperatively or intraoperatively to have the hydrogel resuspended in the provided liquid by the surgical assistant.
  • the hydrogel is introduced into the implant via the special filling and distribution mechanism, where it solidifies into a stable shape due to the functionalization thereby forming the system of implant and regenerative medium.
  • the decision of the surgeon may be taken either preoperatively or intraoperatively. These options refer to when the surgeon chooses or decides on a particular course of action regarding a medical procedure. In the case of a preoperative decision, the surgeon makes the decision before the actual surgical procedure takes place. For example, before the surgery, the surgeon may evaluate the patient's medical history, conduct diagnostic tests, and plan the surgical approach. During this preoperative phase, they might decide on various aspects of the procedure, such as the type of implants or materials to be used, the surgical technique, and the overall surgical plan.
  • the surgeon makes decisions during the surgical procedure itself. This can happen when new information or unexpected circumstances arise once the surgery has begun. For instance, while performing the surgery, the surgeon might encounter a different situation than what was initially expected based on preoperative assessments. In such cases, they may need to adapt their approach, make decisions about which tools or materials to use, or modify the surgical plan in real-time to ensure the best possible outcome for the patient.
  • the instruction manual comprises further information regarding the preparation and/or use of the implant comprising the regenerative medium for the treatment of bone defects.
  • the kit can be used for the treatment of bone defects in that the instruction manual provides detailed instructions on how to form the regenerative medium and how to infuse the regenerative medium into the main cavity and the plurality of channels of the implant in order to effectively treat bone defects.
  • Figure 1 Outward view on a first embodiment of an implant not according to the invention.
  • Figure 2 Sectional view of a first embodiment of an implant not according to the invention.
  • Figure 3 Perspective view of a second embodiment not according to the invention.
  • Figure 4a Sectional view of an implant according to the invention.
  • Figure 4b Perspective view on the implant according to the invention.
  • Figure 4c Detailed sectional view on the implant according to the invention.
  • Figure 5 Shows results of fluid tests with an implant having a design comprising a plurality of channels with cylindrical shape and an implant according to the invention having a design comprising a plurality of channels with a conical shape, wherein A. shows the % fill at first leak for each design; B. shows the amount of leakage at complete fill of each design; C. shows pictures of test examples which have been used for quantification.
  • Figure 6 Shows results of fluid tests with an implant having a design comprising a plurality of channels with cylindrical shape and an implant according to the invention having a design comprising a plurality of channels with a conical shape, wherein A. shows fill at first leak for the design with cylindrical channels; B. shows the amount of leakage at complete fill of the design with cylindrical channels; C. shows fill at first leak for the design with conical channels; D. shows the amount of leakage at complete fill of the design with conical channels.
  • Figure 7 Another embodiment of the implant according to the invention, wherein A. shows a side view; B. shows an isometric view; and C. shows a cross sectional view of said implant; wherein for the plurality of channels 30b the rate of reduction of the cross sectional area remains constant on average over the entire length between the first opening 35 and the second opening 36 (along the second direction Y from the first opening 35 to the second opening 36).
  • Figure 8 Another embodiment of the implant according to the invention, wherein A. shows an isometric view; and B. shows a cross sectional view of said implant, wherein for the plurality of channels the rate of reduction of the cross sectional area is not constant but decreases along the second direction Y from the first opening 35 to the second opening 36.
  • Figure 9 Another embodiment of the implant according to the invention, wherein A. shows an isometric view; and B. shows a cross sectional view of said implant, wherein the walls of the main body and of the plurality of channels are discontinuous.
  • Figure 10 Shows an enlarged and more detailed cross sectional view of the embodiment of Figure 9, wherein the cross sectional areas of the first opening 35, an intermediate opening 37 and the second opening 36 differ not only in size but also in shape.
  • the implants according to the embodiments were obtained as a 2 x 1 cm long cylinder, which was manufactured using FLM 3D printing with Polylactic Acid (PLA) filament.
  • PLA Polylactic Acid
  • Figure 1 is an outward view on an exemplary embodiment of an implant 1 not according to the present invention.
  • the outward appearance of the implant according to different embodiments is the same.
