CN110251279B - 一种磷酸钙骨水泥涂覆的3d打印plga椎间融合器的制备方法 - Google Patents
一种磷酸钙骨水泥涂覆的3d打印plga椎间融合器的制备方法 Download PDFInfo
- Publication number
- CN110251279B CN110251279B CN201910645597.8A CN201910645597A CN110251279B CN 110251279 B CN110251279 B CN 110251279B CN 201910645597 A CN201910645597 A CN 201910645597A CN 110251279 B CN110251279 B CN 110251279B
- Authority
- CN
- China
- Prior art keywords
- plga
- fusion cage
- interbody fusion
- calcium phosphate
- printing
- 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
- 230000004927 fusion Effects 0.000 title claims abstract description 83
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 title claims abstract description 62
- 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 title claims abstract description 57
- 239000001506 calcium phosphate Substances 0.000 title claims abstract description 40
- 229910000389 calcium phosphate Inorganic materials 0.000 title claims abstract description 40
- 235000011010 calcium phosphates Nutrition 0.000 title claims abstract description 40
- 239000004568 cement Substances 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 238000007639 printing Methods 0.000 claims abstract description 43
- 238000010146 3D printing Methods 0.000 claims abstract description 20
- 239000011248 coating agent Substances 0.000 claims abstract description 16
- 238000000576 coating method Methods 0.000 claims abstract description 16
- 238000005516 engineering process Methods 0.000 claims abstract description 10
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims abstract description 10
- 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 claims abstract description 10
- 229920000728 polyester Polymers 0.000 claims abstract description 8
- 229920000642 polymer Polymers 0.000 claims abstract description 4
- 239000000843 powder Substances 0.000 claims description 25
- 239000002639 bone cement Substances 0.000 claims description 23
- 238000000498 ball milling Methods 0.000 claims description 21
- 108010010803 Gelatin Proteins 0.000 claims description 15
- 229920000159 gelatin Polymers 0.000 claims description 15
- 239000008273 gelatin Substances 0.000 claims description 15
- 235000019322 gelatine Nutrition 0.000 claims description 15
