CN114159619A - 一种抗菌缓释钛片的制备方法 - Google Patents

一种抗菌缓释钛片的制备方法 Download PDF

Info

Publication number
CN114159619A
CN114159619A CN202111274154.6A CN202111274154A CN114159619A CN 114159619 A CN114159619 A CN 114159619A CN 202111274154 A CN202111274154 A CN 202111274154A CN 114159619 A CN114159619 A CN 114159619A
Authority
CN
China
Prior art keywords
titanium
release
antibacterial
preparation
silver
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.)
Granted
Application number
CN202111274154.6A
Other languages
English (en)
Other versions
CN114159619B (zh
Inventor
赵红梅
杨建军
苗大刚
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.)
Qingdao University
Original Assignee
Qingdao University
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 Qingdao University filed Critical Qingdao University
Priority to CN202111274154.6A priority Critical patent/CN114159619B/zh
Publication of CN114159619A publication Critical patent/CN114159619A/zh
Application granted granted Critical
Publication of CN114159619B publication Critical patent/CN114159619B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02Inorganic materials
    • A61L27/04Metals or alloys
    • A61L27/06Titanium or titanium alloys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28Materials for coating prostheses
    • A61L27/30Inorganic materials
    • A61L27/306Other specific inorganic materials not covered by A61L27/303 - A61L27/32
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28Materials for coating prostheses
    • A61L27/34Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • CCHEMISTRY; METALLURGY
    • C23COATING 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
    • C23CCOATING 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
    • C23C14/00Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/06Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the coating material
    • C23C14/14Metallic material, boron or silicon
    • C23C14/16Metallic material, boron or silicon on metallic substrates or on substrates of boron or silicon
    • C23C14/165Metallic material, boron or silicon on metallic substrates or on substrates of boron or silicon by cathodic sputtering
    • CCHEMISTRY; METALLURGY
    • C23COATING 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
    • C23CCOATING 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
    • C23C14/00Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/22Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the process of coating
    • C23C14/34Sputtering
    • C23C14/35Sputtering by application of a magnetic field, e.g. magnetron sputtering
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • A61L2300/104Silver, e.g. silver sulfadiazine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602Type of release, e.g. controlled, sustained, slow
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606Coatings
    • A61L2300/608Coatings having two or more layers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/02Methods for coating medical devices
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/08Coatings comprising two or more layers
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Inorganic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Materials Engineering (AREA)
  • Mechanical Engineering (AREA)
  • Metallurgy (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Materials For Medical Uses (AREA)

Abstract

本发明公开了一种抗菌缓释钛片的制备方法,首先对钛片进行预处理,然后采用磁控溅射技术将银薄膜镀覆在钛上,最后在表面包覆聚多巴胺涂层,将钛开发成亲水抗菌缓释样本。采用本发明的方法制备的钛‑银‑聚多巴胺样品,亲水性能高,水接触角小于20°,细胞毒性低,细胞相容性好,对金黄色葡萄球菌和大肠杆菌具有明显的抑制效果,并且具有较好的抗菌缓释性能。

