EP2252238A1 - Dispositif comprenant un agent de gonflement et une enveloppe pour la distraction du cal artificielle - Google Patents

Dispositif comprenant un agent de gonflement et une enveloppe pour la distraction du cal artificielle

Info

Publication number
EP2252238A1
EP2252238A1 EP09722885A EP09722885A EP2252238A1 EP 2252238 A1 EP2252238 A1 EP 2252238A1 EP 09722885 A EP09722885 A EP 09722885A EP 09722885 A EP09722885 A EP 09722885A EP 2252238 A1 EP2252238 A1 EP 2252238A1
Authority
EP
European Patent Office
Prior art keywords
sheath
bone
swelling agent
volume
change
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP09722885A
Other languages
German (de)
English (en)
Inventor
Domonkos Horvath
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
CELGEN3D AG
Original Assignee
Celgen AG
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
Priority claimed from DE102008014560A external-priority patent/DE102008014560A1/de
Application filed by Celgen AG filed Critical Celgen AG
Publication of EP2252238A1 publication Critical patent/EP2252238A1/fr
Withdrawn legal-status Critical Current

Links

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
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
    • A61B17/58—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
    • A61B17/60—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like for external osteosynthesis, e.g. distractors, contractors
    • A61B17/66—Alignment, compression or distraction mechanisms
    • A61B17/663—Alignment, compression or distraction mechanisms for jaw bones, e.g. subcutaneous distractors with external access
    • A61B17/666—Alignment, compression or distraction mechanisms for jaw bones, e.g. subcutaneous distractors with external access for alveolar distraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00831—Material properties
    • A61B2017/00898—Material properties expandable upon contact with fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • Apparatus comprising a swelling agent and a sheath for artificial callus distraction
  • the present invention relates to a device for regenerating a bone, in particular by means of three-dimensional distraction, methods for three-dimensional callus distraction and uses of said device.
  • Bone losses are today usually filled with bone substitute materials or with auto- or allogenic bone.
  • the bone replacement materials are, for example, inorganic materials such as calcium phosphates, hydroxyapatite or bioglasses. These should be replaced after slow absorption with bone. However, this is only applicable to smaller defects, otherwise there is a risk of infection due to lack of vascularization. The absorption of inorganic materials is poor. Such bone materials, ie bone replacement materials, do not emit biomechanical impulses and thus trigger no active regeneration. Furthermore, it is synthetically produced organic materials such as polyesters, polyamino acids, polyanhydrides, polyorthoesters, polyphosphazenes, polylactides or polyglycolides or allogeneic organic materials, which are for example of bovine origin.
  • an autologous cancellous bone graft is the best substitute for a bone.
  • grafts are available only limited and show a high absorption rate after transplantation.
  • the materials and techniques used in the prior art often provide insufficient bone quality, so that, for example, implant bearings are not firmly anchored.
  • the bone substitute is often not sufficiently vascularized, whereby the risk of infection is increased.
  • prior art methods often use growth factors that greatly increase the cost of the methods.
  • a bone substitute missing bone substance can also be partially filled by bone regeneration. Segmental interruptions of bony continuity on long bones can thus be treated by distraction osteogenesis.
  • WO 01/91663 describes a two-dimensionally oriented bone distraction by means of an artificial interface.
  • prior art distraction methods for example in the jaw region, only vertical regeneration is frequently possible.
  • bone regeneration by distraction is not applicable to every bone defect.
  • the devices used for distraction are complex and the distraction procedures take a comparatively long time.
  • the technical problem underlying the present invention is to provide a device which makes it possible to carry out bone regeneration methods which overcome the disadvantages of the prior art.
  • the technical problem underlying the invention is also the provision of devices, uses thereof and methods which allow a simple and inexpensive bone regeneration.
  • the technical problem underlying the present invention is also the Provision of devices, uses thereof, and methods for regenerating bones of improved quality and sufficiently vascularized.
  • the present invention solves the underlying technical problem, in particular by providing devices, methods and uses according to the claims.
  • the present invention solves the technical problem underlying it, in particular by providing a device for regenerating a bone comprising a sheath and a swelling agent surrounded by the sheath, wherein the sheath is biocompatible and predefined and controlled depending on a volume change of the swelling agent triggered force is stretchable, shrinkable and / or deformable.
  • the device is a three-dimensional device.
  • the sheath is predefined and controlled in dependence on the application of force stretchable. According to the invention, the sheath is predefined and controlled in dependence on the force deformable.
  • the volume change of the swelling agent is preferably initiated by contact with and absorption of liquid, preferably from a liquid containing biomolecules and / or cells, particularly preferably blood, by the swelling agent.
  • the liquid is preferably water.
  • the liquid is preferably a body fluid. fluid.
  • the liquid is preferably an interstitial fluid.
  • the liquid is blood.
  • the absorbed liquid preferably contains no solid constituents above 150 kDa, more preferably above 100 kDa, in particular above 50 kDa.
  • the device according to the invention it is possible to introduce this into a bone defect, for example by introducing it surgically.
  • the volume of the swelling agent changes, for example increases or decreases, due to contact with a fluid and an associated fluid migration, in particular a pickup of the fluid.
  • the encapsulation of the swelling device is changed in its shape and / or size, and the surface and thus the enclosed volume are particularly preferably enlarged.
  • the swelling agent preferably expands and thereby presses against the casing from the inside.
  • the pulses generated by the movement, in particular expansion, of the device according to the invention can be transmitted as stimulus to the osteogenic cells directly through the device or via the body's own fibrin scaffold.
  • the casing of the device according to the invention can also have a three-dimensional framework and / or lamellae in an alternative embodiment according to the invention.
  • the pulses can then also be transmitted to the osteogenic cells via the three-dimensional framework and / or the lamellae.
  • the device according to the invention can advantageously be used in methods, preferably methods according to the invention, for bone regeneration, in particular for three-dimensional callus distraction.
  • the present teaching covers devices and methods for bone regeneration, wherein preferably bones in the jaw area and / or in the periodontal area are to be regenerated.
  • the present invention understands the term "bone regeneration” as the regeneration of bone defects, for example after cystectomy, tumor surgery or accident surgery. rurgie etc., regardless of the topography, and / or in particular also the regeneration of minor bone defects that arise, for example, by periodontitis.
  • the device according to the invention preferably transmits biomechanical pulses, in particular strain stimuli or pressure stimuli, to the cells surrounding the device so that they are spaced by distances of at least 0.5 .mu.m, in particular 1 .mu.m, more preferably 2 .mu.m, most preferably 10 .mu.m to preferably 100 .mu.m, particularly preferably 1000 .mu.m, more preferably 1 cm, most preferably up to 10 cm are distracted or compressed.
  • the device according to the invention preferably changes its length and / or width by the preferred widths mentioned above.
  • biomechanical pulses are transmitted to the surrounding cells.
  • cells surrounding the device may also experience a pressure pulse as a result of the width change of the device. It is also possible to transmit the impulses through the body's own fibrin network.
