WO2006028382A2 - Prosthetic element - Google Patents
Prosthetic element Download PDFInfo
- Publication number
- WO2006028382A2 WO2006028382A2 PCT/NO2005/000322 NO2005000322W WO2006028382A2 WO 2006028382 A2 WO2006028382 A2 WO 2006028382A2 NO 2005000322 W NO2005000322 W NO 2005000322W WO 2006028382 A2 WO2006028382 A2 WO 2006028382A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- guide means
- prosthetic element
- prosthetic
- anchoring
- element according
- Prior art date
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Classifications
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- 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
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- A61C8/0003—Not used, see subgroups
- A61C8/0004—Consolidating natural teeth
- A61C8/0006—Periodontal tissue or bone regeneration
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- A61C8/0018—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the shape
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Definitions
- This invention relates generally to a prosthetic element.
- the prosthetic element according to the invention is applicable in joint-replacement surgery, wherein methods for the anchorage of the prosthetic element to living tissue like bone to be utilized.
- the configuration of the prosthetic element, according to the invention facilitates the removal of the prosthetic element if deemed necessary.
- Prosthetic elements like joint-replacement surgery in larger synovial joints like the hip, knee or the shoulder, can be anchored to the bone either by bone cement, or by cementless fixation like press fit, or anchorage by fibrous and bone ongrowth, or ingrowth in pores.
- fixation with bone cement has given the best long- term results both in the elderly as well in younger patients. Consequently, more cementless elements than cemented ones have been removed and subsequently the need for adequate replacement surgery is essential.
- a cementless prosthetic element should permit suitable, rigid anchorage to living tissue, like bone, and in addition, be designed so that it can be retrieved without waste of the living tissue stock needed for successful replacement surgery.
- the object of the present invention is to fulfil these requirements.
- Cementless fixation with prosthetic elements having a plurality of indented or raised portions, provided bone ongrowth, may give good fixation to the bone like the femur. Consequently, such elements may be quite difficult to retrieve.
- indented or raised portions cannot hinder micro-motion at the element/tissue interface. As the micro-motions causes the patients pain on walking, there is a present need for eliminating or at least minimizing these micro-motions. Moreover, such instability leads to undesirable bone remodelling. Such designs have therefore given poor results in patients.
- Precision press fit of prosthetic elements may give good anchorage to bone provided bone tissue ongrowth to a rough surface.
- the more rough the surface the better the anchorage.
- the more rough the surface the more difficult the retrieval.
- the retrieval of a rough-surfaced element can be very cumbersome. And loss of essential bone stock is inevitable.
- the aim of this method is to provide surface porosity to encourage bone ingrowth.
- Such a method has several disadvantages like adversely affecting the properties of the material, difficulties to control the surface geometry of the ball coated implant, and surface balls can migrate from the implant causing severe third body wear in the artificial joint proper. Further, the removal of a totally ball coated hip or shoulder joint stem can be disastrous; even if a major part of the bone is temporarily removed, there is the risk of breaking the bone in several pieces.
- Mesh pads on a portion of the implant have also been used for anchorage in inventions like US 4406023 of September 2. 1983, William H. Harris inventor, and US 4536894 of August 27. 1985, Jorge O. Galante et al. inventors. Like sintered balls, these mesh pads give good anchorage. Although a collar obstructing the access to the stem below is provided only medially in the above inventions, removing such implants can be very difficult. And loss of essential bone stock is inevitable.
- the object of this invention is to "design an effective configuration for the stem of a hip joint prosthesis by which the charging with spongy material is facilitated". Although some of this spongy material might be removed from the hollow space of the prostheses, this procedure alone does not loosen the prosthesis sufficiently to be able to remove the prosthesis from the femur. The removal of such prosthesis involves cutting bone material loose from prosthesis by an extensive approach to the outside of the prosthesis. This operation has features similar to the method used for the totally ball coated stem described above, and results in a relatively extensive loss of bone stock.
- US 4,623,353 discloses a stem-type femoral prosthesis including a collar provided with access slots for resectioning means, November 18. 1986, Fredrick F. Buechel and Michael J. Pappas inventors, have therefore provided one access slot on each side of a collar. This access slot gives access to the proximal part of the stem, but using a saw or chisel onto the outside of a prosthetic element will inevitably lead to loss of bone stock. Moreover, the slots above give access to the uppermost part of the stem only.
- EP 181586 concerns a prosthetic element comprising a prosthetic main part provided with projecting ribs distributed around the circumference of the prosthetic main part.
- the ribs extend in the longitudinal direction along an upper portion of the prosthetic main part.
- Several through holes are formed in the ribs for the ingrowth of bone tissue. A possible removal of the prosthetic element would cause considerable loss of bone.
- the space between the longitudinal ribs may provide some guidance for the cutting tool, but the shape of these spaces does not provide protection so as to minimize the loss of bone stock. Further, each outer edge of the
- the ribs is cogged and the distal portion of the prosthetic element has plural structures to ensure the fixation of the prosthetic element.
- the overall design indicates the intention of the prosthetic element is to provide a prosthesis which ensures a reliable fixation to the femur, while the easy removal of the prosthesis has been no object of the invention of EP 181566.
- the object of present invention is to provide a prosthetic element having a configuration which permits anchorage to living tissue like bone and which minimizes the problems associated with the retrieval of the prosthetic element. This object is achieved in accordance with the independent claim 1 and the embodiments of the invention defined in the following dependent claims.
- the prosthetic element according to the invention may be used for various orthopaedic replacements within the body of man or animal.
- the prosthetic element may be utilized for reconstructions in the skeleton, for larger synovial joints of the lower and upper extremity for instance the hip, knee, shoulder and elbow etc.
- the prosthetic element may function as an implant in the oral cavity.
- the implants may, if deemed necessary for other reasons, be fixed by bone cement, except when designed for the ingrowth of fibrous tissue only (Fig. 3).
- the prosthetic element has an outer surface defining an interface to the surrounding bone or fibrous tissue, wherein the prosthetic element is provided with at least one internal anchoring cavity for the growing of tissue and a least one guide means for a cutting tool.
- Guide elements for a cutting tool are shown in US 6,187,012. As opposed to the invention these guide elements are provided for guiding the cutting tool to perform the cutting operation on the outside of the prosthetic element, whereas the cutting operation for the loosening of the prosthetic element according to the current invention is performed inside the prosthetic element as described above.
- the spaces between the ribs of the prosthetic element disclosed in EP 181 586 may be perceived as guide elements for the cutting tool.
- the prosthetic element of US 6187012 the prosthetic element of EP 181 586 requires access from the outside of the prosthetic element to be removed.
- the spaces between the ribs of EP 181 586 and guide elements are not positioned within the prosthetic element.
- the outer surface of the prosthetic element in accordance with the invention is preferably smooth to facilitate the retrieval of the prosthetic element if deemed necessary.
- the anchorage of the prosthetic element is provided by ingrowth of fibrous or bone tissue, or both, in the anchoring cavities that may be constituted by conventional holes or pores, of any geometrical shape inside the prosthetic element.
- the anchoring cavities are all oriented and connected to one or more of the guide means so that the anchorage to periprosthetic tissue, on retrieval, can be removed by a suitable cutting tool.
- Anchoring cavities may be constituted by holes, slits, gutters, channels, pores or micro-pores or other cavities enabling ingrowth of tissue into the prosthetic element.
- Bone anchorage is best obtained when the diameter of the holes or pores are greater than 0.25 mm, and the prosthetic element is made of a material favouring bone ongrowth like titanium.
- the maximum diameter of pores should preferably be less than 0.1 mm, and the prosthetic element made of a material favouring fibrous tissue encapsulation like stainless steel.
- the guide means and the anchoring cavities are positioned essentially within the perimeter/circumference of the prosthetic element defined by the outer surface of the prosthetic element.
- the anchoring cavities and the guide means are interconnected and at least one of the anchoring cavities and/or the guide means has an opening in the outer surface for growing of tissue into the element.
- the guide elements and/or anchoring cavities may be positioned proximate or deep to the outer surface.
- the guide means may assume various shapes to fulfil the purpose of enabling a cutting tool to remove essentially ingrown, anchoring tissue in pores or holes without compromising periprosthetic tissue stock.
- the guide means may be shaped like grooves, recesses, hollows, gutters, channels or tunnels etc for the insertion of the cutting tools.
- the cross section of the guide means may be spherical, semi-spherical or assume any other suitable form.
- the shape and/or the dimension of cross sections of the guide means may be uniform or vary along the longitudinal direction of guide means.
- the guide means may for instance have a circular cross section in the proximal part of the prosthesis element, whereas the cross section in the distal part is slightly more than semicircular (or semicircular).
- the invention preferably provides one or more guide means longitudinally all along, or to a portion of, the polished stem of the implant.
- These guide means are preferably designed so that the cutting tool like a stiff, or particularly a flexible drill bit, cannot go astray.
- the collar of the stem may be provided with holes guiding a bore exactly to the guide means of the stem.
- the anchoring cavities are oriented with an angle to the guide means, preferably perpendicular to the guide means.
- the guide means extend in the longitudinal direction of the element and the anchoring cavities extend in the transverse direction of the element.
- the anchoring cavities extend both in the longitudinal and the transverse direction of the element and have a longitudinal opening in the outer surface of the prosthesis element.
- the number of guide means and anchoring cavities and their extension in the longitudinal and transverse direction respectively, is to be varied dependent on the conditions of the various fields of appliance.
- the cavities do not necessarily extend from one guide means to the opposite positioned guide means.
- the guide means are positioned close to the outer surface of the element, each guide means having one longitudinal opening in the outer surface, for instance coincidently with the circumference of the prosthetic element.
- each guide means having one longitudinal opening in the outer surface, for instance coincidently with the circumference of the prosthetic element.
- the upper end of these guide means may be threaded so that a suitable, short screw can close them.
- the threaded part may also be used for anchorage of a suitable instrument for the insertion or the removal of the prosthesis.
- the whole guide means may be formed as a thread in order to functions as a fastening surface.
- no cavities are provided between the guide means.
- the surface or a part of the surface inside the guide means may be provided with a layer of a porous material for ingrowth of fibrous or bone tissue.
- the prosthetic elements can be made by conventional means or by a Rapid Prototyping and Rapid Manufacturing technique like The Metal Printing Project (MPP), The Electron Beam Melting (EBM) process, or Laser Engineered Net Shaping (LENS).
- the stem of the prosthetic element may also be curved. This does not lead to any problem when using a flexible bore.
- Fig. 1 is a schematic side-view drawing of a proximal femoral endoprosthesis, with a medial collar, for ingrowth of fibrous or bone tissue in pores or holes transversely oriented to longitudinal, externally open, groves or gutters for a cutting tool.
- Figs. IA and B are transverse sections of Fig. 1.
- Fig. 2 is a schematic side-view drawing of a modification of the proximal femoral endoprosthesis shown in Fig. 1, for ingrowth of fibrous or bone tissue in pores or holes extending right through the implant, open to guide means for a cutting tool on opposite sides of the implant.
- Figs. 2A and B are transverse sections of Fig. 2.
- Fig. 3 is a schematic side-view drawing of a proximal femoral endoprosthesis.
- the circular guide means for a cutting tool may be located within the stem.
- Figs. 3 A, B and C are transverse sections of Fig. 3.
- Fig.5 Diagrams illustrating the effect of the invention when using the embodiment according to a test stem, in principle, designed as figure 4.
- Fig. 6 A sectional view of another embodiment in which the guide gutters are covered by a porous layer (not drawn to scale).
- Fig. 7 is a schematic side-view drawing of the outer shell of an acetabular cup.
- Fig. 7A is a schematic transverse section of Fig. 7.
- Figs. 8-9 are schematic transverse drawings of a dental implant serving as anchorage for an artificial tooth.
- Figure 10 is an embodiment with a curved femoral stem.
- the invention is equally applicable to other types of cementless or cemented prosthesis. That is, the cutting guide means may be applied to other types of devices having different geometries.
- Fig. 1 illustrates a proximal modular type femoral endoprosthesis (1), with a conventional Morse tapered upper end (2) for the ball and a tapered, polished, conical distal end (3).
- a proximal modular type femoral endoprosthesis (1) with a conventional Morse tapered upper end (2) for the ball and a tapered, polished, conical distal end (3).
- several anchorage cavities showr ⁇ as slits or gutters (6) provide access for fibrous or bone tissue ingrowth.
