CN110200727A - A kind of 3D printing tubular porous titanium prosthesis and preparation method thereof for four limbs large segmental bone defect - Google Patents

一种用于四肢大段骨缺损的3D打印管状多孔钛合金假体及其制备方法，根据患者薄层CT扫描数据，结合手术路径及病变部位截骨平面形态设计带有接骨板的中空管状的多孔假体，将假体设计数据导入金属3D打印设备制备得到管状多孔钛合金假体；将制备的管状多孔钛合金假体置于醋酸钙和β甘油磷酸钠的电解液中对管状多孔钛合金假体进行微弧氧化处理后在恒温水浴下再处理，得到表面具有氧化钛的3D打印管状钛合金假体；将其置于Ba(OH)₂溶液中，调节PH值至13反应在氧化钛的3D打印管状钛合金假体表面生成钛酸钡。本发明表面活性处理提高假体生物相容性，诱导新骨生长，达到良好的骨整合效果；一体化接骨板与骨干契合度高，增加固定可靠性。不需附加辅助内固定。

A 3D printed tubular porous titanium alloy prosthesis for large bone defects in limbs and its preparation method. According to the patient's thin-layer CT scan data, combined with the surgical path and the osteotomy plane shape of the lesion, the hollow tubular prosthesis with bone plate is designed. Porous prosthesis, the design data of the prosthesis is imported into the metal 3D printing equipment to prepare the tubular porous titanium alloy prosthesis; the prepared tubular porous titanium alloy prosthesis is placed in the electrolyte of calcium acetate and β-sodium glycerophosphate for the treatment of the tubular porous titanium alloy The prosthesis was subjected to micro-arc oxidation treatment and then treated in a constant temperature water bath to obtain a 3D printed tubular titanium alloy prosthesis with titanium oxide on the surface; it was placed in Ba(OH) ₂ solution, and the pH value was adjusted to 13 to react in titanium oxide. Barium titanate is generated on the surface of the 3D printed tubular titanium alloy prosthesis. The surface active treatment of the invention improves the biocompatibility of the prosthesis, induces new bone growth, and achieves a good osseointegration effect; the integrated bone plate has a high degree of fit with the backbone, increasing the reliability of fixation. No additional auxiliary internal fixation is required.

一种用于四肢大段骨缺损的3D打印管状多孔钛合金假体及其 制备方法A 3D printed tubular porous titanium alloy prosthesis for large bone defects in extremities and its Preparation

技术领域technical field

本发明涉及一种管状多孔钛合金假体，具体涉及一种用于四肢大段骨缺损的3D打印管状多孔钛合金假体及其制备方法。The invention relates to a tubular porous titanium alloy prosthesis, in particular to a 3D printed tubular porous titanium alloy prosthesis for large segmental bone defects in limbs and a preparation method thereof.

背景技术Background technique

创伤、肿瘤、感染等造成的大段骨缺损的修复是目前临床常见且棘手的问题。异体骨和自体带血管的腓骨是目前最常用的长骨缺损修复方法。异体骨的优点在于能够提供骨量和早期支撑，但活化时间长，与受体之间的愈合率低，且容易感染。自体带血管骨优点在于活骨移植，愈合率高，有一定的抗感染能力，然而由于管径细常不宜单独用于下肢骨缺损，腓骨愈合后在重塑过程中二次骨折的发生率高。The repair of large bone defects caused by trauma, tumor, infection, etc. is a common and difficult problem in clinical practice. Bone allograft and autologous vascularized fibula are currently the most commonly used methods for repairing long bone defects. The advantage of allograft bone is that it can provide bone mass and early support, but it takes a long time to activate, has a low healing rate with the recipient, and is prone to infection. The advantages of autologous vascularized bone are living bone transplantation, high healing rate, and certain anti-infection ability. However, due to the small diameter of the vessel, it is not suitable to be used alone for bone defects of the lower limbs, and the incidence of secondary fractures during the remodeling process after fibula healing is high. .