  • the biomechanical pulses are transmitted at a distraction frequency of at most 1 mm / day.
  • the stretch stimuli are preferably transmitted with a distraction frequency of at most 1 mm / day.
  • the pressure stimuli are preferably transmitted with a distraction frequency of at most 1 mm / day.
  • the device according to the invention preferably consists of a jacket and a swelling agent.
  • the device according to the invention preferably consists of a sheath, a swelling agent and at least one lamella, in particular at least two lamellae.
  • the swelling agent is preferably located within the casing, ie it is enclosed by the casing.
  • the sheath preferably forms a cavity in which the swelling agent is located.
  • the device is biodegradable.
  • the components of the device in particular the sheathing and the swelling agent, are preferably biodegradable.
  • the degradation kinetics of the device are adapted to the time diagram of a distraction to be carried out with the device according to the invention.
  • the swelling agent is preferably a hydrogel.
  • the swelling agent is solid.
  • the swelling agent is semisolid.
  • the swelling agent is preferably liquid.
  • the swelling agent in particular the hydrogel, is present as powder.
  • the hydrogel is preferably carboxymethyl cellulose.
  • the hydrogel preferably contains carboxymethyl cellulose.
  • the hydrogel preferably consists of a polysaccharide.
  • the hydrogel preferably contains at least one polysaccharide.
  • the hydrogel is hyaluronic acid.
  • the hydrogel preferably contains hyaluronic acid.
  • the swelling agent preferably contains various components, in particular mixtures of the components disclosed here, such as carboxymethylcellulose, polysaccharides and / or hyaluronic acid.
  • the swelling agent is biocompatible. According to the invention, the swelling agent is preferably biodegradable.
  • the swelling agent is preferably not biogenic, in particular it contains no collagen or is free of collagen. According to the invention, the swelling agent is preferably biogenic.
  • volume of the swelling agent is understood as meaning the volume which is bounded by the outer surfaces of the swelling agent.
  • Initial volume which is characterized by contact with a liquid, in particular by fluid intake, can change to another volume.
  • a change in the volume means a change in the starting volume, in particular a significant change in the starting volume, preferably an increase in the starting volume.
  • the change may, for example, be a change in starting volume of at least 1%, preferably 5%, preferably 10%, preferably 15%, preferably 20%, preferably 30%, preferably 40%, preferably 50% of 60%, preferably of 70%, preferably of 80%, preferably of 90%, in the case of an enlargement preferably of at least 100%, preferably of 150%, preferably of 200% or preferably of 300%, for example by elongation or Deformation of the sheath, be.
  • the volume change of the swelling agent is an increase in volume.
  • the material of the jacket is predefined in dependence on an external force effect and controlled stretch, shrinkage and / or deformable.
  • the material may have plastic or elastic properties. These properties of the material of the sheath allow the inventively provided capacity of the surrounding of the sheath swelling agent volume, reversible or irreversible, predefined and controlled to change.
  • the initial volume of the swelling agent preferably changes at a predetermined speed.
  • the speed with which the initial volume of the swelling agent can change is at most as high as the cells adhering to the device and / or the cells surrounding the device distract at most 1.5 mm / day, more preferably 1.2 mm / day, in particular 1 mm / day, most preferably 0.9 mm / day and / or or compressed.
  • the volume of the swelling agent may change in a predefined and controlled manner at a rate at which stretching or shrinkage of a volume of 1000 ⁇ m 3 to 216000 ⁇ m 3 of at most 0.6 mm per day into at least one spatial coordinate, particularly preferably no more than 0.577 mm per day, in particular not more than 0.55 mm per day, most preferably not more than 0.5 mm per day.
  • the volume may be predefined and controlled at a rate at which a strain or shrinkage of a volume of 1000 ⁇ m 3 to 216000 ⁇ m 3 in at least one spatial coordinate of at least 0.01 mm per day, more preferably at least 0 , 1 mm per day, in particular at least 0.2 mm per day, most preferably at least 0.5 mm per day.
  • the volume of the swelling agent may change in a predefined and controlled manner at a rate at which stretching or shrinking of an area between 10 ⁇ m and 60 ⁇ m long of the volume diagonal of the swelling agent volume of at most 0.6 mm per day is particularly preferred not more than 0,577 mm per day, in particular not more than 0,55 mm per day, most preferably not more than 0,5 mm per day.
  • the volume may change in a predefined and controlled manner at a rate at which a stretch or shrinkage of a see 10 ⁇ m and 60 ⁇ m long section of the volume diagonal of the volume of the swelling agent of at least 0.01 mm per day, more preferably of at least 0.1 mm per day, in particular of at least 0.2 mm per day, most preferably at least at least 0.5 mm per day.
  • the device is preferably designed so that the change in the initial volume of the swelling agent can be carried out continuously. According to the invention, the device is preferably designed so that the change in the initial volume of the swelling agent can be discontinuous.
  • predefined and controlled is understood to mean a change in the initial volume, in particular an expansion or shrinkage, which takes place over a predetermined distance and / or a predetermined volume and its velocity, ie the strain rate, shrinkage velocity or shrinkage
  • a change in the volume may also merely be a change in the shape of the volume.
  • the time of commencement of expansion, shrinkage or volume change may also be predetermined, that is to say deliberately selected.
  • the sheath preferably reacts to the change in volume of the swelling agent by stretching, deformation and / or shrinkage. According to the invention, the sheath preferably reacts to the change in volume of the swelling agent by stretching. According to the invention, the sheath preferably reacts on the volume change of the swelling agent by deformation. According to the invention, the sheath preferably reacts to the volume change of the swelling agent by stretching and deformation.
  • an "expansion” is understood to mean an enlargement of the sheathing along at least one spatial axis .
  • the magnification preferably takes place along a spatial axis.
  • the magnification preferably takes place along two spatial axes.
  • the magnification takes place along all three spatial axes.
  • a “shrinkage” is understood to mean a reduction of the sheathing along at least one spatial axis, preferably along a spatial axis, two spatial axes or all three spatial axes.
  • the sheath preferably contains a material selected from the group consisting of polyglycolic acid, polylactic acid, poly ( ⁇ -caprolactone), poly ( ⁇ -hydroxybutyrate), poly (p-dioxanone), a polyanhydride or a mixture of these, for Example of a mixture of polylactic acid and polyglycolic acid.
  • the sheath preferably contains polylactic acid.
  • the sheath preferably contains poly ( ⁇ -caprolactone).
  • the sheath preferably contains a carbolactone.
  • the material of the sheath preferably contains copolymers, in particular of at least two of the abovementioned materials.
  • the material of the jacket preferably contains polymer blends.
  • the sheath preferably consists of a material selected from the group consisting of polyglycolic acid, polylactic acid, poly ( ⁇ -caprolactone), poly ( ⁇ -hydroxybutyrate), poly (p-dioxanone), a polyanhydride or a mixture of them.
  • the material of the jacket of copolymers preferably consists of at least two of the abovementioned materials.
  • the sheath preferably consists of polylactic acid.
