CN102415920A - Manufacturing method of individual stent used for mandibular defect tissue engineering repair - Google Patents
Manufacturing method of individual stent used for mandibular defect tissue engineering repair Download PDFInfo
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- A—HUMAN NECESSITIES
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- 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
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- 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
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Abstract
Description
技术领域 technical field
本发明涉及一种下颌骨缺损修复用组织工程支架的制造方法。The invention relates to a manufacturing method of a tissue engineering bracket for mandibular defect repair.
背景技术 Background technique
组织工程是应用工程与生命科学的原理与方法来认识哺乳类组织(正常或病理状态下)的结构与功能的关系,并研制人工生物材料以便恢复、维持或改善其功能。组织工程作为面向移植而产生功能组织和器官的科学和技术,集成了CT/MRI等图像测量技术、三维重建技术、快速原型技术、材料工程技术、生物工程技术等不同的学科领域。其基本原则是组织可以从病人身上分离出来,在特殊材料制成的组织支架中生长和扩张,最终形成支架引导的三维组织。这样,生成的三维组织可以移植到同一个病人中,以替代病变组织的功能。Tissue engineering is the application of engineering and life science principles and methods to understand the relationship between the structure and function of mammalian tissues (under normal or pathological conditions), and to develop artificial biomaterials to restore, maintain or improve their functions. As a science and technology for generating functional tissues and organs for transplantation, tissue engineering integrates image measurement technologies such as CT/MRI, 3D reconstruction technology, rapid prototyping technology, material engineering technology, bioengineering technology and other disciplines. The basic principle is that tissue can be separated from the patient, grow and expand in a tissue scaffold made of special materials, and finally form a scaffold-guided three-dimensional tissue. In this way, the resulting three-dimensional tissue can be transplanted into the same patient to replace the function of the diseased tissue.
组织能够再生主要在于组织支架的结构上的可成形性和支架在种子细胞作用下的生物反应器功能。支架由诸如孔、纤维、膜等结构元素通过随机、分形或周期分布规律组合而成,通过工程方法可以被复制和制造。当一个三维组织结构被用于开发人工替代组织时,可以对支架结构中的生物材料进行工程结构设计,以优化结构并满足一定的营养条件。Tissue regeneration mainly lies in the structural formability of the tissue scaffold and the bioreactor function of the scaffold under the action of seed cells. Scaffolds are composed of structural elements such as pores, fibers, and membranes that are randomly, fractally, or periodically distributed, and can be replicated and manufactured through engineering methods. When a three-dimensional tissue structure is used to develop artificial replacement tissues, the biomaterials in the scaffold structure can be engineered to optimize the structure and meet certain nutritional conditions.
近年来,由于肿瘤、感染、交通事故等原因造成的颌面特别是下颌缺损具有逐年增多的趋势,仅在欧洲每年就有150万人需要进行颅颌面外科手术进行骨重建,其中有相当大一部分是下颌骨的手术。下颌缺损修复的难点在于修复手术必须恢复患者容貌和口腔的咀嚼等功能,因此对植入体的外形和结构有特殊要求。目前的下颌缺损修复手术主要采用自体骨移植和金属修复体植入两种修复方式,自体骨移植修复会造成取骨部位的二次创伤,而且供骨的大小有限,同时植入时由于血管化手术非常困难,造成植入体血供不足,导致自体骨植入体吸收很难控制,影响修复效果。金属植入物修复时,虽然目前根据患者自身骨骼结构的个性化定制技术已经比较成熟,但植入体内部结构的设计和制造面临诸多困难,导致植入手术后金属植入体与周围骨骼的骨结合效果不佳,从而影响长久修复的效果。In recent years, maxillofacial defects, especially mandibular defects, have been increasing year by year due to tumors, infections, traffic accidents and other reasons. In Europe alone, 1.5 million people need craniofacial surgery for bone reconstruction each year, of which a considerable number One part is surgery on the mandible. The difficulty in repairing mandibular defects lies in the restoration of the patient's appearance and oral chewing functions, so there are special requirements for the shape and structure of the implant. The current mandibular defect repair surgery mainly adopts autologous bone grafting and metal prosthesis implantation. The operation is very difficult, resulting in insufficient blood supply to the implant, which makes it difficult to control the absorption of the autogenous bone implant, which affects the repair effect. When metal implants are repaired, although the personalized customization technology based on the patient's own bone structure is relatively mature, the design and manufacture of the internal structure of the implant faces many difficulties, which leads to the gap between the metal implant and the surrounding bone after the implantation operation. Poor osseointegration affects the effect of long-term repair.