- 235000011852 gelatine desserts Nutrition 0.000 claims description 15
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000011268 mixed slurry Substances 0.000 claims description 14
- 238000002156 mixing Methods 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 8
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 7
- 238000003760 magnetic stirring Methods 0.000 claims description 6
- 238000000034 method Methods 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
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- 238000001354 calcination Methods 0.000 claims description 4
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 4
- 230000009477 glass transition Effects 0.000 claims description 4
- 238000002390 rotary evaporation Methods 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims 1
- 230000015556 catabolic process Effects 0.000 abstract description 16
- 238000006731 degradation reaction Methods 0.000 abstract description 16
- 239000000463 material Substances 0.000 abstract description 13
- 238000001727 in vivo Methods 0.000 abstract description 7
- 239000007857 degradation product Substances 0.000 abstract description 6
- 210000003484 anatomy Anatomy 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 14
- 239000007788 liquid Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 6
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 4
- 230000006835 compression Effects 0.000 description 4
- 238000007906 compression Methods 0.000 description 4
- 238000001125 extrusion Methods 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 230000005489 elastic deformation Effects 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 206010061619 Deformity Diseases 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000003076 Osteolysis Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229920001688 coating polymer Polymers 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000011363 dried mixture Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/44—Joints for the spine, e.g. vertebrae, spinal discs
- A61F2/4455—Joints for the spine, e.g. vertebrae, spinal discs for the fusion of spinal bodies, e.g. intervertebral fusion of adjacent spinal bodies, e.g. fusion cages
-
- 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