  • a coating containing polylactic acid or consisting of polylactic acid has the advantage that the polylactic acid is degraded to short-chain metabolites.
  • polylactic acid of the jacket entices a certain hardness.
  • the sheath preferably consists of poly ( ⁇ -caprolactone).
  • a sheath containing poly ( ⁇ -caprolactone) or consisting of poly ( ⁇ -caprolactone) has the advantage that poly ( ⁇ -caprolactone) is particularly biocompatible. Also, long chains of poly ( ⁇ -caprolactone) can be formed. From poly ( ⁇ -caprolactone) few or no free acids are formed during the decomposition.
  • the sheath preferably consists of carbolactone.
  • the sheath preferably consists of at least one polymer or contains this, preferably of spatially crosslinked polymers.
  • the material of the casing is easy to process.
  • the material of the sheath is sterilizable.
  • the device is sterilizable.
  • the material of the casing can be adapted well to the regeneration geometry.
  • the material of the casing and / or the device are well storable.
  • the material of the sheathing is preferably glycolic acid or contains these.
  • the material of the sheath is preferably polylactic acid or contains these.
  • the material of the sheath is poly ( ⁇ -caprolactone) or contains this.
  • the material of the sheath is poly ( ⁇ -hydroxybutyrate) or contains this.
  • the material of the sheath is poly (p-dioxanone) or contains this.
  • the material of the sheath is preferably at least one polyanhydride or contains this. According to the invention, other suitable materials may also be used.
  • the material of the sheath preferably consists of at least one polylactite and at least one polyglycolide.
  • copolymers with different physical and mechanical properties can be produced and used as the material of the sheathing by the combination and variation of lactitol and glycolide fractions.
  • the material of the sheath preferably has certain rubber-elastic properties and is mechanically stable enough to overcome the tissue pressure prevailing in the defect region of the bone.
  • the material of the Sheath in a preferred embodiment able to withstand an effective tissue pressure of the surrounding tissue of up to 9.5 mm Hg.
  • the sheath is anisotropic.
  • anisotropy is understood to mean the spatial variation of the macroscopic mechanical properties.
  • the sheath is preferably not biogenic, in particular it contains no collagen or is free of collagen. According to the invention, the sheathing is preferably biogenic.
  • the sheath preferably has at least one cell-adhesive property, that is, it is capable of binding cells, in particular osteoblasts, fibroblasts and / or endothelial cells, preferably binding them specifically and selectively.
  • the cell-adhesive property of the sheath is preferably determined by its surface properties.
  • the sheath is preferably biocompatible. According to the invention, the sheath is preferably biodegradable. According to the invention, the sheath and / or the swelling agent are preferably biodegradable.
  • biodegradable means that the material can be degraded or absorbed by hydrolysis, polymer dissolution, enzymatic degradation, and / or dissociation of the material components, preferably into an organism, for example a human or animal organism
  • the gradation products of the device has a molecular weight of at most 50,000 g / mol, more preferably of at most 40,000 g / mol. Thus, they can be eliminated in the normal way.
  • the biodegradable device is degraded in an organism within a resorption time of two years, more preferably within one year, especially within one month, most preferably within two weeks.
  • the absorption begins after 6 weeks after introduction of the device into an organism.
  • the absorption time of the device is at least four weeks, more preferably at least eight weeks, in particular sixteen weeks, most preferably at least thirty-two weeks. According to the invention, the absorption time of the device is at most fifty-two weeks, more preferably at most thirty-eight weeks, more preferably at most sixteen weeks, most preferably at most eight weeks.
  • the material of the sheath preferably has a density of 1 to 5 g / cm 3 .
  • the material of the sheath preferably has a stiffness, extensibility, strength of 1000 to 8000 MPa.
  • the material of the sheath preferably has an E-modulus of 50 to 500 GPa.
  • the material of the jacket preferably has an elongation at break of 0.2 to 10%.
  • the sheath is preferably coated on the outside with cells, in particular endothelial cells and / or osteoblasts and / or fibroblasts, prior to introduction into a defect region of a bone.
  • the material of the sheath preferably consists of at least one fiber composite material or contains it.
  • the material of the sheath preferably consists of fibers of a fiber composite material or contains these.
  • the material of the jacket is optionally encased in or embedded in a thermoplastic matrix. In accordance with the invention, this provides mechanical protection of the fibers under compressive and shear stress, stress strength and protection of the recipient fabric from the integrated fiber particles.
  • the invention provides, in particular, optionally a sealing of the 3D fiber skeleton surface.
  • the fibers may preferably be embedded in a matrix with, for example, different layer thickness.
  • fibers of a fiber composite material are embedded in a polymer matrix in whole or in part.
  • the properties of the fiber composites with or without matrix can be determined according to the invention preferably by the fiber volume content and by the orientation of the fibers in the fiber architecture. As a result, it is also possible according to the invention to determine the strength and modulus of elasticity of the sheath according to the invention.
  • the sheath is preferably coated.
  • the sheath is preferably coated by thin-layer technology.
  • the sheath is preferably coated by means of vacuum, plasma or ion technology.
  • a thin coating preferred according to the invention it is possible to specifically control a cell adhesion to the sheath and an influence on the cell growth of the adhered cells.
  • the electrical properties of the surface of the sheath can be selectively changed.
  • the fibers of a fiber composite material can be coated so that the cell adhesion is increased.
  • the fibers are preferably coated with titanium.
  • the sheath is preferably coated with titanium.
  • the fibers are preferably coated with titanium oxide.
  • the sheath is preferably coated with titanium oxide.
  • the fibers are preferably coated with sodium alginate.
  • the sheath is preferably coated with sodium alginate.
  • osteoblasts In order to allow the most effective use of the device according to the invention, osteoblasts must be able to bind well to the outside of the device. Improved adhesion between the sheath and osteoblasts when using a device according to the invention, in particular In a method according to the invention, more osteoblasts are activated by the device with one or more biomechanical pulses. Therefore, it is preferably provided according to the invention to make the sheathing or the coating of the sheath so that the best possible osteoblast attachment to the sheath can be achieved.
  • the adhesion of the osteoblasts to the sheath is preferably so strong that the binding is maintained during a portion of the volume expansion, particularly preferably throughout the volume expansion of the swelling agent, in particular when the device is used in a method according to the invention.
  • the material of the sheath is smooth.
  • the coating of the casing is smooth.
  • the material of the casing is rough.
  • the coating of the casing is preferably rough.
  • the sheath is preferably coated with hydroxyapatite.
  • An inventively preferred coating with hydroxyapatite allows a binding-promoting adsorption of proteins.
  • the sheath is preferably coated with a hydrogel.
  • the hydrogel layer is thin.
  • the sheath is preferably coated with at least one protein.
  • the at least one protein preferably contains the amino acid sequence Arg-Gly-Asp, ie RGD.
  • the sheath is preferably coated with at least one peptide.
  • the at least one peptide is preferably a peptide which initiates cell adhesion.
  • the at least one peptide is preferably an RGD peptide.
  • the at least one peptide is synthetically produced.