  • the implant 1 Designed for the treatment of bone defects, the implant 1 comprises a main body 10 with a main cavity 20 aligned in a first direction X. Additionally, there are a plurality of channels 30a, 30b that traverse the main body 10 in a second direction Y, extending outward from the main cavity 20 to the ambience of the main body 10.
  • the first X direction and second Y direction are different from each other wherein an angle a between the first X and second Y direction can be chosen depending on the specific application.
  • the angle can be generally selected from the range of 60° to 120°.
  • a is chosen to be 90°.
  • the main cavity which is formed as an elongated main channel penetrates said main body in the first direction X, which can be described as a vertical direction, and the plurality of channels penetrate said main body in a second direction Y, which can be described as a horizontal direction.
  • the implant 1 has an outer shape adapted to the bone or bone defect, with the main cavity 20 that serves as the starting point for a multi-channeled system. This allows for providing a large, mechanically stable, and at the same time, open-porous structure that can be uniformly filled with a viscous, liquid material.
  • the main body 10 has e.g. a cylindrical or conical shape and has a diameter of 1 to 4 cm, preferably 3 cm.
  • the plurality of channels 30a, 30b are arranged in a circumferential direction and in a vertical direction of the cylindrical main body 10.
  • the implant 1 has an inlet opening 25 which is placed on top of the main body 10.
  • the main cavity 20 penetrates the inlet opening 25.
  • the inlet opening 25 has a smaller diameter than the main cavity 20.
  • Such an embodiment allows for the safe introduction of fluids or substances into the implant to aid in the healing process.
  • the regenerative medium can be immersed into the implant through the inlet opening 25.
  • the regenerative medium will then be channeled through the inlet opening 25 which has a smaller diameter into the main cavity. From there the fluid will be directed through the plurality of channels extending outwardly along the second axis Y from the main cavity.
  • Each of the plurality of channels 30a, 30b has a first opening facing the main cavity (not visible in outward view shown in Figure 1) and a second opening 36 being placed on the outer surface of the main body 10 and facing the ambience of the main body.
  • the channels 30a, 30b are configured to allow for fluid communication from the main cavity 20 through the channel 30a, 30b to the ambience of the main body 10.
  • the implant 1 can be preferably used for the treatment of bone defects.
  • the implant 1 is filled with a regenerative medium.
  • the implant can be used with a higher viscosity regenerative medium.
  • This system can be distributed as a kit-of-parts including the implant 1 and the regenerative medium as separate components. Before using the implant 1 , the implant 1 is filled with the regenerative medium.
  • Figure 2 is a section view of a first embodiment of an implant not according to the invention.
  • the plurality of channels 30a have a cylindrical shape and wherein the diameter of the plurality of channels 30a is constant when penetrating the main body 10 outwardly, i.e. along the second axis Y, from the main cavity 20. Stated differently, there are multiple channels 30a that traverse the main body 10, which upon extending outward from the main cavity 20 maintain a constant diameter.
  • This design can also be described in that the plurality of channels 30a have an inner diameter and an outer diameter wherein the inner diameter is the same as the outer diameter.
  • the inner diameter is the diameter of the channels 30a at the main cavity 20.
  • the outer diameter is the diameter of the channels 30a at the outer periphery of the main body 10.
  • the scaffold has the shape of a tubular bone and is equipped with a removable filling sleeve, i.e. the inlet opening 25, on top.
  • a removable filling sleeve i.e. the inlet opening 25, on top.
  • the 3mm thick wall in combination with the only 0.5mm diameter channels 30a, provides high mechanical strength.
  • the cylindrical shape of the channels 30a is optimized for low-viscosity fluids, where the increase in volume does not generate a strongly exponential increase in intracanal pressure.
  • the implant 1 due to its high wall thickness and low-volume channels, possesses high mechanical durability. Nevertheless, although the initial design exhibits satisfactory mechanical characteristics, it may fail to promote an equitable dispersion of fluid throughout the structure, requiring either a substantial volume of filling material or resulting in areas remaining unfilled.
  • Figure 3 is a perspective view of a second embodiment.