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30003—Material related properties of the prosthesis or of a coating on the prosthesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30003—Material related properties of the prosthesis or of a coating on the prosthesis
- A61F2002/3006—Properties of materials and coating materials
- A61F2002/30062—(bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
- A61F2002/30064—Coating or prosthesis-covering structure made of biodegradable material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/3094—Designing or manufacturing processes
- A61F2002/30985—Designing or manufacturing processes using three dimensional printing [3DP]
-
- 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
- A61L2430/38—Materials or treatment for tissue regeneration for reconstruction of the spine, vertebrae or intervertebral discs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Prostheses (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明涉及一种磷酸钙骨水泥涂覆的3D打印PLGA椎间融合器的制备方法，通过3D打印技术制备可降解聚酯PLGA椎间融合器，再利用磷酸钙骨水泥涂覆聚合物表面，并填充打印间隙，磷酸钙骨水泥固化后形成羟基磷灰石涂层。本发明有望克服可降解类材料在椎间融合器领域应用时面临的体内降解过快、降解产物酸性较大、力学性能不足等问题，同时3D打印技术为临床个性化制备符合人体解剖学形态的椎间融合器提供了新的途径，具有广阔的临床应用前景。
Description
技术领域
本发明涉及一种生物医用材料技术领域的方法，特别是涉及一种磷酸钙骨水泥涂覆的3D打印PLGA椎间融合器的制备方法。
背景技术
随着脊柱椎间融合技术不断发展与完善，椎间融合术成为治疗涉及脊柱退行性变、畸形、骨折、肿瘤、结核等脊柱相关疾病的主流手术模式和金标准。然而，随着脊柱椎间融合手术的不断增多，近年来发生椎间融合器下沉等术后长期并发症的报道也逐渐增加[王鹏，孙桂森，李红旗等，中国组织工程研究，2018]，造成这一现象的因素较多，如患者骨质疏松、老龄等[Brunello G, Sivolella S, Meneghello R, Biotechnology Advances,2016]。
目前临床常用的椎间融合器材料主要为不可降解和可降解两类。可降解融合器因其生物相容性好、体内可吸收、力学性能与自体骨相近等优点，受到了广泛的关注。但这类材料在体内降解速度过快，不足以维持到椎体骨性融合，因此术后易出现融合器塌陷、椎间隙高度丢失、椎体不稳等现象。同时，聚酯类可降解材料还存在降解产物酸性较大的问题，可能引发无菌性炎症、骨质溶解等并发症。
椎间融合器的尺寸和形状也是影响治疗效果的因素之一。理想的椎间融合器的形状应最大限度的与椎间隙形状、大小和上下终板实现完美契合，进而实现良好的骨融合。临床上，可以通过CT数据重建，构建符合病患人体解剖学的椎间融合器模型，并通过3D打印技术个性化制备可降解椎间融合器。但3D打印融合器仍面临体内降解过快、力学强度无法维持至骨性融合等难题，且打印间隙也会放大这类缺陷。
基于以上背景，本发明利用磷酸钙骨水泥具有可塑性的特点，使其填充至3D打印椎间融合器的打印间隙中，并涂覆PLGA表面，降低其与降解介质的接触，碱性的骨水泥固化产物能中和酸性降解产物，降低PLGA的降解速率；另一方面，固化后的磷酸钙骨水泥填充打印间隙，提高了椎间融合器的骨传导性和力学性能，满足临床应用的需求。
发明内容
针对现有技术的不足，本发明的目的在于提供一种磷酸钙骨水泥涂覆的3D打印PLGA椎间融合器的制备方法，一种3D打印技术制备的具有良好力学性能和生物相容性的磷酸钙骨水泥涂覆PLGA椎间融合器的制备方法。
本发明目的通过以下技术方案来实现：一种磷酸钙骨水泥涂覆的3D打印PLGA椎间融合器的制备方法，通过3D打印技术制备可降解聚酯PLGA椎间融合器，再利用磷酸钙骨水泥涂覆聚合物表面，并填充打印间隙，磷酸钙骨水泥固化后形成羟基磷灰石涂层，包括以下步骤：
（1）制备PLGA椎间融合器