Description

一种抗菌缓释钛片的制备方法
技术领域
本发明属于口腔种植体工程技术领域,具体涉及一种抗菌缓释钛片的制备方法。
背景技术
钛是人工关节、骨创伤产品和牙科植入物的首选材料,它具有良好的生物相容性和抗腐蚀性能。然而,钛表面致密的氧化层使该材料具有生物惰性,导致植入后骨结合缓慢;此外,其表面不具备抗菌能力,容易形成细菌粘附和生物膜,从而导致感染或种植体周围炎,甚至治疗失败。种植体周围炎是种植体修复失败的主要并发症之一,其特点是牙周袋的形成和加深,骨组织的逐渐吸收,甚至种植体的松动和脱落。研究表明,种植体周围炎的致病菌来自于口腔环境。因此,提高材料表面的骨结合能力,赋予表面抗菌能力对种植体的应用非常重要。
人们提出了各种表面改性方法,以赋予植入物优良的抗菌活性,从而提高其成功率。目前有许多对钛片进行处理使其可作为骨及牙科植入的新型生物材料的技术。如CN108525019A,CN108728691A等诸多技术。无菌抗菌剂如银、铜和锌不但具有良好的抗菌活性还不存在细菌抗性的风险。在广谱抗菌剂中,银具有抗菌能力强、稳定性高、不引发细菌耐药性等优点,在适当的剂量下无抗药性和无细胞毒性而被广泛用于医疗和健康领域。然而,当浓度过高时,银对哺乳动物细胞也有毒性,包括参与伤口愈合的成纤维细胞,其中Ag+的毒性浓度为50mg/L。因此,加载银的缓释抗菌植入涂层由于其持续释放银离子或原子以达到抗菌和抗细菌的目的,从而避免感染,已经成为一个备受瞩目的话题。
贻贝状的粘性多巴胺分子有儿茶酚和氨基,它们可以自行聚合,形成具有更多活性基团的聚多巴胺。它能牢固地粘附在众多材料表面,以提高生物相容性,并能在材料表面桥接其他生物分子;它还能螯合甚至还原金属离子。这些特性使其成为植入物表面改性的重要选择。近年来,研究人员利用多巴胺的优良特性,结合抗菌剂,制备了多种抗菌涂层。
Liao等在论文A facile method for preparing highly conductive andreflective surface-silvered polyimide films(APPLIED SURFACE SCIENCE,2009年,第255卷19期,8207-8212)中首先将聚多巴胺沉积在聚酰亚胺(PI)薄膜上,然后通过聚多巴胺的还原能力将银纳米颗粒(AgNPs)沉积在PI薄膜上,形成高度抗菌的PI薄膜。Vincent在论文The reduction of Ag+in metallic silver on pseudomelanin films allows forantibacterial activity but does not imply unpaired electrons(Journal ofColloid and Interface Science,2011年,第364卷2期,359-365)中通过同样的原理将聚多巴胺改性的聚苯乙烯浸入硝酸银溶液中获得银纳米颗粒,并证实其具有良好的抗菌能力。Fu发表Chemical Property and Antibacterial Activity of Metronidazole-decorated Ti through Adhesive Dopamine(Journal of Wuhan University ofTechnology-Mater.Sci.Ed.,2009年,第34卷4期,968-972)开发了一种抗菌的钛涂层,作为牙科植入材料具有很大的潜力。在实验中,用多巴胺涂层对钛基材进行了预改性,然后将甲硝唑固定在多巴胺改性的Ti基材表面。Jia在他们的研究Bioinspired anchoring AgNPsonto micro-nanoporous TiO2orthopedic coatings:Trap-killing of bacteria,surface-regulated osteoblast functions and host responses.(Biomaterials,2016年,第75卷,203-222)中开发了一个Trap-Killing系统,通过紧密的物理化学作用将AgNPs牢固地固定在多巴胺表面来制备Ti缓释抗菌涂层。然而,到目前为止,关于聚多巴胺Ti缓释抗菌涂层的研究主要集中在Ti(TiO2)-聚多巴胺-AgNPs结构上。很少有关于Ti-AgNPs-聚多巴胺结构的研究报道。虽然CN113101414A公开了Ti-AgNPs-聚多巴胺结构,但是其Ag+的浓度过高,易引起细胞毒性,而且材料表面的骨结合能力差。因此急需要找到一种具有良好抑菌活性的Ti-AgNPs-聚多巴胺结构的钛片。