目前临床使用的钛合金(Ti-6Al-4V)虽然具有良好的力学强度，但其在临床应用过程中，仍然存在明显缺陷：1、弹性模量(110GPa)远远高于正常骨(皮质骨约15GPa)，产生应力遮挡，导致骨吸收，骨-金属的界面整合不佳；2、钛合金为生物惰性材料，对材料周围骨形成没有良好的刺激作用，导致骨长入数量和长入速度较慢。体相多孔钛合金很好的解决了这一难题，主要表现为内部结构均一，无明显界面效应，内部连通的孔隙结构，也为新生骨组织提供良好的长入环境,并且其材料强度及模量可以通过对多孔结构参数的调节实现与自然骨匹配，因此是一种理想的骨科金属植入材料。Although the currently clinically used titanium alloy (Ti-6Al-4V) has good mechanical strength, it still has obvious defects in the clinical application process: 1. The elastic modulus (110GPa) is much higher than that of normal bone (cortical bone). About 15GPa), resulting in stress shielding, resulting in bone resorption and poor bone-metal interface integration; 2. Titanium alloy is a biologically inert material, which does not have a good stimulating effect on bone formation around the material, resulting in the amount and speed of bone ingrowth slower. Bulk phase porous titanium alloy solves this problem very well, mainly manifested in uniform internal structure, no obvious interface effect, internally connected pore structure, and also provides a good growth environment for new bone tissue, and its material strength and modulus The amount can be matched with natural bone by adjusting the porous structure parameters, so it is an ideal orthopedic metal implant material.

3D打印技术是一种以数字模型为基础，通过逐层打印的方式来构造物体的技术。通过3D打印技术，可以获得与骨缺损精确匹配的多孔钛合金骨修复假体，并通过空隙及结构调整，获得与正常骨质接近的强度；同时3D打印假体不受骨缺损形状的限制，不必过多地修整残留骨质，在尽可能多保留骨质的前提下，实现个体化，精准，精确重建治疗。3D打印多孔钛合金假体具有一定的骨长入能力，能够与骨质紧密结合，同时通过对假体进行压电陶瓷表面改性处理，可进一步提高其骨长入能力。将腓骨与3D打印多孔钛合金假体有机结合起来，从而发挥假体的机械支撑和腓骨的成骨及抗感染效果，可实现机械与生物重建的完美结合。3D printing technology is a technology that constructs objects by printing layer by layer based on digital models. Through 3D printing technology, a porous titanium alloy bone repair prosthesis that precisely matches the bone defect can be obtained, and through the adjustment of the gap and structure, the strength close to that of normal bone can be obtained; at the same time, the 3D printed prosthesis is not limited by the shape of the bone defect, There is no need to modify the residual bone too much, and on the premise of retaining as much bone as possible, individualized, precise and precise reconstruction treatment can be realized. The 3D printed porous titanium alloy prosthesis has a certain bone ingrowth ability and can be tightly integrated with the bone. At the same time, the bone ingrowth ability of the prosthesis can be further improved by modifying the surface of the piezoelectric ceramic. The fibula is organically combined with the 3D printed porous titanium alloy prosthesis, so as to exert the mechanical support of the prosthesis and the osteogenesis and anti-infection effect of the fibula, which can realize the perfect combination of mechanical and biological reconstruction.

发明内容Contents of the invention

本发明的目的在于克服目前四肢大段骨缺损治疗方法的不足，提供了一种用于四肢大段骨缺损的3D打印管状多孔钛合金假体及其制备方法。The purpose of the present invention is to overcome the shortcomings of the current treatment methods for large-segment bone defects in limbs, and provide a 3D printed tubular porous titanium alloy prosthesis for large-segment bone defects in limbs and a preparation method thereof.

