CN112842623A - 一种羟基磷灰石表面修饰3d生物打印可降解人工肋骨的方法 - Google Patents
一种羟基磷灰石表面修饰3d生物打印可降解人工肋骨的方法 Download PDFInfo
- Publication number
- CN112842623A CN112842623A CN202011639939.4A CN202011639939A CN112842623A CN 112842623 A CN112842623 A CN 112842623A CN 202011639939 A CN202011639939 A CN 202011639939A CN 112842623 A CN112842623 A CN 112842623A
- Authority
- CN
- China
- Prior art keywords
- dimensional
- bone
- rib
- repair material
- porous
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229910052588 hydroxylapatite Inorganic materials 0.000 title claims abstract description 23
- 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 title claims abstract description 23
- 238000000034 method Methods 0.000 title claims abstract description 22
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 92
- 239000011148 porous material Substances 0.000 claims abstract description 25
- 230000015556 catabolic process Effects 0.000 claims abstract description 13
- 238000006731 degradation reaction Methods 0.000 claims abstract description 13
- 238000010146 3D printing Methods 0.000 claims abstract description 9
- 230000009286 beneficial effect Effects 0.000 claims abstract description 8
- 230000035699 permeability Effects 0.000 claims abstract description 7
- 238000013329 compounding Methods 0.000 claims abstract description 4
- 239000000463 material Substances 0.000 claims description 60
- 210000000614 rib Anatomy 0.000 claims description 43
- 230000008439 repair process Effects 0.000 claims description 37
- 230000007547 defect Effects 0.000 claims description 16
- 230000004048 modification Effects 0.000 claims description 10
- 238000012986 modification Methods 0.000 claims description 10
- 238000005516 engineering process Methods 0.000 claims description 9
- 239000001506 calcium phosphate Substances 0.000 claims description 5
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 5
- 235000011010 calcium phosphates Nutrition 0.000 claims description 5
- 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 description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 230000008468 bone growth Effects 0.000 claims description 4
- 230000004927 fusion Effects 0.000 claims description 4
- 210000000115 thoracic cavity Anatomy 0.000 claims description 4
- 238000009826 distribution Methods 0.000 claims description 3
- 238000005297 material degradation process Methods 0.000 claims description 3
- 239000013077 target material Substances 0.000 claims description 3
- 235000013619 trace mineral Nutrition 0.000 claims description 3
- 239000011573 trace mineral Substances 0.000 claims description 3
- 210000001519 tissue Anatomy 0.000 abstract description 16
- 230000012010 growth Effects 0.000 abstract description 9