发明内容
为了提高口腔种植体表面的骨结合能力,并赋予其表面抗菌缓释能力。本发明提供了一种抗菌缓释钛片的制备方法,由于表面亲水聚多巴胺层的保护,抗菌钛片具有持续释放银离子或原子以达到抗菌的目的,钛片的骨结合和生物相容性也得到了提高。
为实现上述目的,本发明采用以下技术方案:
一种抗菌缓释钛片的制备方法,所述制备方法包括以下步骤:
(1)钛片进行表面处理;
(2)将表面处理后的钛片经磁控溅射工艺进行镀银处理;
(3)将步骤(2)制得的钛片进行聚多巴胺涂层处理,即得抗菌缓释钛片。
在一些实施方案中,所述步骤(1)中,钛片进行表面处理包括以下步骤:将钛片持续喷涂40-60μm的Al2O3,然后在50-70℃下进行酸蚀;按照去离子水、丙酮、乙醇和去离子水的顺序用超声波分别冲洗处理钛片。在此过程中,本发明预先对钛进行表面粗化处理,处理后的钛片表面见图6。利于磁控溅射镀银粘附,且利于成骨细胞生长,而现有技术中往往对钛片表面光滑处理,不利于磁控溅射镀银粘附力较差,镀银效果差,也不利于成骨细胞生长。
在一些实施方案中,步骤(1)中,所述的酸蚀溶液配比37%HCl:98%H2SO4:H2O=1:1:2。
在一些实施方案中,步骤(1)中,所述的酸蚀时间为8-15min。
在一些实施方案中,步骤(2)中,所述的磁控溅射工艺包括:磁控溅射镀覆参数为:功率90-100W,本底真空度3-4×10-4Pa,工作气压0.5Pa,氩气流量为15sccm,基片旋转速度为30rpm。
在一些实施方案中,步骤(2)中,银层镀覆厚度为10-30nm。优选的,银层镀覆厚度为20-30nm。
在一些实施方案中,步骤(3)中,聚多巴胺涂层处理包括以下步骤:在银镀覆后,将钛-银样品置于磷酸二氢钠缓冲液中,加入盐酸多巴胺,在37℃下持续避光振动18-30小时,聚合完成后超声处理,即得抗菌缓释钛片。在聚合完成后进行超声处理,以分离多余的单体和颗粒。
在一些实施方案中,所述盐酸多巴胺浓度为2mg/mL。
在一些实施方案中,一种抗菌缓释钛片的制备方法包括以下步骤:
(1)钛片进行表面处理;
(2)将表面处理后的钛片经磁控溅射工艺进行镀银处理;
(3)将步骤(2)制得的钛片进行聚多巴胺涂层处理,即得抗菌缓释钛片;
(4)将步骤(2)和步骤(3)交替进行,形成以钛为基材的Ag-聚多巴胺多层结构的钛片。
在一些实施方案中,所述的步骤(4)中,以钛为基材的Ag-聚多巴胺多层结构包括钛-Ag-聚多巴胺-Ag-聚多巴胺层结构,或钛-Ag-聚多巴胺-Ag-聚多巴胺Ag-聚多巴胺层结构。
在一些实施方案中,所述的步骤(4)中,以钛为基材的Ag+-聚多巴胺多层结构为钛-Ag-聚多巴胺-Ag-聚多巴胺结构,其中,与钛结合的Ag层为第一Ag层,第一Ag层厚度为D1,依次为第二Ag层,第二Ag层厚度为D2,则D1>D2。
在一些实施方案中,所述的步骤(4)中,以钛为基材的Ag+-聚多巴胺多层结构为钛-Ag-聚多巴胺-Ag-聚多巴胺-Ag-聚多巴胺层结构,其中,与钛结合的Ag层为第一Ag层,第一Ag层厚度为D1,依次为第二Ag层,第二Ag层厚度为D2,第三Ag层,第三Ag层厚度为D3,则D1>D2>D3。采用本申请所述的钛片结构,在银粒子浓度较低的情况下,充分将银离子结合至钛表面,提高钛的抑菌效果。此外,较单一层而言,通过Ag-聚多巴胺交替形成多层结构,制备的样品亲水性能高,利于提高骨的结合能力,同时提高银离子的缓释效果。
本发明所带来的有益技术效果为:
本发明制备了Ti-AgNPs-聚多巴胺以及多层结构的钛片,载银的缓释抗菌植入涂层可以持续释放银离子或原子以达到抗菌的目的。多巴胺分子有儿茶酚和氨基,它们可以自行聚合,形成具有更多活性基团的聚多巴胺。它能牢固地粘附在众多材料表面,以提高生物相容性,并能在材料表面桥接其他生物分子;它还能螯合甚至还原金属离子。申请了为了获得高质量的抗菌涂层,预先对钛表面进行处理,通过磁控溅射在钛片上沉积了纳米银薄膜。之后,聚多巴胺涂层通过共价凝聚在银膜上原位聚合。通过这种方式,刚性的钛-银-聚多巴胺涂层可以很容易地建立在钛片上。
通过结合磁控溅射技术和贻贝仿生多层钛-银-聚多巴胺涂层,所得涂层表现出Ag+的缓慢释放、对金黄色葡萄球菌和大肠杆菌具有良好的抑菌性和良好的MC3T3-E1(小鼠胚胎成骨细胞前体细胞)细胞相容性。该涂层工艺在可操作性、可重复性和可加工性方面对具有复杂结构和形状的医疗设备,特别是对牙科植入物具有良好的效果。此技术将有助于银涂层在牙科种植体上的安全使用。