以PLGA为3D打印“墨水”，打印针头选用170μm，设置打印参数：每层采用平行式打印，间隙为0.2-0.3mm，Z轴逐层升高0.15mm，打印温度170-190℃，基础速率为1.5-2mm/s，打印平台温度为30℃，使用生物3D打印机进行3D打印，制备PLGA椎间融合器；
（2）制备明胶改性α-TCP粉末
将磷酸氢钙与碳酸钙按摩尔比2:1湿法球磨混合，干燥后用马弗炉在1250-1400℃煅烧2-4h后取出，在鼓风环境下急速冷却，之后用氧化锆球磨罐450rpm湿法球磨6h，得到粒径均一的α-TCP粉末，将上述α-TCP粉末按0.5g/mL加入0.5%（w/v）的明胶溶液中，高速磁力搅拌0.5h后置于-80℃冰箱中冰冻，进行冷冻干燥48h，得到明胶改性α-TCP粉末；
（3）制备磷酸钙骨水泥涂覆PLGA椎间融合器
配制质量分数为2.5%的Na2HPO4溶液作为骨水泥固化液，与明胶改性α-TCP粉末按液固比0.5-1mL/g混合成调和浆，涂覆至PLGA椎间融合器表面并填充打印间隙，涂覆完成后置于37℃100%湿度环境中24h使骨水泥完全固化，最后将融合器置于100℃烘箱中10min，使PLGA玻璃化转变、与固化产物羟基磷灰石两相进一步融合，得到磷酸钙骨水泥涂覆PLGA椎间融合器。
其中，步骤（1）中，所述的PLGA分子量为10W-40W，LA/GA为75/25，分子链两端可为酯基、羟基或羧基封端。
步骤（2）中，所述的磷酸氢钙与碳酸钙湿法球磨为使用无水乙醇作为混合介质的玛瑙球磨，转速400rpm，球磨时间为1-4h，球磨后悬浊液通过旋转蒸发除去乙醇后放入60℃烘箱中干燥过夜。
步骤（2）中，所述明胶溶液的配制方式为50℃加热下磁力搅拌助溶。
以PLGA为打印“墨水”，170-190℃进行熔融打印，打印模型、尺寸、打印间隙等参数可按需求调控；制备α-TCP粉末，加入明胶进行改性，改善骨水泥流动性和固化性能，改性后的粉末与固化液Na2HPO4溶液混合成调和浆；将调和浆涂覆至3D打印椎间融合器孔隙内及聚酯表面，涂覆完成后置于37℃100%湿度环境中24h使骨水泥完全固化，最后将融合器置于100℃烘箱中10min，使PLGA玻璃化转变、与固化产物羟基磷灰石两相进一步融合，得到磷酸钙骨水泥涂覆PLGA椎间融合器。
本发明方法具体包括以下步骤：
1、以PLGA为打印“墨水”，出料针头选用170μm，采用解剖型椎间融合器模型，设置打印参数：每层平行式打印，打印间隙为0.2-0.3mm，Z轴方向逐层升高0.15mm，层与层之间采用垂直交叉式堆叠，打印温度为170-190℃，挤出速度为1.5-2mm/s，接收平台温度为30℃，打印得到解剖型PLGA椎间融合器；
2、将磷酸氢钙与碳酸钙按摩尔比2:1混合均匀，所述混合方式为使用无水乙醇为混合介质的球磨混合，转速400rpm，球磨时间为1-4h，混合后的悬浊液通过旋转蒸发除去乙醇后放入60℃烘箱中干燥；
3、将干燥后的磷酸氢钙与碳酸钙混合物在1250-1400℃炉中锻烧2-4h后取出，在鼓风环境下急速冷却，之后采用氧化锆球磨罐湿法球磨的方式得到粒径均一的α-TCP粉末。
4、将上述α-TCP粉末按0.5g/mL加入0.5%（w/v）的明胶溶液中，高速磁力搅拌0.5h后置于-80℃冰箱中冰冻，进行冷冻干燥48h，得到明胶改性α-TCP粉末。
5、配制质量分数为2.5%的Na2HPO4溶液作为骨水泥固化液，所述配制方式为常温下磁力搅拌。
6、固化液与明胶改性α-TCP粉末按固液比0.5-1mL/g混合成调和浆，涂覆至PLGA椎间融合器打印间隙中和聚酯表面，涂覆完成后置于37℃100%湿度环境中24h使骨水泥完全固化，最后将融合器置于100℃烘箱中10min，使PLGA玻璃化转变、与固化产物羟基磷灰石两相进一步融合，得到磷酸钙骨水泥涂覆PLGA椎间融合器。
具体是通过3D打印技术制备可降解聚酯PLGA椎间融合器，再利用磷酸钙骨水泥涂覆聚合物表面，并填充打印间隙，磷酸钙骨水泥固化后形成羟基磷灰石涂层，能有效提高融合器的生物相容性、骨传导性，中和酸性降解产物、延长降解速率，同时改善融合器的力学性能。
磷酸钙骨水泥固化后在PLGA表面形成羟基磷灰石涂层，并填充3D打印间隙，一方面能有效提高融合器的生物相容性、骨传导性；另一方面，降低PLGA与降解介质的接触，中和酸性降解产物，延长降解速率；同时打印间隙中的骨水泥固化后，进一步提高融合器的力学性能。本发明有望克服可降解类材料在椎间融合器领域应用时面临的体内降解过快、降解产物酸性较大、力学性能不足等问题，同时3D打印技术为临床个性化制备符合人体解剖学形态的椎间融合器提供了新的途径，具有广阔的临床应用前景。
本发明的优点在于：
1、本发明以PLGA为打印“墨水”，通过3D打印技术制备椎间融合器，使融合器具备体内降解能力，同时最大限度与椎间间隙的形状、高度、上下终盘相匹配，适合个性化治疗。
2、利用磷酸钙骨水泥的可塑性和固化特点，以固化产物羟基磷灰石包覆融合器表面、填充打印间隙，降低PLGA与体内降解介质的接触，提高融合器的生物相容性，克服了PLGA体内降解过快、降解酸度较大等缺点，打印间隙的填充也提高了融合器的力学性能。
附图说明
图1是所制备磷酸钙骨水泥涂覆的3D打印PLGA椎间融合器的实物图，固化后的磷酸钙骨水泥均匀涂覆在融合器表面；
图2是实施例1试验组与对照组的体外降解试验结果，涂覆后的PLGA椎间融合器能明显延长降解时间。
