US20020018798A1 - Coating for metallic implant materials - Google Patents

Coating for metallic implant materials Download PDF

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Publication number
US20020018798A1
US20020018798A1 US09/885,287 US88528701A US2002018798A1 US 20020018798 A1 US20020018798 A1 US 20020018798A1 US 88528701 A US88528701 A US 88528701A US 2002018798 A1 US2002018798 A1 US 2002018798A1
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United States
Prior art keywords
coating
collagen
metallic implant
calcium phosphate
process according
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.)
Abandoned
Application number
US09/885,287
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English (en)
Inventor
Andreas Sewing
Michel Dard
Sophie Rossler
Dieter Scharnweber
Hartmut Worch
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Biomet Deutschland GmbH
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Merck Patent GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck Patent GmbH filed Critical Merck Patent GmbH
Assigned to MERCK PATENT GESELLSCHAFT MIT BESCHRAENKTER HAFTUNG reassignment MERCK PATENT GESELLSCHAFT MIT BESCHRAENKTER HAFTUNG ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DARD, MICHEL, ROEBLER, SOPHIE, SCHARNWEBER, DIETER, SEWING, ANDREAS, WORCH, HARTMUT
Publication of US20020018798A1 publication Critical patent/US20020018798A1/en
Priority to US10/414,284 priority Critical patent/US7229545B2/en
Assigned to BIOMET DEUTSCHLAND GMBH reassignment BIOMET DEUTSCHLAND GMBH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MERCK PATENTGESELLSCHAFT MIT BESCHRANKTER HAFTUNG
Abandoned legal-status Critical Current

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Classifications

    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • the invention relates to a biomimetically produced bone-analogous coating, comprising an organic and inorganic main constituent, for metallic implant materials of any desired surface geometry and to a process for its preparation.
  • the main components of this coating are collagen and calcium phosphate phases which form the organic and inorganic main constituent of the bone.
  • the coating according to the invention is suitable to a particular extent as a matrix for the inclusion of further inductive substances such as growth factors, adhesion proteins or pharmacological active compounds.
  • the polarization of the implant leads to an alkalization of the electrolyte near to the surface (2H 2 O+2e ⁇ ⁇ H 2 +2OH ⁇ ), by means of which a precipitation reaction is induced in front of the sample surface and the precipitation product formed is deposited on the metallic implant surface.
  • a further approach to the field of surface modification of implant materials consists in achieving a ‘biologization’ of implant surfaces by utilizing organic compounds occurring in surrounding tissue for the surface modification.
  • immobilized proteins and protein sequences are used which exert their action in the immobilized state (collagen, adhesion proteins, RGD sequences) or proteins which are released over a certain period of time.
  • RGD sequences a largely general, positive action on the biocompatibility of the implant surface (collagen, certain adhesion proteins) or the adhesion of certain cell types is aimed at (extended RGD sequences) [Schaffner et al., J. of Mat. Sci.: Mat. in Med. 10, 837-39 (1999)].
  • WO 99/30672 (Uni Tubingen) describes a coating for prostheses of organic polymer material in whose surface hydroxyapatite or collagen can be included.
  • the polymer material here is only the adhesion promoter; a composite of collagen and a calcium phosphate phase which is similar to bone cannot be referred to.
  • WO 92/13984 Queen's University of Springfield
  • the electrolyte also contains biological non-toxic compounds such as collagen or impurities.
  • the coating is a uniform microporous ceramic material made of associated nonorientated crystallites. This layer can also contain biologically active compounds as precipitation products.
  • the coating described accordingly differs markedly from a mineralized collagen/calcium phosphate matrix.
  • Implants for use in the maxillary area or joint replacement are preferably manufactured from metallic materials in order to meet the mechanical demands.
  • the immediate surface which can differ greatly from the basic material in its properties, is often neglected.
  • the properties of the surface especially are of crucial importance for the interactions between implant and surrounding tissue.
  • conformational changes of adsorbed proteins can contribute significantly to formation of a fibrous intermediate layer, which in turn can result in an inadequate stability of the implant.
  • a teaching of the present invention starts from the object of modifying implant surfaces specifically with biochemical information in order to achieve a rapid osteointegration with formation of high-grade bony tissue after implantation.
  • a bone-analogous coating comprising organic and inorganic main constituents, for implant materials of any desired surface geometry, the coating comprising a collagen matrix mineralized with calcium phosphate.
  • Suitable implant materials are generally conductive materials such as conductive polymers or metals used in dental technology or in the endoprosthesis and trauma fields. Titanium and titanium alloys such as TiAl 6 V 4 are particularly preferred.
  • the coating according to the invention is produced under conditions which make possible the inclusion of organic components.
  • the invention therefore utilizes electrochemically assisted processes, which can be carried out under almost physiological pH and temperature conditions and thus make possible the inclusion of biomolecules.
  • the main components of the layer consist of collagen and hydroxyapatite, the organic and inorganic main component of the bone.
  • the mineralised collagen matrix is constructed in the form of layers. This has the advantage that by means of this the production of graded layers having a varying degree of mineralization of the collagen matrix is also possible.
  • the preferred overall thickness of the matrix coating is about 0.04 ⁇ m-150 ⁇ m, especially about 3-8 ⁇ m.