  • the at least one peptide preferably contains the amino acid sequence Arg-Gly-Asp, ie RGD. According to the invention, the at least one peptide preferably consists of the amino acid sequence Arg-Gly-Asp, ie RGD.
  • the sheath is preferably coated with star-shaped polyethylene-glycol polymers (Star-PEG).
  • Star-PEG star-shaped polyethylene-glycol polymers
  • the at least one protein is preferably bound to the polyethylene-glycol polymer coating, particularly preferably covalently.
  • the at least one peptide is preferably bonded to the polyethylene-glycol polymer coating, particularly preferably covalently.
  • the adhesion of osteoblasts is a receptor-mediated contact between the molecules of the extracellular matrix and the actin fibers of the cytoskeleton. This region is also referred to as the focal contact zone. In focal contacts, both binding molecules and molecules responsible for signal transduction are involved. The formation of focal adhesion is mainly due to integrins. The integrins differ in their bioaffinity from other cell surface receptors. Adhesion proteins in the form of ultrathin coating on the sheath facilitate the adhesion of osteoblasts to the device of the invention. Fibronectin is an extracellular adhesion protein with multiple specific binding sites for receptors and thus serves to bind the osteoblasts to the extracellular matrix.
  • Fibronectin is a large glycoprotein that exists as a dimer of two nearly identical subunits. Fibronectin consists of about 90 amino acids. The cell-binding site of fibronectin was identified as the tripeptide sequence Arg-Gly-Asp (RGD).
  • the sheath preferably consists of a fiber composite of continuous fibers or contains these.
  • the sheath is preferably constructed of a fiber composite material of differently oriented layers.
  • the layer sequence of the fibers may be symmetrical with respect to the center plane of the sheath or at random or in intermediate stages thereof.
  • fibers of a fiber composite material preferably represent the main load-bearing element of the thermoplastic matrix sheath. Because of their higher modulus of elasticity and higher strength, the fibers further determine the mechanical properties of the composite.
  • the device and in particular the sheathing is preferably characterized by its biofunctionality.
  • biofunctionality the physical, mechanical and / or biological properties in function with the temporal biomechanical stimulus delivery are important.
  • the surface of the casing is chemically modified.
  • the surface of the casing is chemically modified by reactive molecules or molecular groups.
  • the molecules or molecule groups with which the surface of the sheath is chemically modified can react with anchor proteins of the extracellular matrix of cells.
  • the surface of the casing is hydrophilic. Hydrophilic surfaces allow better adhesion to cells than hydrophobic ones.
  • the sheath preferably has a thickness of at least 0.01 mm. According to the invention, the sheath preferably has a thickness of at most 1 mm. According to the invention, the sheath preferably has a thickness of at least 0.05 mm and at most 0.5 mm. According to the invention, the sheathing preferably has a thickness of about 0.1 mm.
  • the jacket is permeable to a liquid.
  • the jacket is permeable to water.
  • the sheath is preferably porous.
  • the sheathing preferably has pores which are permeable to water and to solids, for example proteins and sugars, with a mass of less than 100 kDa, more preferably of less than 50 kDa.
  • the sheath preferably has pores that are not permeable to solids, for example proteins and sugars, with a mass of more than 50 kDa, particularly preferably more than 100 kDa, in particular more than 150 kDa.
  • the pores preferably have a size of at most 2 ⁇ m, more preferably of at most 1 ⁇ m. According to the invention, the pores preferably have a size of at least 0.5 microns, more preferably of at most 0.1 microns. According to the invention, the pores preferably have a size of at least 0.01 ⁇ m, more preferably of at least 0.05 ⁇ m. According to the invention, the pores preferably have a size of at least 0.1 .mu.m, more preferably of at least 0.5 .mu.m. According to the invention, the pores preferably have a size of 1 ⁇ m.
  • the pores allow the penetration of a liquid through the jacket into the device to the swelling agent.
  • a volume change in particular an increase in volume of the swelling agent, is triggered.
  • the pores are preferably open.
  • the pores may also preferably be closed with a resorbable film.
  • the resorbable film is preferably closed against a concentration gradient.
  • the resorbable film is absorbed when the device is used, in particular rapidly absorbed, so that a liquid can enter the device through the pores.
  • the sheath preferably completely encloses the swelling agent.
  • the jacket may form a capsule around the swelling agent.
  • the sheath can also be tubular, each with closed ends, for example, jammed ends.
  • the sheath preferably does not completely surround the swelling agent, that is to say partial.
  • the jacket may form a tubular shape open at one or both ends, in which the swelling agent is located.
  • the sheath preferably determines the shape of the device.
  • the sheath preferably has a length and / or width of up to 10 mm.
  • the sheath preferably has a length and / or width of 0.1 to 10 mm, in particular of 0.5 mm to 5 mm, particularly preferably of 1 mm to 2 mm.
  • it can also be alternatively provided to design the casing less than 1 mm in length and / or width.
  • the Ummante- ment greater than 10 mm in length and / or width to design.
  • the sheath preferably has the shape of a tube. According to the invention, the sheath is preferably tubular.
  • the tube formed from the casing is straight.
  • tubes formed in this way in annular form may also be present in optionally linked form.
  • the tube preferably has a diameter of 0.5 mm to 5 mm. According to the invention, the tube preferably has a diameter of at least 0.5 mm. According to the invention, the tube preferably has a diameter of 1 mm to 3 mm. According to the invention, the tube preferably has a diameter of 1 mm to 2 mm. The invention has preferred Tubes have a diameter of 2 mm. According to the invention, the tube has a diameter of 3 mm. The tube can also have different diameters in the length distribution, in particular preferred diameters according to the invention.
  • the tube preferably has a length of 0.5 cm to 15 cm.
  • the tube preferably has a length of 0.5 cm to 5 cm.
  • the tube preferably has a length of 1 cm to 2 cm.
  • the tube has a length of 5 cm to 10 cm.
  • the tube has a length of at least 1 cm.
  • the tube has a length of 10 cm.
  • the tube preferably has a length of more than 10 cm.
  • the sheath in particular if it is tubular, may alternatively be formed as a tube which is more than 5 cm, in particular more than 10 cm long.
  • the tube may then be divided, if necessary, into individual lengths having a desired length to use the device for distraction.
  • the length of the tube preferably refers to the initial state.
  • the tube is preferably elongated by the increase in volume of the swelling agent.
  • the tube is extended by the increase in volume of the swelling agent to approximately 1.5 times to 3 times.
  • the tube is extended by about twice the volume increase of the swelling agent.
  • an initially 1 cm long tube after use by the increase in volume is preferably about 1, 5 to 3 cm long, in particular about 2 cm long.
  • the sheath preferably has the form of a capsule. According to the invention, the sheath is preferably in the shape of a capsule.
  • the capsule preferably consists of one part.
  • the capsule preferably consists of two parts, in particular two halves, which are pushed together in a known manner.
  • the capsule preferably has the shape of a cuboid, in particular the shape of a cube.
  • the capsule is preferably round, for example egg-shaped or torpedo-shaped.