- 239000008280 blood Substances 0.000 abstract description 3
- 210000004369 blood Anatomy 0.000 abstract description 3
- 229920001610 polycaprolactone Polymers 0.000 description 13
- 210000000779 thoracic wall Anatomy 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 5
- 210000000038 chest Anatomy 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000008901 benefit Effects 0.000 description 4
- 230000011164 ossification Effects 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 239000012237 artificial material Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 239000007769 metal material Substances 0.000 description 3
- 238000007639 printing Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229910001069 Ti alloy Inorganic materials 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 239000000956 alloy Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 239000004068 calcium phosphate ceramic Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 210000000078 claw Anatomy 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 206010065687 Bone loss Diseases 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 235000014653 Carica parviflora Nutrition 0.000 description 1
- 206010072960 Chest wall tumour Diseases 0.000 description 1
- 241000243321 Cnidaria Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 206010024971 Lower respiratory tract infections Diseases 0.000 description 1
- 229910000861 Mg alloy Inorganic materials 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 239000004696 Poly ether ether ketone Substances 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000005313 bioactive glass Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 239000002639 bone cement Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 229910010293 ceramic material Inorganic materials 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000011976 chest X-ray Methods 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229920006237 degradable polymer Polymers 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 208000000122 hyperventilation Diseases 0.000 description 1
- 230000000870 hyperventilation Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000000113 methacrylic resin Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 208000018223 neoplasm of chest wall Diseases 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000010883 osseointegration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920002530 polyetherether ketone Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- -1 polytetrafluoroethylene Polymers 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910001285 shape-memory alloy Inorganic materials 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000003313 weakening effect Effects 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