  • the preferred range for the typical dimensions of the hydroxyapatite crystals is about 300-500 nm in length and 50-60 nm in diameter.
  • the inorganic main constituent or the calcium phosphate phase preferably contain amorphous calcium phosphate (Ca 9 (PO 4 ) 6 .nH 2 O), hydroxyapatite (Ca 10 (PO 4 ) 6 (OH 2 ), octacalcium phosphate (Ca 8 H 2 (PO 4 ) 6 .H 2 O) or brushite (CaHPO 4 .2H 2 O).
  • amorphous calcium phosphate Ca 9 (PO 4 ) 6 .nH 2 O
  • hydroxyapatite Ca 10 (PO 4 ) 6 (OH 2 )
  • octacalcium phosphate Ca 8 H 2 (PO 4 ) 6 .H 2 O
  • brushite CaHPO 4 .2H 2 O
  • the calcium phosphate phase can additionally be doped with ions such as fluoride, silver, magnesium or carbonate.
  • type I collagen is preferred, which is responsible in the bone for the elastic properties and in the mineralized state brings about the high strength of the bone together with the hydroxyapatite crystallites.
  • the collagen can also be a mixture of the types I to III.
  • the types I to III belong to the group of fibril-forming collagens.
  • Gelatin can additionally be added to the collagen.
  • collagen which can also be derived from recombinant production, the inclusion of other matrix proteins is also possible.
  • a further advantage of the invention involves the possibility of utilizing the layers described as a matrix for bone-specific proteins (BMP, TGF ⁇ etc.).
  • BMP bone-specific proteins
  • TGF ⁇ vascular endothelial growth factor
  • pharmacological active compounds such as antibiotics
  • the invention further relates to a metallic implant made of a parent substance and of an outer layer carried by this, the outer layer being a coating according to the invention.
  • the invention also relates to a process for the electrochemically assisted coating of metallic implant materials of any desired surface with collagen and calcium phosphate phases (CPP), comprising
  • CPP calcium phosphate phases
  • the preferred ranges for current density and temperature are, respectively about ⁇ 0.2 to ⁇ 50 mA/cm 2 and about 30-40° C., more preferably a current density of about ⁇ 1 to ⁇ 10 mA/cm 2 and a temperature of about 37° C.
  • the coating can be carried out in an electrolysis cell in which the metallic implant is cathodically polarized.
  • the layer deposition takes place near to physiological pH and temperature conditions.
  • the electrolyte comprises a Ca 2+ /H x PO 4 (3 ⁇ x) ⁇ -containing solution, which can additionally contain collagen or other substances (growth factors, antibiotics).
  • the implant surface can have any desired surface geometry (structure; rough, polished, etched), a chemical modification (generation of functional groups), a calcium phosphate layer, a protein layer and a layer prepared according to Patent No. WO 98/17844 (TU Dresden) or DE-19504386 (TU Dresden) or a combination thereof.
  • a mineralized collagen layer can be produced on the titanium surface.
  • the degree of the mineralization i.e. the nature of the calcium phosphate phases (CPP) and degree of coating, are specified here by the electrochemical parameters. This process can be assisted by the addition of groups of substances influencing mineralization (e.g. bone sialoprotein, osteopontin).
  • the coating process comprises firstly carrying out a coating of the sample with calcium phosphate phases (CPP) in an electrochemical process via galvanostatic polarization in an electrolyte solution comprising calcium ions and phosphate ions at defined current density and temperature, followed by a coating of the sample, coated with calcium phosphate phases (CPP), by immersion in a collagen solution at a pH of less than 8 and a temperature of about 4 to 40° C. for a few minutes, and subsequently coating of the collagen/CPP-coated sample with further calcium phosphate phases (CPP) in a fresh electrochemical process by means of galvanostatic polarization under defined current density and temperature.
  • CCPP calcium phosphate phases
  • the process steps mentioned beforehand can preferably also proceed a number of times under alternating conditions, i.e. a sequence of the process steps a) and b) according to the scheme a-b-a-b-a-b etc.
  • the metallic implant material to be coated being electrochemically polarized cathodically in a collagen solution comprising calcium ions and phosphate ions.
  • a process is even more preferred in which a cathodic current flow of ⁇ 0.5 to ⁇ 30 mA/cm 2 flows for approximately 30 minutes during the galvanostatic polarization in process step b).
  • the sample is then immersed in a collagen solution which is prepared in the following manner: acid-soluble freeze-dried calf skin collagen type I is dissolved in 0.01 M acetic acid and adjusted to a concentration of 0.1 mg/ml at 4° C.
  • the collagen molecules are reconstituted in two process steps: pH adjustment to 7.4 using double-concentrated phosphate buffer and temperature increase to 36° C. After 3 hours, the solution consists of native reconstituted fibrils. The sample remains in this solution for 10 minutes, then it is rinsed with deionized water.
  • the sample coated with collagen is incorporated as a working electrode in a three-electrode arrangement, consisting of a saturated calomel electrode as reference electrode and a platinum sheet as counter-electrode in a thermostated electrolysis cell.
  • the electrolyte solution used is a stock solution which is prepared in the following way: 10 ml of stock solution of CaCl 2 and NH 4 H 2 PO 4 in each case, in the concentrations 33 mM and 20 mM, are diluted and mixed so that 200 ml result; 1.67 mM in calcium ions and 1.0 mM in phosphate ions. The pH is adjusted to 6.4 using dilute NH 4 OH solution.