  • the first embodiment shows good mechanical properties it does not facilitate an even distribution of a fluid within the structure, necessitating either a large amount of filling material or leaving unfilled areas.
  • the main cavity 20 and the plurality of channels 30a of the second embodiment have a cylindrical shape and the diameter of the plurality of channels 30a is constant when penetrating the main body 10 outwardly from the main cavity 20.
  • the scaffold has the shape of a tubular bone and is equipped with a removable filling sleeve, i.e. the inlet opening 25, on top.
  • a removable filling sleeve i.e. the inlet opening 25, on top.
  • the 3mm thickness of the wall, in combination with the plurality of 1.5mm diameter channels 30a, provides moderate mechanical strength while maintaining a high fluid capacity.
  • the large-volume, cylindrical shape of the drainage channels 30a is optimized for both moderately to low-viscosity fluids.
  • Figure 4a shows a section view of the implant 1 according to the invention.
  • the implant 1 in accordance with the present invention comprises a main body 10 with a main cavity 20 aligned in a first direction X. Additionally, there are a plurality of channels 30a, 30b that traverse the main body 10 in a second direction Y, extending outward from the main cavity 20 to the ambience of the main body 10.
  • the first X direction and second Y direction are different from each other wherein an angle a between the first X and second Y direction can be chosen depending on the specific application.
  • the angle can be generally selected from the range of 60° to 120°.
  • a is chosen to be 90°.
  • the main cavity which is formed as an elongated main channel penetrates said main body in the first direction X, which can be described as a vertical direction, and the plurality of channels penetrate said main body in a second direction Y, which can be described as a horizontal direction.
  • the implant 1 has an outer shape adapted to the bone or bone defect, with the main cavity 20 that serves as the starting point for a multi-channeled system. This allows for providing a large, mechanically stable, and at the same time, open-porous structure that can be uniformly filled with a viscous, liquid material.
  • the main body 10 has a e.g. cylindrical or conical shape and has a diameter of 1 to 4 cm, preferably 3 cm.
  • the plurality of channels 30a, 30b are arranged in a circumferential direction and in a vertical direction of the cylindrical main body 10.
  • the implant 1 has an inlet opening 25 which is placed on top of the main body 10.
  • the main cavity 20 penetrates the inlet opening 25.
  • the inlet opening 25 has a smaller diameter than the main cavity 20.
  • Such an embodiment allows for the safe introduction of fluids or substances into the implant to aid in the healing process.
  • the regenerative medium can be immersed into the implant through the inlet opening 25.
  • the regenerative medium will then be channeled through the inlet opening 25 which has a smaller diameter into the main cavity. From there the fluid will be directed through the plurality of channels extending outwardly along the second axis Y from the main cavity.
  • Each of the plurality of channels 30a, 30b has a first opening facing the main cavity (not visible in outward view shown in Figure 1) and a second opening 36 being placed on the outer surface of the main body 10 and facing the ambience of the main body.
  • the channels 30a, 30b are configured to allow for fluid communication from the main cavity 20 through the channel 30a, 30b to the ambience of the main body 10.
  • the implant 1 can be preferably used for the treatment of bone defects.
  • the implant 1 is filled with a regenerative medium.
  • the implant can be used with a higher viscosity regenerative medium.
  • This system can be distributed as a kit-of-parts including the implant 1 and the regenerative medium as separate components. Before using the implant 1 , the implant 1 is filled with the regenerative medium.
  • the first embodiment not according to the invention may fail to promote an equitable dispersion of fluid throughout the structure.
  • the larger channels 20, 30a significantly reduce the implant's wall stability in the second embodiment not according to the invention, leading to a reduction in the crucial property of high mechanical strength.
  • the implant according to the present invention minimizes distribution irregularities of low- and high-viscosity fluids within stable, open-porous support structures by considering the hydrodynamic properties of the fluid and the size of the implant 1 in accordance with the present invention.
  • Figure 4b shows a perspective view of the implant of the present invention.
  • the scaffold takes the form of a tubular bone and is equipped with a detachable filling sleeve, i.e. the inlet opening 25, placed on top.