附图说明
图1是本发明实施例1所示抗菌缓释钛片的银离子缓释曲线图;
图2是本发明实施例2所示抗菌缓释钛片的银离子缓释曲线图;
图3是本发明实施例3所示抗菌缓释钛片的银离子缓释曲线图;
图4是本发明实施例所示抗菌缓释钛片的抗菌效果图;a,b,c分别为实施例1,实施例2,实施例3对大肠杆菌的抗菌效果图,d,e,f分别为实施例1,实施例2,实施例3对金黄色葡萄球菌的抗菌效果图;
图5是本发明抗菌缓释钛片骨细胞增殖效果图;A:空白钛片,B:实施例1,C:实施例2,D:实施例3;
图6是喷砂酸蚀后的钛片的电镜图。
具体实施方式
本发明提出了一种抗菌缓释钛片的制备方法,为了使本发明的优点、技术方案更加清楚、明确,下面结合具体实施例对本发明做详细说明。
实施例1:
市售的TC4(Ti-6Al-4V)片的尺寸为直径=15mm,厚度=1mm,以3kg/m2的速度机械喷涂50μm的Al2O3,持续1分钟,然后在60℃下进行酸蚀(37%HCl:98%H2SO4:H2O=1:1:2)10分钟。依次在去离子水、丙酮、乙醇和去离子水中用超声波冲洗处理钛片。
之后,使用磁控溅射系统(JCP-350,TECHNOL)将银薄膜镀覆在钛片上。磁控溅射镀覆参数为:功率100W,本底真空度3×10-4Pa,工作气压0.5Pa,氩气流量为15sccm,基片旋转速度为30rpm,银层镀覆厚度为10nm。
在银镀覆后,将钛-银样品置于磷酸二氢钠缓冲液(50mM,pH=8.5)中,加入盐酸多巴胺(2mg/mL),在37℃下持续避光振动聚合24小时,银涂层的一面朝上。聚合完成后超声处理,干燥即得。
实施例2:
市售的TC4(Ti-6Al-4V)片的尺寸为直径=15mm,厚度=1mm,以3kg/m2的速度机械喷涂50μm的Al2O3,持续1分钟,然后在60℃下进行酸蚀(37%HCL:98%H2SO4:H2O=1:1:2)10分钟。依次在去离子水、丙酮、乙醇和去离子水中用超声波冲洗处理钛片。
之后,使用磁控溅射系统(JCP-350,TECHNOL)将银薄膜镀覆在钛片上。磁控溅射镀覆参数为:功率100W,本底真空度3×10-4Pa,工作气压0.5Pa,氩气流量为15sccm,基片旋转速度为30rpm,银层镀覆厚度为20nm。
在银镀覆后,将钛-银样品置于磷酸二氢钠缓冲液(50mM,pH=8.5)中,加入盐酸多巴胺(2mg/mL),37℃下持续避光振动聚合24小时,银涂层的一面朝上。聚合完成后超声处理,干燥即得。
实施例3:
市售的TC4(Ti-6Al-4V)片的尺寸为直径=15mm,厚度=1mm,以3kg/m2的速度机械喷涂50μm的Al2O3,持续1分钟,然后在60℃下进行酸蚀(37%HCL:98%H2SO4:H2O=1:1:2)10分钟。依次在去离子水、丙酮、乙醇和去离子水中用超声波冲洗处理钛片。
之后,使用磁控溅射系统(JCP-350,TECHNOL)将银薄膜镀覆在钛片上。磁控溅射镀覆参数为:功率100W,本底真空度3×10-4Pa,工作气压0.5Pa,氩气流量为15sccm,基片旋转速度为30rpm,银层镀覆厚度为30nm。
在银镀覆后,将钛-银样品置于磷酸二氢钠缓冲液(50mM,pH=8.5)中,加入盐酸多巴胺(2mg/mL),在37℃下持续避光振动聚合24小时,银涂层的一面朝上。聚合完成后超声处理,干燥即得。
实施例4
市售的TC4(Ti-6Al-4V)片的尺寸为直径=15mm,厚度=1mm,以3kg/m2的速度机械喷涂50μm的Al2O3,持续1分钟,然后在60℃下进行酸蚀(37%HCL:98%H2SO4:H2O=1:1:2)10分钟。依次在去离子水、丙酮、乙醇和去离子水中用超声波冲洗处理过的钛片。
使用磁控溅射系统(JCP-350,TECHNOL)将银薄膜镀覆在钛片上。磁控溅射镀覆参数为:功率100W,本底真空度3×10-4Pa,工作气压0.5Pa,氩气流量为15sccm,基片旋转速度为30rpm,银层镀覆厚度(D1)为12nm。
在银镀覆后,将钛-银样品置于磷酸二氢钠缓冲液(50mM,pH=8.5)中,加入盐酸多巴胺(2mg/mL),在37℃下持续避光振动聚合8小时,银涂层的一面朝上,聚合完成后超声处理,干燥即得抗菌缓释钛片S1。
交替沉积银层和多巴胺层,使用磁控溅射系统(JCP-350,TECHNOL)将银薄膜镀覆在抗菌缓释钛片S1上,银层镀覆厚度(D2)为10nm。再次银镀覆后,将钛-银-多巴胺-银样品置于磷酸二氢钠缓冲液(50mM,pH=8.5)中,加入盐酸多巴胺(2mg/mL),在37℃下持续避光振动聚合10小时,银涂层的一面朝上,聚合完成后超声处理,干燥即得抗菌缓释钛片S2。
