CN111407928B - 载药硬组织修复植入体、包含该载药硬组织修复植入体的载药体系及该载药体系的制备方法 - Google Patents
载药硬组织修复植入体、包含该载药硬组织修复植入体的载药体系及该载药体系的制备方法 Download PDFInfo
- Publication number
- CN111407928B CN111407928B CN202010214029.5A CN202010214029A CN111407928B CN 111407928 B CN111407928 B CN 111407928B CN 202010214029 A CN202010214029 A CN 202010214029A CN 111407928 B CN111407928 B CN 111407928B
- Authority
- CN
- China
- Prior art keywords
- drug
- loaded
- ether
- ketone
- tissue repair
- 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.)
- Expired - Fee Related
Links
- 239000003814 drug Substances 0.000 title claims abstract description 66
- 229940079593 drug Drugs 0.000 title claims abstract description 54
- 239000007943 implant Substances 0.000 title claims abstract description 31
- 230000017423 tissue regeneration Effects 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims description 9
- 238000002513 implantation Methods 0.000 title description 3
- 239000004696 Poly ether ether ketone Substances 0.000 claims abstract description 53
- 229920002530 polyetherether ketone Polymers 0.000 claims abstract description 53
- 239000000463 material Substances 0.000 claims abstract description 41
- 239000002184 metal Substances 0.000 claims abstract description 7
- 239000000758 substrate Substances 0.000 claims abstract description 5
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 28
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 23
- 229960002855 simvastatin Drugs 0.000 claims description 23
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 18
- 229960003638 dopamine Drugs 0.000 claims description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 239000000843 powder Substances 0.000 claims description 12
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 12
- 229910021536 Zeolite Inorganic materials 0.000 claims description 11
- 238000004140 cleaning Methods 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 11
- 239000010457 zeolite Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- -1 zeolite imidazole ester Chemical class 0.000 claims description 10
- 239000008367 deionised water Substances 0.000 claims description 9
- 229910021641 deionized water Inorganic materials 0.000 claims description 9
- 239000011259 mixed solution Substances 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 238000012377 drug delivery Methods 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 238000001132 ultrasonic dispersion Methods 0.000 claims description 5
- MCHZKGNHFPNZDP-UHFFFAOYSA-N 2-aminoethane-1,1,1-triol;hydrochloride Chemical compound Cl.NCC(O)(O)O MCHZKGNHFPNZDP-UHFFFAOYSA-N 0.000 claims description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 4
- 229940098773 bovine serum albumin Drugs 0.000 claims description 4
