EP3038665A1 - Procédé d'amélioration de la biocompatibilité d'une surface - Google Patents

Procédé d'amélioration de la biocompatibilité d'une surface

Info

Publication number
EP3038665A1
EP3038665A1 EP14758341.3A EP14758341A EP3038665A1 EP 3038665 A1 EP3038665 A1 EP 3038665A1 EP 14758341 A EP14758341 A EP 14758341A EP 3038665 A1 EP3038665 A1 EP 3038665A1
Authority
EP
European Patent Office
Prior art keywords
radical
radicals
reactive
biocompatibility
gold
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Withdrawn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
EP14758341.3A
Other languages
German (de)
English (en)
Inventor
Andreas Bollmann
Klaus LÜCKE
Fritz Scholz
Katja VAHL
Robert SMAIL
Ulrich Hasse
Heike Kahlert
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.)
Gilupi GmbH
Original Assignee
Gilupi 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 Gilupi GmbH filed Critical Gilupi GmbH
Publication of EP3038665A1 publication Critical patent/EP3038665A1/fr
Withdrawn legal-status Critical Current

Links

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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C22/00—Chemical surface treatment of metallic material by reaction of the surface with a reactive liquid, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals
    • C23C22/05—Chemical surface treatment of metallic material by reaction of the surface with a reactive liquid, leaving reaction products of surface material in the coating, e.g. conversion coatings, passivation of metals using aqueous solutions
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/02—Inorganic materials
    • A61L31/022—Metals or alloys
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—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
    • 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment

Definitions

  • the present invention relates to a method for improving the biocompatibility of a surface, in particular a solid surface.
  • the invention further relates to a device, for example an implant, a sensor or a cell culture vessel, which is brought into contact with biological systems, with a biocompatible surface.
  • a device for example an implant, a sensor or a cell culture vessel, which is brought into contact with biological systems, with a biocompatible surface.
  • Materials that come into contact with biological systems must have high biocompatibility, i. (I) the materials must not have any deleterious effect on the biological system; and (ii) the biological environment must not undergo changes in material, e.g. Cause corrosion, biodegradation, etc.
  • Surfaces can be chemically modified by direct reactions with specific reagents, by covalent attachment of molecules to the surface, by plasma-based techniques, such as. Plasma assisted etching, deposition or polymerization, and plasma immersion ion implantation (P.K. Chu, J.Y. Chen, L.P. Wang, N. Huang, Mater, Sci. Eng., R 36 (2002) 143-206).
  • titanium surfaces can be treated with acids or alkalis.
  • the chemical modifications also include sol-gel coatings, anodic oxidation, chemical vapor deposition, and biochemical modifications.
  • titanium surfaces can be modified by thermal spraying (eg, flame spraying or plasma spraying), by physical vapor deposition, or by ion implantation and deposition.
  • Electrochemically the biocompatibility of titanium surfaces with the help of anodic oxidation and increased by electrophoretic or cathodic deposition of hydroxyapatite (K.-H. Kim, N. Ramaswamy, Dent. Mater. J. 28 (2009) 20-36).
  • the properties of surfaces can be changed to increase biocompatibility in various respects.
  • the present invention has for its object to provide a method for the treatment of surfaces, which allows to improve the biocompatibility of the surface, in particular to cell cultures and tissues, in a simple manner, and that for a variety of different surfaces, in particular solid surfaces, can be used ,
  • the above object is achieved according to the invention by treating the surface with at least one species of reactive radical.
  • the device mentioned at the beginning solves this problem by treating its biocompatible surface with a method of the present invention.
  • a surface treatment with at least one species of reactive radicals detoxifies the surface and thus improves the biocompatibility of the surface.
  • the surface is detoxified by the reactive radicals, which increases their biocompatibility with biological systems without, for example, applying additional layers to the surface.
  • radicals can be generated in very different ways and thus the method can be adapted to a wide variety of material requirements. If the biocompatibility of, for example, heat-sensitive surfaces is to be improved, the radicals can be produced at room temperature, for example by the Fenton reaction. If the surface is to be treated as free of chemicals as possible, eg photolysis or radiolysis can be used to generate radicals.
  • a "reactive radical” is an atom or molecule with at least one unpaired electron that is reactive, and reactive radicals usually react very quickly, often in less than a second.
  • At least one species of reactive radical includes both versions where the surface is treated with only one type of radical (radical atom, radical ion, radical molecule, or radial molecular ion) as well as those in which different types of radicals come into contact with the surface.
  • an "improvement in biocompatibility" in the context of the present invention is manifested by a detoxification of the surface, ie the surface treated according to the invention is less cytotoxic, that is less damaging to the cell and / or tissue, compared to an untreated surface which is not reactive with free radicals
  • the improved biocompatibility can be determined by a cytotoxicity test in which the untreated surface and once the reactive radical treated surface is contacted with a cell culture and then the cell vitality in the solution is determined the cell vitality can be increased by at least 10%, preferably by at least 25%, and more preferably by 50-100%.
  • the reactive radicals can deactivate active sites that cause biological reactions and have cell and / or tissue damage to the surface.
  • the cytotoxic reactions triggering active sites on the surface are specifically and specifically deactivated by the treatment with reactive radicals. This is surprising and unexpected because one would expect that reactive radicals on surfaces trigger chemical reactions that generate active sites and thereby act as cytotoxic agents.
  • An active site that causes cytotoxic reactions is an atom or substance on the cell surface that is cell and / or tissue damaging.
  • reactive radicals these active sites can be specifically and specifically deactivated, for example, by converting them into non-cytotoxic substances or by leaching them out of the cell surface, for example by reactive cleavage.
  • the reactive radicals may comprise at least one species of oxygen radicals, nitrogen radicals, carbon radicals, sulfur radicals, and / or a species of halogen radicals.
  • the reactive oxygen radicals include all radicals in which the at least one unpaired electron is attached to an oxygen radical. substance atom sits.
  • oxygen radicals are hyperoxide anions, hydroxyl radicals, hydroperoxyl radicals, peroxyl radicals or alkoxyl radicals.
  • nitrogen radicals are nitrogen monoxide and nitrogen.
  • Carbon radicals include, for example, triplet carbene and alkyl radicals
  • sulfur radicals include, for example, thiyl radicals.
  • Halogenated radicals include, among others, chlorine radicals and bromine radicals.
  • reactive radicals can be generated by cleavage of a radical initiator.
  • a radical starter is a molecule that can be converted into at least one reactive radical.
  • the chlorine-chlorine bond in molecular chlorine (Cl 2 ) or the bromine-bromine bond in molecular bromine (Br 2 ) can be cleaved by exposure to light and the molecular radical initiators are thereby converted into reactive radicals.
  • the surface may be contacted with the radical initiator, which is typically stable as opposed to reactive radicals, and the radical initiator subsequently converted to the reactive radical in situ. This ensures that the entire surface is treated evenly.
  • the free radical initiator can be converted into the reactive radical by photolysis, radiolysis, thermolysis, by plasma, and / or by a chemical, for example electrochemical, and / or a biochemical, for example an enzymatic reaction. Radical production can thus be adapted in different ways and to the properties of the surface to be treated, for example non-thermally by light, for example UV radiation, or the use of X-ray and other ionizing radiation.
  • a chemical reaction for example in the form of a chemical or electrochemical Fenton reaction, in which hydrogen peroxide is removed by reaction with Fe (II) ions or with other transition metal ions, e.g. Cu (II), Ti (III), Cr (II) or Co (II) is decomposed in an acidic medium to form the highly reactive hydroxyl radical is also possible at room temperature.
  • the reactive radical may be a hydroxyl radical.