- A61F2/28—Bones
-
- 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
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
-
- 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
- A61F2/30942—Designing or manufacturing processes for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques
-
- 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]
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Vascular Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Transplantation (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Physics & Mathematics (AREA)
- Geometry (AREA)
- Manufacturing & Machinery (AREA)
- Prostheses (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明涉及一种羟基磷灰石表面修饰3D生物打印可降解人工肋骨的方法,所述方法包括以下步骤:步骤1:CT二维图像的获取;步骤2:由多孔结构的孔径大小、渗透率、孔隙率、多孔形态等参数,控制支架降解时间;步骤3:将纳米HA与PCL进行复合,然后3D打印。此方法有利于血液组织沿着此支架生长,在组织长成之后,实现断崖式降解,由此实现自体骨的生长。
Description
技术领域
本发明涉及一种羟基磷灰石表面修饰3D生物打印可降解人工肋骨的方法,属于生物医疗技术领域。
背景技术
起初人们治疗骨缺失的植入体来源于自体骨,虽然自体骨作为骨修复材料避免了免疫排斥反应,并且具有血管化快,抗感染强,然而这种方法通常给患者造成新的创伤而且自体骨数量有限,此外创伤较大的骨缺损无法通过自体骨进行修复[1]。而异体骨来源广泛作为骨修复材料解决了自体骨数量限制等问题,也带来了新的问题,即存在免疫排斥反应和传染疾病的问题,限制了其在临床上广泛应用。正是因为天然骨修复材料存在着问题尚不能很好的解决。相对于自体组织,人工材料对胸壁的骨性支持较好,而且简化了手术操作过程,缩短了手术时间,减少了手术创伤,因此,对于大块胸壁缺损的骨性重建,目前倾向使用人工材料修补。理想的重建材料和技术应满足以下要求:(1)有良好的生物相容性,置入体内无不良反应,不致癌;(2)有足够的坚硬度,能确保胸廓稳定和保护胸内重要组织、器官;(3)有稳定的理化特性,经各种加工、灭菌不影响其性能;(4)塑形和使用简便,易于制作成形;(5)不影响胸部X线检查。(6)长时间保持体内无排斥反应和感染的可能性;(7)杀菌方便;(8)放射线透彻性可以作为解剖学参考,以更好地随访并确定可能的局部肿瘤复发。人的肋骨与胸骨、胸椎共同形成骨性胸壁结构,由于胸壁肿瘤、感染或严重外伤等原因需手术切除多根肋骨,导致大面积骨性胸壁缺如,通常需进行骨性胸壁重建,以维持胸廓的完整性、稳定性和对纵膈脏器的保护。
胸壁重建近些年开始得到关注,传统的手段如自体组织移植,其取材有限,一般仅能实现覆盖、力学性能不理想,现有的人工材料如骨水泥、聚四氟乙烯补片、甲基丙烯酸树脂、金属板(钛合金、形状记忆合金、不锈钢刚等)、有机玻璃板和钢丝网等材料也存在强度不足或强度过大的力学相容性的问题。如中国实用新型专利(申请号为CN201320389626.7)公开了一种人工肋骨,其主要是由高分子材料聚醚醚酮等材料构成,主体呈现扁圆弧状,包括外侧与人体皮肤或软组织相贴合的外表面,以及内侧与人体胸腔相接触的腔面,该人工肋骨形状与强度和人的肋骨相近,但是其与人体生物相容性差。另外中国实用新型专利(申请号CN201520015352.4)公开了一种人工肋骨,其为弧形条状,两段均设有若干肋骨抱爪,每组肋骨抱爪为两个,分别对称设置在人工肋骨两侧。肋骨上均匀分布有若干个缝合孔,人工肋骨两侧面上设有若干个波浪形的定位槽,该人工肋骨能够很好地实现与胸壁组织定位、固定,但是其采用合金材料,与人体组织生物相容性较差,仿生性显著不足,且医学成像有伪影,不利于后续治疗。因此,迫切的需要一种新的方案解决上述技术问题。
发明内容
本发明正是针对现有技术中存在的问题,提供一种羟基磷灰石表面修饰3D生物打印可降解人工肋骨的方法,目前市面上人工肋骨生物相容性较差,本发明的生物相容性较好,与人体其余骨组织可以相对完美契合。
为了实现上述目的,本发明的技术方案如下,一种羟基磷灰石表面修饰3D生物打印可降解人工肋骨的方法,所述方法包括以下步骤:
步骤1:CT二维图像的获取;
步骤2:由多孔结构的孔径大小、渗透率、孔隙率、多孔形态等参数,控制支架降解时间;
步骤3:将纳米HA与PCL进行复合,然后3D打印。此方法有利于血液组织沿着此支架生长,在组织长成之后,实现断崖式降解,由此实现自体骨的生长。
进一步地,步骤1:CT二维图像的获取,具体如下:患者CT、b超、MRI检查身体,获取二维影像数据,通过MIMICS进行三维建模,获得肋骨的立体三维模型,通过镜像等指令设计人工肋骨的外观形态,用三维重建软件对整个胸腔进行逆向建模,将二维影像数据导入三维重建软件中,通过阈值选取,提取整个肋骨,再通过脊柱找到对称平面,获得缺损肋骨的镜像,由此确定需要的肋骨外观形态。
进一步地,步骤2:由多孔结构的孔径大小、渗透率、孔隙率、多孔形态等参数,计算出骨修复材料的孔径(100-500μm),骨修复材料的孔隙率为40%-60%,内部有三维贯通的孔道结构,使骨修复材料具有合适的孔径(100-500μm)且孔径分布合理;骨修复材料有较高的孔隙率(40%-60%)且内部有三维贯通的孔道结构,使骨修复材料在体内降解速率与新骨生成速率完美匹配,骨修复材料能完全重建原生生理状态下骨组织形态,骨传导性、骨诱导性以及血管诱导活性达到平衡,创伤较大的骨缺损部位进行快速有效重建。
进一步地,步骤3:将纳米HA与PCL进行复合,然后3D打印出来,将PCL打印成三维多孔骨支架,可以对骨修复材料结构进行设计,匹配材料降解速率和新骨生长速率问题,然后将HA和人体微量元素进行复合制备靶材,采用PLD技术对PCL三维多孔骨支架进行表面修饰,赋予骨修复材料骨传导性、骨诱导性,当其植入体内后,HA可促进材料表面类磷酸钙层的形成,利于骨组织融合,同时HA颗粒通过水解和弱化作用,可加速PCL骨支架的降解并被新生骨代替,随着骨组织的再生与重建,最终实现骨缺损的修复。
目前市面上人工肋骨没有生物可降解性,长期置于人体内会对人体健康有一定危害。目前市面上人工肋骨形态相对固定,若患者还在生长发育期,会对身体其余骨骼造成不良影响。本发明使用可降解材料,对于人体肋骨起辅助生长的作用。商业化骨移植材料多为成年人提供,并且没有一项成熟技术可以专门治疗儿童骨缺损,主要原因在于儿童骨骼具有生长性,常规的钛合金植入体或陶瓷植入体都无法适应儿童骨骼生长并且具有延展性,易造成骨骼变形。随着应用病例的增多,金属材料的弊端逐渐显现,主要有以下几点不足:(1)金属材料不利于术后X线检查及放疗,特别是金属板的影响更大;(2)固定比较困难,易松动、引起出血、疼痛;(3)易穿出、穿破皮肤甚至有穿破胸内脏器的危险;(4)抗感染能力差,感染后必须将置入金属材料取出;(5)金属丝和金属网在肺过度通气时易断裂;(6)金属板不能根据缺损大小任意剪裁。生物活性材料作为第二代产品,是指材料植入体内后,其表面能与周围组织形成牢固的化学键合作用,包括人工合成和天然衍生可降解聚合物(聚酯类、胶原蛋白等)、磷酸钙(珊瑚、藻类等)、碳酸钙、硫酸钙和生物活性玻璃(SiO2、非SiO2基等)。可降解性是指材料植入体内后,能够通过体液溶解、细胞吞噬吸收或被代谢系统排出体外,使缺损部位完全被新生的骨组织所替代,实现骨缺损的修复,这类材料的特点是材料本身具有生物活性或可降解性,然而同样存在体内降解速率变化等问题。因此,需要一种可根据需求对材料进行结构设计和功能优化达到调控材料机械性能和降解行为一类材料,该类材料以人工合成为主,目前广泛应用的有聚丙交酯、聚已交酯、聚己内酯以及其共聚物,而人工合成的可生物降解材料缺乏生物活性。由此提出了骨修复材料的第三代产品需同时具有生物活性、可降解性,即生物智能型材料,一种是在材料中添加生长因子或活体细胞,诱导干细胞定向分化,从而形成特定的组织,该方法操作繁琐,成本高,细胞活性难以控制;另一种是根据材料本身结构进行优化设计,使得材料具有诱导组织再生的性能。其植入体内后,可在材料组织界面处诱发特定的生物学反应,与组织形成紧密结合。磷酸钙陶瓷与骨矿物质的成分相似,赋予其优异的生物学性能,可刺激骨形成和骨结合。将锶、镁、硅、氟化物等微量元素添加到磷酸钙陶瓷材料中,使得材料既具有促进骨整合的生物学活性,又可以根据需求调控材料降解性能,其中镁合金材料可以在体内降解并被人体代谢,此外镁在加强骨形成和细胞增殖、调节信号传递、加速骨愈合、维持骨骼细胞结构结合骨骼韧性方面有着重要作用。
相对于现有技术,本发明具有如下优点,1)该技术方案中3D打印技术调控三维骨修复材料孔隙率、孔径大小、孔形状以及孔结构;2)该方案中通过对3D打印支架孔隙率、分子量、打印分辨率的调节建立支架本征性质与支架在水相体系中降解速率之间的构效关系;3)PLD技术对骨修复材料表面修饰,赋予骨修复材料生物活性;4)镁元素作为活性因子均匀分散到羟基磷灰石中诱导新骨生长;5)本研究克服了无支架的生物细胞打印局限性,降低了难度,解决了在骨质打印中,尤其是长段骨的打印成型上的难题,增加了该项技术能在临床应用的可行性。用3D生物打印技术可以定制化修复与原肋骨形态相似的组织相容性好的替代组织,同时采用PLD技术对PCL三维多孔骨支架进行表面修饰,赋予骨修复材料骨传导性、骨诱导性,当其植入体内后,HA可促进材料表面类磷酸钙层的形成,利于骨组织融合,同时HA颗粒通过水解和弱化作用,可加速PCL骨支架的降解并被新生骨代替,随着骨组织的再生与重建,最终实现骨缺损的修复,该方案具有良好的骨传导性,有着贯通的网状结构,在骨缺损部位提供支架;具有良好的成骨性,含有细胞成分,可直接成骨;具有良好的骨诱导性,含有骨诱导因子,诱导邻近细胞迁移、募集、发育、分化和成骨,提高骨修复能力。
附图说明
图1为本发明整体流程示意图;
图2为本发明产品示意图。
具体实施方式:
为了加深对本发明的理解,下面结合附图对本实施例做详细的说明。
实施例1:参见图1,一种羟基磷灰石表面修饰3D生物打印可降解人工肋骨的方法,所述方法包括以下步骤:
步骤1:CT二维图像的获取;
步骤2:由多孔结构的孔径大小、渗透率、孔隙率、多孔形态等参数,控制支架降解时间;
步骤3:将纳米HA与PCL进行复合,然后3D打印。此方法有利于血液组织沿着此支架生长,在组织长成之后,实现断崖式降解,由此实现自体骨的生长。
步骤1:CT二维图像的获取,具体如下:患者CT、b超、MRI检查身体,获取二维影像数据,通过MIMICS进行三维建模,获得肋骨的立体三维模型,通过镜像等指令设计人工肋骨的外观形态,用三维重建软件对整个胸腔进行逆向建模,将二维影像数据导入三维重建软件中,通过阈值选取,提取整个肋骨,再通过脊柱找到对称平面,获得缺损肋骨的镜像,由此确定需要的肋骨外观形态。
步骤2:由多孔结构的孔径大小、渗透率、孔隙率、多孔形态等参数,计算出骨修复材料的孔径(100-500μm),骨修复材料的孔隙率为40%-60%,内部有三维贯通的孔道结构,使骨修复材料具有合适的孔径(100-500μm)且孔径分布合理;骨修复材料有较高的孔隙率(40%-60%)且内部有三维贯通的孔道结构,使骨修复材料在体内降解速率与新骨生成速率完美匹配,骨修复材料能完全重建原生生理状态下骨组织形态,骨传导性、骨诱导性以及血管诱导活性达到平衡,创伤较大的骨缺损部位进行快速有效重建。
步骤3:将纳米HA与PCL进行复合,然后3D打印出来,将PCL打印成三维多孔骨支架,可以对骨修复材料结构进行设计,匹配材料降解速率和新骨生长速率问题,然后将HA和人体微量元素进行复合制备靶材,采用PLD技术对PCL三维多孔骨支架进行表面修饰,赋予骨修复材料骨传导性、骨诱导性,当其植入体内后,HA可促进材料表面类磷酸钙层的形成,利于骨组织融合,同时HA颗粒通过水解和弱化作用,可加速PCL骨支架的降解并被新生骨代替,随着骨组织的再生与重建,最终实现骨缺损的修复。