  • the capsule preferably has the shape of an ellipsoid or the shape of a sphere.
  • the capsular shell preferably forms a macrocapsule.
  • the macrocapsule preferably has a volume of 0.5 cm 3 to 2 cm 3 , more preferably of about 1 cm 3 , in particular of 1 cm 3 .
  • the volume of the macrocapsule preferably refers to the initial state.
  • the macrocapsule preferably has a side length of 1 cm as a cube.
  • At least one side, in particular one side, of the macrocapsule is preferably extended by the increase in volume of the swelling agent.
  • the at least one side of the macrocapsule by the increase in volume of the swelling agent to about 1, 5-fold to 3-fold.
  • the at least one side of the macrocapsule is preferably extended by about twice the volume increase of the swelling agent.
  • the capsular shell preferably forms a microcapsule.
  • the microcapsule preferably has a volume of 0.5 mm 3 to 3 mm 3 , more preferably of about 1 mm 3 , in particular of 1 mm 3 .
  • the volume of the microcapsule preferably refers to the initial state.
  • the microcapsule as a cube preferably has a side length of 0.5 mm to 3 mm, in particular of 1 mm to 2 mm.
  • the microcapsule as sphere or ellipsoid preferably has a diameter of 0.5 mm to 3 mm, in particular of 1 mm to 2 mm.
  • the side length and the diameter of the microcapsule preferably refer to the initial state.
  • At least one side, in particular one side of the microcapsule is preferably elongated by the increase in volume of the swelling agent.
  • the at least one side of the microcapsule preferably extends to about 1.5 times to 3 times as a result of the increase in volume of the swelling agent.
  • the at least one side of the microcapsule preferably extends by about twice the volume increase of the swelling agent.
  • the change in volume of the swelling agent according to the invention can preferably bring about a deformation of the sheathing.
  • the sheathing may have certain sections or parts which allow deformation, in particular a directed deformation. For example, such a portion or part of the sheath may have the concertina-like shape of a bellows or corrugated hose.
  • At least part of the casing preferably has the shape of a bellows.
  • At least part of the casing preferably has the shape of a corrugated tube.
  • the sheath preferably has the shape of a bellows.
  • the sheath in particular if it is tube or capsule-shaped, may have a plurality of sections which have the shape of a bellows or a corrugated hose.
  • a bellows or a corrugated hose may be provided in the form of a bellows or a corrugated hose.
  • the sheath preferably has the shape of a corrugated hose.
  • the tubular sheath preferably has the shape of a bellows or corrugated hose.
  • the part of the wrapping formed as a bellows or corrugated hose can be pulled apart or pushed together like the similar part of a bent straw.
  • the bellows or corrugated hose preferably consists of at least one, particularly preferably at least two, in particular a multiplicity of folds.
  • the folds of the bellows or corrugated tube preferably have a length of 0.5 mm to 2 mm, calculated from the inner circumference of the sheath toward the distal end of the folds, which form the outer periphery as it were.
  • the folds of the bellows or corrugated hose preferably have a length of 1 mm.
  • the at least one part of the casing shaped as a bellows or corrugated hose is pushed together in the initial state, ie before the device according to the invention is used. Due to the change in volume, in particular increase in volume of the swelling agent, the preferred at least one bellows-shaped or hose-shaped part of the sheath is pushed apart.
  • At least one bellows or corrugated hose is preferably provided in a capsular embodiment of the sheath.
  • At least one bellows or corrugated hose is preferably provided in a tubular embodiment of the sheathing.
  • the bellows or corrugated hose expands due to the increase in volume and thus leads to a change in shape of the sheath, in particular to an extension of a tubular or a capsule-shaped sheathing.
  • the change in shape or size change of the sheath can also be caused by stretching or shrinkage of the sheath.
  • the swelling agent preferably forces the tube-shaped casing apart only in the longitudinal direction, in particular with the aid of at least one bellows or corrugated tube.
  • the casing in particular a tubular casing, is not bulged due to the change in volume of the swelling agent.
  • the outer surface of the casing in particular by the arrangement of contours, is increased. This enlargement not only increases the surface available to the cells, but also affects the organization of cell growth.
  • the outer surface of the casing is enlarged by a lattice-like framework.
  • the framework can completely or at least partially surround the casing.
  • the framework may be connected to the casing, in particular fixed to the casing.
  • the framework can therefore also be part of the sheathing.
  • the framework material may be, for example, a material suitable for the sheathing. In a particular embodiment, it may be the same material as the material used for the sheathing. TERIAL.
  • the framework can form a three-dimensional grid that transmits the pulses from the volume-changing, particularly enlarging, sheath to the osteogenic cells that adhere to the lattice.
  • the outer surface of the casing is enlarged by lamellae.
  • the lamellae are rod-shaped or tubular extensions.
  • the lamellae are surface-formed extensions, in particular wall-like, plate-like, leaf-like, fan-like, wing-like or otherwise flat projections.
  • the lamellae are enlarged in surface area, in particular by lamella substructures, branches, protuberances or net-like structures.
  • the invention preferably carries the outside of the jacket at least one lamella. According to the invention preferably carries the outside of the jacket at least two fins. According to the invention, preferably, the outside of the casing carries a plurality of lamellae. According to the invention preferably carries the outside of the casing 2 to 20 fins.
  • the at least one lamella may preferably be part of the sheathing.
  • the at least one lamella preferably consists of the same material as the sheathing.
  • the at least one lamella is preferably not part of the sheathing.
  • the at least one lamella preferably consists of a different material than the sheathing.
  • the at least one lamella is preferably part of a tubular casing. According to the invention, the at least one lamella is preferably part of a capsular shell.
  • the at least two lamellae are preferably parallel to one another.
  • the at least one lamella is preferably rigid.
  • the at least one lamella is preferably round in cross section.
  • the at least one lamella is preferably rectangular in cross section.
  • the at least one lamella is preferably square in cross section.
  • the at least one lamella can also have any other geometric shape, for example oval in cross-section or polygonal.
  • the at least one lamella preferably surrounds the casing such that the casing lies in the middle of the lamellar surface.
  • the blade accordingly surrounds the entire circumference of the sheath and extends in the distal direction thereof.
  • the at least one lamella preferably has a side length of 0.2 to 2 cm. According to the invention, the at least one lamella preferably has a side length of 0.5 to 1 cm. inventions According to preferred, the at least one lamella has a side length of 1 cm.
  • the at least one lamella preferably has a diameter of 0.2 to 2 cm. According to the invention, the at least one lamella preferably has a diameter of 0.5 to 1.5 cm. According to the invention, the at least one lamella preferably has a diameter of 1 cm.
  • the at least one lamella preferably has a thickness of 0.05 mm to 0.5 mm. According to the invention, the at least one lamella preferably has a thickness of 0.1 mm to 0.3 mm. According to the invention, the at least one lamella preferably has a thickness of 0.2 mm.
  • the at least one lamella preferably has no pores.
  • the at least one lamella preferably has pores.
  • the at least one lamella is therefore preferably perforated according to the invention.
  • the pores preferably have a diameter of 0.5 to 2 mm, more preferably about 1 mm, in particular 1 mm.
  • the sheath preferably has no lamellae.
  • two, several or many devices according to the invention comprising a casing and a swelling agent surrounded by the casing, can be connected to one another via a framework and / or via slats.
  • a framework such as a grid
  • two, three, four, five to to ten, more than ten or many devices according to the invention can be connected to each other.
  • two, three, four, five to ten, more than ten or many devices according to the invention to be connected to one another via one or more slats.
  • at least two devices according to the invention can be connected to one another via a framework, for example a grid.
  • the invention also relates to a device for regenerating a bone, comprising at least two devices described above, wherein the at least two devices are connected to each other via at least one Lammelle.
  • the invention thus also relates to a device for regenerating a bone, comprising at least two devices described above, wherein the at least two devices are connected to one another via a framework, in particular a grid.
  • a plurality of devices may also be present in the form of granules.
  • the basic units of the granules, ie the individual devices are identical or similar, but are not grouped together in a superstructure.
  • the individual granulate particles, ie the individual devices are fixed to one another with a biodegradable adhesive and can thus be incorporated into the defect.
  • the invention also relates to the provision of a method for producing a device according to the invention, wherein a sheathing formed from at least one biocompatible material is and before, during or after the forming of the sheath into the sheath a swelling agent is introduced, wherein the sheath is controlled in response to a force deformable, stretchable and / or shrinkable.
  • the swelling agent is preferably introduced after the sheathing has been formed.
  • the swelling agent is preferably introduced in powder form.
  • the material of the sheath is preferably not biogenic.
  • the sheath is preferably closed after introduction of the swelling agent, in particular closed by jamming.
  • the invention also relates to the use of a biocompatible material which is deformed, stretchable and / or shrinkable in a predefined and controlled manner as a function of an internal or external force and has a cell-adhesive property for producing a device comprising a casing of the biocompatible material and a swelling agent enclosed therein for regenerating a bone, wherein the device can be introduced into a defect area of a bone.
  • the invention also relates to the use of a biocompatible
  • the material which is predefined and controlled in response to an external force, deformable, expandable and / or shrinkable, for the manufacture of a device comprising a sheath of the biocompatible material and a swelling agent surrounded by the sheath, for the regeneration of a bone, wherein the device is introduced into a defect area of a bone.
  • the material preferably has a cell-adhesive property.
  • kits preferably comprise at least one surgical instrument, more preferably at least one applicator, for example a syringe, and a capsule for receiving the device, for example the device in granular form.
  • the kit preferably contains an instruction manual.
  • the kit preferably contains a packaging, particularly preferably a packaging which allows a sterile storage of the device.
  • the kit preferably contains an adhesive, in particular an adhesive for fixing the device in a bone defect.
  • the invention also relates to a method for regenerating a bone, wherein at least one device, comprising a sheath and a swelling agent surrounded by the sheath, wherein the sheath is biocompatible and predefined and controlled in response to a force expansion and / or shrinkable, and wherein the force is triggered by a volume change of the swelling agent is introduced into a defect area of a bone and wherein the shell is subjected to a force by a change in volume of the swelling agent.
  • the invention solves the underlying technical problem and therefore also relates to the provision of a method for the regeneration of a bone, wherein at least one aforementioned device according to the invention, comprising a sheath and a surrounding of the sheath swelling agent, is introduced into a defect area of a bone, said the sheath is biocompatible, predefined and controlled as a function of a force expansion and / or shrinkable and has a cell-adhesive property, in particular for osteoblasts, fibroblasts and / or endothelial cells, and wherein the force by a predefined and controlled volume change of the swelling agent is triggered.
  • a device in particular a device according to the invention, is introduced into a defect region of a bone.
  • the device is enclosed by a blood clot, that is, the sheath of the device contacts the autologous cells contained in the blood clot.
  • a change in volume ie in particular a reduction or enlargement of the volume of the swelling agent, is triggered by a liquid. This leads to the expansion and / or shape change and thus to the desired biomechanical irritation of the attached osteogenic cells and thus to the distraction and thus bone regeneration.
  • the force is preferably applied within the body, in particular within the bone defect.
  • the volume change of the swelling agent may be in different orders of magnitude. It is preferably about 10% of the length of the cells or cell groups adhering to the device.
  • the change in the elongation distance is preferably at least 0.5 ⁇ m, particularly preferably at least 1 ⁇ m, more preferably at least 10 ⁇ m, even more preferably at least 100 ⁇ m, very preferably at least 1000 ⁇ m, very particularly preferably at least 10 mm, most preferably at least 100 mm.
  • the change in the elongation distance is preferably at most 100 mm, particularly preferably at most 10 mm, more preferably at most 1000 ⁇ m, even more preferably at least 100 ⁇ m, very preferably at most 10 ⁇ m, very particularly preferably at most 1 ⁇ m, most preferably at most 0 , 5 ⁇ m.
  • the distraction distance is 5 mm to 10 mm.
  • the distraction force of the device must be greater than the shrinkage force of the fibrin scaffold or of the blood coagula.
  • the distraction begins by the deformation, elongation or shrinkage of the device 1 day after the introduction of the device into the bone defect.
  • Distraction preferably begins by the deformation, expansion or shrinkage of the device one week after the device has been introduced into the bone defect.
  • the beginning of the distraction can be predetermined and thus controlled, for example, by the absorption rate of occlusions of the pores in the sheath, for example by resorbable films.
  • the distraction preferably takes place over a period of several days, in particular over a period of 5 to 20 days, particularly preferably over a period of about 10 days, in particular of 10 days.
  • the rate of change of the volume is at least as high as to distract cells adhering to the device at least 1 ⁇ m / day.
  • the rate of change of the volume is such that cells adhering to the device are distracted between 0.5 mm / day and 1 mm / day.
  • the rate of change of the volume is preferably at most so high that cells or osteogenic, callus-forming tissue adhering to the device are distracted at most 1 mm / day. A faster distraction frequency than 1 mm / day leads to the differentiation of connective tissue instead of bone.
  • the device transmits biomechanical stimuli to the cells contained in the blood clot and adhered to the device, triggering the body's own regenerative forces, thereby forming new autologous bone material. This does not differ from the original bone material surrounding the defect.
  • the volume change of the device results in a biomechanical transmission of stimuli over the entire space occupied by the device, so that a significantly larger number of cells can be biologically transmitted.
  • mechanical stimulus is transmitted as in a Disreteoidsosteo- genese from the prior art.
  • the biomechanical stimulus is transmitted from the device directly to osteoblasts.
  • the biomechanical stimuli according to the invention can preferably be transferred not only directly to osteoblasts adhering to the device, but also indirectly through fibroblasts.
  • fibroblasts adhering to the device preferably transmit the distraction stimulus in doses to osteoblasts.
  • the fibroblasts in the so-called null zone become osteoblasts and also form bones.
  • the number of fibroblasts that precede osteoblasts changes.
