CN115725968A - 一种生物医用钛合金表面的复合涂层及其制备方法 - Google Patents
一种生物医用钛合金表面的复合涂层及其制备方法 Download PDFInfo
- Publication number
- CN115725968A CN115725968A CN202211447228.6A CN202211447228A CN115725968A CN 115725968 A CN115725968 A CN 115725968A CN 202211447228 A CN202211447228 A CN 202211447228A CN 115725968 A CN115725968 A CN 115725968A
- Authority
- CN
- China
- Prior art keywords
- coating
- titanium alloy
- antibacterial peptide
- composite coating
- polypeptide
- 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.)
- Pending
Links
- 238000000576 coating method Methods 0.000 title claims abstract description 46
- 239000011248 coating agent Substances 0.000 title claims abstract description 45
- 229910001069 Ti alloy Inorganic materials 0.000 title claims abstract description 28
- 239000002131 composite material Substances 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 239000003910 polypeptide antibiotic agent Substances 0.000 claims abstract description 31
- 239000007943 implant Substances 0.000 claims abstract description 21
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 13
- 238000005516 engineering process Methods 0.000 claims abstract description 10
- 238000005488 sandblasting Methods 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 6
- 150000001413 amino acids Chemical class 0.000 claims abstract description 6
- 238000002444 silanisation Methods 0.000 claims abstract description 6
- 238000005530 etching Methods 0.000 claims abstract description 4
- 230000008878 coupling Effects 0.000 claims abstract 3
- 238000010168 coupling process Methods 0.000 claims abstract 3
- 238000005859 coupling reaction Methods 0.000 claims abstract 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 29
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 25
- 229920001184 polypeptide Polymers 0.000 claims description 24
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 13
- 239000010936 titanium Substances 0.000 claims description 13
- 229910052719 titanium Inorganic materials 0.000 claims description 13
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 10
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 235000004279 alanine Nutrition 0.000 claims description 9
- 238000003786 synthesis reaction Methods 0.000 claims description 9
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 8
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 239000002923 metal particle Substances 0.000 claims description 6
- 238000007745 plasma electrolytic oxidation reaction Methods 0.000 claims description 6
- 239000011347 resin Substances 0.000 claims description 6
- 229920005989 resin Polymers 0.000 claims description 6
- 235000001014 amino acid Nutrition 0.000 claims description 5
