面向3D打印植介入体的生物力学设计

医用植介入体至少包含两类重要的生物力学问题:一是其自身结构的强度等生物力学问题,二是与宿主之间的相互作用;二者对于其成败都非常重要。增材制造技术(3D打印)为个性化植入假体的应用推广带来希望,个性化植入假体具有巨大的临床和市场需求。然而,个性化植入假体设计与临床应用仍有亟待解决的科学和关键技术问题,现有的临床案例主要考虑基于解剖影像几何特征的个性化适配连同医生个人经验进行个性化假体的结构设计,但往往缺乏植入体与宿主组织相互作用的生物力学与力学生物学定量化预测和可靠性评测。本文针对骨盆、肢体修复和足部关节融合所需的个性化植入假体,研究基于生物力学的个性化植入假体的结构优化(强度、可靠性、疲劳特性数值化分析和仿真)技术;探索基于应力影响骨肌相关细胞、组织生长、改重建规律定量化仿真的个性化植入假体的优化设计方法。面向增材制造的多孔植入体对于植入后组织细胞的生长具有诱导性,由于不同形态孔隙的多孔假体,其力学特性、传质特性不同,从而致使其细胞组织相容性差异较大,本文开展了多孔结构拓扑优化研究。开展假体改重建定量生物力学仿真、大规模微孔结构生物力学仿真、疲劳断裂风险数值分析评价、临床特征参数提取、无量纲微孔结构元素库构建、假体高精度制备及处理等关键技术研究。在适宜制备技术方面,研究集成激光清扫的3D打印SLM专用成型设备系统。针对生物医用领域对Ti基合金粉末材料的特殊要求,优化增材制造专用Ti基合金粉末材料的合金体系及化学成分,并结合合金元素对于增材制造过程中激光微熔池行为、凝固组织特征与性能的作用机理研究,微调增材制造用粉末材料的化学成分,研发国产Ti基打印粉材。同时探索个性化植入假体的检测与监管技术。在上述研究基础上开展了临床应用研究。     

多孔碳酸化羟基磷灰石水泥植入修复兔包容性骨缺损的力学分析

背景:采用发泡剂成孔技术,制成了有知识产权的新型骨修复材料多孔碳酸化羟基磷灰石,既保留了碳酸化羟基磷灰石骨水泥原位固化性能等所有的优点,同时又形成多孔结构。目的:通过动物实验观察新型的骨修复材料多孔碳酸化羟基磷灰石水泥修复骨缺损的力学效果。方法:30只新西兰大白兔,手术组25只在双侧股骨髁制备直径为5.5mm、深12mm的骨缺损动物模型,左侧植入多孔碳酸化羟基磷灰石骨水泥为实验组,右侧植入碳酸化羟基磷灰石骨水泥为对照组。非手术组5只,用于正常力学对照。将多孔碳酸化羟基磷灰石骨水泥和碳酸化羟基磷灰石骨水泥试件经模仿体液浸泡,检测力学强度。同时在手术组背肌内分别植入多孔碳酸化羟基磷灰石骨水泥和碳酸化羟基磷灰石骨水泥标准试件。分别于术后2,4,8,12,16周分批处死动物,进行试件骨内和肌内植入的力学实验分析和试件在模仿体液中浸泡后的抗压强度测试。结果与结论:多孔碳酸化羟基磷灰石骨水泥:2周时的骨内力学强度较低,4周时降到最低,8周时接近正常松质骨强度,12周时超过正常松质骨强度,16周时恢复到正常松质骨水平。碳酸化羟基磷灰石骨水泥:2周时骨内植入强度较多孔碳酸化羟基磷灰石骨水泥略高,4周时有所降低,8,12,16周时略升高,但是始终低于正常松质骨的强度。多孔碳酸化羟基磷灰石骨水泥和碳酸化羟基磷灰石骨水泥在SBF中浸泡的抗压强度变化不大。试件植入肌内后抗压强度变化非常显著。结果表明,多孔碳酸化羟基磷灰石水泥具有原位固化性能和一定的力学支撑作用,能作为自体骨移植的一种替代物修复骨缺损。     