  • distraction osteogenesis of the prior art transmits biomechanical stimuli via a two-dimensional interface of bone or other material only to those cells which directly contact this two-dimensional interface.
  • the invention thus provides a method in which a device is introduced into a bone defect and the device changes its volume and / or shape in the bone defect.
  • biomechanical stimuli are transmitted to cells, in particular osteoblasts, which are located on the outer surface of the device, whereby the cells are stimulated to form bone.
  • the device thus transmits biomechanical stimuli for the utilization of the body's own regenerative powers.
  • a "three-dimensional distraction” is understood to mean a distractive bone regeneration in which biomechanical stimuli are transmitted not only at the interface to a bone fragment, ie two-dimensional, but also a transmission of stimuli over a certain volume. So three-dimensional, takes place.
  • the distraction takes place along a spatial axis.
  • This can be done, for example, by using a preferred tube-shaped device according to the invention, in which the length of the tube changes, for example, by a bellows.
  • the method according to the invention uses the body's own wound healing mechanisms as bioreactor. Bone formation thus occurs under natural conditions, so that the necessary aspects such as growth factors, hormones, cell composition are implicitly taken into account.
  • the method according to the invention overcomes both problems that can arise due to the highly complex control in a bone regeneration, as well as the problems of slow and complicated bone regeneration by distraction from the prior art.
  • the bone defect is preferably refreshed before the introduction of the device according to the invention.
  • this defect is surgically refreshed, in particular produces a hemorrhage. Due to the surgical refresher and the created bleeding, a blood clot forms in the defect.
  • a device according to the invention is preferably introduced into the bone defect according to the invention.
  • the device is enclosed by the blood clot formed, in particular completely enclosed.
  • the swelling agent of the device preferably comes into contact with a liquid, for example with one of the blood of the blood coagula.
  • the at least one device is preferably introduced into a defect region of a bone such that the swelling agent comes into contact with a liquid.
  • the swelling agent thus preferably changes its volume after a defined time.
  • the swelling agent preferably changes its volume after one day.
  • the swelling agent preferably changes its volume after one week.
  • the blood coagula will not shrink, but will increase in proportion to the increase in volume of the swelling agent.
  • the cells activated by the device can transform into proliferating osteoblasts, produce the extracellular matrix, and a leukemia can develop, which then ossifies. If the device according to the invention is preferably biodegradable, this is then resorbed and / or metabolized.
  • the bone defect can fill with bone tissue, which according to the invention zugt by the described biomechanical stimuli of the device is created.
  • the newly formed bone material differs according to the invention preferably neither histologically nor in its biological or medical value of the original bone surrounding it.
  • the absorption time of the device is about 1 to 2 years, more preferably about 1.5 years, in particular 1.5 years.
  • the space that is created by the degradation of the device can be used for the extracellular matrix.
  • the degradation of the device can preferably be set so that after only a few weeks the device degrades, after it has delivered the biomechanical stimuli, and the resulting space is occupied by the extracellular matrix.
  • a device in the context of the method according to the invention, the casing of which has cell-adhesive properties.
  • the surface of the sheath has cell-adhesive properties.
  • the surface of the sheath plays a role in the growth of cells from the blood coagulate.
  • a preferred adhesion of the cells to the sheath according to the invention can be achieved by its surface chemistry and surface physics as well as by the surface topography to be influenced.
  • the surface of the casing is hydrophilic. For the ingrowing cells, the interaction between the negatively charged cell membrane and the electrical properties of the surface of the sheath is preferred according to the invention.
  • a biodegradable device is preferably introduced into the defect region of a bone.
  • the resorption of the device begins 6 weeks after the device has been introduced into a defect region of a bone.
  • the invention relates to a further method according to the invention for bone regeneration, in particular a further three-dimensional distraction method, wherein in particular an aforementioned device is introduced into a defect region of a bone and moved there.
  • the device In this defect area, the device is enclosed by a blood clot, that is, the surfaces of the device contact the autologous cells contained in the blood clot. Since the device is constructed three-dimensionally, the device surface in the entire space which is filled by the device can come into contact with the autologous cells contained in the blood clot.
  • the device is moved in the bone defect. The movement takes place in a controlled and directed manner, ie in a predefined direction with a defined speed.
  • the device transmits biomechanical stimuli to the cells contained in the blood clot and adhered to the device, which trigger the body's own regenerative forces, thereby causing forms new autologous bone material. This does not differ from the original bone material surrounding the defect.
  • the movement of the device results in such a biomechanical stimulus transmission over the entire space occupied by the device, so that a biomechanical stimulus is transmitted to substantially more cells than in the case of distraction osteogenesis from the prior art.
  • the invention thus provides a method in which a device according to the invention is introduced into a bone defect and the device is moved in the bone defect.
  • a volume change of the swelling agent is not necessary in this embodiment, but possible.
  • biomechanical stimuli are transmitted to cells, in particular osteoblasts, which are located on the casing of the device, which stimulates the cells to form bone.
  • the device thus transmits biomechanical stimuli for the utilization of the body's own regenerative forces.
  • a method for regeneration of a bone wherein at least one device according to the invention is introduced into a defect region of a bone, wherein the device is biocompatible and the sheath has a cell-adhesive property, and wherein the device after insertion into the defect region as a function of a force predefined and controlled in the bone defect is moved.
  • the device is preferably moved at a speed of at least 1 ⁇ m / day and / or at most 1.5 mm per day, particularly preferably at most 1 mm per day. According to the invention, the movement preferably takes place continuously or discontinuously.
  • a biodegradable device is preferably introduced into the defect region of a bone.
  • the resorption of the device begins 6 weeks after the device has been introduced into a defect region of a bone.
  • the volume of the swelling agent in the process does not change during the movement of the device.
  • the inventive method for stimulus transmission by means of volume change of the swelling agent of a device according to the invention can preferably be combined with the method according to the invention for stimulus transmission by means of movement of a device.
  • the disclosed preferred features of the method according to the invention for stimulus transmission by means of volume change are, in particular, also preferred features of the method according to the invention for stimulus transmission by means of movement.
  • the movement of the device can be carried out by at least one externally supplied force.
  • the force is preferably added by means of a pull rope or tie rod.
  • the supplied force is ultrasound.
  • the force is preferably supplied by a magnet.
  • FIG. 1 schematically shows a kit comprising devices in an applicator in the form of a syringe.
  • FIG. 2 schematically shows a device introduced into a bone defect before and after the volume change of the swelling agent contained in the device.
  • FIG. 3 schematically shows a preferred embodiment of a device according to the invention without lamellae.
  • FIG. 4 schematically shows a preferred embodiment of a device according to the invention with fins.
  • FIG. 5 schematically shows a preferred embodiment of a device according to the invention with laminar lamellae before and after the volume change of the swelling agent contained in the device.
  • FIG. 6 schematically shows a preferred embodiment of two devices according to the invention which are connected to one another via lamellae.
  • FIG. 7 schematically shows a preferred embodiment of four devices according to the invention, which are connected to one another via a grid-like framework. example
  • FIG. 1 shows a kit 100 comprising an applicator syringe 10 made of sterilizable metal, at the open end 20 of which a disposable capsule 30, for example made of plastic, is attached.