- 239000000463 material Substances 0.000 claims description 5
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 4
- 239000004472 Lysine Substances 0.000 claims description 4
- 238000010532 solid phase synthesis reaction Methods 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 238000005520 cutting process Methods 0.000 claims description 3
- 239000003792 electrolyte Substances 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 239000012071 phase Substances 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 238000002953 preparative HPLC Methods 0.000 claims description 3
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 claims description 3
- 235000012239 silicon dioxide Nutrition 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims 2
- 229910000077 silane Inorganic materials 0.000 claims 2
- 239000006087 Silane Coupling Agent Substances 0.000 claims 1
- 210000004872 soft tissue Anatomy 0.000 abstract description 7
- 102000044503 Antimicrobial Peptides Human genes 0.000 abstract description 6
- 108700042778 Antimicrobial Peptides Proteins 0.000 abstract description 6
- 210000000988 bone and bone Anatomy 0.000 abstract description 6
- 238000010883 osseointegration Methods 0.000 abstract description 3
- 230000000845 anti-microbial effect Effects 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 abstract 1
- 210000004409 osteocyte Anatomy 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 238000004381 surface treatment Methods 0.000 abstract 1
- 239000012756 surface treatment agent Substances 0.000 abstract 1
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000005660 hydrophilic surface Effects 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- -1 lysine (Lys Chemical class 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 230000003239 periodontal effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
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
- A61L27/02—Inorganic materials
- A61L27/04—Metals or alloys
- A61L27/06—Titanium or titanium 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/30—Inorganic materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/06—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/20—Partition-, reverse-phase or hydrophobic interaction chromatography
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- 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
- C23C22/68—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 using aqueous solutions with pH between 6 and 8
-
- 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
- C23C22/82—After-treatment
- C23C22/83—Chemical after-treatment
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