需要说明的是上述实施例,并非用来限定本发明的保护范围,在上述技术方案的基础上所作出的等同变换或替代均落入本发明权利要求所保护的范围。
Claims (4)
1.一种羟基磷灰石表面修饰3D生物打印可降解人工肋骨的方法,其特征在于,所述方法包括以下步骤:
步骤1:CT二维图像的获取;
步骤2:由多孔结构的孔径大小、渗透率、孔隙率、多孔形态等参数,控制支架降解时间;
步骤3:将纳米HA与PCL进行复合,然后3D打印。
2.根据权利要求1所述的羟基磷灰石表面修饰3D生物打印可降解人工肋骨的方法,其特征在于,步骤1:CT二维图像的获取,具体如下:患者CT、b超、MRI检查身体,获取二维影像数据,通过三维重建软件进行三维建模,获得肋骨的立体三维模型,通过镜像等指令设计人工肋骨的外观形态,用三维重建软件对整个胸腔进行逆向建模,将二维影像数据导入三维重建软件中,通过阈值选取,提取整个肋骨,再通过脊柱找到对称平面,获得缺损肋骨的镜像,由此确定需要的肋骨外观形态。
3.根据权利要求3所述的羟基磷灰石表面修饰3D生物打印可降解人工肋骨的方法,其特征在于,步骤2:由多孔结构的孔径大小、渗透率、孔隙率、多孔形态等参数,计算出骨修复材料的孔径(100-500μm),骨修复材料的孔隙率为40%-60%,内部有三维贯通的孔道结构,使骨修复材料具有合适的孔径(100-500μm)且孔径分布合理;骨修复材料有较高的孔隙率(40%-60%)且内部有三维贯通的孔道结构。
4.根据权利要求2或3所述的羟基磷灰石表面修饰3D生物打印可降解人工肋骨的方法,其特征在于,步骤3:将纳米HA与PCL进行复合,然后3D打印出来,将PCL打印成三维多孔骨支架,可以对骨修复材料结构进行设计,匹配材料降解速率和新骨生长速率问题,然后将HA和人体微量元素进行复合制备靶材,采用PLD技术对PCL三维多孔骨支架进行表面修饰,赋予骨修复材料骨传导性、骨诱导性,当其植入体内后,HA可促进材料表面类磷酸钙层的形成,利于骨组织融合,同时HA颗粒通过水解和弱化作用,可加速PCL骨支架的降解并被新生骨代替,随着骨组织的再生与重建,最终实现骨缺损的修复。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011639939.4A CN112842623A (zh) | 2020-12-31 | 2020-12-31 | 一种羟基磷灰石表面修饰3d生物打印可降解人工肋骨的方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011639939.4A CN112842623A (zh) | 2020-12-31 | 2020-12-31 | 一种羟基磷灰石表面修饰3d生物打印可降解人工肋骨的方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN112842623A true CN112842623A (zh) | 2021-05-28 |
Family
ID=76000614
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202011639939.4A Pending CN112842623A (zh) | 2020-12-31 | 2020-12-31 | 一种羟基磷灰石表面修饰3d生物打印可降解人工肋骨的方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN112842623A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113749826A (zh) * | 2021-08-25 | 2021-12-07 | 西安交通大学 | 一种3d打印的可降解胸肋骨植入物 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103785059A (zh) * | 2014-01-03 | 2014-05-14 | 朱小龙 | 一种骨修复再生材料及其制备方法 |
CN104826174A (zh) * | 2015-04-20 | 2015-08-12 | 云南省第一人民医院 | 一种制备仿骨羟基磷灰石骨修复材料的方法 |
CN107823715A (zh) * | 2017-10-20 | 2018-03-23 | 昆明理工大学 | 一种pcl/ha复合多孔骨组织工程支架及其制备方法 |
CN108030960A (zh) * | 2017-12-22 | 2018-05-15 | 重庆医科大学附属永川医院 | 一种促进骨创伤愈合的植入材料及其制备方法 |
CN110075360A (zh) * | 2019-05-21 | 2019-08-02 | 福建吉特瑞生物科技有限公司 | 一种壳聚糖/ha基个性化颅、颌面、脊椎骨修复材料及其制备方法 |
CN111110404A (zh) * | 2020-01-10 | 2020-05-08 | 苏州诺普再生医学有限公司 | 一种3d打印的多结构骨复合支架 |
-
2020
- 2020-12-31 CN CN202011639939.4A patent/CN112842623A/zh active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103785059A (zh) * | 2014-01-03 | 2014-05-14 | 朱小龙 | 一种骨修复再生材料及其制备方法 |
CN104826174A (zh) * | 2015-04-20 | 2015-08-12 | 云南省第一人民医院 | 一种制备仿骨羟基磷灰石骨修复材料的方法 |
CN107823715A (zh) * | 2017-10-20 | 2018-03-23 | 昆明理工大学 | 一种pcl/ha复合多孔骨组织工程支架及其制备方法 |
CN108030960A (zh) * | 2017-12-22 | 2018-05-15 | 重庆医科大学附属永川医院 | 一种促进骨创伤愈合的植入材料及其制备方法 |
CN110075360A (zh) * | 2019-05-21 | 2019-08-02 | 福建吉特瑞生物科技有限公司 | 一种壳聚糖/ha基个性化颅、颌面、脊椎骨修复材料及其制备方法 |