多孔钛修复兔桡骨骨缺损

背景：已有将多孔钛植入小型骨缺损的报道。 目的：验证多孔钛修复兔桡骨节段性骨缺损的疗效。 方法：成年健康新西兰大白兔 21只,建立双侧桡骨10 mm缺损模型,骨缺损处分别植入多孔钛和多孔羟基磷灰石材料。 结果：材料植入后第4,8,16周取材观察：①4周时多孔钛组和多孔羟基磷灰石组在材料与宿主骨交界处均有少量骨痂形成,第8和16周时孔隙被新生骨组织填充,与自体骨吻合好。②第8,16周时多孔钛组新骨细胞长入量和骨重建效果几乎接近多孔羟基磷灰石组。两组骨面积在新生骨质长入量上差异无显著性意义(P > 0.05)。③第8,16周时多孔钛组的最大承载负荷值明显优于多孔羟基磷灰石组。表明多孔钛支架材料可以促进新骨的形成并有利于节段骨缺损的修复。     

多孔碳酸化羟基磷灰石骨水泥的生物相容性研究

目的探讨一种新型的代骨材料--多孔碳酸化羟基磷灰石骨水泥的组织相容性.方法合成碳酸化羟基磷灰石骨水泥,添加成孔剂,制备能原位固化形成多孔结构的碳酸化羟基磷灰石代骨材料,并通过细胞毒性实验和肌内埋植实验检测其组织相容性.结果多孔碳酸化羟基磷灰石骨水泥的浸提液对骨髓基质细胞的生长无影响.细胞于材料表面的生长速度、形态与空白对照组无差别.肌内植入实验发现,材料周围纤维组织包膜的最大厚度为22.5μm,未发现炎性细胞反应.结论多孔碳酸化羟基磷灰石骨水泥具有良好的组织相容性,材料测试结果符合和标准.     

降钙素促进骨质疏松骨床中植入体的骨整合

背景：降钙素具有提高骨量、骨质量,降低骨折发生的效果。 目的：评价鲑鱼降钙素对羟基磷灰石植入体骨整合的影响,及其在治疗骨质疏松症同时促进植入体生物学固定的能力。 方法：将SD大鼠随机分为假手术+羟基磷灰石棒组、卵巢切除+羟基磷灰石棒组、卵巢切除+降钙素+羟基磷灰石棒组,后2组建立绝经后骨质疏松动物模型。建模后分别在3组大鼠的胫骨平台处开孔植入多孔羟基磷灰石假体,卵巢切除+降钙素+羟基磷灰石棒组大鼠皮下注射鲑鱼降钙素12周。 结果与结论：卵巢切除后,大鼠的腰椎骨密度降低,而持续皮下注射鲑鱼降钙素后,大鼠的腰椎骨密度逐渐改善。应用降钙素处理后的大鼠,其骨结合率较卵巢切除+羟基磷灰石棒组提高了22.0%(P < 0.05)。结果证实,全身给予鲑鱼降钙素能提高骨质疏松大鼠骨床和植入体周围骨量、促进主体骨-植入体的骨整合。     

钛合金表面新型生物玻璃/羟基磷灰石涂层的体内动物实验

目的为促进钛合金植入体与骨的结合,在其表面制备了生物玻璃/羟基磷灰石复合涂层,并植入兔子股骨内进行动物试验,采用等离子喷涂羟基磷灰石涂层和未涂层的Ti6Al4V合金作为对照。方法种植到期的植入体取出后进行组织学切片,采用品红-苦味酸染色后进行组织学观察,采用SEM高倍观察种植体与骨的结合界面,并对骨接触率和凹槽内骨长入量进行了统计分析和比较。结果三种植入体都具有良好的生物相容性。Ti6Al4V合金与骨之间是一种形态固定,而生物玻璃/羟基磷灰石涂层、等离子喷涂羟基磷灰石涂层可与骨形成骨键合。生物玻璃/羟基磷灰石涂层在植入期间与基体没有脱落,同时其与骨的接触率和凹槽内骨长入量要明显高于其余两个植入体,显示出促进骨生长的作用。结论由于具有良好的生物相容性和促进新骨生长的能力,生物玻璃/羟基磷灰石涂层可加快植入体与骨的愈合速度,在骨替代修复方面显示出优势和广阔的应用前景。     

