CN108939155B - 一种镁基组织工程材料抗菌涂层及其制备方法 - Google Patents
一种镁基组织工程材料抗菌涂层及其制备方法 Download PDFInfo
- Publication number
- CN108939155B CN108939155B CN201710349726.XA CN201710349726A CN108939155B CN 108939155 B CN108939155 B CN 108939155B CN 201710349726 A CN201710349726 A CN 201710349726A CN 108939155 B CN108939155 B CN 108939155B
- Authority
- CN
- China
- Prior art keywords
- coating
- magnesium
- antibacterial
- calcium
- compound
- 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.)
- Active
Links
- 238000000576 coating method Methods 0.000 title claims abstract description 127
- 239000011248 coating agent Substances 0.000 title claims abstract description 125
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 67
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 title claims abstract description 61
- 239000011777 magnesium Substances 0.000 title claims abstract description 61
- 229910052749 magnesium Inorganic materials 0.000 title claims abstract description 61
- 239000000463 material Substances 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 230000000975 bioactive effect Effects 0.000 claims abstract description 52
- ZQBZAOZWBKABNC-UHFFFAOYSA-N [P].[Ca] Chemical compound [P].[Ca] ZQBZAOZWBKABNC-UHFFFAOYSA-N 0.000 claims abstract description 50
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims abstract description 34
- 229910000389 calcium phosphate Inorganic materials 0.000 claims abstract description 22
- 239000001506 calcium phosphate Substances 0.000 claims abstract description 21
- 235000011010 calcium phosphates Nutrition 0.000 claims abstract description 20
- 150000002736 metal compounds Chemical class 0.000 claims abstract description 15
- 238000002791 soaking Methods 0.000 claims abstract description 15
- 239000002245 particle Substances 0.000 claims abstract description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 229940100890 silver compound Drugs 0.000 claims description 15
- 239000005749 Copper compound Substances 0.000 claims description 11
- 150000003752 zinc compounds Chemical class 0.000 claims description 10
- 150000001880 copper compounds Chemical class 0.000 claims description 8
- 239000011817 metal compound particle Substances 0.000 claims description 7
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 7
- 150000003379 silver compounds Chemical class 0.000 claims description 6
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Chemical compound [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 claims description 6
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 5
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 4
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 claims description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 3
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 claims description 3
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 claims description 3
- SDLBJIZEEMKQKY-UHFFFAOYSA-M silver chlorate Chemical compound [Ag+].[O-]Cl(=O)=O SDLBJIZEEMKQKY-UHFFFAOYSA-M 0.000 claims description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 2
- PLKATZNSTYDYJW-UHFFFAOYSA-N azane silver Chemical compound N.[Ag] PLKATZNSTYDYJW-UHFFFAOYSA-N 0.000 claims description 2
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 claims description 2
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 2