- 238000005530 etching Methods 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 2
- 239000013153 zeolitic imidazolate framework Substances 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 description 26
- 239000012621 metal-organic framework Substances 0.000 description 14
- 238000000576 coating method Methods 0.000 description 13
- 239000011248 coating agent Substances 0.000 description 12
- 239000002131 composite material Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000008439 repair process Effects 0.000 description 6
- 238000001878 scanning electron micrograph Methods 0.000 description 6
- 230000007547 defect Effects 0.000 description 5
- 238000009826 distribution Methods 0.000 description 5
- 239000002105 nanoparticle Substances 0.000 description 5
- 229920001690 polydopamine Polymers 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000011148 porous material Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 239000011664 nicotinic acid Substances 0.000 description 3
- 239000013110 organic ligand Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000011049 pearl Substances 0.000 description 3
- 229920002465 poly[5-(4-benzoylphenoxy)-2-hydroxybenzenesulfonic acid] polymer Polymers 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 238000004873 anchoring Methods 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical group OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 2
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 230000002188 osteogenic effect Effects 0.000 description 2
- 230000002138 osteoinductive effect Effects 0.000 description 2
- 235000015170 shellfish Nutrition 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- QNRATNLHPGXHMA-XZHTYLCXSA-N (r)-(6-ethoxyquinolin-4-yl)-[(2s,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]methanol;hydrochloride Chemical compound Cl.C([C@H]([C@H](C1)CC)C2)CN1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OCC)C=C21 QNRATNLHPGXHMA-XZHTYLCXSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000237536 Mytilus edulis Species 0.000 description 1
- 206010031256 Osteomyelitis chronic Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 241000490567 Pinctada Species 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 229910021417 amorphous silicon Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 150000002466 imines Chemical group 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 235000020638 mussel Nutrition 0.000 description 1
- 238000010883 osseointegration Methods 0.000 description 1
- 230000009818 osteogenic differentiation Effects 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change 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