交替沉积银层和多巴胺层,使用磁控溅射系统(JCP-350,TECHNOL)将银薄膜镀覆在抗菌缓释钛片S2上,银层镀覆厚度(D3)为8nm。再次银镀覆后,将钛-银-多巴胺-银-多巴胺-银样品置于磷酸二氢钠缓冲液(50mM,pH=8.5)中,加入盐酸多巴胺中(2mg/mL),在37℃下持续避光振动聚合12小时,干燥即得抗菌缓释钛片S3。
对比例1:
市售的TC4(Ti-6Al-4V)片的尺寸为直径=15mm,厚度=1mm,打磨光滑,依次在去离子水、丙酮、乙醇和去离子水中用超声波冲洗处理钛片。
之后,使用磁控溅射系统(JCP-350,TECHNOL)将银薄膜镀覆在钛片上。磁控溅射镀覆参数为:功率100W,本底真空度3×10-4Pa,工作气压0.5Pa,氩气流量为15sccm,基片旋转速度为30rpm,银层镀覆厚度为30nm。
在银镀覆后,将钛-银样品在置于磷酸二氢钠缓冲液(50mM,pH=8.5)中,加入盐酸多巴胺(2mg/mL),在37℃下持续避光振动聚合24小时,银涂层的一面朝上。聚合完成后彻底超声处理,干燥即得。
实验例1
(1)抗菌缓释钛片亲水性测试方法:
本发明样品的亲水性是用接触角测试仪测量的。将一滴体积为10μL的蒸馏水滴在样品上,将水滴在样品表面保持60秒来测量接触角。在测试之前,将准备好的样品分成两组。一组置于大气环境中,另一组浸泡在去离子水中,两组都将在24小时和1周后进行测试。
表1抗菌缓释钛片亲水效果测试
Figure BDA0003328852990000081
从实验结果可以看出,样品制备24小时后的亲水性与空白钛片相比有较好的改善。但是如果样品放置在空气中一周后,与空白样相比变化不大,但放在水中一周还会保持很好的亲水性。并且相比于对比例1,本申请的所述的实施例在水中的亲水性更优。
实验例2
(1)银离子缓释效果测试
测试方法:将试样(n=3)浸泡在6mL的磷酸盐缓冲溶液(PBS)中,在37℃下持续测试一个月,并在预定的时间点收集所有溶液,并相应补充新鲜的PBS。之后,用电感耦合等离子体原子发射光谱法(ICP-OES)对收集的缓冲液进行分析,绘制Ag+的释放曲线和速率。此外,通过将样品涂层溶解在4%的稀硝酸中来计算总的银含量。
通过计算,实施例一、二、三总银的含量分别为27.35±1.13μg、54.65±1.21μg、82.68±1.46μg,通过图1-3可以看出,在PBS中浸泡一个月实施例一-三银释放量逐渐降低并稳定,持续释放量分别占总银量的25.5%、16.7%、13.6%。众所周知,过量的Ag+释放可能导致一些细胞毒性。而本发明的实施例样品在30天内的Ag+释放浓度都低于银离子的生物安全浓度(1.6mg/L)和有毒浓度(10mg/L)。
(2)抗菌效果测试(大肠杆菌和金黄色葡萄球菌)
测试方法:本发明通过利用革兰氏阳性细菌金黄色葡萄球菌和革兰氏阴性细菌大肠杆菌的抑菌圈实验来确定实施例样品(n=3)的抗菌活性。样品面朝下放在均匀涂有细菌(20μL,106CFU/mL)的固体琼脂培养基上。在37℃下培养24小时后,对细菌生长抑制的区域(样品周围的透明区域)进行拍照观察,以表明各种样品表面的抗菌能力。详见图4。
从抗菌测试结果可以看出,实施例样品均具有较好抗菌效果,特别对金黄色葡萄球菌效果更好。
(3)骨细胞增殖粘附作用
测试方法:本发明为了测试实施例制备样品对骨细胞的增殖粘附效果,将MC3T3-E1细胞与空白TC4样品和实施例样品一起培养。将所有样品置于12孔板中,将MC3T3-E1细胞以4×104细胞/孔的密度播种在样品上,培养24小时。随后,弃去细胞培养液,用PBS溶液冲洗样品三次,以去除松散的粘附细胞。之后,在室温下用4%多聚甲醛溶液固定样品上的细胞20分钟。然后用0.5%聚乙二醇辛基苯基醚溶液处理细胞膜3分钟。随后用4'6-二脒基-2-苯基吲哚和罗丹明标记鬼笔环肽分别对细胞核和细胞骨架进行染色。图像由倒置的荧光显微镜拍摄。详见附图5。
从实验结果可以看出实施例样品都有较好的骨细胞增殖和粘附效果,尤其是实施例二和实施例三,比空白钛片有更明显骨增殖和粘附效果,这可能是由于较好的亲水性所导致。
有必要指出的是,上述实施例只用于对本发明进一步说明,不能理解为对本发明保护范围的限制,从事该领域的技术人员根据上述发明内容的指导,对本发明所做出的一些非本质性的改进和调整仍属于本发明的保护范围。