  • Hydroxyl radicals can easily from biologically harmless substances, eg. As water, are generated. Hydroxyl radicals can be formed in particular: a) in a Fenton reaction; b) by photolysis of a peroxide; c) by radiolysis of water or other oxygenate radiolysable to hydroxyl radicals; or d) by a plasma reaction of an oxygen compound which can be converted by means of plasma treatment into hydroxyl radicals, preferably water or a peroxide.
  • the surface whose biocompatibility is improved by means of the method according to the invention can comprise, for example, a noble metal, a noble metal compound or a polymer, or a polymer.
  • Precious metals, such as gold, are often used as electrodes in biosensors and as implant material.
  • Implants and cell culture vessels are often made of polymers which, although in a biological environment do not cause any material change, such as corrosion, but which have cell and / or tissue damage to biological systems, thus can be improved by the method according to the invention in their biocompatibility.
  • the surface may belong to an implant, a sensor or a cell culture vessel.
  • the implant, the sensor or the culture vessel can first be prepared and then treated according to the invention.
  • the method of the invention is universal, i. can be used for every kind of surface and every surface type, because for a given surface type or a given surface type with particularly suitable reactive radicals can be provided by different methods adapted to the material requirements.
  • Also contemplated in accordance with the present invention is a device that is contacted with biological systems, such as an implant, a sensor, or a cell culture vessel having a biocompatible surface treated according to any of the above methods.
  • the device is characterized by a surface with improved biocompatibility, which is easily demonstrated by comparison of a surface before treatment with reactive radicals and a surface treated with reactive radicals, the latter has a significantly higher cell vitality, if with a Cell culture is brought into contact.
  • Another feature of the device according to the invention is that the active sites that trigger biological reactions and cell and / or tissue damage, deliberately deactivated, ie converted into biologically inactive molecules or, z. B. in the case of biologically active gold ions, detached from the surface.
  • FIG. 1 shows a schematic representation of the method according to the invention for improving the biocompatibility of a surface according to a first embodiment
  • FIG. 2 shows a schematic illustration of a method for improving the biocompatibility of a surface according to a second embodiment
  • the surface 1 is brought into contact with reactive radicals 2.
  • the radical may have a number of n unpaired electrons (represented by a ⁇ ). If the radical contains two unpaired electrons, one speaks of a diradical, with three unpaired electrons of a triradical, etc.
  • the surface 1 may be the surface of a device 3, for example an implant, a sensor or a cell culture vessel, whose biocompatibility is to be improved.
  • the reactive radicals 2 cause active sites 4, which cause biological reactions and have cell and / or tissue damage, to be deactivated from the surface 1.
  • the active center 4 is schematically indicated in the figures as a circle with a star located therein, wherein the star symbolizes the cytotoxic effect, ie the cell or tissue damaging property of the active center 4.
  • the reactive radical 2 deactivates the active center 4 of the surface 1.
  • the deactivation can be done, for example, by the active center 4 being split off from the surface and being dissolved out at the surface, as shown on the right side of FIG. 1 above.
  • the deactivation may also be such that the active center 4 is converted by the reactive radical 2 so that it no longer has a cell- or tissue-damaging effect, which is symbolized in FIG. 1, bottom right, by the star indicating the cytotoxic effect no longer exists.
  • reactive radicals 2 are generated by cleaving a radical initiator 5.
  • the radical starter 5 is stable, ie less reactive and more durable.
  • the radical starter 5 is first brought into contact with the surface 1 of the device 3. Subsequently, the radical starter 5 is reacted in situ, ie in place in the reactive radical 2. To implement the radical starter 5 is converted by a cleavage agent 6 in the reactive radical 2.
  • the cleavage agent 6 may be both a chemical substance or an enzyme, as well as radiation such as UV, X-ray or ionizing radiation, as well as the change of a parameter, for example the temperature or the pressure, which the cleavage of the radical initiator 5 in the reactive Radical 2 causes.
  • a cleavage agent 6 and thus a conversion method of the radical initiator 5 can be selected which does not modify the properties of the surface 1, with the exception of biocompatibility, which is improved according to the invention.
  • a photolysis light irradiation
  • radiolysis ionizing radiation
  • the process according to the invention of the second embodiment proceeds analogously to the process shown in FIG. 1, by reactive radicals 2 rendering the biocompatibility of the surface 1 improved by active centers 4 of the surface 1 are specifically deactivated.
  • the cell vitality of electrodeposited gold layers on stainless steel wires was investigated after gamma sterilization. Untreated and oxygen radical-treated gold layers were subjected to a cytotoxicity test with human adult skin fibroblasts (NHDF cells). For this eluates were prepared from the wires and their influence on the cell vitality of the NHDF cells was examined by means of a colorimetric assay (TTC assay) (for detailed description see: N. Saucedo-Zeni et al., Int. J. Oncol. 41 (2012 ) 1241-1250).
  • the radicals were generated using Fenton solutions and UV photolysis of hydrogen peroxide.
  • the total treatment time was 120 minutes, replacing the "old" Fenton solution with a fresh Fenton solution every 5 minutes.
  • Both the mechanically polished and the Fenton-treated gold sheets were AFM images taken (see Fig. 4a and 4c) and determines the surface roughness factors (see Table 1).
  • the AFM measurements were made using a "NanoScope I” (Digital Instruments, USA) in contact mode.
  • the gold sheets were implanted in the peritoneal cavity of mice (one gold sheet per mouse). After 14 days, the gold sheets were removed from the mice and AFM images of the gold surfaces were taken again (see FIGS. 4b and 4d) and the roughness factors determined (see Table 1).
  • the AFM images and roughness factors make it clear that the gold surfaces treated only by mechanical polishing are smoothed in the peritoneal cavity of the mice, ie biologically active, ie cell-damaging, gold is detached from the implants.
  • the mechanically polished and subsequently radical-treated gold surfaces show no change in the roughness of the surface because the active sites are deactivated when reactive radicals are treated. Therefore, no gold was detached from the gold surfaces in the peritoneal cavity. This proves that implants have a higher biocompatibility through pre-treatment with radicals (not to be attacked).
  • Table 1 Roughness factors of differently treated gold surfaces
  • Device for example, implant, sensor or cell culture vessel