- 229920000642 polymer Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 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 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 238000005406 washing Methods 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
- A61L27/50—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
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
-
- 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
-
- 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
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
-
- 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
-
- 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
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
- A61L2300/624—Nanocapsules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明公开了一种载药硬组织修复植入体，载药硬组织修复植入体为将负载有药物的金属框架材料包埋式的结合到多孔聚醚醚酮基底材料表面所得。
Description
技术领域
本发明涉及人工仿生骨技术领域，具体涉及一种金属有机框架材料-聚醚醚酮包埋式复合的载药硬组织修复植入体、包含该载药硬组织修复植入体的载药体系及该载药体系的制备方法。
背景技术
骨骼缺损在临床中颇为常见，主要病因包括先天性骨异常、慢性骨髓炎、恶性肿瘤切除以及意外事故引起的创伤等。临床上有限骨缺损的治疗可采用植骨以修补缺陷，通常较为理想的植入材料是自体骨或同种异体骨，但当骨缺损长度达骨干直径的1.5倍时将超过骨骼自体修复的临界状态，极易出现骨吸收和不愈合情况致使植骨手术失败，同时两类骨源有限，并不可避免地对病人造成二次伤害，增加了病人的经济负担和生命安全风险。因此，为解决上述临床问题，开发人工仿生骨替代自体骨和异体骨是目前生物医用材料领域内的重要研究课题之一。
聚醚醚酮(PEEK)是目前人造骨修复材料领域的研究热点，其优异的热塑性、力学性能和生物相容性等特性，满足了骨植入体的基本性能要求。与已投入临床应用的金属类人工骨相比，PEEK具有与人体骨骼更为相近的弹性模量，能有效避免由应力屏蔽引起的骨质疏松、骨吸收和植入体脱落等情况。此外，PEEK还具有优异的射线可透性和磁共振成像兼容性，便于观察周围骨组织的修复和重建情况。并且医用级PEEK已被美国食品与药品管理局(FDA)认证为“最佳长期骨移值材料”。但PEEK是一种不可降解的生物惰性聚合物，在体内的PEEK植入物周围会形成纤维包装，影响骨整合性能，这限制了PEEK人工骨在临床中的使用。
针对PEEK固有的生物惰性，国内外相继开发出多种改性技术，包括硫酸酸蚀(磺化)、等离子体喷射、紫外/臭氧处理等表面修饰技术，掺杂羟基磷灰石、磷酸三钙、非晶硅等物质的复合改性方式。上述改性技术不仅可赋予PEEK良好的生物活性、抗菌性和骨整合等特性，而且改性后生成的三维拓扑表面结构也有利于相关成骨活性药物或生物分子的吸附与递送，达到药物协同治疗的效用，以满足实际临床应用中缩短骨修复时间和增加骨总量的需要。
然而，在人工PEEK基载药材料的研究中，为保持植入体能够长期并有效的发挥成骨诱导性和成骨传导性，药物/生物分子的高效负载、可控释放以及活性保持是亟待解决的科学性、技术性难题。现有的研究成果主要是利用PEEK改性表面的孔隙结构或附加涂层的方法对活性物质进行负载，这些方法或多或少存在着上述应着重考虑的问题，最终增加骨植入手术失败的风险。
聚多巴胺由于富含邻苯二酚(儿茶酚)、胺及亚胺等官能团，得益于此，可将其用作多功能粘合剂应用于PEEK基表面涂覆工程。聚多巴胺涂层虽然能够促进成骨前体细胞在生物材料表面的粘附以及之后的成骨分化，但是聚多巴胺涂层若由于外界干扰或在体内存留时间过长等原因使其从基材表面发生脱落，产生的多巴胺碎片反而会在局部引发细胞凋亡以及炎症反应，这对植入体周围组织的重建造成了极大的障碍。
金属有机框架材料(MOF)大多具有极高的比表面积和孔隙率，并且可以通过控制其组成的金属节点和有机配体的种类来调节孔隙率、孔道性质以及整体的结构和功能性，这种复杂且可调的空间网络结构和表面易功能化不仅为药物或生物分子提供丰富的空间位置，从而大大增加了载药效率并保持包封物质的活性，并且可以轻易赋予MOF材料良好的生物相容性、稳定性以及环境敏感性等特殊功能，因此将MOF设计为独立的药物负载系统用于骨修复材料是一种完全可行的办法。但大多数MOF在水环境中通常会由于水分子对金属-有机配位键的“攻击”作用而发生解离，这就会造成在植入体周围短时间内富集有大量金属离子、有机配体以及释放出来的活性物质，这也会对表面粘附细胞和组织的生长造成不利影响。
发明内容
本发明的目的在于提供一种载药硬组织修复植入体、包含该载药硬组织修复植入体的载药体系及该载药体系的制备方法，解决现有技术中的问题。
为了实现上述目的，本发明采用的技术手段如下所述：
一种载药硬组织修复植入体，载药硬组织修复植入体为将负载有药物的金属框架材料包埋式的结合到多孔聚醚醚酮基底材料表面所得。
作为一种优选方式，金属框架材料为沸石咪唑脂框架材料。
作为一种优选方式，聚醚醚酮为表面三维拓扑结构的磺化聚醚醚酮。
作为一种优选方式，磺化聚醚醚酮，其制备包括以下过程：分别用丙酮、去离子水和乙醇在超声条件下对聚醚醚酮片进行清洗，在超声条件下将聚醚醚酮片置于硫酸中酸蚀，并用丙酮和去离子水各清洗得到表面呈三维网络结构的磺化聚醚醚酮。
作为一种优选方式，该载药硬组织修复植入体的制备方法，包括以下过程：将沸石咪唑脂框架材料溶于三羟甲基氨基甲烷-盐酸水溶液，并进行超声分散后加入多巴胺粉末；将磺化聚醚醚酮片置于上述加入多巴胺粉末的混合液中、震荡、超声清洗、干燥得到所述该植入体。
一种载药体系，该载药体系包含权利要求上述任一项所述的载药硬组织修复植入体及该载药硬组织修复植入体负载的药物。