为达到上述目的，本发明采用的技术方案是：In order to achieve the above object, the technical scheme adopted in the present invention is:

1)个性化3D打印假体的制备：1) Preparation of personalized 3D printed prosthesis:

根据患者薄层CT扫描数据，结合手术路径及病变部位截骨平面形态设计带有接骨板的孔隙率为50％-80％，孔径为500μm-700μm的腓骨植入的中空管状的多孔假体，将假体设计数据导入金属3D打印设备，在650℃以30mA的电子束流，15000mm/s的扫描速度预热钛合金粉末，然后以6mA的电子束流，400mm/s的扫描速度逐层熔化合金粉末制备成与预期形状一致的管状多孔钛合金假体；According to the patient's thin-section CT scan data, combined with the surgical path and the osteotomy plane shape of the lesion, a hollow tubular porous prosthesis is designed with a bone plate with a porosity of 50%-80% and a pore diameter of 500μm-700μm implanted in the fibula. Import the prosthesis design data into the metal 3D printing equipment, preheat the titanium alloy powder at 650°C with an electron beam current of 30mA and a scanning speed of 15000mm/s, and then melt it layer by layer with an electron beam current of 6mA and a scanning speed of 400mm/s The alloy powder is prepared into a tubular porous titanium alloy prosthesis consistent with the expected shape;

2)3D打印管状钛合金假体表面活性处理2) Surface active treatment of 3D printed tubular titanium alloy prosthesis

2-1)构建微米级氧化钛活性表面涂层2-1) Construction of micron-sized titanium oxide active surface coating

将制备的管状多孔钛合金假体作为工作电极，采用恒电压模式制备涂层：将制备的管状多孔钛合金假体置于醋酸钙浓度为0.2mol/L，β甘油磷酸钠浓度为0.04mol/L的电解液中，在频率为200Hz，占空比为15％，以恒定350V电压下脉冲-直流电源对管状多孔钛合金假体进行微弧氧化处理后在恒温水浴下再处理5min，得到表面具有氧化钛的3D打印管状钛合金假体；The prepared tubular porous titanium alloy prosthesis was used as the working electrode, and the coating was prepared in constant voltage mode: the prepared tubular porous titanium alloy prosthesis was placed in a concentration of calcium acetate of 0.2 mol/L, and a concentration of β-glycerophosphate sodium of 0.04 mol/L. In the electrolyte of L, at a frequency of 200 Hz and a duty ratio of 15%, the tubular porous titanium alloy prosthesis was subjected to micro-arc oxidation treatment with a pulse-DC power supply at a constant voltage of 350 V, and then treated in a constant temperature water bath for 5 minutes to obtain a surface 3D printed tubular titanium alloy prostheses with titanium oxide;

2-2)构建纳米级钛酸钡压电活性表面涂层2-2) Construction of nanoscale barium titanate piezoelectric active surface coating

以表面具有氧氧化钛的3D打印管状钛合金假体作为钛源，原位自转化合成钛酸钡压电陶瓷涂层：在100-120℃不锈钢高压反应釜中，将表面具有氧化钛的3D打印管状钛合金假体置于Ba²⁺浓度为0.25mol/L的Ba(OH)₂溶液中，采用NaOH调节PH值至13，在反应压力为0.7-1.1MPa，反应1-3小时，氧化钛溶解与溶液中的钡离子原位反应在氧化钛的3D打印管状钛合金假体表面生成钛酸钡。Using the 3D printed tubular titanium alloy prosthesis with titanium oxide on the surface as the titanium source, in situ self-transformation to synthesize the barium titanate piezoelectric ceramic coating: in a stainless steel autoclave at 100-120°C, the 3D titanium alloy prosthesis with titanium oxide on the surface The printed tubular titanium alloy prosthesis is placed in a Ba(OH) ₂ solution with a Ba ²⁺ concentration of 0.25mol/L, the pH value is adjusted to 13 with NaOH, and the reaction pressure is 0.7-1.1MPa, reacted for 1-3 hours, and oxidized The in-situ reaction between titanium dissolution and barium ions in the solution produces barium titanate on the surface of the titanium oxide 3D printed tubular titanium alloy prosthesis.

按以上制备方法制得的用于四肢大段骨缺损的3D打印管状多孔钛合金假体包括带有接骨板的孔隙率为50％-80％，孔径为500μm-700μm的腓骨植入的中空管状的多孔假体，所述接骨板形状与骨干外形契合。The 3D printed tubular porous titanium alloy prosthesis for large segmental bone defects of extremities prepared according to the above preparation method includes a hollow tubular implanted fibula with a bone plate with a porosity of 50%-80% and a pore size of 500μm-700μm. A porous prosthesis, the shape of the bone plate fits the shape of the bone.