  • a cylinder of TiAl 6 V 4 is prepared as in Example 1.
  • the construction of the electrolysis cell and the electrolyte for calcium phosphate deposition are identical to that in Example 1.
  • coating with CPP is carried out by means of galvanostatic polarization under cathodic current flow at ⁇ 10 mA/cm 2 .
  • cathodic polarization is interrupted, and the sample is taken out of the electrolyte solution and rinsed with deionized water.
  • a crystalline CPP, hydroxyapatite is now present on the TiAl 6 V 4 surface.
  • the sample is now immersed in a collagen solution which is identical to that in Example 1.
  • the sample coated with hydroxyapatite remains in this solution for 10 minutes, then it is rinsed with deionized water and again incorporated into the electrolysis cell. After connection to the potentiostat, deposition of hydroxyapatite again takes place by means of galvanostatic polarization under cathodic current flow at ⁇ 10 mA/cm 2 . After 20 min, the sample is taken out and rinsed with deionized water. The deposited layer appears whitish. Electron-microscopic examination shows a closed layer which consists of agglomerates of small needles. A network of mineralized collagen fibrils is situated on this layer. IR-spectroscopic and X-ray diffraction investigations furnish proof that the mineral phase consists of hydroxyapatite. The characteristic amide bands in the IR spectrum furthermore show that the collagen is not present in denatured form, but on the contrary a good agreement exists between the mineralized layer and a spectrum for native bone.
  • a cylinder of TiAl 6 V 4 is prepared as in Example 1.
  • the construction of the electrolysis cell is identical to that in Example 1.
  • a collagen solution containing native assembled collagen fibrils is prepared as in Example 1. This solution is centrifuged at 5 000 g and 4° C. for 15 min, and the pellet is taken up with deionized water and dispersed by shaking. The solution is then centrifuged at 5 000 g and 4° C. again for 15 min. The pellet obtained in the centrifugation is now taken up in the electrolyte for calcium phosphate deposition described in Example 1 and homogenized by means of a disperser.
  • This solution is used as an electrolyte for a simultaneously carried-out process for the deposition and mineralization of collagen.
  • mineralization is carried out by means of galvanostatic polarization under cathodic current flow at ⁇ 10 mA/cm 2 . After 30 minutes, the cathodic polarization is complete, and the sample is taken out of the electrolyte solution and rinsed with deionized water.
  • the deposited layer appears whitish. Electron-microscopic examination shows a composite of collagen fibrils and CPP. IR-spectroscopic and X-ray diffraction investigations furnish proof that the mineralization of the fibrils takes place mainly by means of the crystalline phase hydroxyapatite. The more readily soluble amorphous calcium phosphate phase is partially found. The characteristic amide bands in the IR spectrum furthermore show that the collagen is not present in denatured form, but on the contrary a good agreement exists between the mineralized layer and a spectrum for native bone.
  • a cylinder of TiAl 6 V 4 is prepared as in Example 1.
  • the construction of the electrolysis cell and the electrolyte for the calcium phosphate deposition are identical to that in Example 1.
  • coating with CPP by means of galvanostatic polarization is carried out under cathodic current flow at ⁇ 10 mA/cm 2 .
  • cathodic polarization is interrupted, and the sample is taken out of the electrolyte solution and rinsed with deionized water.
  • a crystalline CPP, hydroxyapatite is now present on the TiAl 6 V 4 surface.
  • the sample is now immersed in a collagen solution which is identical to that in Example 1.
  • the sample coated with hydroxyapatite remains in this solution for 10 minutes, then it is rinsed with deionized water and again incorporated into the electrolysis cell. After connection to the potentiostat, partial mineralization of the collagen is carried out under cathodic current flow at ⁇ 10 mA/cm 2 for 15 min. Finally, the sample is rinsed with deionized water. The deposited layer appears whitish.
  • the binding of integrin-specific cell-selective peptide sequences to the immobilized collagen layer is carried out. The binding is carried out covalently by means of a thiol anchor and SMPB (sulfosuccinimidyl 4-(pmaleimidophenyl)butyrate) to the phosphate groups of the collagen.
  • SMPB sulfosuccinimidyl 4-(pmaleimidophenyl)butyrate
  • Electron-microscopic examination shows a homogeneous layer of hydroxyapatite needles, on which a partially mineralized network of collagen fibrils is present.
  • the activity of the RGD sequences is evident from adhesion and proliferation experiments using MC3T3-E1 cells. Relative to comparable pure collagen layers, the RGDcoated surfaces show increased cell adherence and cell proliferation beginning after shorter times.
  • FIG. 1 [0048]FIG. 1
  • [0049] shows the cell proliferation of MC 3 T 3 mouse osteoblasts on hydroxyapatite and on the bone-analogous collagen/hydroxyapatite matrix, in each case on TiAl 6 V 4 substrates.
  • the absorption is proportional to the cell count (WST-1 test).