Claims (9)

1.一种抗菌缓释钛片的制备方法,其特征在于:所述制备方法包括以下步骤:
(1)钛片进行表面处理;
(2)将表面处理后的钛片经磁控溅射工艺进行镀银处理;
(3)将步骤(2)制得的钛片进行聚多巴胺涂层处理,即得抗菌缓释钛片。
2.根据权利要求1所述的抗菌缓释钛片的制备方法,其特征在于:步骤(1)中,钛片进行表面处理包括以下步骤:将钛片持续喷涂40-60μm的Al2O3,然后在50-70℃下进行酸蚀;按照去离子水、丙酮、乙醇和去离子水的顺序用超声波分别冲洗处理钛片。
3.根据权利要求2的抗菌缓释钛片的制备方法,其特征在于:步骤(1)中,所述酸蚀溶液配比37%HCl:98%H2SO4:H2O=1:1:2。
4.根据权利要求2的抗菌缓释钛片的制备方法,其特征在于:步骤(1)中,所述酸蚀时间为8-15min。
5.根据权利要求1的抗菌缓释钛片的制备方法,其特征在于:步骤(2)中,所述磁控溅射工艺包括:磁控溅射镀覆参数为:功率90-100W,真空度3-4×10-4Pa,气压0.5Pa,氩气流量为15sccm,基片旋转速度为30rpm。
6.根据权利要求1的抗菌缓释钛片的制备方法,其特征在于:步骤(2)中,银层镀覆厚度为10-30nm,优选的,银层镀覆厚度为20-30nm。
7.根据权利要求1的抗菌缓释钛片的制备方法,其特征在于:步骤(3)中,聚多巴胺涂层处理包括以下步骤:在银镀覆后,将钛-银样品置于磷酸二氢钠缓冲液中,加入盐酸多巴胺,在37℃下持续避光振动18-30小时,聚合完成后超声处理,即得抗菌缓释钛片。
8.根据权利要求7的抗菌缓释钛片的制备方法,其特征在于:步骤(3)中,盐酸多巴胺浓度为2mg/mL。
9.根据权利要求1所述的抗菌缓释钛片的制备方法,其特征在于:所述制备方法包括以下步骤:
(1)钛片进行表面处理;
(2)将表面处理后的钛片经磁控溅射工艺进行镀银处理;
(3)将步骤(2)制得的钛片进行聚多巴胺涂层处理,即得抗菌缓释钛片;
(4)将步骤(2)和步骤(3)交替进行,形成以钛为基材的Ag-聚多巴胺多层结构的钛片。
CN202111274154.6A 2021-10-29 2021-10-29 一种抗菌缓释钛片的制备方法 Active CN114159619B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111274154.6A CN114159619B (zh) 2021-10-29 2021-10-29 一种抗菌缓释钛片的制备方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111274154.6A CN114159619B (zh) 2021-10-29 2021-10-29 一种抗菌缓释钛片的制备方法