具体实施方式
以下实施例以发明技术方案为前提进行实施，给出了详细的实施方式和具体的操作过程，但本发明的保护范围并不限于下述的实施例。
对照组为现有市售产品。
实施例1
一种磷酸钙骨水泥涂覆的3D打印PLGA椎间融合器，通过3D打印技术制备可降解聚酯PLGA椎间融合器，再利用磷酸钙骨水泥涂覆聚合物表面，并填充打印间隙，磷酸钙骨水泥固化后形成羟基磷灰石涂层，按以下步骤制备：
1、3D打印PLGA椎间融合器的制备：
以PLGA（Mw=20W）为打印“墨水”，3D打印机为Bio-Architect ®-WS，材料置于高温喷头料筒中，打印针头为170μm，设置打印参数：每层采用平行式打印，间隙为0.2mm，Z轴方向逐层升高0.15mm，层与层间采用垂直交叉式堆叠，打印温度190℃，挤出速度设为2mm/s，接收平台温度为30℃。打印得到颈椎椎间融合器，将该融合器作为对照组。
2、明胶改性α-TCP的制备：
按摩尔比2:1称量磷酸氢钙粉末和碳酸钙粉末，使用适量无水乙醇为介质湿法球磨，转速400rpm，球磨时间4h，球磨珠与粉末质量比为2:1。原料混合液通过旋转蒸发除去乙醇，置于60℃烘箱中干燥24h；将干燥后的粉末置于马弗炉中，1400℃煅烧2h后取出，在鼓风环境下急速冷却；将冷却后的粉末以无水乙醇为介质湿法球磨，转速450rpm，用氧化锆球磨罐球磨6h，球磨珠与粉末质量比为4:1；粉末悬浊液置于80℃烘箱中充分干燥，制备得到α-TCP粉末。称取α-TCP粉末20g，加入40mL0.5%（w/v）的明胶溶液，1000rpm磁力搅拌0.5h，进行冷冻干燥，得到明胶改性α-TCP粉末。
常温下磁力搅拌配制质量分数为2.5%的Na2HPO4溶液作为骨水泥固化液，称取2g明胶改性α-TCP粉末，按固液比0.8mL/g与固化液混合成调和浆，涂覆至PLGA椎间融合器打印间隙中和表面，涂覆完成后置于37℃100%湿度环境中24h使骨水泥完全固化，最后将融合器置于100℃烘箱中10min得到磷酸钙骨水泥涂覆PLGA椎间融合器，产品结构如图1所示。该融合器作为试验组，在弹性形变范围内抗压强度为98.5MPa，对照组抗压强度为80.7MPa；1个月内降解速率与对照组相比明显降低，如附图2所示。
实施例2
一种磷酸钙骨水泥涂覆的3D打印PLGA椎间融合器，按以下步骤制备：
1、3D打印PLGA椎间融合器的制备：
以PLGA（Mw=20W）为打印“墨水”，3D打印机为Bio-Architect ®-WS，材料置于高温喷头料筒中，打印针头为170μm，设置打印参数：每层采用平行式打印，间隙为0.25mm，Z轴方向逐层升高0.15mm，层与层间采用垂直交叉式堆叠，打印温度190℃，挤出速度设为2mm/s，接收平台温度为30℃。打印得到颈椎椎间融合器，将该融合器作为对照组。
2、明胶改性α-TCP的制备同实施例1。
3、常温下磁力搅拌配制质量分数为2.5%的Na2HPO4溶液作为骨水泥固化液，称取2g明胶改性α-TCP粉末，按固液比0.8mL/g与固化液混合成调和浆，涂覆至PLGA椎间融合器打印间隙中和表面，涂覆完成后置于37℃100%湿度环境中24h使骨水泥完全固化，最后将融合器置于100℃烘箱中10min得到磷酸钙骨水泥涂覆PLGA椎间融合器。该融合器在弹性形变范围内抗压强度为82.4MPa，对照组抗压强度为65.4MPa。
实施例3
一种磷酸钙骨水泥涂覆的3D打印PLGA椎间融合器，按以下步骤制备：
1、3D打印PLGA椎间融合器的制备：
以PLGA（Mw=20W）为打印“墨水”，3D打印机为Bio-Architect ®-WS，材料置于高温喷头料筒中，打印针头为170μm，设置打印参数：每层采用平行式打印，间隙为0.3mm，Z轴方向逐层升高0.15mm，层与层间采用垂直交叉式堆叠，打印温度190℃，挤出速度设为2mm/s，接收平台温度为30℃。打印得到颈椎椎间融合器，将该融合器作为对照组。
2、明胶改性α-TCP的制备同实施例1。
3、常温下磁力搅拌配制质量分数为2.5%的Na2HPO4溶液作为骨水泥固化液，称取2g明胶改性α-TCP粉末，按固液比0.8mL/g与固化液混合成调和浆，涂覆至PLGA椎间融合器打印间隙中和表面，涂覆完成后置于37℃100%湿度环境中24h使骨水泥完全固化，最后将融合器置于100℃烘箱中10min得到磷酸钙骨水泥涂覆PLGA椎间融合器。该融合器在弹性形变范围内抗压强度为73.6MPa，对照组抗压强度为42.1MPa。
Claims (3)
1.一种磷酸钙骨水泥涂覆的3D打印PLGA椎间融合器的制备方法，其特征在于，通过3D打印技术制备可降解聚酯PLGA椎间融合器，再利用磷酸钙骨水泥涂覆聚合物表面，并填充打印间隙，磷酸钙骨水泥固化后形成羟基磷灰石涂层，包括以下步骤：
（1）制备PLGA椎间融合器
以PLGA为3D打印“墨水”，打印针头选用170μm，设置打印参数：每层采用平行式打印，间隙为0.2-0.3mm，Z轴逐层升高0.15mm，打印温度170-190℃，基础速率为1.5-2mm/s，打印平台温度为30℃，使用生物3D打印机进行3D打印，制备PLGA椎间融合器；
（2）明胶改性α-TCP粉末