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)
US09/885,287 2000-06-21 2001-06-21 Coating for metallic implant materials Abandoned US20020018798A1 (en)

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Applications Claiming Priority (2)

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DE10029520A DE10029520A1 (de) 2000-06-21 2000-06-21 Beschichtung für metallische Implantatmaterialien
DEDE10029520.7 2000-06-21

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EP (1) EP1166804B1 (es)
JP (1) JP4970665B2 (es)
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CA (1) CA2351009C (es)
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20040032297A (ko) * 2002-10-09 2004-04-17 (주)아미티에 생분해성 골접합용 코팅 임플란트
US20040236432A1 (en) * 2003-05-13 2004-11-25 Suong-Hyu Hyon Bone-adherent implant with shock-absorbing property and manufacturing method thereof
US20050079198A1 (en) * 2003-08-15 2005-04-14 Berthold Nies Chitosan-coated metallic article, and process for the production thereof
EP1618904A1 (en) * 2004-06-30 2006-01-25 Friadent GmbH Implant with a biofunctionalized surface and method for its production
US7067169B2 (en) 2003-06-04 2006-06-27 Chemat Technology Inc. Coated implants and methods of coating
US20060216494A1 (en) * 2002-11-25 2006-09-28 Helga Furedi-Milhofer Organic-inorganic nanocomposite coatings for implant materials and methods of preparation thereof
US20070110890A1 (en) * 2005-11-14 2007-05-17 Berckmans Bruce Iii Deposition of discrete nanoparticles on an implant surface
US20070190101A1 (en) * 2004-03-31 2007-08-16 Chunlin Yang Flowable bone grafts
US20070196419A1 (en) * 2004-03-13 2007-08-23 Marianne Teller Composite Materials Based On Polysilicic Acid And Method For The Production Thereof
US20070289876A1 (en) * 2006-06-15 2007-12-20 Benli Luan Bioceramic coating of a metal-containing substrate
US20080312748A1 (en) * 2007-06-18 2008-12-18 Zimmer, Inc. Process for forming a ceramic layer
US20090012615A1 (en) * 2006-01-13 2009-01-08 Fell Barry M Surgically implantable prosthesis with active component
US20090098310A1 (en) * 2007-10-10 2009-04-16 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
US20090130456A1 (en) * 2007-11-06 2009-05-21 Mei Wei Ceramic/structural protein composites and method of preparation thereof
US20090130168A1 (en) * 2007-11-06 2009-05-21 Mei Wei Ceramic/structural protein composites and method of preparation thereof
US20090187256A1 (en) * 2008-01-21 2009-07-23 Zimmer, Inc. Method for forming an integral porous region in a cast implant
US20090191507A1 (en) * 2008-01-28 2009-07-30 Biomet 3I, Llc Implant surface with increased hydrophilicity
US20090198286A1 (en) * 2008-02-05 2009-08-06 Zimmer, Inc. Bone fracture fixation system
US20090216336A1 (en) * 2004-11-23 2009-08-27 Marco Springer Bioresorbable, mineralised material for filling osseous defects
WO2009111300A3 (en) * 2008-02-29 2009-12-10 Smith & Nephew, Inc. Gradient coating for biomedical applications
US20100094430A1 (en) * 2006-10-12 2010-04-15 Susan Pran Krumdieck Device
US7718616B2 (en) 2006-12-21 2010-05-18 Zimmer Orthobiologics, Inc. Bone growth particles and osteoinductive composition thereof
US20110008407A1 (en) * 2008-02-29 2011-01-13 Smith & Nephew, Inc. Coating and coating method
US20110089041A1 (en) * 2009-10-19 2011-04-21 Biomet Manufacturing Corp. Methods of depositing discrete hydroxyapatite regions on medical implants
US20110143127A1 (en) * 2009-12-11 2011-06-16 Biomet Manufacturing Corp. Methods for coating implants
US20110165199A1 (en) * 2000-12-22 2011-07-07 Thorne Kevin J Composition and Process for Bone Growth and Repair
US20110230973A1 (en) * 2007-10-10 2011-09-22 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
US20110233169A1 (en) * 2010-03-29 2011-09-29 Biomet 3I, Llc Titanium nano-scale etching on an implant surface
US8309521B2 (en) 2007-06-19 2012-11-13 Zimmer, Inc. Spacer with a coating thereon for use with an implant device
KR101230016B1 (ko) 2005-10-18 2013-03-05 주식회사 워랜텍 생분해성 고분자, 성장인자 및 수성 용매를 포함하는임플란트 코팅용 조성물 및 전기분사법을 이용한 코팅 방법
US8613938B2 (en) 2010-11-15 2013-12-24 Zimmer Orthobiologics, Inc. Bone void fillers
US20140005796A1 (en) * 2010-11-17 2014-01-02 Zimmer, Inc. Ceramic monoblock implants with osseointegration fixation surfaces
US9078832B2 (en) 2012-03-22 2015-07-14 The University Of Connecticut Biomimetic scaffold for bone regeneration