- YRNNKGFMTBWUGL-UHFFFAOYSA-L copper(ii) perchlorate Chemical compound [Cu+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O YRNNKGFMTBWUGL-UHFFFAOYSA-L 0.000 claims description 2
- IJCCOEGCVILSMZ-UHFFFAOYSA-L copper;dichlorate Chemical compound [Cu+2].[O-]Cl(=O)=O.[O-]Cl(=O)=O IJCCOEGCVILSMZ-UHFFFAOYSA-L 0.000 claims description 2
- 229940102001 zinc bromide Drugs 0.000 claims description 2
- GTQFPPIXGLYKCZ-UHFFFAOYSA-L zinc chlorate Chemical compound [Zn+2].[O-]Cl(=O)=O.[O-]Cl(=O)=O GTQFPPIXGLYKCZ-UHFFFAOYSA-L 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 2
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 2
- 229960001763 zinc sulfate Drugs 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 1
- 229910000861 Mg alloy Inorganic materials 0.000 abstract description 42
- 239000000956 alloy Substances 0.000 abstract description 18
- 230000007797 corrosion Effects 0.000 abstract description 18
- 238000005260 corrosion Methods 0.000 abstract description 18
- 239000011159 matrix material Substances 0.000 abstract description 18
- 239000000243 solution Substances 0.000 abstract description 16
- 238000000034 method Methods 0.000 abstract description 14
- 239000010410 layer Substances 0.000 abstract description 8
- 238000006243 chemical reaction Methods 0.000 abstract description 5
- 230000011164 ossification Effects 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 5
- 230000033115 angiogenesis Effects 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 239000012266 salt solution Substances 0.000 abstract description 2
- 239000002344 surface layer Substances 0.000 abstract description 2
- 230000001105 regulatory effect Effects 0.000 abstract 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 37
- 229910052709 silver Inorganic materials 0.000 description 27
- 239000004332 silver Substances 0.000 description 27
- 229910052751 metal Inorganic materials 0.000 description 25
- 239000002184 metal Substances 0.000 description 25
- 239000011701 zinc Substances 0.000 description 22
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 20
- 229910052802 copper Inorganic materials 0.000 description 20
- 239000010949 copper Substances 0.000 description 20
- 229910052725 zinc Inorganic materials 0.000 description 20
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 19
- 150000001875 compounds Chemical class 0.000 description 18
- 229960001714 calcium phosphate Drugs 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 15
- 210000000988 bone and bone Anatomy 0.000 description 11
- 239000011575 calcium Substances 0.000 description 10
- 239000007943 implant Substances 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 229910045601 alloy Inorganic materials 0.000 description 8
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 description 8
- 229910021642 ultra pure water Inorganic materials 0.000 description 8
- 239000012498 ultrapure water Substances 0.000 description 8
- 229910019142 PO4 Inorganic materials 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- 230000015556 catabolic process Effects 0.000 description 6
- 239000002131 composite material Substances 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 229910000388 diammonium phosphate Inorganic materials 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 159000000007 calcium salts Chemical class 0.000 description 5
- 150000007529 inorganic bases Chemical class 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 239000002105 nanoparticle Substances 0.000 description 5
- 210000000963 osteoblast Anatomy 0.000 description 5
- 235000021317 phosphate Nutrition 0.000 description 5
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 4
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- 238000000861 blow drying Methods 0.000 description 4
- 238000007664 blowing Methods 0.000 description 4
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 4
- 238000002513 implantation Methods 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 230000000399 orthopedic effect Effects 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 208000035143 Bacterial infection Diseases 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 229910001093 Zr alloy Inorganic materials 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 239000010839 body fluid Substances 0.000 description 3
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 3
- 238000000151 deposition Methods 0.000 description 3
- -1 hydroxyl ions Chemical class 0.000 description 3
- 238000007654 immersion Methods 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000013386 optimize process Methods 0.000 description 3
- 238000007745 plasma electrolytic oxidation reaction Methods 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 3
- 206010059866 Drug resistance Diseases 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 229910015818 MPO4 Inorganic materials 0.000 description 2
- 229910003023 Mg-Al Inorganic materials 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 241000191963 Staphylococcus epidermidis Species 0.000 description 2
- 229910001069 Ti alloy Inorganic materials 0.000 description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
- 229940062672 calcium dihydrogen phosphate Drugs 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000000224 chemical solution deposition Methods 0.000 description 2
- 239000011247 coating layer Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 235000019691 monocalcium phosphate Nutrition 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- FJOLTQXXWSRAIX-UHFFFAOYSA-K silver phosphate Chemical compound [Ag+].[Ag+].[Ag+].[O-]P([O-])([O-])=O FJOLTQXXWSRAIX-UHFFFAOYSA-K 0.000 description 2
- 229940019931 silver phosphate Drugs 0.000 description 2
- 229910000161 silver phosphate Inorganic materials 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000007740 vapor deposition Methods 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229910014497 Ca10(PO4)6(OH)2 Inorganic materials 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- RAOSIAYCXKBGFE-UHFFFAOYSA-K [Cu+3].[O-]P([O-])([O-])=O Chemical compound [Cu+3].[O-]P([O-])([O-])=O RAOSIAYCXKBGFE-UHFFFAOYSA-K 0.000 description 1
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 description 1
- 229910000387 ammonium dihydrogen phosphate Inorganic materials 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 230000007234 antiinflammatory process Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229960002713 calcium chloride Drugs 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019838 diammonium phosphate Nutrition 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002082 metal nanoparticle Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 235000019837 monoammonium phosphate Nutrition 0.000 description 1
- 229910000150 monocalcium phosphate Inorganic materials 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 229910000392 octacalcium phosphate Inorganic materials 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 230000001582 osteoblastic effect Effects 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- YIGWVOWKHUSYER-UHFFFAOYSA-F tetracalcium;hydrogen phosphate;diphosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[Ca+2].OP([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O YIGWVOWKHUSYER-UHFFFAOYSA-F 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000002341 toxic gas Substances 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- LRXTYHSAJDENHV-UHFFFAOYSA-H zinc phosphate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O LRXTYHSAJDENHV-UHFFFAOYSA-H 0.000 description 1
- 229910000165 zinc phosphate Inorganic materials 0.000 description 1
Images
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
- A61L27/30—Inorganic materials
- A61L27/32—Phosphorus-containing materials, e.g. apatite
-
- 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
- A61L27/047—Other specific metals or alloys not covered by A61L27/042 - A61L27/045 or A61L27/06
-
- 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
- A61L27/306—Other specific inorganic materials not covered by A61L27/303 - A61L27/32
-
- 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
-
- 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
- A61L27/56—Porous materials, e.g. foams or sponges
-
- 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
- A61L27/58—Materials at least partially resorbable by the body
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
- A61L2300/104—Silver, e.g. silver sulfadiazine
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
- A61L2300/604—Biodegradation
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
- A61L2300/608—Coatings having two or more layers
-
- 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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/08—Coatings comprising two or more layers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Animal Behavior & Ethology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Inorganic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Materials For Medical Uses (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
本发明公开了一种镁基组织工程材料抗菌涂层及其制备方法。所述涂层由里至外包括设于所述多孔镁及镁合金材料表层的生物活性钙磷涂层和纳米金属化合物抗菌涂层；制备时，将多孔镁基材料置于含磷酸钙盐溶液浸泡，化学沉积生物活性钙磷涂层；然后将沉积钙磷层后的多孔镁基材料置于金属化合物溶液恒温动态浸泡反应，在外层钙磷层表面制备载上述纳米金属化合物抗菌涂层，即得。本发明制备的涂层既显著降低了基体多孔镁及镁合金的腐蚀速率，还提高了基体的表面生物活性，可促进成骨及成血管，并具有高效广谱抗菌功效。操作工艺简便、易行，制备的涂层与基体结合力强，所载纳米金属化合物在表面密度、粒径可调控。
Description
技术领域
本发明涉及一种镁基组织工程材料抗菌涂层及其制备方法，属于生物医用材料制备技术领域。
背景技术
在骨科内植入物领域，镁及镁合金因其独特的生物可降解性、生物相容性及与人骨相似的杨氏模量，有希望替代传统医学中的不锈钢、钛及钛合金等骨科内植入材料，被认为是骨科领域内“革命性的医用植入材料”。具有三维贯通开孔结构的多孔镁及镁合金材料，在植入部位不仅起到组织填充的作用，还可以促进血管及周围组织的长入，在完成对植入部位的修复或整形的过程中被逐渐降解吸收，达到自体修复的效果。然而，多孔镁及镁合金材料作为骨科内植入物填充材料存在降解过快，生物相容性有待进一步提高等问题，且在植入后常出现细菌感染，在植入物表层形成细菌膜，影响骨组织的正常生长，甚至导致植入失效，限制了其进一步的临床应用，因此有必要对多孔镁及镁合金材料进行表面改性，一方面提高多孔镁及镁合金材料的耐蚀性和生物相容性，另一方面抑制细菌在材料表面的粘附和增殖，以满足其临床应用。
在多孔镁及镁合金材料表面构筑生物活性钙磷涂层，不仅能提高植入物的生物相容性，对骨组织在镁合金材料表面沉积有积极的诱导作用，促进骨的生长，而且可以延缓基体在体液中的降解速率，是镁合金骨内植入材料表面改性的一个重要方向。尽管生物活性钙磷涂层提高了多孔镁及镁合金耐蚀性和生物相容性，但是也有利于细菌的粘附和增殖，有必要在生物活性钙磷涂层表面制备一层具有抗菌性能的涂层，以预防细菌感染。
目前常见采用的抗菌涂层主要有四种：抗生素涂层、NO释放涂层、二氧化钛释放涂层和活性金属释放涂层。对于涂覆生物活性钙磷涂层的多孔镁及镁合金来说，抗生素涂层易产生抗药性，NO释放涂层不易实现，二氧化钛涂层仅在阳光下起作用，因此，活性金属释放涂层是最佳的选择。在活性金属释放涂层中，银释放涂层具有广谱抗菌性、抗病毒、抗炎症反应、低毒性、长效释放、无抗药性和低成本等优势；锌释放涂层不仅具有优异的抗菌性能，还能促进成骨；铜释放涂层也具有良好的抗菌效果和生物相容性。因此，将抗菌性的金属与多孔镁及镁合金生物活性钙磷涂层材料复合，可以得到抗菌性的骨组织工程支架，达到预防感染的目的。虽然诸如银、铜或锌等金属化合物的抗菌性能优异，但是过量的金属离子释放对成骨细胞存在毒性，会阻碍骨的生长，因此，开发一种针对多孔镁及镁合金抗菌促成骨性能的新型制备方法，优化多孔镁及镁合金抗菌生物活性涂层表面金属化合物含量，对于多孔镁及镁合金组织工程支架的临床应用有着重要的意义。目前镁及镁合金表面载活性金属抗菌涂层相关专利很少。专利公布号CN101899700A采用超声-微弧氧化复合技术在钛或镁合金表面制备载银抗菌涂层。但是受制于微弧氧化工艺特点，基体材料形状受限。同时，镁合金表面微弧氧化陶瓷膜厚度较薄，且表面存在大量的微孔、裂纹，直接影响了膜层对镁基体腐蚀降解的保护性能。而本发明专利采用化学溶液沉积方法制备的钙磷盐层具有致密的膜层结构，有效抑制基体镁降解，同时表面微米尺度粗糙度的板状钙磷盐晶体形貌对促成骨有益。此外，专利公布号CN 103436874A公开了一种采用高温下银化合物热分解后银单质气相沉积技术在镁合金表面制备亚微米抗菌银颗粒，但存在主要问题和局限在于：(1)银颗粒直接与镁合金基体接触，由于镁和银电极电位差相差较大，易发生电偶腐蚀，加速镁基体降解甚至产生局部点蚀，会缩短植入物服役时间，同时由于镁降解产物(镁离子、氢氧根离子和氢气)的迅速大量生成还会影响生物相容性。(2)制备需要150～300℃高温条件，同时硝酸银化合物高温下分解会产生有毒气体氮氧化物。(3)受气相沉积制备方法限制，较适用于简单平整表面的银颗粒沉积，不适合应用于多孔的复杂结构镁基体。
发明内容
本发明的目的在于针对现有技术存在的上述不足，提供一种组织工程用三维多孔镁及镁合金钙磷载纳米金属(银、锌、铜)化合物抗菌生物活性涂层及其制备方法。本发明制备的生物活性钙磷载纳米金属(银、锌、铜)化合物抗菌生物活性涂层方法，具体是指在组织工程用三维多孔镁及镁合金材料表面沉积生物活性钙磷涂层及在生物活性钙磷涂层表面继续反应生成纳米金属(银、锌、铜)化合物抗菌生物活性涂层的制备方法。本发明解决了目前多孔镁及镁合金材料无法有效抗菌的问题，在多孔镁及镁合金材料表面制备生物活性钙磷载纳米金属(银、锌、铜)化合物抗菌生物活性涂层，既显著降低了基体多孔镁及镁合金在体液中的腐蚀速率(腐蚀速率降低30～70％)，还提高了基体的表面生物活性可促进成骨及成血管，同时具有缓释银离子和优异的广谱杀菌抗炎症性能；操作工艺简便、易行，制备的涂层与基体结合力强，所载纳米金属(银、锌、铜)化合物表面密度可调。
本发明是通过以下技术方案实现的：
第一方面，本发明提供了一种镁基组织工程材料抗菌涂层，其包括由内向外依次设置的生物活性钙磷涂层和抗菌纳米金属化合物颗粒。
所述镁基组织工程材料为由镁或镁合金制备的骨组织工程支架等骨修复相关的内固定物或填充物。其中的镁为纯镁，所述镁合金为Mg-Al系、Mg-Zn系、Mg-Ca系、Mg-Mn系或Mg-RE系等未经任何改性处理的裸金属镁合金系列。
作为优选方案，所述生物活性钙磷涂层的厚度为200～500nm，所述抗菌纳米金属化合物颗粒的粒径为0.05～1μm。
作为优选方案，所述金属化合物包括银化合物、铜化合物或锌化合物。
第二方面，本发明还提供了一种如前述的镁基组织工程材料中的抗菌涂层的制备方法，其包括如下步骤：
S1：将镁基组织工程材料在含磷酸钙盐的溶液中恒温浸泡，在镁基组织工程材料表面形成生物活性钙磷涂层；
S2：转至金属化合物溶液中恒温浸泡，在所述生物活性钙磷涂层表面生成抗菌纳米金属化合物颗粒。
作为优选方案，步骤S1中所述生物活性钙磷涂层的成分包括透钙磷石、磷酸三钙、磷酸八钙和羟基磷灰石中的至少一种。
作为优选方案，步骤S1中所述的含磷酸钙盐的溶液为含有磷酸钙盐和无机碱的水溶液或含有钙盐和磷酸盐的水溶液，所述含有磷酸钙盐和无机碱的水溶液中，磷酸钙盐的重量份数为7～9份，所述无机碱的重量份数为1～3份；所述含有钙盐和磷酸盐的水溶液，钙盐的重量份数为5～7份，磷酸盐的重量份数为3～5份。
作为优选方案，所述含有磷酸钙盐和无机碱的水溶液中，磷酸钙盐选自磷酸钙、磷酸一氢钙和磷酸二氢钙中的至少一种；所述无机碱选自氢氧化钠、氢氧化钾和氨水中的至少一种。
作为进一步优选方案，所述含磷酸钙盐的溶液具体为如下任一配方：
a)Ca(NO3)2：(NH4)2HPO4＝6.75:3.25(wt.％)；
b)Ca(NO3)2：(NH4)2HPO4＝6.2:3.8(wt.％)；
c)Ca(NO3)2：(NH4)2HPO4＝6.5:3.5(wt.％)；
d)Ca3(PO4)2：NaOH＝7:3(wt.％)；
e)CaHPO4：NaOH＝8:2(wt.％)；
f)Ca(H2PO4)2：NaOH＝9:1(wt.％)；
作为优选方案，所述含有钙盐和磷酸盐的水溶液中，钙盐选自磷酸钙、磷酸一氢钙、磷酸二氢钙、氯化钙和硝酸钙中的至少一种；磷酸盐选自磷酸二氢铵、磷酸氢二铵、磷酸氢二钠和磷酸二氢钠中的至少一种。
作为优选方案，步骤S2中所述的恒温浸泡是通过在4～50℃下的动态浸泡实现的。
作为优选方案，步骤S2中所述的所述金属化合物浓度为0.02mM～50mM；所述金属化合物为银化合物、锌化合物和铜化合物中的至少一种，所述银化合物为银氨溶液、硝酸银和氯酸银溶液中的一种或多种，所述锌化合物为硫酸锌、硝酸锌、溴化锌、氯酸锌、氯化锌和碘化锌中的一种或多种，所述铜化合物为溴化铜、高氯酸铜、氯酸铜、氯化铜、硝酸铜和硫酸铜中的一种或多种。
本发明的基本原理为：通常，活性金属释放涂层的制备有两种方法，一种是直接掺杂活性金属纳米颗粒或金属化合物，另一种是在材料表面原位还原或沉积。将涂覆生物活性钙磷涂层多孔镁基工程材料浸没在包含一种或多种活性金属离子的可溶性盐溶液，采用原位沉淀法在多孔镁基钙磷涂层表面异相形核，生成均匀分布的不溶性金属化合物晶核，并长大成纳米至亚微米尺度的金属化合物颗粒，以达到载金属(银、锌、铜)的目的。
含活性金属(银、锌、铜)离子可溶性盐与生物活性钙磷涂层反应原位生成纳米金属(银、锌、铜)化合物抗菌层，其化学反应方程式可表达为：
MX+CaHPO4·2H2O→MPO4↓+Ca2++X-+H++2H2O
2MX+Ca3(PO4)2→2MPO4↓+3Ca2++2X-
6MX+Ca8(HPO4)2(PO4)4·5H2O→6MPO4↓+8Ca2++6X-+2H++5H2O
6MX+Ca10(PO4)6(OH)2→6MPO4↓+10Ca2++6X-+2OH-
其中，M为金属(银、锌、铜)，MX为金属可溶性盐，MPO4为纳米金属(银、锌、铜)化合物。
因此，本发明专利采用低温化学溶液沉积方法，可在复杂结构的多孔镁合金表面制备一层钙磷载纳米金属(银、锌、铜)化合物抗菌涂层，内层生物活性钙磷涂层显著提高基体的耐蚀性，提高基体的生物活性，同时外层载纳米金属(银、锌、铜)化合物具备优异的抗菌性能，抗菌生物活性涂层的制备方法简便、易行，显示出该涂层的先进性。
与现有技术相比，本发明具有如下的有益效果：
1、本发明提出一种组织工程用三维多孔镁及镁合金具备表面生物活性及抗菌特性的涂层，该涂层由生物活性钙磷涂层和载纳米金属(银、锌、铜)化合物颗粒组成；
2、本发明解决了目前多孔镁及镁合金在植入时或植入后无法有效抗菌的问题，在多孔镁及镁合金表面制备生物活性钙磷载抗菌纳米金属(银、锌、铜)化合物颗粒，既显著降低了基体多孔镁及镁合金在体液中的腐蚀速率，还提高了基体的表面生物活性可促进成骨及成血管，同时具有缓释金属(银、锌、铜)离子和优异的杀菌抗炎症性能，解决多孔镁及镁合金植入物细菌感染问题；
3、本发明可通过改变生物活性钙磷涂层厚度和钙磷涂层表面载纳米金属(银、锌、铜)化合物表面密度来调节多孔镁及镁合金的降解速率及金属(银、锌、铜)离子释放量；
4、本发明工艺简便、易操作，成本低；
5、本发明适用范围广，适用于目前所有的镁及镁合金。
附图说明
通过阅读参照以下附图对非限制性实施例所作的详细描述，本发明的其它特征、目的和优点将会变得更明显：
图1为组织工程用三维多孔纯镁表面钙磷载纳米银化合物抗菌生物活性涂层的SEM照片；
图2为多孔纯镁表面制备的钙磷载纳米银化合物抗菌生物活性涂层的XRD衍射图谱；
图3为优化工艺下得到的多孔纯镁表面制备的钙磷载纳米银化合物抗菌生物活性涂层表面形貌、EDS元素分布及银离子释放曲线；
图4为优化工艺下得到的多孔AZ31镁合金表面制备的钙磷载纳米铜化合物抗菌生物活性涂层表面的成骨细胞粘附SEM图；
图5为优化工艺下得到的多孔Mg-Nd-Zn-Zr镁合金表面制备的钙磷载纳米锌化合物抗菌生物活性涂层的杀菌率实验结果照片，分别选用金黄色葡萄球菌和表皮葡萄球菌评价抗菌效果。
具体实施方式
下面结合具体实施例对本发明进行详细说明。以下实施例将有助于本领域的技术人员进一步理解本发明，但不以任何形式限制本发明。应当指出的是，对本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进。这些都属于本发明的保护范围。
实施例1
在组织工程用多孔纯镁表面制备用于抗菌的生物活性钙磷载纳米银化合物抗菌生物活性涂层，其结构见附图1。制备时，首先将多孔纯镁制作成
的试样，用无水乙醇和丙酮分别超声清洗5min，吹干。将试样放入CaHPO4:NaOH＝8:2(wt.％)的溶液中水浴恒温(20℃)浸泡48h，取出后用超纯水清洗两次，吹干。将涂覆钙磷涂层的多孔纯镁样品浸没在0.1mM的氯酸银溶液避光反应6小时，取出后用超纯水清洗两次，吹干，即可得到用于抗菌的生物活性钙磷载纳米银化合物涂层。扫描电镜观察到Ca-P涂层厚度约为50μm，Ca/P原子比为1.2:1，载纳米银化合物涂层为弥散分布的银基纳米颗粒，粒径为300～800nm，进一步XRD检测显示该钙磷涂层为透钙磷石，银基纳米颗粒的成分为磷酸银(附图2)。抗菌涂层表面是由粒径为300～800nm的颗粒组成，EDS元素分布结果表明抗菌涂层表面载有0.46at.％的银元素(附图3)。浸没实验结果表明生物活性钙磷载纳米银化合物涂层显著提高了基体的耐蚀性(腐蚀速率降低约70％)。银离子释放实验结果表明，钙磷载纳米银化合物抗菌涂层的银离子释放缓慢可控(附图3)。
实施例2
在多孔AZ31(Mg-Al系)合金表面制备生物活性钙磷载纳米铜化合物抗菌生物活性涂层。首先将多孔AZ31镁合金制作成
的试样，用无水乙醇和丙酮分别超声清洗10min，吹干。将试样放入Ca(H2PO4)2:NaOH＝9:1(wt.％)的溶液中在25℃浸泡10h，取出后用超纯水清洗两次，吹干，得到钙磷涂层。将涂覆钙磷涂层的多孔AZ31合金样品浸没在0.8mM的硝酸铜溶液避光超声反应3小时，取出后用超纯水清洗两次，吹干，即可得到用于抗菌的生物活性钙磷载纳米铜化合物涂层。扫描电镜观察到Ca-P涂层厚度约为20μm，Ca/P原子比为1:1，载纳米铜化合物涂层为弥散分布的磷酸铜纳米颗粒，粒径为200～400nm。浸没实验结果表明生物活性钙磷载纳米铜化合物涂层显著降低了基体的腐蚀速率(腐蚀速率降低约45％)。采用MC3T3-E1成骨细胞评价钙磷载纳米铜化合物涂层的生物相容性，SEM观察到多孔AZ31合金抗菌涂层表面粘附有大量的成骨细胞(附图4)，载纳米铜化合物涂层对成骨细胞的铺展、粘附和增殖具有促进作用。
实施例3
在多孔Mg-Nd-Zn-Zr合金表面制备用于抗菌的生物活性钙磷载纳米锌化合物涂层。将多孔Mg-Nd-Zn-Zr镁合金制作成
的试样，用无水乙醇和丙酮分别超声清洗10min，吹干。将试样放在20％HF溶液中水浴恒温(20℃)浸泡8h，先后用去离子水、无水乙醇清洗，吹干。然后将氟化处理过的试样放入Ca(NO3)2：(NH4)2HPO4＝6.2:3.8(wt.％)的溶液中在4℃浸泡6h，取出后用超纯水清洗两次，吹干，得到生物活性钙磷复合涂层。将涂覆钙磷涂层的多孔Mg-Nd-Zn-Zr合金浸没在5.0mM的硝酸锌溶液避光振荡反应10分钟，取出后用超纯水清洗两次，吹干，即可得到用于抗菌的生物活性钙磷载纳米锌化合物涂层。扫描电镜观察到Ca-P涂层厚度约为6μm，Ca/P原子比为1.33：1，载纳米锌化合物涂层为弥散分布的磷酸锌纳米颗粒，粒径为300～600nm。浸没实验结果表明生物活性钙磷载纳米锌化合物涂层显著提高了基体的耐蚀性(腐蚀速率降低约35％)。采用金黄色葡萄球菌和表皮葡萄球菌评价制备涂层的抗菌性能，载纳米锌化合物抗菌涂层杀菌率均达到了99.9％以上(附图5)。该抗菌涂层的成骨细胞毒性在0-1级间,满足细胞相容性要求。
实施例4
在多孔ZK60(Mg-Zn系)合金表面制备生物活性钙磷载纳米银化合物抗菌生物活性涂层。首先将多孔ZK60镁合金制作成
的试样，用无水乙醇和丙酮分别超声清洗5min，吹干。将试样放入Ca(NO3)2：(NH4)2HPO4＝6.75:3.25(wt.％)的溶液中在20℃浸泡24h，取出后用超纯水清洗两次，吹干，得到生物活性钙磷涂层。将涂覆钙磷涂层的多孔ZK60合金浸没在2.0mM的硝酸银混合溶液避光静置反应30分钟，取出后用超纯水清洗两次，吹干，即可得到用于抗菌的生物活性钙磷载纳米银化合物涂层。扫描电镜观察到Ca-P涂层厚度为40μm，Ca/P原子比为1.67：1，载纳米银化合物抗菌涂层为弥散分布的磷酸银纳米颗粒，粒径为200～500nm。析氢实验结果表明生物活性钙磷载纳米银化合物涂层显著提高了基体的耐蚀性(腐蚀速率降低约55％)。该抗菌涂层的细胞毒性在0-1级间,满足细胞相容性要求。采用大肠杆菌评价其抗菌性能，结果表明制备的抗菌涂层对大肠杆菌的杀菌率达到了99.9％以上。SD大鼠体内植入实验结果表明，多孔Mg-Nd-Zn-Zr合金钙磷载纳米银化合物抗菌涂层不仅具有优异的广谱杀菌性能，还可以促进成骨和成血管。
以上对本发明的具体实施例进行了描述。需要理解的是，本发明并不局限于上述特定实施方式，本领域技术人员可以在权利要求的范围内做出各种变形或修改，这并不影响本发明的实质内容。
Claims (3)
1.一种镁基组织工程材料抗菌涂层，其特征在于，包括由内向外依次设置的生物活性钙磷涂层和抗菌纳米金属化合物颗粒；所述生物活性钙磷涂层的成分为透钙磷石；
所述的镁基组织工程材料中的抗菌涂层的制备方法，包括如下步骤：
S1：将镁基组织工程材料在含磷酸钙盐的溶液中恒温浸泡，在镁基组织工程材料表面形成生物活性钙磷涂层；以含磷酸钙盐的溶液的总质量计，所述的含磷酸钙盐的溶液具体配方为：CaHPO4：NaOH =8:2；
S2：转至金属化合物溶液中恒温浸泡，在所述生物活性钙磷涂层表面生成抗菌纳米金属化合物颗粒；所述金属化合物浓度为0.1mM~50mM；步骤S2中，所述的恒温浸泡是通过在4~50℃下的动态浸泡实现的；所述金属化合物为银化合物、锌化合物和铜化合物中的至少一种。
2.如权利要求1所述的镁基组织工程材料抗菌涂层，其特征在于，所述生物活性钙磷涂层的厚度为200~500nm，所述抗菌纳米金属化合物颗粒的粒径为0.05~1μm。
3.如权利要求1所述的镁基组织工程材料抗菌涂层，其特征在于，所述银化合物为银氨溶液、硝酸银和氯酸银中的一种或多种，所述锌化合物为硫酸锌、硝酸锌、溴化锌、氯酸锌、氯化锌和碘化锌中的一种或多种，所述铜化合物为溴化铜、高氯酸铜、氯酸铜、氯化铜、硝酸铜和硫酸铜中的一种或多种。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710349726.XA CN108939155B (zh) | 2017-05-17 | 2017-05-17 | 一种镁基组织工程材料抗菌涂层及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710349726.XA CN108939155B (zh) | 2017-05-17 | 2017-05-17 | 一种镁基组织工程材料抗菌涂层及其制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108939155A CN108939155A (zh) | 2018-12-07 |
| CN108939155B true CN108939155B (zh) | 2021-09-28 |
Family
ID=64461742
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710349726.XA Active CN108939155B (zh) | 2017-05-17 | 2017-05-17 | 一种镁基组织工程材料抗菌涂层及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108939155B (zh) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109913922A (zh) * | 2019-03-15 | 2019-06-21 | 石狮市星火铝制品有限公司 | 用于抗菌镁铝合金微弧氧化的电解液、抗菌镁铝合金及其制备方法 |
| CN111359009B (zh) * | 2020-03-25 | 2022-06-24 | 天衍医疗器材有限公司 | 具有生物活性功能多孔钽植入物及加工工艺 |
| CN111686299A (zh) * | 2020-07-08 | 2020-09-22 | 东莞理工学院 | 一种医用镁合金及其制备方法与应用 |
| CN113648467B (zh) * | 2021-08-05 | 2022-08-23 | 百思博睿医疗科技(苏州)有限公司 | 一种双面异构可降解金属膜及其制备方法 |
| CN114369808B (zh) * | 2021-12-20 | 2024-02-06 | 中国兵器科学研究院宁波分院 | 一种镁及镁合金表面制备抗菌涂层的方法 |
| CN116730746A (zh) * | 2023-05-05 | 2023-09-12 | 湖南鹏登精密陶瓷有限公司 | 一种氧化锆种植体材料及其表面涂层方法 |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1374132A (zh) * | 2002-03-22 | 2002-10-16 | 上海交通大学 | 羟基磷灰石与脂质体的核－壳式纳米复合粒子的制备方法 |
| CN101254314A (zh) * | 2007-03-02 | 2008-09-03 | 北京奥精医药科技有限公司 | 羟基磷灰石涂层镁合金医用内植入材料及其制备方法 |
| CN101264339A (zh) * | 2007-03-14 | 2008-09-17 | 北京奥精医药科技有限公司 | 镁合金骨外科内固定及植入材料 |
| CN102206819A (zh) * | 2011-04-07 | 2011-10-05 | 上海交通大学 | 骨内植物用镁合金表层制备生物活性钙-磷涂层的方法 |
| WO2012071014A1 (en) * | 2010-11-24 | 2012-05-31 | Nanyang Technological University | Method for coating particles with calcium phosphate and particles, microparticles and nanoparticles formed thereof |
| WO2014207754A1 (en) * | 2013-06-25 | 2014-12-31 | Council Of Scientific & Industrial Research | Reduced graphene oxide-silver phosphate (rgo-agp) and a process for the preparation thereof for the photodegradation of organic dyes |
| CN106110395A (zh) * | 2016-08-18 | 2016-11-16 | 陕西东望科贸有限公司 | 一种具有自修复、抗菌功效的骨修复支架及其制作方法 |
| CN106215958A (zh) * | 2016-07-22 | 2016-12-14 | 中北大学 | 一种可循环利用的光催化材料的制备方法 |
| WO2017025433A1 (en) * | 2015-08-11 | 2017-02-16 | Basf Se | Antimicrobial polymer |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102268711B (zh) * | 2011-06-22 | 2013-04-10 | 沈阳理工大学 | 一种在镁基材料表面制备生物复合涂层的方法 |
| US10426869B2 (en) * | 2014-05-05 | 2019-10-01 | The University Of Toledo | Biodegradable magnesium alloys and composites |
-
2017
- 2017-05-17 CN CN201710349726.XA patent/CN108939155B/zh active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1374132A (zh) * | 2002-03-22 | 2002-10-16 | 上海交通大学 | 羟基磷灰石与脂质体的核－壳式纳米复合粒子的制备方法 |
| CN101254314A (zh) * | 2007-03-02 | 2008-09-03 | 北京奥精医药科技有限公司 | 羟基磷灰石涂层镁合金医用内植入材料及其制备方法 |
| CN101264339A (zh) * | 2007-03-14 | 2008-09-17 | 北京奥精医药科技有限公司 | 镁合金骨外科内固定及植入材料 |
| WO2012071014A1 (en) * | 2010-11-24 | 2012-05-31 | Nanyang Technological University | Method for coating particles with calcium phosphate and particles, microparticles and nanoparticles formed thereof |
| CN102206819A (zh) * | 2011-04-07 | 2011-10-05 | 上海交通大学 | 骨内植物用镁合金表层制备生物活性钙-磷涂层的方法 |
| WO2014207754A1 (en) * | 2013-06-25 | 2014-12-31 | Council Of Scientific & Industrial Research | Reduced graphene oxide-silver phosphate (rgo-agp) and a process for the preparation thereof for the photodegradation of organic dyes |
| WO2017025433A1 (en) * | 2015-08-11 | 2017-02-16 | Basf Se | Antimicrobial polymer |
| CN106215958A (zh) * | 2016-07-22 | 2016-12-14 | 中北大学 | 一种可循环利用的光催化材料的制备方法 |
| CN106110395A (zh) * | 2016-08-18 | 2016-11-16 | 陕西东望科贸有限公司 | 一种具有自修复、抗菌功效的骨修复支架及其制作方法 |
Non-Patent Citations (1)
| Title |
|---|
| Cytocompatible 3D chitosan/hydroxyapatite composites endowed with antibacterial properties: toward a self-sterilized bone tissue engineering scaffold;Yongjun Qiao等;《Sci. Bull.》;20150620;第60卷(第13期);第1194页第2.2-2.3节，第1201页第4节 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108939155A (zh) | 2018-12-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108939155B (zh) | 一种镁基组织工程材料抗菌涂层及其制备方法 | |
| Rahman et al. | HA coating on Mg alloys for biomedical applications: A review | |
| Dorozhkin | Calcium orthophosphate coatings on magnesium and its biodegradable alloys | |
| Tian et al. | Surface modification of biodegradable magnesium and its alloys for biomedical applications | |
| Huang et al. | Fabrication of silver-and strontium-doped hydroxyapatite/TiO2 nanotube bilayer coatings for enhancing bactericidal effect and osteoinductivity | |
| Huang et al. | Strontium and copper co-substituted hydroxyapatite-based coatings with improved antibacterial activity and cytocompatibility fabricated by electrodeposition | |
| Zhang et al. | Advances in hydroxyapatite coatings on biodegradable magnesium and its alloys | |
| Wu et al. | Surface design of biodegradable magnesium alloys—A review | |
| Ling et al. | Recent advances in hydrothermal modification of calcium phosphorus coating on magnesium alloy | |
| Huang et al. | Antibacterial efficacy, corrosion resistance, and cytotoxicity studies of copper-substituted carbonated hydroxyapatite coating on titanium substrate | |
| CA2716589C (en) | Coating and coating method for a medical implant | |
| Yan et al. | Preparation and characterization of chitosan-silver/hydroxyapatite composite coatings onTiO2 nanotube for biomedical applications | |
| Gray‐Munro et al. | The mechanism of deposition of calcium phosphate coatings from solution onto magnesium alloy AZ31 | |
| Yajing et al. | Magnesium substituted hydroxyapatite coating on titanium with nanotublar TiO2 intermediate layer via electrochemical deposition | |
| Ding et al. | In vitro cytocompatibility and corrosion resistance of zinc-doped hydroxyapatite coatings on a titanium substrate | |
| Huang et al. | A prospective material for orthopedic applications: Ti substrates coated with a composite coating of a titania-nanotubes layer and a silver-manganese-doped hydroxyapatite layer | |
| Zhao et al. | Ag-incorporated FHA coating on pure Mg: degradation and in vitro antibacterial properties | |
| Vranceanu et al. | In vitro evaluation of Ag doped hydroxyapatite coatings in acellular media | |
| EP0904421A1 (en) | Process for the preparation of hydroxyapatite coatings | |
| CN111973812B (zh) | 可降解镁基骨内植物表面具有生物活性、分级结构的羟基磷灰石涂层及制备方法 | |
| Park et al. | Bioactive calcium phosphate coating prepared on H2O2-treated titanium substrate by electrodeposition | |
| JP5757943B2 (ja) | 網状又は島状の低結晶水酸化アパタイトでコーティングされたインプラント及びそのコーティング方法 | |
| US20180289858A1 (en) | Bifunctional Bioactive Antibacterial Coatings, and Process for Coating Implant Surfaces Therewith | |
| US20200289710A1 (en) | Products of manufacture having enhanced biocompatibility and antibacterial properties and methods of making and using them | |
| CN112076348B (zh) | 一种医用金属表面抗感染-促进骨整合的涂层、制备方法及应用 |
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 | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20231107 Address after: 201306 Room 202, building 14, No. 600, Xinyuan South Road, Lingang xinpian District, China (Shanghai) pilot Free Trade Zone, Pudong New Area, Shanghai Patentee after: HUCHUANG MEDICAL TECHNOLOGY (SHANGHAI) CO.,LTD. Address before: 200240 No. 800, Dongchuan Road, Shanghai, Minhang District Patentee before: SHANGHAI JIAO TONG University |