将磷酸氢钙与碳酸钙按摩尔比2:1湿法球磨混合，干燥后用马弗炉在1250-1400℃煅烧2-4h后取出，在鼓风环境下急速冷却，之后用氧化锆球磨罐450rpm湿法球磨6h，得到粒径均一的α-TCP粉末，将所述α-TCP粉末按0.5g/mL加入0.5%（w/v）的明胶溶液中，高速磁力搅拌0.5h后置于-80℃冰箱中冰冻，进行冷冻干燥48h，得到明胶改性α-TCP粉末；
（3）磷酸钙骨水泥涂覆PLGA椎间融合器
配制质量分数为2.5%的Na2HPO4溶液作为骨水泥固化液，与明胶改性α-TCP粉末按液固比0.5-1mL/g混合成调和浆，涂覆至PLGA椎间融合器表面并填充打印间隙，涂覆完成后置于37℃100%湿度环境中24h使骨水泥完全固化，最后将融合器置于100℃烘箱中10min，使PLGA玻璃化转变、与固化产物羟基磷灰石两相进一步融合，得到磷酸钙骨水泥涂覆PLGA椎间融合器；其中，
步骤（1）所述的PLGA分子量为10W-40W，LA/GA为75/25，分子链两端可为酯基、羟基或羧基封端。
2.根据权利要求1所述磷酸钙骨水泥涂覆的3D打印PLGA椎间融合器的制备方法，其特征在于，步骤（2）所述的磷酸氢钙与碳酸钙湿法球磨为使用无水乙醇作为混合介质的玛瑙球磨，转速400rpm，球磨时间为1-4h，球磨后悬浊液通过旋转蒸发除去乙醇后放入60℃烘箱中干燥过夜。
3.根据权利要求1所述磷酸钙骨水泥涂覆的3D打印PLGA椎间融合器的制备方法，其特征在于，步骤（2）所述明胶溶液的配制方式为50℃加热下磁力搅拌助溶。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910645597.8A CN110251279B (zh) | 2019-07-17 | 2019-07-17 | 一种磷酸钙骨水泥涂覆的3d打印plga椎间融合器的制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910645597.8A CN110251279B (zh) | 2019-07-17 | 2019-07-17 | 一种磷酸钙骨水泥涂覆的3d打印plga椎间融合器的制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110251279A CN110251279A (zh) | 2019-09-20 |
| CN110251279B true CN110251279B (zh) | 2021-06-04 |
Family
ID=67926709
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910645597.8A Active CN110251279B (zh) | 2019-07-17 | 2019-07-17 | 一种磷酸钙骨水泥涂覆的3d打印plga椎间融合器的制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110251279B (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110665057B (zh) * | 2019-11-07 | 2021-10-01 | 上海健康医学院 | 一种羟基磷灰石/plga双层支架的制备方法 |
| CN114259604B (zh) * | 2021-12-17 | 2022-12-27 | 上海纳米技术及应用国家工程研究中心有限公司 | 一种3d打印促有序血管化的载药骨修复支架的制备方法及其产品和应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101125223B (zh) * | 2007-09-27 | 2010-10-27 | 天津大学 | 磷酸钙骨水泥/壳聚糖-明胶复合多孔支架的制备方法 |
| CN102716512A (zh) * | 2012-06-29 | 2012-10-10 | 上海大学 | 药物分级缓释型骨修复体制备方法 |
| CN104338179A (zh) * | 2013-08-09 | 2015-02-11 | 山东百多安医疗器械有限公司 | 一种可吸收涂层自增强骨板及其制造方法 |
| CN106178124B (zh) * | 2016-07-13 | 2019-10-18 | 华南理工大学 | 一种可降解高分子网络/磷酸钙骨水泥复合骨修复材料及其制备方法与应用 |
| CN107715171A (zh) * | 2017-10-31 | 2018-02-23 | 上海纳米技术及应用国家工程研究中心有限公司 | 快速降解的药物控释可注射型骨水泥的制备方法及其产品和应用 |
| CN108478879A (zh) * | 2018-03-30 | 2018-09-04 | 华南理工大学 | 一种多孔磷酸钙/天然高分子复合支架及其制备方法与应用 |
-
2019
- 2019-07-17 CN CN201910645597.8A patent/CN110251279B/zh active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN110251279A (zh) | 2019-09-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Sun et al. | 3D printed calcium phosphate scaffolds with controlled release of osteogenic drugs for bone regeneration | |