所述的中空管状形态的多孔假体的多孔空间结构采用正十六面体金刚石结构。The porous spatial structure of the hollow tubular porous prosthesis adopts a regular hexahedral diamond structure.

所述的中空管状形态的多孔假体管壁形状与缺损区骨干相仿，管壁的厚度大于骨皮质0.5mm-1.0mm。The shape of the wall of the hollow tubular porous prosthesis is similar to that of the backbone of the defect area, and the thickness of the wall is 0.5mm-1.0mm greater than that of the cortical bone.

本发明具有以下优点：The present invention has the following advantages:

1.腓骨与假体复合进一步提高了骨缺损重建材料的强度，利于早期活动，早期受力，力学刺激将发挥压电陶瓷的压电特性，进一步促进假体的骨长入，最终完成骨与假体的整合，实现早期骨缺损修复治疗；2.所设计假体将传统假体固定后单一的外到内的骨生长方向，变为外到内，内到外的双向骨生长，促进假体的骨长入，增加假体的稳定性，有利于骨缺损的早期愈合及远期稳定性；3.3D打印个性化定制假体外形与骨缺损区高度契合，利于手术实施，避免重建后双侧肢体不等长；4.假体管壁全层均为多孔结构，降低应力遮挡效应；孔隙结构有利于植入，增强了与骨组织界面的稳定性；5.表面活性处理提高假体生物相容性，诱导新骨生长，达到良好的骨整合效果；6.一体化接骨板与骨干契合度高，增加固定可靠性。不需附加辅助内固定，更具有经济性。1. The combination of the fibula and the prosthesis further improves the strength of the bone defect reconstruction material, which is conducive to early movement and early stress. The mechanical stimulation will exert the piezoelectric characteristics of piezoelectric ceramics, further promote the bone ingrowth of the prosthesis, and finally complete the bone and The integration of the prosthesis realizes early bone defect repair treatment; 2. The designed prosthesis changes the single outside-to-inside bone growth direction after the traditional prosthesis is fixed into the outside-to-inside and inside-to-outside two-way bone growth, which promotes the prosthesis The bone ingrowth of the body increases the stability of the prosthesis, which is beneficial to the early healing and long-term stability of the bone defect; The length of the side limbs is unequal; 4. The whole layer of the prosthesis wall is porous structure, which reduces the stress shielding effect; the pore structure is conducive to implantation and enhances the stability of the interface with bone tissue; 5. Surface active treatment improves the biological Compatibility, induce new bone growth, and achieve good osseointegration effect; 6. The integrated bone plate has a high degree of fit with the backbone, increasing the reliability of fixation. There is no need for additional auxiliary internal fixation, which is more economical.

进一步的孔隙结构采用正十六面体金刚石结构，提高了假体承重能力；假体管壁形状与缺损区骨干相仿，利于假体植入后与上下端契合；厚度大于骨皮质0.5mm-1.0mm，确保具有足够的承重能力避免切割骨皮质；接骨板与管型假体为复合结构一体化打印，提高结合强度。接骨板形状与骨干高度契合以利于固定。假体预留腓骨植入区，便于腓骨植入及血管吻合。The further pore structure adopts the regular hexahedral diamond structure, which improves the load-bearing capacity of the prosthesis; the shape of the prosthesis tube wall is similar to the backbone of the defect area, which facilitates the fit of the prosthesis to the upper and lower ends after implantation; the thickness is 0.5mm-1.0mm larger than the cortical bone, Ensure sufficient load-bearing capacity to avoid cutting the cortical bone; the bone plate and tubular prosthesis are printed as a composite structure to improve the bonding strength. The shape of the bone plate fits the height of the bone to facilitate fixation. The prosthesis reserves the fibula implantation area to facilitate fibula implantation and vascular anastomosis.

附图说明Description of drawings

图1是本发明的整体结构示意图；Fig. 1 is the overall structural representation of the present invention;

图2是图1的侧视图；Fig. 2 is a side view of Fig. 1;

图3是图1的左视图。Fig. 3 is a left side view of Fig. 1 .