Publications (2)

Publication Number Publication Date
CN114159619A true CN114159619A (zh) 2022-03-11
CN114159619B CN114159619B (zh) 2023-03-17

Family

ID=80477480

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111274154.6A Active CN114159619B (zh) 2021-10-29 2021-10-29 一种抗菌缓释钛片的制备方法

Country Status (1)

Country Link
CN (1) CN114159619B (zh)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007087269A2 (en) * 2002-12-18 2007-08-02 Chameleon Scientific Corporation Antimicrobial coating methods
TW201740981A (zh) * 2016-05-17 2017-12-01 國立高雄大學 緩釋型奈米銀改質表面及其製備方法
CN107447197A (zh) * 2017-07-17 2017-12-08 天津师范大学 磁控多靶共溅射技术制备的生物性TiN‑Ag纳米复合多层膜及应用
CN111041490A (zh) * 2019-12-28 2020-04-21 高岩 一种能够促进接触成骨的纯钛表面处理方法
CN113101414A (zh) * 2021-03-18 2021-07-13 常熟中科世纪生物科技有限公司 一种具有抗感染功能的人工关节假体

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007087269A2 (en) * 2002-12-18 2007-08-02 Chameleon Scientific Corporation Antimicrobial coating methods
TW201740981A (zh) * 2016-05-17 2017-12-01 國立高雄大學 緩釋型奈米銀改質表面及其製備方法
CN107447197A (zh) * 2017-07-17 2017-12-08 天津师范大学 磁控多靶共溅射技术制备的生物性TiN‑Ag纳米复合多层膜及应用
CN111041490A (zh) * 2019-12-28 2020-04-21 高岩 一种能够促进接触成骨的纯钛表面处理方法
CN113101414A (zh) * 2021-03-18 2021-07-13 常熟中科世纪生物科技有限公司 一种具有抗感染功能的人工关节假体