| CN111973811B (zh) | 一种含锌人工骨及其制备方法 | |
| Tan et al. | Injectable bone cement with magnesium-containing microspheres enhances osteogenesis via anti-inflammatory immunoregulation | |
| US7060287B1 (en) | Tissue augmentation material and method | |
| TWI394597B (zh) | 骨科用生物可分解性補綴物 | |
| CN104056305B (zh) | 一种磷酸钙基复合自固化骨修复材料及其制备方法 | |
| CN110251279B (zh) | 一种磷酸钙骨水泥涂覆的3d打印plga椎间融合器的制备方法 | |
| EP1429817A1 (en) | Porous ceramic composite bone grafts | |
| AU2002325762A1 (en) | Porous ceramic composite bone grafts | |
| US20180161477A1 (en) | Structured Mineral Bone Replacement Element | |
| CN102813962B (zh) | 一种可注射且可降解骨水泥及其制备方法和应用 | |
| CN104826171A (zh) | 一种多尺度仿生人工骨支架的增材制造方法 | |
| CN109650872A (zh) | 一种基于自由挤出式3d打印技术的磷酸钙多孔生物陶瓷支架及其制备方法 | |
| CN110665057B (zh) | 一种羟基磷灰石/plga双层支架的制备方法 | |
| WO2001012247A9 (en) | Tissue augmentation material and method | |
| CN114591066B (zh) | 陶瓷化磷酸钙骨水泥及其制备方法 | |
| Zhang et al. | DLP 3D printed silica-doped HAp ceramic scaffolds inspired by the trabecular bone structure | |
| CN110982335A (zh) | 一种自固化羟基磷灰石3d打印墨水的制备方法 | |
| CN110171979B (zh) | 一种大尺寸个性化生物活性陶瓷植入体的制备方法 | |
| CN110540404A (zh) | 一种具有中空贯通结构的磷酸钙骨水泥、制备方法及其应用 | |
| CN111773432A (zh) | 镁基非晶-磷酸钙/硅酸钙复合填充物及其制备与应用 | |
| Wu et al. | Degradable calcium deficient hydroxyapatite/poly (lactic-glycolic acid copolymer) bilayer scaffold through integral molding 3D printing for bone defect repair | |
| Kamaraj et al. | Modulation of 3D printed calcium-deficient apatite constructs with varying Mn concentrations for osteochondral regeneration via endochondral differentiation | |
| Daguano et al. | Shear-thinning sacrificial ink for fabrication of Biosilicate® osteoconductive scaffolds by material extrusion 3D printing | |
| CN110882419A (zh) | 一种自固化磷酸钙骨水泥支架及其制备方法和应用 |
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: 20240108 Address after: Building C, No. 888 Huanhu West Second Road, Pudong New Area, Shanghai, April 2012 Patentee after: Guona Star (Shanghai) Nanotechnology Development Co.,Ltd. Address before: 201109 Shanghai city Minhang District Jianchuan Road No. 468 Patentee before: SHANGHAI NATIONAL ENGINEERING RESEARCH CENTER FOR NANOTECHNOLOGY Co.,Ltd. |