- C25D11/00—Electrolytic coating by surface reaction, i.e. forming conversion layers
- C25D11/02—Anodisation
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
- C25D11/00—Electrolytic coating by surface reaction, i.e. forming conversion layers
- C25D11/02—Anodisation
- C25D11/26—Anodisation of refractory metals or alloys based thereon
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Materials Engineering (AREA)
- Transplantation (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Metallurgy (AREA)
- Dermatology (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Mechanical Engineering (AREA)
- Electrochemistry (AREA)
- Biomedical Technology (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明提供了一种生物医用钛合金表面的复合涂层及其制备方法，可以有效增强种植体的抗菌性能和软组织亲和及骨结合能力。首先，采用喷砂酸蚀技术处理钛合金表面，再利用硅烷化制备一层涂层，然后，再通过滴入抗菌肽KLA及其类似物溶液，制备出喷砂酸蚀‑硅烷化偶联载抗菌肽涂层。通过调整抗菌肽氨基酸的序列，可以调整抗菌肽涂层的抗菌性能，调控骨细胞的生物反应，促周围软组织和新骨生长，适合应用于钛合金骨植入体的表面处理。
Description
技术领域
本发明属于生物医学技术领域，特别涉及一种生物医用钛合金表面的复合涂层及其制备方法。
背景技术
钛种植体植入患者口腔后，种植体表面与术区牙槽骨能否形成结构和功能性连接是种植体植入成功的关键，同时，余留牙软组织周围的牙周致病菌往往会转移到种植体表面，引起周围软组织发生炎症，种植体的初期稳定性遭到破坏，牙槽骨吸收，最终导致种植体失败。因此，如何能够提高钛种植体的生物相容性，以及将钛和钛合金种植体具有抗菌性成为钛种植体在口腔中应用的研究热点。
抗菌肽因其细胞毒性小、高度选择性和免疫调节性的特点，引起广泛学者的关注。抗菌肽在口腔医学领域的研究主要集中于如何预防龋病和牙周病，近期抗菌肽应用于生物医学材料表面改性处理成为一大研究热点。目前，部分理论倾向于抗菌肽亲水性表面利于成骨细胞的粘附和伸展，从而促进早期成骨。然而，抗菌肽的疏水性在多肽与细胞膜作用中起到重要的作用，疏水性可以影响多肽与疏水性磷脂层的相互作用程度。疏水性过高会引起抗菌肽对原核和真核细胞膜的破坏程度增强。
有学者发现抗菌肽KLA(序列为(KLAKKLA)2)具有良好的抗菌活性和较低的细胞毒性而受到广泛研究。基于此，我们以抗菌肽KLA为模板，利用亲水性较强的色氨酸(Trp,W)和疏水性较强的亮氨酸(Leu,L)分别对抗菌肽 KLA中的丙氨酸(Ala，A)进行单点取代和双点取代，从而研究亲疏水性不同的抗菌肽涂层对钛种植体生物相容性和抗菌活性的影响规律。通过研究抗菌肽亲疏水性平衡问题，我们力求寻找到一种抗菌肽的生物涂层，能在提高钛种植体生物活性的同时实现其抗菌功能，这对改善患者的生活质量有着至关重要的意义。
因此，发明一种生物医用钛合金表面的复合涂层及其制备方法来解决上述问题很有必要。
发明内容
针对上述问题，本发明提供了一种生物医用钛合金表面的复合涂层及其制备方法，以解决上述背景技术中提出的问题。
为实现上述目的，本发明提供如下技术方案：一种生物医用钛合金表面的复合涂层，所述该涂层由具有抗菌肽KLA及其类似物溶液组成，采用喷砂酸蚀技术处理钛合金表面，再利用硅烷化制备一层涂层，然后，再通过滴入抗菌肽KLA及其类似物溶液，制备出喷砂酸蚀-硅烷化偶联载抗菌肽涂层。
进一步的，所述该涂层含有可吸收金属颗粒和有机物。
进一步的，所述的金属颗粒为纯钛、钛合金颗粒。
进一步的，所述的有机物可以是所有的可吸收氨基酸组成的多肽材料，包括赖氨酸(Lys,K)、丙氨酸(Ala,A)和亮氨酸(Leu,L)。
本发明还公开了一种生物医用钛合金表面的复合涂层及其制备方法，其特征在于：包括以下步骤：
S1抗菌肽的合成与制备：利用Fmoc多肽固相合成技术，使用Rink MBHA 树脂为载体，进行多肽的化学合成，合成结束后，用三氟乙酸将合成好的粗肽从树脂上切下来，利用制备型高效液相色谱反相柱技术进行分离和纯化多肽；
S2钛种植体加载抗菌肽涂层的制备：利用硅酸和磷酸盐体系电解液，再经NaOH溶液处理，制备超声微弧氧化碱处理涂层，将无水乙醇与水按照10:1 的体积比制成pH＝7的溶液，加入硅烷偶联剂，制备出超声微弧氧化碱处理硅烷涂层，滴入亲疏水性不同的抗菌肽溶液，制备出超声微弧氧化碱处理硅烷偶联载抗菌肽涂层。
本发明的技术效果和优点：
1、本发明通过一种生物医用钛合金表面的复合涂层，可增强种植体的抗菌性能和软组织亲和及骨结合性能，具有良好的生物相容性，有机物均可产生一定抗菌效果，高分子聚合物在人体中可以通过CO2和H2O等方式排除体外，不会产生毒性。
2.本发明所述的生物医用钛合金表面的复合涂层，通过合理的成分配比和制备方法，可以制备出促成骨能力和软组织亲和性能良好的复合涂层，可用作生物医用增强种植体的抗菌性能和软组织亲和及骨结合的复合涂层的植入材料。
3.本发明所述的生物医用钛合金表面的复合涂层是利用氨基酸合成，其制备工艺简单、且具有优异的性能和可靠性，易实现大规模化工业生产。
本发明的其它特征和优点将在随后的说明书中阐述，并且，部分地从说明书中变得显而易见，或者通过实施本发明而了解。本发明的目的和其他优点可通过在说明书所指出的结构来实现和获得。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚，下面对本发明实施例中的技术方案进行清楚、完整地说明，显然，所描述的实施例是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例1