作为一种优选方式，药物负载在沸石咪唑脂框架材料上。
作为一种优选方式，药物为辛伐他汀。
一种制备上述载药体系的方法，该方法包括以下步骤：
S1:将沸石咪唑脂框架材料与药物在PBS和牛血清白蛋白的混合溶液中超声分散、搅拌离心、固液分离、干燥，得到负载药物的沸石咪唑脂框架材料；
S2：将负载药物的沸石咪唑脂框架材料溶于三羟甲基氨基甲烷-盐酸水溶液，并进行超声分散后加入多巴胺粉末；将磺化聚醚醚酮片置于上述加入多巴胺粉末的混合液中、震荡、超声清洗、干燥得到所述该植入体。
本发明与现有技术相比，其有益效果为：
本发明受贻贝分泌黏附蛋白，以及珍珠贝类和珠母贝类在遭到外源性物质、寄生虫和组织病变等刺激时启动自身防御机制从而在外套膜与外壳之间产生珍珠的两类自然现象所启发，设想通过不依赖于材料且易于制备的聚多巴胺涂层策略将MOF包埋式的结合到多孔PEEK基底材料表面。这种仿生的表面结构不仅能实现MOF中负载户型物质可控性的持续释放，同时涂层能够降低由MOF分解在短时间内富集的金属离子以及有机配体分子对周围组织和细胞有害影响，并且MOF纳米颗粒的引入能够起到将聚多巴胺涂层锚固到多孔PEEK基材表面上的作用。
附图说明
图1为ZIF-8的形貌及及结构表征，图1(a)为ZIF-8的SEM图，图1(b)为ZIF-8的TEM图，图1(c)为ZIF-8的XDR表征，图1(d)为SIM、ZIF-8、SIM@ZIF-8的ζ电位图。
图2(a)为PEEK的SEM图、图2(b)为SPEEK的SEM图、图2(c)ZIF-8-PEEK的SEM图、图2(d)为SIM@ZIF-8-PEEK的SEM图。
图3(a)为C、O和Zn元素在ZIF-8-PEEK表面上的分布、图3(b)为C、O和Zn元素在SIM@ZIF-8-PEEK表面上的分布。
具体实施方式
本发明的目的在于克服现有技术的缺陷，提供金属有机框架材料-聚醚醚酮包埋式复合的载药硬组织修复植入体材料，下面结合实施例对本发明作进一步详细说明。
实施例
金属有机框架材料-聚醚醚酮包埋式复合的载药硬组织修复植入体材料，其制备方法包括以下过程：
第一，负载辛伐他汀的ZIF-8(SIM@ZIF-8)的合成，其合成步骤如下：
(1)ZIF-8(沸石咪唑酯骨架结构材料)的合成：称取0.585g的Zn(NO3)2·6H2O粉末溶解于4mL去离子水中(溶液I)，称量11.35g的2-甲基咪唑固体与40mL去离子水，磁力搅拌至完全溶解(溶液Ⅱ)，向溶液Ⅱ中加入6mL二甲亚砜(DMSO)，再将溶液I倒入上述混合液中，磁力搅拌5min，在120000rpm的转速下离心20min收集沉淀固体，并用乙醇和去离子水清洗交替洗涤三次，最后离心收集的固体在35℃下干燥过夜，得到ZIF-8白色晶体。
(2)负载辛伐他汀ZIF-8的合成：由于辛伐他汀为不溶于水的药物，因此本发明中涉及溶解辛伐他汀(SIM)药物的溶剂均为PBS添加2％DMSO和0.5％的牛血清白蛋白(BSA)配制而成的混合溶液(溶液Ⅲ)。称量ZIF-8粉末100mg，辛伐他汀50mg，置于100mL溶液Ⅲ中超声条件下分散5min，室温下磁力搅拌过夜，通过12000rpm离心30min分离固液，35℃下干燥过夜，得到负载辛伐他汀的ZIF-8(SIM@ZIF-8)。
图1(a)和(b)分别为ZIF-8样品的SEM和TEM图，合成的ZIF-8样品为粒径约190nm纳米颗粒，颗粒大多呈现出规则的菱形十二面体几何形貌，图1(c)中XRD图谱显示了在2θ＝7.27°、12.63°和17.96°处分别对应于(011)、(112)和(222)晶面，并与ZIF-8基谱中特征峰位置基本一致。图1(d)中Zeta电位表明带负电的辛伐他汀药物会通过静电作用被带正电的ZIF-8吸附。ZIF-8按技术方案对药物(辛伐他汀)进行负载，ZIF-8的多孔结构赋予了其优秀的载药能力，并且可对药物实现有效封装，起到保护药物免受外界干扰从而维持药物活性的作用，另一方面，载药体系与药物之间通过静电吸引作用进行结合，可以实现药物的可控、缓慢和持续性的释放，另外ZIF-8的孔隙结构也具有该种效果。
第二，金属有机框架(ZIF-8)-聚醚醚酮(PEEK)包埋式复合的载药植入材料的合成，其合成步骤如下：
(1)PEEK表面三维拓扑结构的构建：定制尺寸2mm×8mm的PEEK片，分别用丙酮、去离子水和乙醇在超声条件下各清洗20min，60℃下干燥30min。在超声条件下将PEEK片置于98％硫酸中酸蚀5min，并用丙酮和去离子水各清洗20min，60℃下干燥30min，得到表面呈三维网络结构的磺化PEEK(SPEEK)。
(2)包埋式ZIF-8-SPEEK复合材料的合成：称量ZIF-8或SIM@ZIF-8样品溶于Tris(三羟甲基氨基甲烷)-HCl水溶液(1.21mg/mL，pH＝8.5)中超声分散5min，使其浓度为300μg/mL，再向其中加入多巴胺粉末，使其浓度为2mg/mL。将SPEEK片置于48孔板中，每孔加入500μL上述Tris-HCl混合液，置于37℃水平震荡24h，超声清洗5min，35℃下干燥30min，得到包埋式ZIF-8-SPEEK复合材料以及SIM@ZIF-8-SPEEK复合载药材料。
从SEM图来看，如图2(b)所示，磺化PEEK表面形成的三维多孔拓扑结构有利于本发明中进一步修饰多巴胺涂层。进一步的，如图2(c)、(d)所示，形成的ZIF-8-PEEK和SIM@ZIF-8-PEEK从表面看到分布有大量纳米颗粒，根据元素分布分析，分别如图3(a)、(b)所示。得知纳米颗粒均为被多巴胺涂层包裹的ZIF-8或SIM@ZIF-8颗粒，并且ZIF-8和SIM@ZIF-8不止分布于基材表面，在涂层内部呈现出三维分布的状态。这种类似于珍珠贝外套膜的仿生表面使SIM@ZIF-8中的药物不仅需要通过ZIF-8包封，而且还要通穿过多巴胺涂层的包裹，才能得以释放，这就能实现药物在体内进行缓慢、可控和持续性的释放，此外，由于在基材孔洞与涂层交界处的纳米颗粒可局部增强涂层与基材表面之间的附着力从而起到锚固的作用，可避免多巴胺出现大块脱落的情况。
按照上述实施例，便可很好地实现本发明。值得说明的是，基于上述结构设计的前提下，为解决同样的技术问题，即使在本发明上做出的一些无实质性的改动或润色，所采用的技术方案的实质仍然与本发明一样，故其也应当在本发明的保护范围内。
Claims (5)
1.一种载药硬组织修复植入体，其特征在于，载药硬组织修复植入体为将负载有药物的金属框架材料包埋式的结合到多孔聚醚醚酮基底材料表面所得；金属框架材料为沸石咪唑酯框架材料，聚醚醚酮为表面三维拓扑结构的磺化聚醚醚酮；磺化聚醚醚酮，其制备包括以下过程：
分别用丙酮、去离子水和乙醇在超声条件下对聚醚醚酮片进行清洗，在超声条件下将聚醚醚酮片置于硫酸中酸蚀，并用丙酮和去离子水各清洗得到表面呈三维网络结构的磺化聚醚醚酮；该载药硬组织修复植入体的制备方法，包括以下过程：将沸石咪唑酯框架材料溶于三羟甲基氨基甲烷-盐酸水溶液，并进行超声分散后加入多巴胺粉末；将磺化聚醚醚酮片置于上述加入多巴胺粉末的混合液中、震荡、超声清洗、干燥得到所述该植入体。
2.一种载药体系，其特征在于，该载药体系包含权利要求1所述的载药硬组织修复植入体及该载药硬组织修复植入体负载的药物。
3.根据权利要求2所述的一种载药体系，其特征在于，药物负载在沸石咪唑酯框架材料上。
4.根据权利要求3所述的一种载药体系，其特征在于，药物为辛伐他汀。
5.一种制备权利要求2~4所述的载药体系的方法，其特征在于，该方法包括以下步骤：
S1:将沸石咪唑酯框架材料与药物在PBS和牛血清白蛋白的混合溶液中超声分散、搅拌离心、固液分离、干燥，得到负载药物的沸石咪唑酯框架材料；
S2：将负载药物的沸石咪唑酯框架材料溶于三羟甲基氨基甲烷-盐酸水溶液，并进行超声分散后加入多巴胺粉末；将磺化聚醚醚酮片置于上述加入多巴胺粉末的混合液中、震荡、超声清洗、干燥得到所述该植入体。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010214029.5A CN111407928B (zh) | 2020-03-24 | 2020-03-24 | 载药硬组织修复植入体、包含该载药硬组织修复植入体的载药体系及该载药体系的制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010214029.5A CN111407928B (zh) | 2020-03-24 | 2020-03-24 | 载药硬组织修复植入体、包含该载药硬组织修复植入体的载药体系及该载药体系的制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111407928A CN111407928A (zh) | 2020-07-14 |
| CN111407928B true CN111407928B (zh) | 2022-01-14 |
Family
ID=71486312
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010214029.5A Expired - Fee Related CN111407928B (zh) | 2020-03-24 | 2020-03-24 | 载药硬组织修复植入体、包含该载药硬组织修复植入体的载药体系及该载药体系的制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111407928B (zh) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112876724B (zh) * | 2021-01-28 | 2021-11-19 | 吉林大学 | 含促进成骨药物的聚醚醚酮复合材料及其制备方法和应用 |
| CN113171492B (zh) * | 2021-05-21 | 2022-04-29 | 四川大学 | 一种骨缺损修复材料及其制备方法和应用 |
| CN113679891B (zh) * | 2021-05-21 | 2022-08-30 | 四川大学 | 一种zif-8载药水凝胶促成骨支架、制备方法及应用 |
| CN113908340B (zh) * | 2021-11-03 | 2023-01-03 | 广州医科大学附属第三医院（广州重症孕产妇救治中心、广州柔济医院） | 一种用紫胶混合溶液改性医用聚醚醚酮材料的制备方法 |
| CN115581804B (zh) * | 2022-09-21 | 2023-08-29 | 南方科技大学 | 一种金属有机骨架改性的聚醚醚酮骨移植材料及其制备方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110279890A (zh) * | 2019-04-15 | 2019-09-27 | 首都医科大学附属北京世纪坛医院 | 基于脂质体的地塞米松/米诺环素在peek表面的修饰方法及应用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9375678B2 (en) * | 2012-05-25 | 2016-06-28 | Georgia Tech Research Corporation | Metal-organic framework supported on porous polymer |
| US9694344B2 (en) * | 2016-05-02 | 2017-07-04 | LiSo Plastics, L.L.C. | Multilayer polymeric membrane and process |
| CN106188590B (zh) * | 2016-07-14 | 2020-04-24 | 复旦大学 | 金属有机骨架结构改性的聚合物杂化质子交换膜及其制备方法 |
-
2020
- 2020-03-24 CN CN202010214029.5A patent/CN111407928B/zh not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110279890A (zh) * | 2019-04-15 | 2019-09-27 | 首都医科大学附属北京世纪坛医院 | 基于脂质体的地塞米松/米诺环素在peek表面的修饰方法及应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111407928A (zh) | 2020-07-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111407928B (zh) | 载药硬组织修复植入体、包含该载药硬组织修复植入体的载药体系及该载药体系的制备方法 | |
| Chao et al. | Preparation and characterization of gelatin–hydroxyapatite composite microspheres for hard tissue repair | |