- the anchorage cavities may have a longitudinal extension all along the length of the prosthesis or along a portion of the length.
- Longitudinal guide means for a cutting tool (5) are located somewhat deep in the stem, outward open by the slit (6) as illustrated in Figs. IA-B.
- the guide means may also be located quite superficial as illustrated in Fig. 2 in which the shape of the cross section of the guide means (5) preferably is slightly more than semicircular so to hinder a cutting tool to go astray.
- a medial collar only (4) is indicated in the drawing.
- the guide means goes right through the collar, and such a collar will thus not obstruct a controlled retrieval of the prosthesis.
- Tissue growing into the guide means (5) is possible directly as shown in Fig. 2A-B or via the slits (6) illustrated in Fig IA. Further anchorage, and the most important one, is provided by tissue growth into pores, holes or small channels (7) transversely interconnecting the guide means (5), or holes or pores extending right through the implant from one guide means to one on the other side of the implant (Figs. 2A-B and 4), or both.
- the uppermost end of the guide means may be threaded so that a suitable, short screw can close the guide.
- An example of the threaded part (5a) is illustrated in Fig. 2.
- the threaded part (5 a) may also be used for anchorage of a suitable instrument for the insertion or the removal of the prosthesis, or a drill guide.
- tissue ongrowth promoting material like hydroxy apatite, or sustained drug release substances as described in US 4,913,903, 1990, inventors Einar Sudmann et al.
- a prosthetic element may by be anchored to living tissue by tissue ingrowth. Whether anchorage by bone or by fibrous tissue only will give the best long-term results in patients has yet to be decided. However, the very best anchored "implant" in man and animals, the tooth, is anchored by fibrous tissue, by multiple small collagen fibrils. And such anchorage by fibrous tissue only has stood the test of millions of years.
- Fig. 3 illustrates a prosthetic implant for fibrous tissue anchorage.
- pores for fibrous tissue anchorage should preferably have a maximal diameter of less than 0.1 mm.
- the pores (8) in Fig. 3 are thus not drawn to scale.
- the essential part is that the pores are oriented perpendicular (Figs. 3A-B), or at any angle, to the guide means (5) for the cutting tool.
- the external opening of each pore, or hole (8) may be pointed at the distal perimeter (9) acting as a miniature cutting device, cutting the ingrown tissue therein on retrieval (Fig. 3C, 8-9).
- Fig 3 A shows an example of plural pores/holes connected to each guide means.
- the guide means (5) are connected to through holes (8) running from one side to the other of the prosthesis element, whereas in the right portion of the prosthesis element additional holes are provided in a direction perpendicular to the thickness direction.
- additional holes are provided in a direction perpendicular to the thickness direction.
- FIGS 4 A-D describe a further embodiment of the invention.
- the collar 4 of the prosthesis element has a special design.
- the upper part has a certain thickness and is provided with holes 9 ending in the respective guide means or channels 5.
- Figure 5 illustrates the effect of the invention.
- the upper curve (A) in the graphs shows the load necessary for push-out/withdrawal of a test prosthetic element, while the lower curve (B) illustrates the markedly reduced load needed after a treatment according to the invention.
- FIG. 6 Another embodiment is proposed in figure 6.
- Configurations for instance as shown in figures 2 or 4, may be constructed without the cavities 7. Instead, at least a part of the inner surface of the guide, means 5 is provided with a layer 11 that is suitable for bone or fibrous tissue ingrowth.
- the layer may have a thickness of 500 ⁇ with communicating pores. The dimension of the pores should be small, for instance less than lOO ⁇ , if only ingrowth of fibrous tissue is wanted.
- Fig. 7 illustrates how an acetabular shell for the hip joint liner may be designed.
- the guide means (5) for a flexible cutting instrument radiate out from the dome, and the anchoring pores or holes (7) interconnect these guide means, or goes right through the shell.
- Fig. 8 illustrates a dental implant serving as a base for an artificial tooth.
- anchorage is secured by bone or fibrous tissue, or both, in holes or pores (7) open to longitudinal guide means (5) for a cutting device.
- the implant may be circular as illustrated, or any desirable shape.
- the surface is polished, and for primary fixation in the jaw, a circular implant may be formed like a screw.