本发明提供了一种生物医用钛合金表面的复合涂层，所述该涂层由具有抗菌肽KLA及其类似物溶液组成，采用喷砂酸蚀技术处理钛合金表面，再利用硅烷化制备一层涂层，然后，再通过滴入抗菌肽KLA及其类似物溶液，制备出喷砂酸蚀-硅烷化偶联载抗菌肽涂层。
作为本发明的一种具体实施方式，所述该涂层含有可吸收金属颗粒和有机物；所述的金属颗粒为纯钛、钛合金颗粒；所述的有机物可以是所有的可吸收氨基酸组成的多肽材料，包括赖氨酸(Lys,K)、丙氨酸(Al a,A)和亮氨酸(Leu,L)。
本发明还公开了一种生物医用钛合金表面的复合涂层的制备方法，其特征在于：包括以下步骤：
S1抗菌肽的合成与制备：利用Fmoc多肽固相合成技术，使用Ri nk MBHA 树脂为载体，进行多肽的化学合成，合成结束后，用三氟乙酸将合成好的粗肽从树脂上切下来，利用制备型高效液相色谱反相柱技术进行分离和纯化多肽；
S2钛种植体加载抗菌肽涂层的制备：利用硅酸和磷酸盐体系电解液，再经NaOH溶液处理，制备超声微弧氧化碱处理涂层，将无水乙醇与水按照10:1 的体积比制成pH＝7的溶液，加入硅烷偶联剂，制备出超声微弧氧化碱处理硅烷涂层，滴入亲疏水性不同的抗菌肽溶液，制备出超声微弧氧化碱处理硅烷偶联载抗菌肽涂层。
实施例2
采用抗菌肽KLA为模板，其序列为(KLAKKLA)2。抗菌肽设计依据：本研究的核心是寻找到抗菌肽的亲疏水性平衡，因此保留含有电荷的赖氨酸(Lys, K)，改变不含电荷的亮氨酸和丙氨酸，从而保证所有的抗菌肽类似物含有相同的电荷，变量只有抗菌肽的亲疏水性。因此，利用色氨酸的侧链残基比丙氨酸的侧链亲水性要强，多肽亲水性的增加是通过在模板多肽用色氨酸替代原有的丙氨酸来完成的。利用亮氨酸的侧链残基比丙氨酸的侧链疏水性要强，多肽疏水性的增加是通过在模板多肽用亮氨酸替代原有的丙氨酸来完成的。我们设计了单一亮氨酸取代、亮氨酸双取代和多取代的多肽，使得亲疏水性得到不同程度的增加。通过氨基酸定点取代得到母肽KLA类似物，从而设计一系列亲疏水性不同的抗菌肽。
本研究中采用Fmoc多肽固相合成法合成抗菌肽。多肽类似物的序列见表 1。
表1.本研究中多肽类似物的序列
尽管参照前述实施例对本发明进行了详细的说明，本领域的普通技术人员应当理解：其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换；而这些修改或者替换，并不使相应技术方案的本质脱离本发明各实施例技术方案的精神和范围。
Claims (5)
1.一种生物医用钛合金表面的复合涂层，其特征在于：所述涂层由具有抗菌肽KLA及其类似物溶液组成，采用喷砂酸蚀技术处理钛合金表面，再利用硅烷化制备一层涂层，再通过滴入抗菌肽KLA及其类似物溶液，制备出喷砂酸蚀-硅烷化偶联载抗菌肽涂层。
2.根据权利要求1所述的一种生物医用钛合金表面的复合涂层，其特征在于：所述该涂层含有可吸收金属颗粒和有机物。
3.根据权利要求2所述的一种生物医用钛合金表面的复合涂层，其特征在于：所述的金属颗粒为纯钛、钛合金颗粒。
4.根据权利要求2所述的一种生物医用钛合金表面的复合涂层，其特征在于：所述的有机物可以是所有的可吸收氨基酸组成的多肽材料，包括赖氨酸(Lys,K)、丙氨酸(Ala,A)和亮氨酸(Leu,L)。
5.权利要求1-4任意一项所述的生物医用钛合金表面的复合涂层的制备方法，其特征在于：包括以下步骤：
S1抗菌肽的合成与制备：利用Fmoc多肽固相合成技术，使用Rink MBHA树脂为载体，进行多肽的化学合成，合成结束后，用三氟乙酸将合成好的粗肽从树脂上切下来，利用制备型高效液相色谱反相柱技术进行分离和纯化多肽；
S2钛种植体加载抗菌肽涂层的制备：利用硅酸和磷酸盐体系电解液，再经NaOH溶液处理，制备超声微弧氧化碱处理涂层，将无水乙醇与水按照10:1的体积比制成pH＝7的溶液，加入硅烷偶联剂，制备出超声微弧氧化碱处理硅烷涂层，滴入亲疏水性不同的抗菌肽溶液，制备出超声微弧氧化碱处理硅烷偶联载抗菌肽涂层。
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211447228.6A CN115725968A (zh) | 2022-11-18 | 2022-11-18 | 一种生物医用钛合金表面的复合涂层及其制备方法 |
| PCT/CN2023/089484 WO2024103630A1 (zh) | 2022-11-18 | 2023-04-20 | 一种生物医用钛合金表面的复合涂层及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211447228.6A CN115725968A (zh) | 2022-11-18 | 2022-11-18 | 一种生物医用钛合金表面的复合涂层及其制备方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115725968A true CN115725968A (zh) | 2023-03-03 |
Family
ID=85296796
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211447228.6A Pending CN115725968A (zh) | 2022-11-18 | 2022-11-18 | 一种生物医用钛合金表面的复合涂层及其制备方法 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN115725968A (zh) |
| WO (1) | WO2024103630A1 (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116271210A (zh) * | 2023-04-21 | 2023-06-23 | 国纳之星(上海)纳米科技发展有限公司 | 一种仿生骨修复涂层改性的钛合金及其制备方法 |