US9131995B2 (en) 2012-03-20 2015-09-15 Biomet 3I, Llc Surface treatment for an implant surface
US9138508B2 (en) 2006-02-27 2015-09-22 Globus Medical, Inc. Bone graft materials derived from mineralized gelatin
KR102110512B1 (ko) * 2019-12-12 2020-05-13 이영욱 임플란트 시술방법용 상악동 내막 재생 촉진 픽스츄어
CN115518206A (zh) * 2022-10-18 2022-12-27 华中科技大学同济医学院附属协和医院 一种自矿化gbr膜及其制备方法

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10142879A1 (de) * 2001-09-03 2003-03-27 Merck Patent Gmbh Verwendung von Kollagen bei der Beschichtung von Zahnimplantaten
DE10143410A1 (de) * 2001-09-05 2003-03-27 Rossendorf Forschzent Biomaterial und Verfahren zu dessen Herstellung
US7776600B2 (en) * 2002-04-18 2010-08-17 Carnegie Mellon University Method of manufacturing hydroxyapatite and uses therefor in delivery of nucleic acids
JP4472267B2 (ja) * 2003-05-02 2010-06-02 株式会社ジーシー 骨結合を得るためのチタン製インプラント及びその表面処理方法
CU23352A1 (es) * 2003-10-16 2009-03-16 Centro Nacional De Investigaciones Cientificas Biomateriales compuestos para implantes óseos
EP1735022B1 (de) * 2004-04-15 2009-07-08 Nexilis AG Osteogenes matrixkomposit, verfahren zu dessen herstellung sowie implantat und scaffold für das tissue engineering mit einer beschichtung aus einem osteogenen matrixkomposit
DE102004021244A1 (de) * 2004-04-30 2005-11-24 Immundiagnostik Ag Bioaktive Werkstoffe und Verfahren zur Verbesserung der Einwachseigenschaften von Knochenimplantaten
WO2006004778A2 (en) * 2004-06-30 2006-01-12 Dentsply International Inc. Implant with a biofunctionalized surface and method for its production
US20060045902A1 (en) * 2004-09-01 2006-03-02 Serbousek Jon C Polymeric wrap for in vivo delivery of osteoinductive formulations
JP4356683B2 (ja) * 2005-01-25 2009-11-04 セイコーエプソン株式会社 デバイス実装構造とデバイス実装方法、液滴吐出ヘッド及びコネクタ並びに半導体装置
US8535722B2 (en) * 2005-03-16 2013-09-17 North Carolina State University Functionally graded biocompatible coating and coated implant
US8491936B2 (en) * 2005-03-16 2013-07-23 North Carolina State University Functionally graded biocompatible coating and coated implant
US8012338B2 (en) * 2006-02-10 2011-09-06 Syracuse University Method for preparing biomedical surfaces
US7892577B2 (en) * 2006-02-27 2011-02-22 Globus Medical, Inc. Bone graft materials derived from mineralized gelatin
US20080051834A1 (en) * 2006-08-28 2008-02-28 Mazzocca Augustus D High strength suture coated with collagen
US8048857B2 (en) 2006-12-19 2011-11-01 Warsaw Orthopedic, Inc. Flowable carrier compositions and methods of use
WO2009073548A1 (en) * 2007-11-30 2009-06-11 Purdue Research Foundation Aligned collagen and method therefor
US9616153B2 (en) 2008-04-17 2017-04-11 Warsaw Orthopedic, Inc. Rigid bone graft substitute
US20090263507A1 (en) * 2008-04-18 2009-10-22 Warsaw Orthopedic, Inc. Biological markers and response to treatment for pain, inflammation, neuronal or vascular injury and methods of use
US8613943B2 (en) 2009-01-23 2013-12-24 Royal College Of Surgeons In Ireland Process for producing a multi-layered scaffold suitable for osteochondral repair
US20140335142A1 (en) * 2009-04-02 2014-11-13 Smith & Nephew Orthopaedics Ag Method of surface treatment of an implant, an implant treated by said method and an electrolyte solution for use in said method
US8696759B2 (en) 2009-04-15 2014-04-15 DePuy Synthes Products, LLC Methods and devices for implants with calcium phosphate
US20100268227A1 (en) * 2009-04-15 2010-10-21 Depuy Products, Inc. Methods and Devices for Bone Attachment
ES2672806T3 (es) 2009-07-03 2018-06-18 Armbruster Biotechnology Gmbh Injerto óseo y material biocompuesto
US8475536B2 (en) * 2010-01-29 2013-07-02 DePuy Synthes Products, LLC Methods and devices for implants with improved cement adhesion
ES2637799T3 (es) 2011-11-15 2017-10-17 Ashwin-Ushas Corporation, Inc. Dispositivo electrocrómico con polímeros complementarios
JPWO2013157638A1 (ja) * 2012-04-19 2015-12-21 国立研究開発法人物質・材料研究機構 ＨＡｐ／Ｃｏｌ複合体によって被覆された生体材料
US9207515B2 (en) 2013-03-15 2015-12-08 Ashwin-Ushas Corporation, Inc. Variable-emittance electrochromic devices and methods of preparing the same
US9463264B2 (en) * 2014-02-11 2016-10-11 Globus Medical, Inc. Bone grafts and methods of making and using bone grafts
DE102014105732B3 (de) * 2014-04-23 2015-04-09 Syntellix Ag Verfahren zur Oberflächenbehandlung eines biokorrodierbaren Implantats und nach dem Verfahren erhaltenes Implantat
US9632059B2 (en) 2015-09-03 2017-04-25 Ashwin-Ushas Corporation, Inc. Potentiostat/galvanostat with digital interface