具体实施方式Detailed ways

下面结合附图对本发明做进一步详细说明。The present invention will be described in further detail below in conjunction with the accompanying drawings.

1)3D打印管状多孔钛合金假体制备1) Preparation of 3D printed tubular porous titanium alloy prosthesis

参见图1，2，采用计算机辅助设计软件，根据患者薄层CT扫描数据，结合手术路径及病变部位截骨平面形态，设计带有接骨板1的中空管状的多孔假体2，参见图3，为便于腓骨移植多孔假体2设计为中空管状的植骨槽，管壁3为多孔孔隙结构，形状与缺损区骨干相仿，管壁厚度大于植入区骨干0.5mm-1.0mm，孔隙结构为正十六面体金刚石结构，其孔隙率一般为50％-80％，孔径范围为500μm-700μm，管壁留有中空结构的植骨槽，便于腓骨植入及血管吻合等操作，植入腓骨可实现由管壁内侧向外侧的骨长入，多孔假体2与接骨板1为一体化连接，在固定骨折端的同时，可将假体与残留骨端锁定，而不需其他辅助固定，简化手术流程、提高经济效益。接骨板形状与骨干高度契合，利于增强固定的稳定性，避免术后内固定松动。假体设计完成后，使用有限元方法进行强度分析，根据分析结果优化接骨板置钉位置、植骨槽开口大小。设计完成后将数据导入打印设备，在650℃以30mA的电子束流，以15000mm/s的扫描速度预热钛合金粉末(Ti-6Al-4V)，然后以6mA的电子束流，400mm/s的扫描速度由计算机控制，按照设定好的程序逐层熔化合金粉末。最后制备成与预期形状一致的3D打印管状多孔钛合金假体。Referring to Figures 1 and 2, a hollow tubular porous prosthesis 2 with an osteosynthesis plate 1 is designed according to the patient's thin-section CT scan data, combined with the surgical path and the osteotomy plane shape of the lesion, using computer-aided design software, as shown in Figure 3, In order to facilitate the implantation of the fibula, the porous prosthesis 2 is designed as a hollow tubular bone grafting groove. The tube wall 3 has a porous structure, which is similar in shape to the backbone of the defect area. The hexahedral diamond structure generally has a porosity of 50%-80%, and a pore diameter range of 500μm-700μm. There is a hollow bone graft groove on the tube wall, which is convenient for fibula implantation and vascular anastomosis. The inner side of the tube wall grows into the outer bone, and the porous prosthesis 2 is integrated with the bone plate 1. While fixing the fracture end, the prosthesis can be locked with the residual bone end without other auxiliary fixation, which simplifies the operation process. Improve economic efficiency. The shape of the bone plate matches the height of the bone, which is conducive to enhancing the stability of the fixation and avoiding loosening of the internal fixation after surgery. After the design of the prosthesis is completed, the strength analysis is carried out using the finite element method, and the position of the bone plate and the opening size of the bone graft groove are optimized according to the analysis results. After the design is completed, import the data into the printing device, preheat the titanium alloy powder (Ti-6Al-4V) at 650°C with an electron beam current of 30mA and a scanning speed of 15000mm/s, and then use an electron beam current of 6mA at a scanning speed of 400mm/s The scanning speed of the machine is controlled by the computer, and the alloy powder is melted layer by layer according to the set program. Finally, a 3D printed tubular porous titanium alloy prosthesis was prepared in accordance with the expected shape.

2)3D打印管状钛合金假体表面活性处理2) Surface active treatment of 3D printed tubular titanium alloy prosthesis

2-1)构建微米级氧化钛活性表面涂层2-1) Construction of micron-sized titanium oxide active surface coating