| Jiang et al. | Bioinspired adhesive and tumor microenvironment responsive nanoMOFs assembled 3D-printed scaffold for anti-tumor therapy and bone regeneration | |
| Chen et al. | Osteogenic activity and antibacterial effect of porous titanium modified with metal‐organic framework films | |
| Volpato et al. | Preservation of FGF-2 bioactivity using heparin-based nanoparticles, and their delivery from electrospun chitosan fibers | |
| WO2018072679A1 (zh) | 一种仿生生物矿化人工骨修复材料及其制备方法与应用 | |
| Dorozhkin | Functionalized calcium orthophosphates (CaPO 4) and their biomedical applications | |
| Nga et al. | Enhanced biomineralization and protein adsorption capacity of 3D chitosan/hydroxyapatite biomimetic scaffolds applied for bone-tissue engineering | |
| US11471561B2 (en) | Injectable composite material for bone repair, and preparation method thereof | |
| CN103495210B (zh) | 壳聚糖-羟基磷灰石原位负载淫羊藿苷复合微球 | |
| Le Ray et al. | Vancomycin encapsulation in biodegradable poly (ε-caprolactone) microparticles for bone implantation. Influence of the formulation process on size, drug loading, in vitro release and cytocompatibility | |
| Chen et al. | In vivo degradation and bone response of a composite coating on Mg–Zn–Ca alloy prepared by microarc oxidation and electrochemical deposition | |
| Paris et al. | Fabrication of a nanoparticle-containing 3D porous bone scaffold with proangiogenic and antibacterial properties | |
| US6752938B2 (en) | Method of preparing microsphere composite of collagen and bioceramic powder | |
| Jia et al. | Constructing multilayer silk protein/Nanosilver biofunctionalized hierarchically structured 3D printed Ti6Al4 V scaffold for repair of infective bone defects | |
| CN104906637B (zh) | 一种可注射‑多孔‑载药的聚甲基丙烯酸甲酯基复合支架骨移植材料及其制备方法 | |
| Han et al. | Application of biomolecules modification strategies on PEEK and its composites for osteogenesis and antibacterial properties | |
| KR101105285B1 (ko) | 다공성 마이크로스피어 및 이의 제조방법 | |
| Wang et al. | Porous surface with fusion peptides embedded in strontium titanate nanotubes elevates osteogenic and antibacterial activity of additively manufactured titanium alloy | |
| Tian et al. | Chitosan-based biomaterial scaffolds for the repair of infected bone defects | |
| Kolanthai et al. | Effect of solvent; enhancing the wettability and engineering the porous structure of a calcium phosphate/agarose composite for drug delivery | |
| CN109395175B (zh) | 引导组织再生膜及其制备方法 | |
| Patil et al. | Preparation and characterization of HAp coated chitosan‐alginate PEC porous scaffold for bone tissue engineering | |
| WO2015167045A1 (ko) | 기능성 인자를 함유하는 나노 스캐폴드 및 이의 제조방법 | |
| CN111265716A (zh) | 一种骨材表面原位修饰金属有机框架的方法及其骨修复应用 |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20220114 |