- Fig. 9 illustrates a dental implant serving as a base for an artificial tooth.
- Anchorage is here, however, provided by fibrous tissue ingrowth in pores (8) as in Fig. 3.
- the implant may be circular as illustrated, or any desirable shape.
- the surface is polished, and for primary fixation in the jaw a circular implant may be formed like a screw.
- FIG 10 there is shown an embodiment with a curved prosthetic element (3).
- the upper part of the guide means is threaded (5a), like the ones shown in figure 2.
- a flexible bore must be used.
- Anchoring pegs in an implant like knee or ankle prosthesis may be designed as illustrated in Figs. 8-9. These pegs may be conical, circular, oval, or any shape in between, in transverse section.
- guide means and cavities may be modified, as well as their relationship.
- longitudinal threaded guide means, or gutter, 5 mentioned above will be suitable for anchorage by bone tissue ongrowth only, not by fibrous tissue.
- the stem may be straight, or conical as shown but the invention will also be suitable by curved stems, using flexible bores.
Abstract
Description
Claims
Priority Applications (13)
Application Number | Priority Date | Filing Date | Title |
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CA002580714A CA2580714A1 (en) | 2004-09-08 | 2005-09-07 | Prosthetic element |
EA200700577A EA009582B1 (en) | 2004-09-08 | 2005-09-07 | Prosthetic element |
EP05791904A EP1804727B1 (en) | 2004-09-08 | 2005-09-07 | Prosthetic element |
AU2005280808A AU2005280808A1 (en) | 2004-09-08 | 2005-09-07 | Prosthetic element |
US11/574,673 US7875083B2 (en) | 2004-09-08 | 2005-09-07 | Prosthetic element |
PL05791904T PL1804727T3 (en) | 2004-09-08 | 2005-09-07 | Prosthetic element |
DE602005015879T DE602005015879D1 (en) | 2004-09-08 | 2005-09-07 | prosthetic element |
JP2007529756A JP4633119B2 (en) | 2004-09-08 | 2005-09-07 | Prosthetic device |
AT05791904T ATE438359T1 (en) | 2004-09-08 | 2005-09-07 | PROSTHETIC ELEMENT |
DK05791904T DK1804727T3 (en) | 2004-09-08 | 2005-09-07 | prosthetic element |
IL181770A IL181770A0 (en) | 2004-09-08 | 2007-03-07 | Prosthetic element |
NO20071814A NO331888B1 (en) | 2004-09-08 | 2007-04-10 | Prosthetic Element |
US12/965,946 US20110208318A1 (en) | 2004-09-08 | 2010-12-13 | Prosthetic element |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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GBGB0419961.8A GB0419961D0 (en) | 2004-09-08 | 2004-09-08 | Prosthetic element |
GB0419961.8 | 2004-09-08 |
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US12/965,946 Division US20110208318A1 (en) | 2004-09-08 | 2010-12-13 | Prosthetic element |
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WO2006028382A2 true WO2006028382A2 (en) | 2006-03-16 |
WO2006028382A3 WO2006028382A3 (en) | 2006-06-15 |
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PCT/NO2005/000322 WO2006028382A2 (en) | 2004-09-08 | 2005-09-07 | Prosthetic element |
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US (2) | US7875083B2 (en) |
EP (1) | EP1804727B1 (en) |
JP (2) | JP4633119B2 (en) |
KR (1) | KR20070104518A (en) |
CN (1) | CN101068510A (en) |
AT (1) | ATE438359T1 (en) |
AU (1) | AU2005280808A1 (en) |
CA (1) | CA2580714A1 (en) |
DE (1) | DE602005015879D1 (en) |
DK (1) | DK1804727T3 (en) |
EA (1) | EA009582B1 (en) |
ES (1) | ES2331525T3 (en) |
GB (1) | GB0419961D0 (en) |
IL (1) | IL181770A0 (en) |
PL (1) | PL1804727T3 (en) |
WO (1) | WO2006028382A2 (en) |
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WO2011023153A1 (en) * | 2009-07-25 | 2011-03-03 | Bernhard Hildebrandt | Structuring of the bone contact surface of endoprostheses |