将制备的管状多孔钛合金假体作为工作电极，采用恒电压模式制备涂层：将制备的管状多孔钛合金假体置于醋酸钙浓度为0.2mol/L，β甘油磷酸钠浓度为0.04mol/L的电解液中，在频率为200Hz，占空比为15％，以恒定350V电压下脉冲-直流电源对管状多孔钛合金假体进行微弧氧化处理后在恒温水浴下再处理5min，得到表面具有氧化钛的3D打印管状钛合金假体；The prepared tubular porous titanium alloy prosthesis was used as the working electrode, and the coating was prepared in constant voltage mode: the prepared tubular porous titanium alloy prosthesis was placed in a concentration of calcium acetate of 0.2 mol/L, and a concentration of β-glycerophosphate sodium of 0.04 mol/L. In the electrolyte of L, at a frequency of 200 Hz and a duty ratio of 15%, the tubular porous titanium alloy prosthesis was subjected to micro-arc oxidation treatment with a pulse-DC power supply at a constant voltage of 350 V, and then treated in a constant temperature water bath for 5 minutes to obtain a surface 3D printed tubular titanium alloy prostheses with titanium oxide;

2-2)构建纳米级钛酸钡压电活性表面涂层2-2) Construction of nanoscale barium titanate piezoelectric active surface coating

以表面具有氧氧化钛的3D打印管状钛合金假体作为钛源，原位自转化合成钛酸钡压电陶瓷涂层：在100-120℃不锈钢高压反应釜中，将表面具有氧化钛的3D打印管状钛合金假体置于Ba²⁺浓度为0.25mol/L的Ba(OH)₂溶液中，采用NaOH调节PH值至13，在反应压力为0.7-1.1MPa，反应1-3小时，氧化钛溶解与溶液中的钡离子原位反应在氧化钛的3D打印管状钛合金假体表面生成钛酸钡。Using the 3D printed tubular titanium alloy prosthesis with titanium oxide on the surface as the titanium source, in situ self-transformation to synthesize the barium titanate piezoelectric ceramic coating: in a stainless steel autoclave at 100-120°C, the 3D titanium alloy prosthesis with titanium oxide on the surface The printed tubular titanium alloy prosthesis is placed in a Ba(OH) ₂ solution with a Ba ²⁺ concentration of 0.25mol/L, the pH value is adjusted to 13 with NaOH, and the reaction pressure is 0.7-1.1MPa, reacted for 1-3 hours, and oxidized The in-situ reaction between titanium dissolution and barium ions in the solution produces barium titanate on the surface of the titanium oxide 3D printed tubular titanium alloy prosthesis.

按本发明的制备方法制得的用于四肢大段骨缺损的3D打印管状多孔钛合金假体包括带有接骨板1的孔隙率为50％-80％，孔径为500μm-700μm的腓骨植入的中空管状的多孔假体2，所述接骨板1形状与骨干外形契合，所述的中空管状形态的多孔假体2的多孔空间结构采用正十六面体金刚石结构，中空管状形态的多孔假体2管壁形状与缺损区骨干相仿，管壁3的厚度大于骨皮质0.5mm-1.0mm。The 3D printed tubular porous titanium alloy prosthesis for large-segment bone defects of limbs prepared according to the preparation method of the present invention includes a fibula implant with a porosity of 50%-80% and a diameter of 500 μm-700 μm with a bone plate 1 Hollow tubular porous prosthesis 2, the shape of the bone plate 1 fits the shape of the backbone, the porous space structure of the hollow tubular porous prosthesis 2 adopts a regular hexahedral diamond structure, and the hollow tubular porous prosthesis 2 The shape of the tube wall is similar to that of the backbone of the defect area, and the thickness of the tube wall 3 is 0.5mm-1.0mm greater than that of the cortical bone.

本发明在保留压电陶瓷压电特性的前提下，大大提高了其与基底材料的结合强度，解决了压电陶瓷涂层与基底材料结合能力较差的问题，使得力学-电学效应在促进骨长入中所发挥效能。赋予多孔钛合金假体一定的压电性能，提高其骨诱导长入能力，促进其早期形成骨整合。On the premise of retaining the piezoelectric properties of piezoelectric ceramics, the present invention greatly improves the bonding strength between the piezoelectric ceramic coating and the base material, solves the problem of poor bonding ability between the piezoelectric ceramic coating and the base material, and makes the mechanical-electrical effect promote bone The effectiveness of growing up. Endow the porous titanium alloy prosthesis with certain piezoelectric properties, improve its osteoinductive ingrowth ability, and promote its early formation of osseointegration.