  • the 3 mm wall thickness, combined with the 96 channels 30b decreasing in diameter provides high mechanical strength while maintaining a high fluid capacity and nearly complete distribution.
  • the shape of the channels 30b is optimized for both high and low-viscosity fluids, ensuring a high capacity without significant loss of mechanical stability.
  • the implant 1 of the present invention minimizes distribution irregularities of low and high viscosity liquids in stable, open-pored support structures by taking into account the hydrodynamic properties of the liquid and the size of the implant.
  • the diameter of the channels 30b decreases as the distance to the filling point increases and is minimal at the exit points. This ensures rapid, uniform perfusion with a high intra-implant fluid volume while maintaining wall thickness and thus mechanical strength.
  • the size of the pores and the degree of decrease in the pore size are determined by the viscosity and the wetting behavior of the liquid compared to the carrier material and adjusted accordingly.
  • Figure 4c is a detailed section view of the implant of the present invention. This view highlights the variation of the diameter of the plurality of channels 30b upon extending outwardly along the Y direction from the main cavity 10.
  • Each of the plurality of channels 30a, 30b has a first opening 35 facing the main cavity and a second opening 36 facing the ambience of the main body.
  • the channels 30a, 30b are configured to allow for fluid communication from the main cavity 20 through the channels 30a, 30b to the ambience of the main body 10.
  • the plurality of channels 30b have a conical shape in such a way that the channels have an inner diameter DI and an outer diameter DO.
  • the inner diameter DI is the diameter of the channels 30b at the first opening 35 facing the main cavity 20.
  • the outer diameter DO is the diameter of the channels 30b at the outer periphery of the main body 10.
  • the inner diameter DI is larger than the outer diameter DO.
  • the inner diameter DI ranges from 1.25 mm to 1.55 mm while the outer diameter DO ranges from 0.25 mm to 0.75 mm.
  • the diameter decreases from 1.45 to 0.5 mm.
  • the inner diameter may range from 1.25 mm to 4 mm and the outer diameter may range from 0.2 mm to 3 mm.
  • Fluidic testing of the implant of the present invention Fluidic validations were performed using implants with a simplified design comparing conical vs. cylindrical fluidic channels with a repeating pattern. The fillable volume of both designs was comparable. The geometries were manufactured via masked stereolithography using transparent PLA UV resin and processed according to the manufacturer's specifications.
  • a polypropylene glycol-water mixture (200 mPa s), coloured with 1% black ink, was injected into the printed designs at a constant flow rate of 6 mL/min. Time frames were used to quantify the entered volume. The degree of filling without leakage (% fill, entered volume/geometry volume) and the additional volume required for complete filling of the geometry (reported as % leak, leak volume/geometry volume) were used to compare the designs. The evaluation was carried out with four technical replicates per design group, reported as the average with standard deviation, and statistical significance was tested using a t-test ( Figure 5A, B).
  • the design with conical channels shows a significantly higher degree of filling when the first liquid starts to leak, when compared to the corresponding design with cylindrical channels (Fig. 6A).
  • the design with conical channels shows a significantly lower degree of leakage filling when the channels of the design are fully filled, when compared to the corresponding design with cylindrical channels (Fig. 6B) for which leakage is substantially more pronounced.
  • Figure 7 it is shown another embodiment of the implant according to the invention, wherein Figure 7 A. shows a side view; Figure 7B. shows an isometric view; and Figure 7C. shows a cross sectional view of said implant.
  • the embodiment of Figure 7 differs from the embodiment of Figure 4 mainly in that the main body is formed of multiple helices of “V” shape wound around the main cavity. One helix is wound clockwise the 2nd helix is wound counterclockwise, wherein the helices penetrate each other, and hence form a mesh with tapered channels 30b.
  • the cross sectional areas of the first opening 35 and of the second opening 36 have diamond shapes which increase the outer surface area of the implant for more cell surface interaction.
  • Figure 8 shows a further embodiment of the implant of the invention, wherein Figure 8A. shows an isometric view; and Figure 8B. shows a cross sectional view of said implant.