Abstract

La présente invention concerne un procédé d'amélioration de la biocompatibilité d'une surface (1), notamment d'une surface solide, ainsi qu'un dispositif (3), par exemple un implant, un capteur ou un récipient de culture cellulaire qui est amené en contact avec des systèmes biologiques, ayant une surface biocompatible. Selon l'invention, pour améliorer la biocompatibilité des surfaces, notamment vis-à-vis de cultures cellulaires et de tissus, d'une manière simple et pour une variété de surfaces différentes, la surface (1) est amenée en contact avec des radicaux réactifs (2). Le dispositif (3) de l'invention comprend une surface biocompatible (1) qui a été traité selon le procédé de l'invention.
EP14758341.3A 2013-08-27 2014-08-27 Procédé d'amélioration de la biocompatibilité d'une surface Withdrawn EP3038665A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102013217085.8A DE102013217085A1 (de) 2013-08-27 2013-08-27 Verfahren zur Verbesserung der Biokompatibilität einer Oberfläche
PCT/EP2014/068160 WO2015028503A1 (fr) 2013-08-27 2014-08-27 Procédé d'amélioration de la biocompatibilité d'une surface

Publications (1)

Publication Number Publication Date
EP3038665A1 true EP3038665A1 (fr) 2016-07-06

Family

ID=51454677

Family Applications (1)

Application Number Title Priority Date Filing Date
EP14758341.3A Withdrawn EP3038665A1 (fr) 2013-08-27 2014-08-27 Procédé d'amélioration de la biocompatibilité d'une surface

Country Status (9)

Country Link
US (1) US20160208389A1 (fr)
EP (1) EP3038665A1 (fr)
JP (1) JP2016529015A (fr)
CN (1) CN105744963A (fr)
AU (1) AU2014314261A1 (fr)
DE (1) DE102013217085A1 (fr)
MX (1) MX2016002584A (fr)
RU (1) RU2016109458A (fr)
WO (1) WO2015028503A1 (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050153309A1 (en) 2003-12-22 2005-07-14 David Hoon Method and apparatus for in vivo surveillance of circulating biological components
US11160542B2 (en) 2016-06-09 2021-11-02 Haimachek, Inc. Collector for detection and reversible capturing of cells from body fluids in vivo
JP2018175127A (ja) * 2017-04-07 2018-11-15 東海電気株式会社 体内管導入物用マーカー及び体内管導入物，並びにそれらの製造方法
CN113797398A (zh) * 2021-09-26 2021-12-17 苏州纽创医疗科技有限公司 一种具有抗凝血涂层的钛合金支架的制备方法及支架

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6033582A (en) * 1996-01-22 2000-03-07 Etex Corporation Surface modification of medical implants
ES2199815T3 (es) * 1999-03-19 2004-03-01 The Regents Of The University Of Michigan Mineralizacion y desarrollo celular supeerficial sobre biomateriales.

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2015028503A1 *

Also Published As

Publication number Publication date
RU2016109458A (ru) 2017-10-03
JP2016529015A (ja) 2016-09-23
WO2015028503A1 (fr) 2015-03-05
CN105744963A (zh) 2016-07-06
US20160208389A1 (en) 2016-07-21
AU2014314261A1 (en) 2016-04-07
DE102013217085A1 (de) 2015-03-05
MX2016002584A (es) 2016-10-26

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