| WO2024103630A1 (zh) * | 2022-11-18 | 2024-05-23 | 东莞宜安科技股份有限公司 | 一种生物医用钛合金表面的复合涂层及其制备方法 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5789542A (en) * | 1994-04-22 | 1998-08-04 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Amphipathic peptides |
| EP2399618A1 (en) * | 2010-06-22 | 2011-12-28 | Planton GmbH | Antimicrobial medical devices |
| CN105169498B (zh) * | 2015-09-09 | 2018-10-09 | 华南理工大学 | 一种硅表面的抗菌处理方法 |
| CN107137762A (zh) * | 2017-05-11 | 2017-09-08 | 华南理工大学 | 一种医用钛或钛合金表面抗菌涂层的构建方法 |
| JP6613499B2 (ja) * | 2017-08-24 | 2019-12-04 | 学校法人藤田学園 | 細胞殺傷剤 |
| CN115725968A (zh) * | 2022-11-18 | 2023-03-03 | 东莞宜安科技股份有限公司 | 一种生物医用钛合金表面的复合涂层及其制备方法 |
-
2022
- 2022-11-18 CN CN202211447228.6A patent/CN115725968A/zh active Pending
-
2023
- 2023-04-20 WO PCT/CN2023/089484 patent/WO2024103630A1/zh unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024103630A1 (zh) * | 2022-11-18 | 2024-05-23 | 东莞宜安科技股份有限公司 | 一种生物医用钛合金表面的复合涂层及其制备方法 |
| CN116271210A (zh) * | 2023-04-21 | 2023-06-23 | 国纳之星(上海)纳米科技发展有限公司 | 一种仿生骨修复涂层改性的钛合金及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2024103630A1 (zh) | 2024-05-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN115725968A (zh) | 一种生物医用钛合金表面的复合涂层及其制备方法 | |
| US7534761B1 (en) | Charged peptide-amphiphile solutions and self-assembled peptide nanofiber networks formed therefrom | |
| CN106890357B (zh) | 一种稳定和高性能的种植体表面制备方法 | |
| CN105617460B (zh) | 一种在医用植入材料表面制备无毒法抗菌涂层的方法 | |
| Natalio et al. | Bioengineering of the silica-polymerizing enzyme silicatein-α for a targeted application to hydroxyapatite | |
| CN102747403B (zh) | 在医用钛合金表面制备掺镁羟基磷灰石/二氧化钛活性膜层的方法 | |
| CN102090982B (zh) | 一种人工牙根或关节材料及其微弧氧化制备方法 | |
| CN108276487B (zh) | 一种可促进成骨并抑制破骨的活性多肽及其应用 | |
| DE3810803C2 (zh) | ||
| US20220371958A1 (en) | Biomaterial composite, peptide-based adhesives and methods of use thereof | |
| CN110338921B (zh) | 一种牙科种植体及其制备方法 | |
| WO2005003292A2 (en) | Composition and method for self-assembly and mineralization of peptide amphiphiles | |
| Zhang et al. | Functionally Tailored Metal–Organic Framework Coatings for Mediating Ti Implant Osseointegration | |
| CN101565824A (zh) | 紫外光照射提高钛及其合金表面生物活性的方法 | |
| CN105624762A (zh) | 一种在钛或钛合金表面制备生物活性复合涂层的方法 | |
| WO2017101026A1 (zh) | 贻贝粘蛋白与生长因子的组合物 | |
| EP2118136B1 (en) | Consensus peptide | |
| CN101161295A (zh) | 电化学法对医用金属移植体表面胶原改性的方法 | |
| CN115887768A (zh) | 一种生物医用钛合金的自组装多肽涂层及其制备方法 | |
| CN101311327A (zh) | 生物活性钛基表面复合材料及其制备方法 | |
| CN115671392A (zh) | 一种牢固的具有成骨活性涂层的人工骨材料及其制备方法与应用 | |
| Morris et al. | Development of a resorbable tricalcium phosphate (TCP) amine antibiotic composite | |
| CN113908340B (zh) | 一种用紫胶混合溶液改性医用聚醚醚酮材料的制备方法 | |
| CN111471093B (zh) | 一种多肽抗生素及其制备方法和用途 | |
| JP7475051B2 (ja) | 新規化合物及びそれを含む血管新生剤 |
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 |