  • the embodiment of Figure 8 differs from the embodiment of Figure 7 mainly in that the channels 30b are formed with inconstant tapering, wherein for the plurality of channels 30b the rate of reduction of the cross sectional area is not constant but decreases along the second direction Y from the first opening 35 to the second opening 36.
  • Figure 9 another embodiment of the implant according to the invention is presented, wherein Figure 9A. shows an isometric view; and Figure 9B. shows a cross sectional view of said implant.
  • the embodiment of Figure 9 differs from the embodiment of Figure 4 in that the walls of the main body and the walls of the plurality of channels are formed discontinuous i.e. with breaks in the walls.
  • the main body is not formed as monolith with channels carved therein but is presented as open scaffold, wherein the channels 30b of the plurality of channels have not only a first opening 35 and a second opening 36 but may have one or more intermediate openings 37 arranged between the first opening 35 and the second opening 36 along the second direction Y.
  • each of the first opening 35, the second opening 36 and the intermediate opening 37 is formed with a different shape, wherein the cross sectional area decreases from the first opening 35 having the largest cross sectional area over the intermediate opening 37 having an intermediate cross sectional area towards the second opening 36 having the smallest cross sectional area.

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  • Health & Medical Sciences (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Cardiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Prostheses (AREA)

Abstract

La présente invention concerne un implant comprenant une pluralité de canaux (30a, 30b). L'implant (1) comprend un corps principal (10), une cavité principale (20) du corps principal étant accessible par l'intermédiaire d'une ouverture d'entrée (25). La pluralité de canaux ont une première ouverture (35) et une seconde ouverture (36) configurées pour permettre une communication fluidique, à travers la pluralité de canaux, de la cavité principale vers l'environnement du corps principal. En outre, l'invention concerne un kit comprenant l'implant et en outre un milieu régénératif et/ou un manuel d'instruction.
PCT/EP2024/080305 2023-10-26 2024-10-25 Implant comprenant une pluralité de canaux WO2025088167A1 (fr)

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EP23206176.2 2023-10-26
EP23206176 2023-10-26

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001059068A2 (fr) 2000-02-08 2001-08-16 Schmitt-Waldburg Gbr Copeaux osseux artificiels, procedes permettant de les produire et utilisation
WO2007003324A2 (fr) 2005-06-30 2007-01-11 Transtissue Technologies Gmbh Greffon acellulaire
WO2012028182A1 (fr) * 2010-09-01 2012-03-08 Smith & Nephew Orthopaedics Ag Système d'implant orthopédique
US20160166284A1 (en) * 2014-12-16 2016-06-16 Oxford Performance Materials, Inc. Methods and Systems For Local Administration of Therapeutics
WO2016205077A1 (fr) * 2015-06-17 2016-12-22 Joint Purification Systems Llc Dispositifs et procédés de contrôle des infections de prothèse totale de hanche
CN112426189A (zh) * 2020-11-19 2021-03-02 中山大学 一种具生物活性的可降解多孔镁基界面螺钉
US11291556B2 (en) 2012-04-17 2022-04-05 Warsaw Orthopedic, Inc. Interbody bone implant device

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001059068A2 (fr) 2000-02-08 2001-08-16 Schmitt-Waldburg Gbr Copeaux osseux artificiels, procedes permettant de les produire et utilisation
WO2007003324A2 (fr) 2005-06-30 2007-01-11 Transtissue Technologies Gmbh Greffon acellulaire
WO2012028182A1 (fr) * 2010-09-01 2012-03-08 Smith & Nephew Orthopaedics Ag Système d'implant orthopédique
US11291556B2 (en) 2012-04-17 2022-04-05 Warsaw Orthopedic, Inc. Interbody bone implant device
US20160166284A1 (en) * 2014-12-16 2016-06-16 Oxford Performance Materials, Inc. Methods and Systems For Local Administration of Therapeutics
WO2016205077A1 (fr) * 2015-06-17 2016-12-22 Joint Purification Systems Llc Dispositifs et procédés de contrôle des infections de prothèse totale de hanche
CN112426189A (zh) * 2020-11-19 2021-03-02 中山大学 一种具生物活性的可降解多孔镁基界面螺钉

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