针对目前下颌骨缺损修复中存在的问题,本发明提出一种与病人面部结构相匹配的个性化支架,通过具有良好生物相容性的生物材料快速成型制造出来,经过生物培养和植入手术后,用于下颌骨缺损的组织工程化修复。应用该支架一方面可以较好的恢复患者的外表和容貌;另一方面,通过支架降解并引导新骨生长,最终使骨缺损部位完全被患者自身生成的骨骼取代,在完成种植牙修复后,使患者口腔功能得到完全恢复。Aiming at the problems existing in the current repair of mandibular defects, the present invention proposes a personalized bracket that matches the patient's facial structure, which is manufactured through rapid prototyping of biomaterials with good biocompatibility, and after biological culture and implantation surgery , for tissue engineering repair of mandibular defects. On the one hand, the application of the scaffold can better restore the appearance and appearance of the patient; on the other hand, through the degradation of the scaffold and guide the growth of new bone, the bone defect will be completely replaced by the patient's own bone. After the implant restoration is completed, The patient's oral function is fully restored.
发明内容 Contents of the invention
为了克服已有下颌骨缺损修复过程的植入手术后金属植入体与周围骨骼的骨结合效果不佳,影响长久修复的效果的不足,本发明提供一种植入体与周围骨骼的骨结合效果良好、有利于长久修复的用于下颌骨缺损组织工程化修复的个性化支架的制造方法。In order to overcome the inadequacy of the osseointegration effect between the metal implant and the surrounding bone after implantation in the existing mandibular defect repair process, which affects the effect of long-term repair, the present invention provides an osseointegration effect between the implant and the surrounding bone A method for manufacturing a personalized scaffold for mandibular defect tissue engineering repair that is good and beneficial to long-term repair.
本发明解决其技术问题所采用的技术方案是:The technical solution adopted by the present invention to solve its technical problems is:
一种用于下颌骨缺损组织工程化修复的个性化支架的制造方法,通过患者CT数据重建出下颌骨的原始模型后,利用镜像算法或者曲面补孔的方式设计出修复模型,然后通过切割算法得到缺损区域的修复体,得到个性化外形,再通过支架外部形状和内部微结构之间的BOOL运算,得到个性支架的设计模型,最后通过SLS方法以生物材料制造出个性化支架。A manufacturing method of a personalized bracket for the tissue engineering repair of mandibular defects. After reconstructing the original model of the mandible from the patient's CT data, the repair model is designed by using the mirror algorithm or the method of surface filling holes, and then through the cutting algorithm. The restoration of the defect area is obtained, the personalized shape is obtained, and the design model of the personalized bracket is obtained through the BOOL operation between the external shape of the bracket and the internal microstructure, and finally the personalized bracket is manufactured with biomaterials by the SLS method.
进一步,所述制造方法包括以下步骤:Further, the manufacturing method includes the following steps:
1)CT数据采集:拍摄患者口腔部位的CT图像;1) CT data acquisition: take CT images of the patient's oral cavity;
2)下颌骨原型的三维模型重建:利用三维重建软件重建患者口腔部位的骨骼模型,重建模型包括牙齿、下颌神经管;2) Three-dimensional model reconstruction of the mandible prototype: use three-dimensional reconstruction software to reconstruct the bone model of the patient's oral cavity, including teeth and mandibular canal;
3)下颌骨的修复模型设计:根据下颌骨缺损所在的区域位置不同,提供两种修复方案:3) Mandibular repair model design: According to the location of the mandibular defect, two repair options are provided:
(3.1)当缺损区域没有跨中心对称平面,利用镜像方法将健侧的骨骼对称到患侧,并替换掉破损骨骼,通过模型合并算法得到完整的修复模型;(3.1) When there is no cross-central symmetry plane in the defect area, use the mirror image method to symmetry the bone on the healthy side to the affected side, replace the damaged bone, and obtain a complete repair model through the model merging algorithm;
(3.2)当缺损区域跨过了中心对称平面,利用曲面补孔的方式进行修复,即根据缺损区域周边曲面的曲率变化,设计修补曲面使其与周围边界曲面曲率连续;(3.2) When the defect area crosses the central symmetry plane, it is repaired by means of surface patching, that is, according to the curvature change of the surrounding surface of the defect area, the repair surface is designed to make it continuous with the curvature of the surrounding boundary surface;
4)设计修复假体,得到个性化支架的外形:将在下颌骨原形的模型上设计出缺损区域的截骨线,利用该截骨线在修复模型上将修复假体切割分离出来,该修复假体的外形即为个性化支架的外形;4) Design the prosthesis to obtain the shape of the personalized bracket: design the osteotomy line in the defect area on the mandible original model, and use the osteotomy line to cut and separate the prosthesis on the repair model. The shape of the prosthesis is the shape of the personalized bracket;
5)设计支架的内部多孔结构:笛卡尔正交桁架结构作为内部连通孔的基本单元,首先生成基本单元,然后分别通过向X、Y、Z三个坐标方向的阵列运算得到内部连通孔的运算框架;5) Design the internal porous structure of the support: the Cartesian orthogonal truss structure is used as the basic unit of the internal connected hole, first generate the basic unit, and then obtain the operation of the internal connected hole through the array operation in the three coordinate directions of X, Y, and Z respectively frame;
6)将修复假体与内部结构模型进行布尔运算,得到个性化支架;6) Perform Boolean operations on the prosthesis and the internal structure model to obtain a personalized bracket;
7)利用SLS快速成型制造方法,采用生物材料制造出个性化支架。7) Utilize the SLS rapid prototyping manufacturing method to manufacture personalized scaffolds using biomaterials.
更进一步,所述步骤(3.2)中,补孔过程中,如果孔洞大小超出预设值,利用镜像模型作为辅助得到部分修补数据。Furthermore, in the step (3.2), if the size of the hole exceeds the preset value during the hole repairing process, the mirror image model is used as an auxiliary to obtain part of the repairing data.
本发明的技术构思为:个性化支架是将个性化外形、内部微结构经BOOL运算设计后,通过SLS方法制造出来,经体外培养和生物方法处理后,手术植入体内进行骨重建修复,最终通过牙种植恢复患者口腔全部功能的个性化支架,所述个性化外形由如下方法制备:(1)重建出下颌骨的原始模型,(2)设计修复模型,(3)获得缺损区域的修复体,所述内部微结构是根据力学和生物学约束转换来的几何约束设计的规则的微结构,所述体外培养是将生长因子和骨原细胞加入个性化支架中进行的,所述几何约束是指孔隙率、孔径。The technical idea of the present invention is: the personalized scaffold is manufactured by SLS method after the personalized shape and internal microstructure are designed by BOOL operation, and after being cultured in vitro and treated by biological methods, it is surgically implanted in the body for bone reconstruction and repair, and finally A personalized bracket to restore the full function of the patient's oral cavity through dental implants. The personalized shape is prepared by the following methods: (1) reconstruct the original model of the mandible, (2) design the repair model, (3) obtain the restoration of the defect area , the internal microstructure is a regular microstructure designed according to geometric constraints converted from mechanical and biological constraints, and the in vitro culture is carried out by adding growth factors and osteogenic cells into personalized scaffolds, and the geometric constraints are Refers to porosity, pore size.
具体的,所述的方法是通过患者CT数据重建出下颌骨的原始模型后,利用镜像算法或者曲面补孔的方式设计出修复模型,然后通过切割算法得到缺损区域的修复体,得到个性化外形,再通过支架外部形状和内部微结构之间的BOOL运算,通过SLS方法制造出来,加入生长因子和骨原细胞进行体外培养和生物方法处理后,手术植入体内进行骨重建修复,最终通过牙种植恢复患者的全部功能。Specifically, the method described is to reconstruct the original model of the mandible from the patient's CT data, then design the repair model by using the mirror image algorithm or the method of filling holes on the curved surface, and then obtain the restoration of the defect area through the cutting algorithm to obtain a personalized shape , and then through the BOOL operation between the external shape of the scaffold and the internal microstructure, it is manufactured by the SLS method, and after adding growth factors and osteoprogenitor cells for in vitro culture and biological treatment, it is surgically implanted in the body for bone reconstruction and repair, and finally through dental implantation. The implant restores the patient's full function.
本发明的有益效果主要表现在:可以快速制造出具有良好生物相容性的生物材料,经过生物培养和植入手术后,用于下颌骨缺损的组织工程化修复。应用该支架可以较好的恢复患者的外表和容貌,并通过支架降解并引导新骨生长,最终使骨缺损部位完全被患者自身生成的骨骼取代,在完成种植牙修复后,使患者口腔功能得到完全恢复。The beneficial effect of the present invention is mainly manifested in that the biomaterial with good biocompatibility can be rapidly produced, and after bioculture and implantation, it can be used for tissue engineering repair of mandibular defect. The application of the scaffold can better restore the appearance and appearance of the patient, and through the degradation of the scaffold and guide the growth of new bone, the bone defect will be completely replaced by the patient's own bone. After the implant restoration is completed, the oral function of the patient will be improved. full recovery.
附图说明 Description of drawings
图1是缺损区域的位置图。Figure 1 is a map of the location of the defect area.
图2是基于镜像算法的修复模型设计图,其中,(a)是原始模型,(b)是镜像模型,(c)是缺损修复体,(d)是修复模型。Fig. 2 is a design diagram of a restoration model based on the mirror image algorithm, where (a) is the original model, (b) is the mirror image model, (c) is the defective restoration, and (d) is the restoration model.
图3是利用镜像与补孔的修复模型设计图,其中,(a)是原始模型,(b)是镜像模型,(c)是缺损修复体,(d)是合并模型,(e)是补孔;(f)是修复模型。Fig. 3 is the design drawing of the restoration model using mirror image and filling holes, where (a) is the original model, (b) is the mirror image model, (c) is the defect restoration, (d) is the merged model, and (e) is the supplementary model. hole; (f) is the repair model.
图4是修复假体图。Figure 4 is a diagram of the prosthetic prosthesis.
图5是正交桁架结构图。Figure 5 is a structural diagram of an orthogonal truss.
图6是支架结构基本单元图。Fig. 6 is a basic unit diagram of the stent structure.
图7是内部结构运算框架图。Fig. 7 is a frame diagram of internal structure operation.
图8是个性化支架图。Figure 8 is a diagram of a personalized stent.
具体实施方式 Detailed ways
下面结合附图对本发明作进一步描述。The present invention will be further described below in conjunction with the accompanying drawings.
参照图1,一种用于下颌骨缺损组织工程化修复的个性化支架的制造方法,通过患者CT数据重建出下颌骨的原始模型后,利用镜像算法或者曲面补孔的方式设计出修复模型,然后通过切割算法得到缺损区域的修复体,得到个性化外形,再通过支架外部形状和内部微结构之间的BOOL运算,得到个性支架的设计模型,最后通过SLS方法以生物材料制造出个性化支架。Referring to Figure 1, a manufacturing method of a personalized bracket for tissue engineering repair of mandibular defects, after reconstructing the original model of the mandible from the CT data of the patient, the repair model is designed by using the mirror algorithm or the method of filling holes on a curved surface. Then the restoration of the defect area is obtained through the cutting algorithm, and the personalized shape is obtained, and then the design model of the personalized bracket is obtained through the BOOL operation between the external shape of the bracket and the internal microstructure, and finally the personalized bracket is manufactured with biomaterials by the SLS method .