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
张嘉敏等: "SLA表面PDA/CPP复合涂层的制备及其性能研究", 《无机材料学报》 *
张文等: "《实用口腔医学》", 30 November 2013, 北京:科学技术文献出版社 *
谭英等: "聚多巴胺修饰钛表面纳米载银及其抗菌和细胞相容性", 《无机材料学报》 *

Also Published As

Publication number Publication date
CN114159619B (zh) 2023-03-17

Similar Documents

Publication Publication Date Title
Wang et al. NanoZnO-modified titanium implants for enhanced anti-bacterial activity, osteogenesis and corrosion resistance
Hadidi et al. Electrophoretic-deposited hydroxyapatite-copper nanocomposite as an antibacterial coating for biomedical applications
Huang et al. Fabrication of silver-and strontium-doped hydroxyapatite/TiO2 nanotube bilayer coatings for enhancing bactericidal effect and osteoinductivity
JP5619416B2 (ja) 表面にパラジウムを含む金属粒子を有する電子供与表面を有する基体
Li et al. Polydopamine-induced nanocomposite Ag/CaP coatings on the surface of titania nanotubes for antibacterial and osteointegration functions
CN100551450C (zh) 一种抗菌型生物活性钛涂层的制备方法
Han et al. Mg/Ag ratios induced in vitro cell adhesion and preliminary antibacterial properties of TiN on medical Ti-6Al-4V alloy by Mg and Ag implantation
CN110064075B (zh) 一种基于纳米银/d-半胱氨酸的自组装抗菌涂层及制备方法
Shimabukuro et al. Investigation of realizing both antibacterial property and osteogenic cell compatibility on titanium surface by simple electrochemical treatment
EP2373844A1 (en) Active polymeric films
Cheng et al. The bifunctional regulation of interconnected Zn-incorporated ZrO 2 nanoarrays in antibiosis and osteogenesis
Jia et al. Strontium-calcium doped titanium dioxide nanotubes loaded with GL13K for promotion of antibacterial activity, anti-Inflammation, and vascularized bone regeneration
CN102912335A (zh) 一种表面改性的医用金属材料及其制备方法
Uhm et al. Fabrication of bioactive, antibacterial TiO2 nanotube surfaces, coated with magnetron sputtered Ag nanostructures for dental applications
Jeyachandran et al. The effect of thickness of titanium nitride coatings on bacterial adhesion
Kang et al. The characteristics of an antibacterial TiAgN thin film coated by physical vapor deposition technique
Du et al. A multifunctional hybrid inorganic-organic coating fabricated on magnesium alloy surface with antiplatelet adhesion and antibacterial activities
Awonusi et al. In vitro and in vivo studies on bacteria and encrustation resistance of heparin/poly-L-lysine-Cu nanoparticles coating mediated by PDA for ureteral stent application
Song et al. Controllable Ag/Ta ratios of co-implanted TiN films on titanium alloys for osteogenic enhancement and antibacterial responses
Peng et al. Polyelectrolytes fabrication on magnesium alloy surface by layer-by-layer assembly technique with antiplatelet adhesion and antibacterial activities
TW201720472A (zh) 一種兼具抗菌及促進細胞生長特性之表面改質牙材及其製備方法
Bian et al. Dopamine-mediated copper-loaded ZnTiO3 antimicrobial coating with immunomodulatory properties effectively enhances vascularised osteogenesis on titanium implants
Durdu et al. Characterization and investigation of properties of copper nanoparticle coated TiO2 nanotube surfaces on Ti6Al4V alloy
Zhao et al. Enhanced antibacterial activity, corrosion resistance and endothelialization potential of Ti-5Cu alloy by oxygen and nitrogen plasma-based surface modification
Yin et al. One-step fabrication of Ag@ Polydopamine film modified NiTi alloy with strong antibacterial property and enhanced anticorrosion performance

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant