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CN1318001C - Photocureable rapid shaping indirect manufacturing method for controllable microtube structure stand - Google Patents

Photocureable rapid shaping indirect manufacturing method for controllable microtube structure stand Download PDF

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CN1318001C
CN1318001C CNB2004100733244A CN200410073324A CN1318001C CN 1318001 C CN1318001 C CN 1318001C CN B2004100733244 A CNB2004100733244 A CN B2004100733244A CN 200410073324 A CN200410073324 A CN 200410073324A CN 1318001 C CN1318001 C CN 1318001C
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CN1613435A (en
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李涤尘
李祥
卢秉恒
王臻
王林
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Xian Jiaotong University
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Abstract

本发明公开了一种可控微管道结构支架的光固化快速成型间接制造方法,方法以计算机辅助设计(CAD)和光固化快速成型设备为基础,精确设计和控制支架内部微观结构,实现支架外形与内部可控微结构一体化制造。根据实际CT数据,应用三维CAD软件重构骨骼外形;依据利于细胞生长和促进成骨的原则,设计不同结构的支架内部微管道,控制微管道的尺寸、形状、走向、分支以及相互连通性。利用光固化快速成型设备构造相应的树脂模具,在模具中填充生物材料,待其固化后,通过热分解去除树脂模具,形成具有可控微结构的组织工程支架。

Figure 200410073324

The invention discloses a light-cured rapid prototyping indirect manufacturing method of a controllable micro-pipe structure support. The method is based on computer-aided design (CAD) and light-cured rapid prototyping equipment, precisely designs and controls the internal microstructure of the support, and realizes the shape and shape of the support. Integrated manufacturing of internal controllable microstructure. According to the actual CT data, three-dimensional CAD software is used to reconstruct the bone shape; according to the principle of promoting cell growth and osteogenesis, the internal microchannels of different structures are designed, and the size, shape, direction, branching and interconnection of the microchannels are controlled. Use photocuring rapid prototyping equipment to construct corresponding resin molds, fill the molds with biomaterials, and after curing, remove the resin molds by thermal decomposition to form tissue engineering scaffolds with controllable microstructures.

Figure 200410073324

Description

可控微管道结构支架的光固化快速成型间接制造方法Light-curing rapid prototyping indirect manufacturing method of controllable microchannel structure scaffold

技术领域technical field

本发明属于光固化快速成型制造技术,涉及一种组织工程支架的制备,特别涉及可控微管道结构支架的光固化快速成型间接制造方法。The invention belongs to the light-curing rapid prototyping manufacturing technology, relates to the preparation of a tissue engineering support, in particular to the indirect manufacturing method of the light-curing rapid prototyping of the controllable micro-pipe structure support.

背景技术Background technique

众所周知,在骨组织工程中,支架作为细胞的临时载体,其外形不但要与所替代部位一致,而且内部微结构一定要满足如下条件:有利于细胞/组织长入,有利于营养成分和血液的供给,有利于气体的交换等。因骨骼的外形十分复杂,如果使用传统的加工方法来制造与骨骼外形相匹配的支架,是很困难的。传统支架的制孔方法(如:相分离/乳化、纤维粘接、溶液浇铸/粒子沥滤、熔融成型、气体发泡以及这几种方法的并用)应用已经十分广泛。但传统的支架制造方法存在着致命的缺点,主要表现为制造过程为人工操作,使用有毒的有机溶剂,很难制造出与骨骼相匹配的外形轮廓,无法准确控制支架内部微孔或微管道的分布、尺寸、空间走向、连通性等结构特征。As we all know, in bone tissue engineering, as a temporary carrier of cells, the scaffold should not only have the same appearance as the replaced part, but also the internal microstructure must meet the following conditions: it is conducive to the growth of cells/tissues, and the absorption of nutrients and blood. supply, which is conducive to the exchange of gases, etc. Because the shape of the bone is very complex, it is very difficult to manufacture a bracket that matches the shape of the bone using traditional processing methods. The pore-making methods of traditional scaffolds (such as: phase separation/emulsification, fiber bonding, solution casting/particle leaching, fusion molding, gas foaming and the combination of these methods) have been widely used. However, there are fatal shortcomings in the traditional scaffold manufacturing method, mainly manifested in the fact that the manufacturing process is manual, using toxic organic solvents, it is difficult to manufacture a shape that matches the bone, and it is impossible to accurately control the internal micropores or microchannels of the scaffold. Structural features such as distribution, size, spatial orientation, and connectivity.