US9482880B1 (en) 2015-09-15 2016-11-01 Ashwin-Ushas Corporation, Inc. Electrochromic eyewear
EP3231453B1 (de) 2016-04-14 2019-12-25 Immundiagnostik AG Bone-sialopreotein(bsp)-funktionalisierte knochenersatzkörper
JP7267881B2 (ja) * 2019-09-11 2023-05-02 京セラ株式会社 生体インプラント

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4713076A (en) * 1984-04-19 1987-12-15 Klaus Draenert Coating composition and anchorage component for surgical implants
US5066122A (en) * 1990-11-05 1991-11-19 Welch Allyn, Inc. Hooking cap for borescope
US5167961A (en) * 1988-06-02 1992-12-01 Ed. Geistlich Sohne Ag Fur Chemische Industrie Process for preparing high purity bone mineral
US5279831A (en) * 1990-04-05 1994-01-18 Norian Corporation Hydroxyapatite prosthesis coatings
US5508267A (en) * 1991-10-22 1996-04-16 Isis Innovation Limited Bioactive material
US5573771A (en) * 1988-08-19 1996-11-12 Osteomedical Limited Medicinal bone mineral products
US5776193A (en) * 1995-10-16 1998-07-07 Orquest, Inc. Bone grafting matrix
US6300315B1 (en) * 1999-08-28 2001-10-09 Ceramedical, Inc. Mineralized collagen membrane and method of making same
US6384197B1 (en) * 1998-03-24 2002-05-07 Merck Patent Gesellschaft Process for the preparation of mineralized collagen fibrils and their use as bone substitute material
US6384195B1 (en) * 1988-10-20 2002-05-07 Polymasc Pharmaceuticals Plc. Process for fractionating polyethylene glycol (PEG) —protein adducts and an adduct of PEG and granulocyt-macrophage colony stimulating factor
US6524718B1 (en) * 1996-10-24 2003-02-25 Merck Patent Gmbh Metallic object with a thin polyphase oxide coating and process for the manufacture thereof

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS54115645A (en) * 1978-02-28 1979-09-08 Ngk Insulators Ltd Electrochemical treatment
DE3409372A1 (de) * 1984-03-14 1985-09-19 Dr. Ruhland Nachf. GmbH, 8425 Neustadt Material zum vitalisieren von implantatoberflaechen
US4780450A (en) * 1985-12-20 1988-10-25 The University Of Maryland At Baltimore Physically stable composition and method of use thereof for osseous repair
US5306500A (en) * 1988-11-21 1994-04-26 Collagen Corporation Method of augmenting tissue with collagen-polymer conjugates
JPH0629126B2 (ja) * 1989-03-29 1994-04-20 京都大学長 生体活性水酸アパタイト膜のコーティング法
US5205921A (en) * 1991-02-04 1993-04-27 Queen's University At Kingston Method for depositing bioactive coatings on conductive substrates
BE1006963A3 (fr) * 1993-04-01 1995-02-07 Cockerill Rech & Dev Procede de depot par electropolymerisation d'un film d'un materiau composite sur une surface conductrice d'electricite.
US5458863A (en) * 1994-11-25 1995-10-17 Klassen; Robert D. Cold process for hydroxyapatite coatings
US6376573B1 (en) * 1994-12-21 2002-04-23 Interpore International Porous biomaterials and methods for their manufacture
DE19504386C2 (de) * 1995-02-10 1997-08-28 Univ Dresden Tech Verfahren zur Herstellung einer gradierten Beschichtung aus Calciumphosphatphasen und Metalloxidphasen auf metallischen Implantaten
DE19755334A1 (de) 1997-12-15 1999-06-24 Wilhelm Dr Aicher Beschichtungsmaterial für Prothesen und hiermit beschichtetes Prothesenteil
DE19811900C2 (de) * 1998-03-18 2003-12-11 Kallies Feinchemie Ag Biokompatibles Kompositmaterial, Verfahren zu seiner Herstellung und seine Verwendung
DE19812713A1 (de) * 1998-03-24 1999-09-30 Merck Patent Gmbh Verfahren zur Herstellung von mineralisierten Kollagenfibrillen und deren Verwendung als Knochenersatzwerkstoff
US6428978B1 (en) * 1998-05-08 2002-08-06 Cohesion Technologies, Inc. Methods for the production of gelatin and full-length triple helical collagen in recombinant cells
US6113993A (en) * 1998-10-28 2000-09-05 Battelle Memorial Institute Method of coating a substrate with a calcium phosphate compound
US6506217B1 (en) * 1999-03-29 2003-01-14 Arnett Facial Reconstruction Courses, Inc. Moldable post-implantation bone filler and method

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4713076A (en) * 1984-04-19 1987-12-15 Klaus Draenert Coating composition and anchorage component for surgical implants
US5167961A (en) * 1988-06-02 1992-12-01 Ed. Geistlich Sohne Ag Fur Chemische Industrie Process for preparing high purity bone mineral
US5573771A (en) * 1988-08-19 1996-11-12 Osteomedical Limited Medicinal bone mineral products
US6384195B1 (en) * 1988-10-20 2002-05-07 Polymasc Pharmaceuticals Plc. Process for fractionating polyethylene glycol (PEG) —protein adducts and an adduct of PEG and granulocyt-macrophage colony stimulating factor
US5279831A (en) * 1990-04-05 1994-01-18 Norian Corporation Hydroxyapatite prosthesis coatings
US5066122A (en) * 1990-11-05 1991-11-19 Welch Allyn, Inc. Hooking cap for borescope
US5508267A (en) * 1991-10-22 1996-04-16 Isis Innovation Limited Bioactive material
US5776193A (en) * 1995-10-16 1998-07-07 Orquest, Inc. Bone grafting matrix
US6524718B1 (en) * 1996-10-24 2003-02-25 Merck Patent Gmbh Metallic object with a thin polyphase oxide coating and process for the manufacture thereof
US6384197B1 (en) * 1998-03-24 2002-05-07 Merck Patent Gesellschaft Process for the preparation of mineralized collagen fibrils and their use as bone substitute material
US6300315B1 (en) * 1999-08-28 2001-10-09 Ceramedical, Inc. Mineralized collagen membrane and method of making same

Cited By (72)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110165199A1 (en) * 2000-12-22 2011-07-07 Thorne Kevin J Composition and Process for Bone Growth and Repair
US8690874B2 (en) 2000-12-22 2014-04-08 Zimmer Orthobiologics, Inc. Composition and process for bone growth and repair
KR20040032297A (ko) * 2002-10-09 2004-04-17 (주)아미티에 생분해성 골접합용 코팅 임플란트
US20060216494A1 (en) * 2002-11-25 2006-09-28 Helga Furedi-Milhofer Organic-inorganic nanocomposite coatings for implant materials and methods of preparation thereof
US20040236432A1 (en) * 2003-05-13 2004-11-25 Suong-Hyu Hyon Bone-adherent implant with shock-absorbing property and manufacturing method thereof
US7341756B2 (en) 2003-06-04 2008-03-11 Chemat Technology, Inc. Coated implants and methods of coating
US7067169B2 (en) 2003-06-04 2006-06-27 Chemat Technology Inc. Coated implants and methods of coating
US20060141002A1 (en) * 2003-06-04 2006-06-29 Jiankai Liu Coated implants and methods of coating
US7648726B2 (en) 2003-06-04 2010-01-19 Chemat Technology, Inc. Coated implants and methods of coating
US20080152785A1 (en) * 2003-06-04 2008-06-26 Jiankai Liu Coated implants and methods of coating
US20050079198A1 (en) * 2003-08-15 2005-04-14 Berthold Nies Chitosan-coated metallic article, and process for the production thereof
US20070196419A1 (en) * 2004-03-13 2007-08-23 Marianne Teller Composite Materials Based On Polysilicic Acid And Method For The Production Thereof
US20070190101A1 (en) * 2004-03-31 2007-08-16 Chunlin Yang Flowable bone grafts
EP1618904A1 (en) * 2004-06-30 2006-01-25 Friadent GmbH Implant with a biofunctionalized surface and method for its production
US20090216336A1 (en) * 2004-11-23 2009-08-27 Marco Springer Bioresorbable, mineralised material for filling osseous defects
KR101230016B1 (ko) 2005-10-18 2013-03-05 주식회사 워랜텍 생분해성 고분자, 성장인자 및 수성 용매를 포함하는임플란트 코팅용 조성물 및 전기분사법을 이용한 코팅 방법
US9763751B2 (en) 2005-11-14 2017-09-19 Biomet 3I, Llc Deposition of discrete nanoparticles on an implant surface
US8486483B2 (en) 2005-11-14 2013-07-16 Biomet 3I, Llc Deposition of discrete nanoparticles on an implant surface
US20070112353A1 (en) * 2005-11-14 2007-05-17 Berckmans Bruce Iii Deposition of discrete nanoparticles on an implant surface
US7771774B2 (en) 2005-11-14 2010-08-10 Biomet 3l, LLC Deposition of discrete nanoparticles on an implant surface
US20070110890A1 (en) * 2005-11-14 2007-05-17 Berckmans Bruce Iii Deposition of discrete nanoparticles on an implant surface
US20090012615A1 (en) * 2006-01-13 2009-01-08 Fell Barry M Surgically implantable prosthesis with active component
US8080059B2 (en) 2006-01-13 2011-12-20 Fell Barry M Surgically implantable prosthesis with active component
US9138508B2 (en) 2006-02-27 2015-09-22 Globus Medical, Inc. Bone graft materials derived from mineralized gelatin
US7767250B2 (en) 2006-06-15 2010-08-03 National Research Council Of Canada Bioceramic coating of a metal-containing substrate
US20070289876A1 (en) * 2006-06-15 2007-12-20 Benli Luan Bioceramic coating of a metal-containing substrate
US20100094430A1 (en) * 2006-10-12 2010-04-15 Susan Pran Krumdieck Device
US7718616B2 (en) 2006-12-21 2010-05-18 Zimmer Orthobiologics, Inc. Bone growth particles and osteoinductive composition thereof
US20100196489A1 (en) * 2006-12-21 2010-08-05 Zimmer Orthobiologics, Inc. Bone growth particles and osteoinductive composition thereof
US8742072B2 (en) 2006-12-21 2014-06-03 Zimmer Orthobiologics, Inc. Bone growth particles and osteoinductive composition thereof
US8663337B2 (en) 2007-06-18 2014-03-04 Zimmer, Inc. Process for forming a ceramic layer
US8133553B2 (en) 2007-06-18 2012-03-13 Zimmer, Inc. Process for forming a ceramic layer
US20080312748A1 (en) * 2007-06-18 2008-12-18 Zimmer, Inc. Process for forming a ceramic layer
US8309521B2 (en) 2007-06-19 2012-11-13 Zimmer, Inc. Spacer with a coating thereon for use with an implant device
US8608049B2 (en) 2007-10-10 2013-12-17 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
US8602290B2 (en) 2007-10-10 2013-12-10 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
US20090098310A1 (en) * 2007-10-10 2009-04-16 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
US20110230973A1 (en) * 2007-10-10 2011-09-22 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
US20110233263A1 (en) * 2007-10-10 2011-09-29 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
US20090130168A1 (en) * 2007-11-06 2009-05-21 Mei Wei Ceramic/structural protein composites and method of preparation thereof
US20090130456A1 (en) * 2007-11-06 2009-05-21 Mei Wei Ceramic/structural protein composites and method of preparation thereof
US9149563B2 (en) 2007-11-06 2015-10-06 The University Of Connecticut Calcium phosphate/structural protein composites and method of preparation thereof
US8084095B2 (en) 2007-11-06 2011-12-27 The University Of Connecticut Ceramic/structural protein composites and method of preparation thereof
US20090187256A1 (en) * 2008-01-21 2009-07-23 Zimmer, Inc. Method for forming an integral porous region in a cast implant
US20090191507A1 (en) * 2008-01-28 2009-07-30 Biomet 3I, Llc Implant surface with increased hydrophilicity
US9198742B2 (en) 2008-01-28 2015-12-01 Biomet 3I, Llc Implant surface with increased hydrophilicity
US8309162B2 (en) 2008-01-28 2012-11-13 Biomet 3I, Llc Implant surface with increased hydrophilicity
US8852672B2 (en) 2008-01-28 2014-10-07 Biomet 3I, Llc Implant surface with increased hydrophilicity
US20090198286A1 (en) * 2008-02-05 2009-08-06 Zimmer, Inc. Bone fracture fixation system
WO2009111300A3 (en) * 2008-02-29 2009-12-10 Smith & Nephew, Inc. Gradient coating for biomedical applications
US20110014258A1 (en) * 2008-02-29 2011-01-20 Smith & Nephew, Inc. Gradient coating for biomedical applications
US9839720B2 (en) 2008-02-29 2017-12-12 Smith & Nephew, Inc. Coating and coating method
US8821911B2 (en) 2008-02-29 2014-09-02 Smith & Nephew, Inc. Coating and coating method
US9011965B2 (en) 2008-02-29 2015-04-21 Smith & Nephew, Inc. Gradient coating for biomedical applications
US20110008407A1 (en) * 2008-02-29 2011-01-13 Smith & Nephew, Inc. Coating and coating method
AU2009222165B2 (en) * 2008-02-29 2015-07-09 Smith & Nephew, Inc. Gradient coating for biomedical applications
US20110089041A1 (en) * 2009-10-19 2011-04-21 Biomet Manufacturing Corp. Methods of depositing discrete hydroxyapatite regions on medical implants
US20110143127A1 (en) * 2009-12-11 2011-06-16 Biomet Manufacturing Corp. Methods for coating implants
US9283056B2 (en) 2010-03-29 2016-03-15 Biomet 3I, Llc Titanium nano-scale etching on an implant surface
US9757212B2 (en) 2010-03-29 2017-09-12 Biomet 3I, Llc Titanium nano-scale etching on an implant surface
US10765494B2 (en) 2010-03-29 2020-09-08 Biomet 3I, Llc Titanium nano-scale etching on an implant surface
US9034201B2 (en) 2010-03-29 2015-05-19 Biomet 3I, Llc Titanium nano-scale etching on an implant surface
US8641418B2 (en) 2010-03-29 2014-02-04 Biomet 3I, Llc Titanium nano-scale etching on an implant surface
US10182887B2 (en) 2010-03-29 2019-01-22 Biomet 3I, Llc Titanium nano-scale etching on an implant surface
US20110233169A1 (en) * 2010-03-29 2011-09-29 Biomet 3I, Llc Titanium nano-scale etching on an implant surface
US8613938B2 (en) 2010-11-15 2013-12-24 Zimmer Orthobiologics, Inc. Bone void fillers
US20140005796A1 (en) * 2010-11-17 2014-01-02 Zimmer, Inc. Ceramic monoblock implants with osseointegration fixation surfaces
US9248020B2 (en) * 2010-11-17 2016-02-02 Zimmer, Inc. Ceramic monoblock implants with osseointegration fixation surfaces
US9131995B2 (en) 2012-03-20 2015-09-15 Biomet 3I, Llc Surface treatment for an implant surface
US9078832B2 (en) 2012-03-22 2015-07-14 The University Of Connecticut Biomimetic scaffold for bone regeneration
KR102110512B1 (ko) * 2019-12-12 2020-05-13 이영욱 임플란트 시술방법용 상악동 내막 재생 촉진 픽스츄어
CN115518206A (zh) * 2022-10-18 2022-12-27 华中科技大学同济医学院附属协和医院 一种自矿化gbr膜及其制备方法

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