本实施例中,制造方法应用到下颌骨的缺损修复过程中,具体包括以下步骤:In this embodiment, the manufacturing method is applied to the process of mandibular defect repair, which specifically includes the following steps:
1)CT数据采集:拍摄患者口腔部位的CT图像;1) CT data acquisition: take CT images of the patient's oral cavity;
2)下颌骨原型的三维模型重建:利用三维重建软件重建患者口腔部位的骨骼模型,重建模型包括牙齿、下颌神经管;2) Three-dimensional model reconstruction of the mandible prototype: use three-dimensional reconstruction software to reconstruct the bone model of the patient's oral cavity, including teeth and mandibular canal;
3)下颌骨的修复模型设计:根据图1所示下颌骨缺损所在的区域位置不同,提供两种修复模型设计方法。3) Mandibular repair model design: According to the location of the mandibular defect shown in Figure 1, two repair model design methods are provided.
(3.1)当缺损区域位于图1中所示的1和2区域时,由于缺损部位没有跨中心对称平面,所以利用镜像方法将健侧的骨骼对称到患侧,并替换掉破损骨骼,通过模型合并算法得到完整的修复模型。如图2所示。(3.1) When the defect area is located in
(3.2)当缺损区域位于图1中所示的第3区域时,由于缺损部位跨过了中心对称平面,所以利用曲面补孔的方式进行修复,即根据缺损区域周边曲面的曲率变化,设计修补曲面使其与周围边界曲面曲率连续。补孔过程中,如果孔洞较大,可以利用镜像模型作为辅助得到部分修补数据,以提高所补曲面的真实性。如图3所示。(3.2) When the defect area is located in the third area shown in Figure 1, since the defect part straddles the central symmetry plane, repairing is carried out by means of surface filling, that is, according to the curvature change of the surrounding surface of the defect area, the repair is designed The surface is made to be curvature continuous with the surrounding boundary surfaces. In the hole patching process, if the hole is large, the mirror model can be used as an auxiliary to obtain part of the patching data to improve the authenticity of the patched surface. As shown in Figure 3.
4)设计修复假体,得到个性化支架的外形:将在下颌骨原形的模型上设计出缺损区域的截骨线,利用该截骨线在修复模型上将修复假体切割分离出来。该修复假体的外形即为个性化支架的外形,如图4所示。4) Design the prosthesis to obtain the shape of the personalized bracket: design the osteotomy line in the defect area on the original mandible model, and use the osteotomy line to cut and separate the prosthesis on the repair model. The shape of the prosthetic prosthesis is the shape of the personalized bracket, as shown in FIG. 4 .
5)设计支架的内部多孔结构:图5所示的笛卡尔正交桁架结构作为内部连通孔的基本单元,通过调节图中圆轴直径r和两圆轴的中心距t两个参数来改变支架的孔隙率。首先生成图6所示的基本单元,然后分别通过向X、Y、Z三个坐标方向的阵列运算得到内部连通孔的运算框架,如图7所示。5) Design the internal porous structure of the support: the Cartesian orthogonal truss structure shown in Figure 5 is used as the basic unit of the internal communication hole, and the support is changed by adjusting the two parameters of the diameter r of the circular shaft and the center distance t between the two circular shafts in the figure porosity. First generate the basic unit shown in Figure 6, and then obtain the calculation framework of the internal connected holes through array operations in the three coordinate directions of X, Y, and Z, as shown in Figure 7.
6)将修复假体与内部结构模型进行布尔运算,得到个性化支架,如图8所示。6) Perform Boolean operations on the prosthetic prosthesis and the internal structure model to obtain a personalized bracket, as shown in Figure 8.
7)利用SLS快速成型制造方法,以聚醋酸乙酯(PCL)为生物材料,制造出个性化支架。7) Using the SLS rapid prototyping method, polyvinyl acetate (PCL) was used as the biomaterial to manufacture personalized scaffolds.
8)该支架经过体外培养和体内植入后,可用于下颌骨的缺损修复。8) After being cultured in vitro and implanted in vivo, the scaffold can be used for mandibular defect repair.
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