快速成型(Rapid Prototyping,RP)技术是近年来形成的一门新型制造技术,其最大的优势是直接由数字驱动,不受形状复杂程度的限制,直接成型三维实体。使用快速成型技术来制造骨组织工程支架不但可以避免上述缺点,而且还可以有效结合CAD技术,实现对支架结构的优化与仿生设计,以及对支架制造过程的精确控制。快速成型技术在支架构造方面的应用,国内外都已见报道,多数是利用熔融沉积(FDM)和三维打印(3DP)技术直接构造三维多孔支架。使用这类方法构造的支架,支架材料多数采用聚合物,因此缺乏足够得机械强度。不能作为承重部位的骨替代物。Rapid Prototyping (RP) technology is a new manufacturing technology formed in recent years. Its biggest advantage is that it is directly driven by numbers, and it is not limited by the complexity of the shape, and it can directly form a three-dimensional entity. The use of rapid prototyping technology to manufacture bone tissue engineering scaffolds can not only avoid the above shortcomings, but also effectively combine CAD technology to realize the optimization and bionic design of the scaffold structure, as well as the precise control of the scaffold manufacturing process. The application of rapid prototyping technology in scaffold construction has been reported at home and abroad, and most of them use fused deposition (FDM) and three-dimensional printing (3DP) technologies to directly construct three-dimensional porous scaffolds. The stent constructed by this method is mostly made of polymer, and thus lacks sufficient mechanical strength. Not intended as a bone substitute in weight-bearing areas.

发明内容Contents of the invention

本发明的目的在于,提供一种采用光固化快速成型制造技术间接制备可控微管道结构支架的方法。The object of the present invention is to provide a method for indirectly preparing a controllable micro-pipe structure support by using photocuring rapid prototyping manufacturing technology.

实现上述目的的技术解决方案是,一种可控微管道结构支架的光固化快速成型间接制造方法,以临床CT数据和计算机辅助设计为基础,采用光固化快速成型设备并结合快速铸造制备可控微管道结构支架,其特征在于,包括下列步骤:The technical solution to achieve the above purpose is an indirect manufacturing method of light-cured rapid prototyping of controllable micro-pipe structure support, based on clinical CT data and computer-aided design, using light-cured rapid prototyping equipment combined with rapid casting to prepare controllable The micro-pipe structure support is characterized in that it comprises the following steps:

1)依据制备的部位相匹配的骨组织实际临床CT数据,应用CAD软件实现骨骼外形三维重构,设计支架内部微结构;1) According to the actual clinical CT data of bone tissue matched with the prepared part, CAD software is used to realize the three-dimensional reconstruction of the bone shape and design the internal microstructure of the scaffold;

2)将上述CAD软件设计的实体数据转换成STL格式文件,经过Rpdata软件分层切片处理,生成光固化快速成型设备默认的格式文件,输入到光固化快速成型设备中;2) Convert the entity data designed by the above-mentioned CAD software into an STL format file, and after layered slicing processing by the Rpdata software, generate the default format file of the light-curing rapid prototyping equipment, and input it into the light-curing rapid prototyping equipment;

上述光固化快速成形设备的激光光源为230-355nm波长的固体激光器,其控制参数如下:The laser light source of the above photocuring rapid prototyping equipment is a solid-state laser with a wavelength of 230-355nm, and its control parameters are as follows:

填充扫描速度:Vs1=5000mm/sFilling scanning speed: Vs 1 =5000mm/s

轮廓扫描速度:Vs2=3000mm/sContour scanning speed: Vs 2 =3000mm/s

扫描间距:Gs=0.10mmScanning distance: Gs=0.10mm

层厚:Lh=0.10mmLayer thickness: Lh=0.10mm

光斑直径:D1=0.2mmSpot diameter: D1=0.2mm

3)由光固化快速成型设备制造出上述相应支架的树脂模具;并在上述树脂模具中填充注射型自固化磷酸钙骨水泥、β-磷酸三钙生物陶瓷或羟基磷灰石生物材料,待其固化后热分解去模并烧结成型,即可获得可控微管道结构支架;3) Manufacture the resin mold of the above-mentioned corresponding bracket by light-curing rapid prototyping equipment; and fill the injection-type self-curing calcium phosphate bone cement, β-tricalcium phosphate bioceramic or hydroxyapatite biomaterial in the above-mentioned resin mold, and wait for the After curing, thermally decompose and remove the mold and sinter to form a controllable micro-pipe structure support;

上述填充生物材料热分解去除树脂模具并烧结成型的方法分别是:The methods for thermally decomposing and sintering the filled biomaterials to remove the resin mold are as follows:

A.将固化后并注射型自固化磷酸钙骨水泥的树脂模具放入高温箱式电阻炉,入炉温度为室温,升温速度设定为100℃/h,升至500℃后,将升温速度改为300℃/h,升至900℃,并保温180分钟,随炉冷却至室温后取出,即可去除树脂模具,得到与设计相符的可控微管道结构支架;A. Put the resin mold of cured and injected self-curing calcium phosphate bone cement into a high-temperature box-type resistance furnace. The furnace temperature is room temperature, and the heating rate is set at 100°C/h. Change it to 300°C/h, raise it to 900°C, and keep it warm for 180 minutes. After cooling to room temperature with the furnace, take it out, and the resin mold can be removed to obtain a controllable micropipeline structure support that matches the design;

B.将固化后的β-磷酸三钙生物陶瓷的树脂模具放入到高温箱式电阻炉,其烧结温度是1150℃;当温度达到900℃时,树脂模具被热分解,再进一步烧结,得到可控微管道结构支架;B. Put the resin mold of the cured β-tricalcium phosphate bioceramic into a high-temperature box-type resistance furnace, and the sintering temperature is 1150°C; when the temperature reaches 900°C, the resin mold is thermally decomposed, and then further sintered to obtain Controllable micro-channel structure scaffold;

C.将固化后的羟基磷灰石树脂模具放入到高温箱式电阻炉,其烧结温度是1250℃,当温度达到900℃时,树脂模具被热分解,再进一步烧结,得到可控微管道结构支架。C. Put the cured hydroxyapatite resin mold into a high-temperature box-type resistance furnace. The sintering temperature is 1250°C. When the temperature reaches 900°C, the resin mold is thermally decomposed and further sintered to obtain a controllable micropipe structural support.

本发明的方法克服了传统支架制造方法中外形构造困难、内部微管道结构不可控的缺点,利用CAD技术可以方便准确的设计出有利于细胞-组织长入和存活、有利于氧气和营养供给、有利于代谢物排出的三维空间结构。通过快速成型技术实现对制造过程的准确控制,从而构造出无论是外形还是内部微管道的形状、尺寸、分布、空间走向以及相互连通性都与设计完全相符的骨组织工程支架。The method of the present invention overcomes the shortcomings of difficult shape and structure and uncontrollable internal micro-pipe structure in the traditional scaffold manufacturing method, and can be conveniently and accurately designed by using CAD technology, which is beneficial to cell-tissue growth and survival, oxygen and nutrient supply, A three-dimensional structure that facilitates the excretion of metabolites. Accurate control of the manufacturing process is achieved through rapid prototyping technology, so that the bone tissue engineering scaffold that is completely consistent with the design in terms of shape, size, distribution, spatial orientation, and interconnectivity of the internal microchannels can be constructed.

附图说明Description of drawings

图1是支架及其负型CAD模型图片;Fig. 1 is a picture of the support and its negative CAD model;

图2是重构所得狗股骨远端外形以及所设计的内部微管道结构CAD模型图片;Fig. 2 is the CAD model picture of the reconstructed dog femur distal end shape and the designed internal micro-canal structure;

图3是本发明的方法制备可控微结构支架流程图。Fig. 3 is a flowchart of preparing a controllable microstructure scaffold by the method of the present invention.

以下结合发明人给出的实施例对本发明作进一步的详细描述。The present invention will be described in further detail below in conjunction with the examples given by the inventor.

具体实施方式Detailed ways

按照本发明的技术方案,本发明采用的CAD设计软件选用商业化三维CAD设计软件Unigraphics 18.0作为设计工具。所设计的支架为圆柱体,内部结构为轮辐形。直径14.5mm,高11.6mm;如图1a所示。相应的支架负型如图1b所示。其内部特征描述如下:x-y平面内是300μm×300μm的矩形通道,从支架中心沿径向延伸到外表面;z方向是直径为500μm的圆柱形通道从支架顶端一直贯串到底部,而且这些圆柱形通道在x-y平面内有环形通道将其连通。由这些微管道所产生的孔隙率为21.6%。According to the technical scheme of the present invention, the CAD design software adopted in the present invention selects commercialized three-dimensional CAD design software Unigraphics 18.0 as a design tool. The designed support is a cylinder with a spoke-shaped internal structure. 14.5mm in diameter and 11.6mm in height; as shown in Figure 1a. The corresponding scaffold negative is shown in Fig. 1b. Its internal features are described as follows: in the x-y plane is a rectangular channel of 300 μm × 300 μm, extending radially from the center of the scaffold to the outer surface; in the z direction is a cylindrical channel with a diameter of 500 μm running from the top to the bottom of the scaffold, and these cylindrical The channels are connected by circular channels in the x-y plane. The porosity generated by these microchannels is 21.6%.

将支架负型CAD实体数据转换三角面片(STL)数据格式,经过Rpdata软件分层切片处理,生成快速成型默认格式文件后,输入到光固化快速成形设备(SPS600),制造出相应的树脂原型模具。光固化快速成形设备的控制参数如下:The negative CAD entity data of the bracket is converted into the triangular surface (STL) data format, and after the Rpdata software layered slice processing, the default format file of rapid prototyping is generated, and then input to the light-curing rapid prototyping equipment (SPS600) to manufacture the corresponding resin prototype mold. The control parameters of the photocuring rapid prototyping equipment are as follows:

填充扫描速度Vs1=5000mm/sFilling scanning speed Vs 1 =5000mm/s

轮廓扫描速度Vs2=3000mm/sContour scanning speed Vs 2 =3000mm/s

扫描间距Gs=0.10mmScanning distance Gs=0.10mm

层厚Lh=0.10mmLayer thickness Lh=0.10mm

光斑直径D1=0.2mmSpot diameter D1=0.2mm

激光光源:固体激光器(355nm波长)Laser light source: solid-state laser (355nm wavelength)

将注射型自固化磷酸钙(Calcium phosphate cement,CPC)骨水泥生物材料填充到树脂模具中,待其固化后放入到高温箱式电阻炉,入炉温度为室温,升温速度设定为100℃/h,升至500℃后,将升温速度改为300℃/h,升至900℃,并保温180分钟,随炉冷却至室温后取出,即可去除树脂模具,得到与设计相符的可控微管道结构支架。Fill the injection-type self-curing calcium phosphate cement (Calcium phosphate cement, CPC) bone cement biomaterial into the resin mold, and put it into a high-temperature box-type resistance furnace after it is cured. The furnace temperature is room temperature, and the heating rate is set at 100°C /h, after rising to 500°C, change the heating rate to 300°C/h, rise to 900°C, and keep it warm for 180 minutes, then take it out after cooling to room temperature with the furnace, and then remove the resin mold, and get a controllable Structural Scaffolds for Micropipes.

如果支架形状为方形,其内部结构为正交网架形,按照上述步骤也很容易得到与设计相符的可控微管道结构支架。If the shape of the scaffold is square and its internal structure is in the shape of an orthogonal network frame, it is also easy to obtain a controllable micropipe structure scaffold conforming to the design according to the above steps.

下面给出狗股骨远端仿生支架的具体实施例:Provide the specific embodiment of dog femur distal end bionic support below:

采用发明的方法制备狗股骨远端仿生支架的图片参见图2,其流程如图3所示。根据临床CT数据,经过一系列图像处理后,将连续的CT图片按顺序输入到Mimics软件,获取狗股骨远端点云数据,并以IGES格式文件存储,再将获取的点云数据输入到Surface软件进行曲面重构,由于股骨远端关节表面形状复杂,曲率变化大,加上所获取的点云数据存在一定偏差,如果单纯采用传统的构面方法,如:Loft、Sweep、Through Curve和Through CurveMesh等,都不能很有效地构建出高质量的关节曲面。因此应用点数据贴和自由曲面(fit freeform)和点数据与边界曲线建构曲面(fit freeform with cloud&boundary curve)这两种构面方式,完成关节曲面的三维重构,并以IGES格式文件存储。然后再输入到Unigraphics软件,进行骨外形三维实体重构,并依照利于细胞/组织生长、营养输送和促进成骨的原则设计内部微管道结构,主要包括内部微管道的分布、尺寸、形状、空间走向、分支、相互连通性。重构所得狗的股骨远端外形以及所设计的内部微管道结构CAD模型如图2所示。然后将这些CAD实体数据转换成STL格式文件,经过Rpdata软件分层切片处理,生成快速成型默认格式文件后,输入到光源特征为230-355nm光源的光固化快速成型设备,构造出相应的树脂模型。在树脂模具中填充自固化CPC生物材料,待其固化后放入到高温箱式电阻炉,入炉温度为室温,升温速度设定为100℃/h,升至500℃后,将升温速度改为300℃/h,升至900℃,使树脂模具被热分解,并保温180分钟,随炉冷却至室温后取出。从而形成外形与狗股骨远端个体化匹配,同时又具有可控微管道结构的三维多孔支架。See Figure 2 for a picture of the bionic scaffold for the distal femur of a dog prepared by the inventive method, and the process flow is shown in Figure 3 . According to the clinical CT data, after a series of image processing, the continuous CT images are input into the Mimics software in order to obtain the point cloud data of the distal femur of the dog, and store them in IGES format files, and then input the obtained point cloud data into the Surface The software performs surface reconstruction. Due to the complex shape of the joint surface of the distal femur, large curvature changes, and certain deviations in the obtained point cloud data, if only traditional faceting methods are used, such as: Loft, Sweep, Through Curve and Through CurveMesh, etc., cannot effectively construct high-quality joint surfaces. Therefore, the three-dimensional reconstruction of the joint surface is completed by using the two faceting methods of point data paste and freeform surface (fit freeform) and point data and boundary curve construction surface (fit freeform with cloud&boundary curve), and the files are stored in IGES format. Then input it into the Unigraphics software to reconstruct the three-dimensional entity of the bone shape, and design the internal microchannel structure according to the principles of facilitating cell/tissue growth, nutrient delivery, and promoting osteogenesis, mainly including the distribution, size, shape, and space of the internal microchannels. Trends, branches, interconnectedness. Figure 2 shows the reconstructed dog's distal femur shape and the designed internal microcanal structure CAD model. Then convert these CAD entity data into STL format files, and after layered slice processing by Rpdata software, the default rapid prototyping format files are generated, and then input to the photocuring rapid prototyping equipment with light source characteristics of 230-355nm light source to construct the corresponding resin model . Fill the resin mold with self-curing CPC biomaterial, put it into a high-temperature box-type resistance furnace after curing, enter the furnace at room temperature, and set the heating rate at 100°C/h. After rising to 500°C, change the heating rate to The temperature is 300°C/h, raised to 900°C to decompose the resin mold and keep it warm for 180 minutes, then take it out after cooling to room temperature with the furnace. In this way, a three-dimensional porous scaffold with a controllable micro-canal structure and an individualized shape matching the distal femur of a dog is formed.

当然,采用本发明的方法的上述步骤即可制备任何形状的可控微管道结构支架。也可选用其它生物材料,如β-磷酸三钙(TCP)生物陶瓷,其烧结温度是1150℃;羟基磷灰石(HA),其烧结温度是1250℃。当温度达到900℃时,树脂模具被热分解,再进一步烧结,得到可控微管道结构支架。Certainly, the controllable micro-pipe structure scaffold of any shape can be prepared by adopting the above-mentioned steps of the method of the present invention. Other biological materials can also be used, such as β-tricalcium phosphate (TCP) bioceramics, whose sintering temperature is 1150°C; hydroxyapatite (HA), whose sintering temperature is 1250°C. When the temperature reaches 900 °C, the resin mold is thermally decomposed, and then further sintered to obtain a controllable micro-pipe structure scaffold.