CN111110404A (zh) * | 2020-01-10 | 2020-05-08 | 苏州诺普再生医学有限公司 | 一种3d打印的多结构骨复合支架 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113749826A (zh) * | 2021-08-25 | 2021-12-07 | 西安交通大学 | 一种3d打印的可降解胸肋骨植入物 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2016206180A1 (zh) | 一种生物可吸收骨修复材料及其应用与制作方法 | |
Beier et al. | Axial vascularization of a large volume calcium phosphate ceramic bone substitute in the sheep AV loop model | |
Kim | Application of the three-dimensionally printed biodegradable polycaprolactone (PCL) mesh in repair of orbital wall fractures | |
Matsuo et al. | Clinical application of a custom-made bioresorbable raw particulate hydroxyapatite/poly-L-lactide mesh tray for mandibular reconstruction | |
Kanno et al. | Computed tomographic evaluation of novel custom-made artificial bones,“CT-bone”, applied for maxillofacial reconstruction | |
TW201215369A (en) | Spinal implant structure and method for manufacturing the same | |
CN110180027A (zh) | 具有改进的操作特征的脱矿质骨基质 | |
Grecchi et al. | Reconstruction of the zygomatic bone with smartbone®: Case report | |
RU171823U1 (ru) | Ячеистый цилиндрический биоактивный имплантат для замещения циркулярных дефектов трубчатых костей | |
RU2218895C1 (ru) | Способ контурной пластики, восстановления, коррекции, устранения или замещения дефектов, повреждений или деформаций костной или хрящевой ткани и имплантат для его реализации | |
CN112386345B (zh) | 一种牙槽骨增量支架系统 | |
CN112842623A (zh) | 一种羟基磷灰石表面修饰3d生物打印可降解人工肋骨的方法 | |
CN114452441A (zh) | 一种颅骨修复聚醚醚酮材料及其制备方法 | |
RU2565375C1 (ru) | Способ восстановления стенок орбиты | |
RU173377U1 (ru) | Имплантат биоактивный ячеистый треугольный для замещения дефекта большеберцовой кости | |
CN105536047A (zh) | 一种颅骨修复材料及其制备方法 | |
RU195801U1 (ru) | Каркас индивидуальный для исправления дефектов мозгового и лицевого отделов скелета головы | |
JP3860417B2 (ja) | 長期安定性を有する移植用プロテーゼ | |
CN213525691U (zh) | 一种基于3d打印多孔钛合金的仿真颌骨植入物 | |
Ayoub et al. | Biomaterials in the Reconstruction of the Oral and Maxillofacial Region | |
RU2375007C1 (ru) | Способ замещения костных дефектов | |
RU25996U1 (ru) | Имплантат для контурной пластики, восстановления, коррекции, устранения или замещения дефектов, повреждений или деформаций костной или хрящевой ткани | |
CN211561236U (zh) | 一种骨缺损修复支架 | |
Kinoshita et al. | Functional reconstruction of the jaw bones using poly (l-lactide) mesh and autogenic particulate cancellous bone and marrow | |
RU2624873C1 (ru) | Способ получения остеопластического материала |
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 | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210528 |
|
RJ01 | Rejection of invention patent application after publication |