  • the disposable capsule 30 is provided with a protective cap 40 towards the outside.
  • a plurality of devices 50 in the form of granules. These are injected by means of the syringe in a bone defect, not shown, for example, in the jaw area.
  • the kit 100 serves to inject the granules from the devices 50 into a bone defect.
  • the volume of the source material of the device 50 changes, resulting in stretching, shrinkage, and / or shape change of the sheath of the device.
  • the bone cells which in the meantime have attached to the device, are distracted for regeneration of the bone.
  • FIG. 2A shows a device 50 made of an elastic polymer in a bone defect 200, immediately after insertion of this device 50 into the bone defect 200, for example by means of a kit 100.
  • the device 50 is constructed from a sheath 60 and a swelling agent 70. After introduction into the defect 200, the swelling agent 70 comes into contact with the liquid present in the bone defect, in particular blood, whereby, as shown schematically in FIG. 2A by the double arrow, the volume of the swelling agent 70 increases in the longitudinal axis.
  • These voices Increasing the size of the swelling agent is accompanied by an elongation of the sheathing 60 in the longitudinal axis, so that, as can be seen from FIG. 2B, a stretched sheath 60 results. Elongation results in distraction of the cells 80 attached and adhered to the device 50.
  • Figure 3 does not show to scale a preferred embodiment of the device 50.
  • This consists of a tubular sheath 60, which is partially formed as a corrugated hose or bellows 65 with folds 63.
  • the tubular sheath is closed at the tube ends.
  • pores in the sheath 60 through which a liquid can pass through the sheath 60 to the swelling agent 70, which is located in the sheath 60. Due to the fluid intake, the swelling agent 70 can increase its volume, as a result of which the folds 63 of the bellows-type or pleated tube-like part 65 of the sheath 60 are pressed apart. This results in an expansion of the sheath 60 along the course of the tube.
  • FIG. 4 does not show to scale a further preferred embodiment of the device 50.
  • the basic structure corresponds to the embodiment of FIG. 3.
  • the device 50 of FIG. 4 has a plurality of lamellae 90 on the sheathing 60. By the expansion of the sheath 60 described in Figure 3, the slats 90 are pressed apart. Cells 80, which adhere to the lamellae, experience biomechanical impulses through distraction.
  • the rod-like fins 90 shown in longitudinal section may, in three-dimensional view, be layered or leaf-shaped lamellae which are arranged around the entire circumference of the tubular sheathing 60 (compare FIG. 5).
  • FIG. 5 does not show to scale a further preferred embodiment of the device 50.
  • FIG. 5A shows this embodiment in its initial state.
  • the folds 63 of the corrugated tube 65 of the device 50 are folded together here.
  • the two laminar lamellae 90 have a spacing, so that cells 80, for example osteoblasts, can bind to both lamellae 90.
  • a device according to the invention may also have a plurality of fins 90.
  • FIG. 5B shows the device 50 during or after the use according to the invention.
  • the folds 63 of the corrugated tube 65 are pressed apart by the swelling means 70, so that the two sheet-like lamellae 90 are at a greater distance from one another. Adherent cells 80 thereby experience a stretch impulse which allows distraction osteogenesis.
  • Figure 6 does not show to scale a further preferred embodiment of the invention.
  • Two devices 50 are connected to one another via a plurality of lamellae 90. Of course, more than two devices 50 may be interconnected via fins 90.
  • the basic structure of a device 50 corresponds to the embodiment of FIG. 4.
  • the expansion of the sheaths 60 of the two devices 50 described in FIG. 3 forces the lamellae 90 apart.
  • Cells 80 attached to the lamellae experience biomechanical impulses through distraction.
  • the rod-like lamellae 90 shown in longitudinal section can be layered or sheet-shaped in three-dimensional view. be arranged around the entire circumference of the tubular casing 60 around.
  • Figure 7 does not show to scale a further preferred embodiment of the invention.
  • Four devices 50 are connected to one another via a grid-like framework 95. Of course, more than four devices 50 may be interconnected via the framework 95.
  • the devices 50 consist of a capsular, expandable sheath 60.
  • the capsular sheath surrounds a swelling agent which is not shown.
  • pores in the sheath 60 through which a liquid can pass through the sheath 60 to the swelling agent, which is located in the sheath 60.
  • the swelling agent can increase its volume, whereby the sheaths 60 are stretched. This stretching of the sheathings 60 causes the grid-like framework 95 to move.
  • the stretching of the sheaths 60 causes the two grids 96 and 97 of the framework 95 to be pushed apart from one another. Cells 80 adhering to the lattices 96 and 97 thereby experience biomechanical pulses by distraction.
  • the devices 50 may also be designed as shown in FIG. 3, ie be tubular and have a bellows.

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Abstract

L'invention concerne un dispositif (50) pour la régénération d'un os, en particulier par distraction tridimensionnelle, un procédé de distraction du cal tridimensionnelle, ainsi que des utilisations du dispositif précité. Le dispositif comprend une enveloppe (60) et un agent de gonflement.
EP09722885A 2008-03-15 2009-03-14 Dispositif comprenant un agent de gonflement et une enveloppe pour la distraction du cal artificielle Withdrawn EP2252238A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102008014560A DE102008014560A1 (de) 2008-03-15 2008-03-15 Vorrichtung, umfassend ein Quellmittel und eine Ummantelung, zur künstlichen Kallusdistraktion
PCT/EP2009/001875 WO2009115251A1 (fr) 2008-03-15 2009-03-14 Dispositif comprenant un agent de gonflement et une enveloppe pour la distraction du cal artificielle

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EP2252238A1 true EP2252238A1 (fr) 2010-11-24

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EP09722885A Withdrawn EP2252238A1 (fr) 2008-03-15 2009-03-14 Dispositif comprenant un agent de gonflement et une enveloppe pour la distraction du cal artificielle

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US (1) US9050190B2 (fr)
EP (1) EP2252238A1 (fr)
JP (1) JP5382739B2 (fr)
WO (1) WO2009115251A1 (fr)

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IL248472A0 (en) 2016-10-13 2017-01-31 Zion Karmon Ben Devices for tissue growth

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EP1745759B1 (fr) 2000-05-29 2009-05-06 CelGen AG Membranes médicales pour la régénération osseuse
FI20010540A0 (fi) * 2001-03-16 2001-03-16 Yli Urpo Antti Komposiitti pehmyt- ja kovakudosvammojen korjaamiseksi ja mainitun komposiitin käyttö
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RU2477099C1 (ru) * 2011-10-03 2013-03-10 Эмиль Рустам оглы Ибрагим Внутрикостное дистракционное устройство

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JP2011514212A (ja) 2011-05-06
US20110009978A1 (en) 2011-01-13
US9050190B2 (en) 2015-06-09
JP5382739B2 (ja) 2014-01-08
WO2009115251A1 (fr) 2009-09-24

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