FR2986962A1 (en) * | 2012-02-20 | 2013-08-23 | Pierre-Etienne Moreau | ORTHOPEDIC IMPLANT CUP, ORTHOPEDIC IMPLANT COMPRISING SUCH A CUPULE AND METHOD FOR PRODUCING SUCH A CUPULE |
US8597361B2 (en) | 2010-11-11 | 2013-12-03 | Bioshift, Llc | Joint implant fixation system |
FR3077198A1 (en) * | 2018-01-26 | 2019-08-02 | Conri Pierre Emmanuel Agissant Au Nom Et Pour Le Compte De La Societe Evok En Cours De Formation | FEMORAL COMPONENT FOR FORMING A HIP PROSTHESIS |
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US11213397B2 (en) | 2009-05-21 | 2022-01-04 | Depuy Ireland Unlimited Company | Prosthesis with surfaces having different textures and method of making the prosthesis |
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US20140067080A1 (en) | 2012-09-05 | 2014-03-06 | Christopher G. Sidebotham | Hip stem prosthesis with a porous collar to allow for bone ingrowth |
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US9668760B2 (en) | 2013-08-08 | 2017-06-06 | Scott Kelley | Methods and systems for preparing the acetabulum to receive an acetabular component in a hip replacement surgical procedure |
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US11298102B2 (en) | 2016-01-11 | 2022-04-12 | Kambiz Behzadi | Quantitative assessment of prosthesis press-fit fixation |
US11375975B2 (en) | 2016-01-11 | 2022-07-05 | Kambiz Behzadi | Quantitative assessment of implant installation |
US11234840B2 (en) | 2016-01-11 | 2022-02-01 | Kambiz Behzadi | Bone preparation apparatus and method |
US11458028B2 (en) | 2016-01-11 | 2022-10-04 | Kambiz Behzadi | Prosthesis installation and assembly |
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US11751807B2 (en) | 2016-01-11 | 2023-09-12 | Kambiz Behzadi | Invasive sense measurement in prosthesis installation and bone preparation |
US20170290667A1 (en) * | 2016-04-07 | 2017-10-12 | Kambiz Behzadi | Mechanical assembly including exterior surface preparation |
US11839549B2 (en) | 2016-04-07 | 2023-12-12 | Kambiz Behzadi | Materials in orthopedics and fracture fixation |
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FR2986962A1 (en) * | 2012-02-20 | 2013-08-23 | Pierre-Etienne Moreau | ORTHOPEDIC IMPLANT CUP, ORTHOPEDIC IMPLANT COMPRISING SUCH A CUPULE AND METHOD FOR PRODUCING SUCH A CUPULE |
WO2013124576A1 (en) * | 2012-02-20 | 2013-08-29 | Galactic | Cup for an orthopaedic implant, orthopaedic implant comprising such a cup and method for producing such a cup |
FR3077198A1 (en) * | 2018-01-26 | 2019-08-02 | Conri Pierre Emmanuel Agissant Au Nom Et Pour Le Compte De La Societe Evok En Cours De Formation | FEMORAL COMPONENT FOR FORMING A HIP PROSTHESIS |
Also Published As
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KR20070104518A (en) | 2007-10-26 |
CA2580714A1 (en) | 2006-03-16 |
EP1804727A2 (en) | 2007-07-11 |
WO2006028382A3 (en) | 2006-06-15 |
CN101068510A (en) | 2007-11-07 |
IL181770A0 (en) | 2007-07-04 |
JP2008512137A (en) | 2008-04-24 |
AU2005280808A1 (en) | 2006-03-16 |
JP4633119B2 (en) | 2011-02-16 |
DK1804727T3 (en) | 2009-11-30 |
US20110208318A1 (en) | 2011-08-25 |
ATE438359T1 (en) | 2009-08-15 |
EA009582B1 (en) | 2008-02-28 |
US20070233243A1 (en) | 2007-10-04 |
JP2010188158A (en) | 2010-09-02 |
ES2331525T3 (en) | 2010-01-07 |
PL1804727T3 (en) | 2010-01-29 |
EP1804727B1 (en) | 2009-08-05 |
GB0419961D0 (en) | 2004-10-13 |
DE602005015879D1 (en) | 2009-09-17 |
US7875083B2 (en) | 2011-01-25 |
EA200700577A1 (en) | 2007-08-31 |
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