由于本发明采用了生物材料,能够制造出外形所替代部位相匹配、内部拥有利于细胞-组织生长微管道结构的生物活性人工骨支架。能够克服目前临床上应用十分广泛的金属(如:不锈钢、钛合金)骨替代物不能被人体吸收降解的缺点,具有生物活性的人工骨支架在植入体内后,生物材料不断降解,而与此同时新骨在支架微管道中不断生成,最终生物材料完全降解,而基于支架所新生的骨组织与体内原有的骨组织长在一起,形成一个新的有机整体。Because the invention adopts biomaterials, it can manufacture bioactive artificial bone scaffolds that match the replaced parts in shape and have microchannel structures that are conducive to cell-tissue growth inside. It can overcome the shortcomings of metal (such as stainless steel, titanium alloy) bone substitutes that are widely used in clinical practice that cannot be absorbed and degraded by the human body. At the same time, new bone is continuously generated in the microchannel of the scaffold, and finally the biomaterial is completely degraded, and the new bone tissue based on the scaffold grows together with the original bone tissue in the body to form a new organic whole.

Claims (1)

1. the photocureable rapid shaping indirect manufacturing method of a controllable microtube structure stand, based on Clinical CT data and computer-aided design, adopt light-curing rapid forming equipment and combination casting preparation controllable microtube structure stand fast, it is characterized in that, comprise the following steps:
1) the osseous tissue actual clinical CT data that are complementary according to the position for preparing are used CAD software and are realized skeleton profile three-dimensionalreconstruction, design internal stent micro structure;
2) solid data with above-mentioned CAD software design converts the STL formatted file to, through Rpdata software hierarchy slicing treatment, generates the formatted file of light-curing rapid forming equipment acquiescence, is input in the light-curing rapid forming equipment;
The LASER Light Source of above-mentioned light-curing rapid forming equipment is the solid state laser of 230-355nm wavelength, and its control parameter is as follows:
Fill scanning speed: Vs 1=5000mm/s
Profile scan speed: Vs 2=3000mm/s
Sweep span: Gs=0.10mm
Bed thickness: Lh=0.10mm
Spot diameter: D1=0.2mm
3) produce the resin die of above-mentioned support by light-curing rapid forming equipment, and in above-mentioned resin die filling injection type self-curable calcium phosphate bone cement, bata-tricalcium phosphate bioceramic or hydroxylapatite biology material, treat that it solidifies the back thermal decomposition and goes mould and sinter molding, can obtain controllable microtube structure stand;
The method that resin die and sinter molding are removed in the thermal decomposition of filling injection type self-curable calcium phosphate bone cement is, injection-type self-curable calcium phosphate bone cement is filled in the resin die, treat to put into high temperature box type resistance furnace after it solidifies, charging temperature is a room temperature, programming rate is set at 100 ℃/h, after rising to 500 ℃, change programming rate into 300 ℃/h, rise to 900 ℃, and be incubated 180 minutes, take out after cooling to room temperature with the furnace, can remove resin die, obtain and design the controllable microtube structure stand that conforms to;
Fill the thermal decomposition of bata-tricalcium phosphate bioceramic and remove the method for resin die and sinter molding and be, the bata-tricalcium phosphate bioceramic is filled in the resin die, treat to put into high temperature box type resistance furnace after it solidifies, its sintering temperature is 1150 ℃; When temperature reached 900 ℃, resin die was thermal decomposited, and further again sintering obtains controllable microtube structure stand;
The method of filling hydroxylapatite biology material thermal decomposition removal resin die and sinter molding is, hydroxyapatite is filled in the resin die, treat to put into high temperature box type resistance furnace after it solidifies, its sintering temperature is 1250 ℃, when temperature reaches 900 ℃, resin die is thermal decomposited, and further again sintering obtains controllable microtube structure stand.
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