计算机辅助设计纳米羟基磷灰石／聚氨酯复合骨植入物的个性化快速制造

采用原位复合法,以纳米羟基磷灰石为增强体,以聚氨酯预聚体为基体,制备了快速成型所需的HA /PU 基质复合材料,采集个体股骨近端骨缺损部位的 CT 影像数据,利用计算机辅助医学影像 Mimics 软件进行三维重建,直接得到股骨近端的三维模型,再将三维模型信息转换成快速成型的“STL”数据文件,以此直接驱动三维打印机制造出 ABS 实体模型,然后经硅胶模具和浇注成型手段,将 HA /PU 复合预聚体基质浇注到硅胶模具中,进行固化成型,得到符合个性化需求的 HA /PU 股骨近端植入体。为克服批量生产植入体型号、尺寸与个体需求不匹配的弊端,制造高附加值人工骨产品提供实验基础和技术支持。     

放射性核素骨显像在骨缺损修复实验中的研究

目的：通过动物实验探讨多孔纳米羟基磷灰石人工骨（nano-HA）的骨缺损修复作用及放射性核素骨显像在骨重建过程中的应用，为临床运用于骨缺损修复领域提供依据。方法：采用新西兰大白兔24只在单侧桡骨制备骨缺损动物模型，然后用多孔纳米羟基磷灰石人工骨材料进行植入骨缺损处进行修复作为实验组，以普通羟基磷灰石人工骨材料作为对照组；术后2周，4周，8周和12周分别行放射性核素骨显像监测两组人工骨对骨缺损的修复能力。结果：通过ROI方法定量对比两种材料植入区和正常区放射性浓集比值，nano-HA人工骨组成骨作用优于HA人工骨组，骨缺损修复能力优于后者，差异有统计学意义（P〈0．05）。结论：纳米羟基磷灰石人工骨具有良好的成骨能力，可望成为新型的骨缺损修复材料，放射性核素骨显像在骨修复过程中具有良好的监测作用。     

纳米羟基磷灰石/I型胶原复合人工骨组成结构及成骨活性的实验研究

按照仿生的方法合成纳米羟基磷灰石/I型胶原人工骨支架材料.采用扫描电镜、X线衍射分析、孔隙率测定的方法对人工骨支架材料进行分析.制作兔颅骨缺损模型,植入人工骨支架材料,组织切片观察支架材料在体内的反应.纳米羟基磷灰石/I型胶原人工骨支架材料呈疏松海绵状,具有100～300 μm的孔径和90%以上的孔隙率,具有类似天然骨的结构.植入兔颅骨缺损模型未出现急性或慢性的炎症反应,在4周左右人工骨支架内出现大量新生毛细血管,12周新生骨完全修复骨缺损,并形成成熟的骨小梁结构.纳米羟基磷灰石和I型胶原复合人工骨约3个月左右降解完全.     

羟基磷灰石/胶原-聚乳酸三维多孔框架材料的制备成形及分析

目的：合成新型的复合生物材料框架作为骨组织工程研究的细胞外基质材料。方法：本研究采用材料学自组装技术的原理，以Ⅰ型胶原蛋白为分子模板，引导钙磷盐在液相中的矿化，制备具有天然骨基质层状结构的羟基磷灰石／胶原复合材料，并以热致分相法制备了羟基磷灰石／胶原-聚乳酸复合三维多孔框架。结果：羟基磷灰石／胶原复合材料具有与天然骨基质相似的成分与结构，加入聚乳酸制备成三维多孔框架，孔隙直径界于50um-300um。结论：羟基磷灰石／胶原-聚乳酸复合三维多孔框架可能作为骨组织工程良好的细胞外基质材料。     

Various preparation methods of highly porous hydroxyapatite/polymer nanoscale biocomposites for bone regeneration

Tissue engineering utilizes expertise in the fields of materials science, biology, chemistry, transplantation medicine, and engineering to design materials that can temporarily serve in a structural and/or functional capacity during regeneration of a defect. Hydroxyapatite (HAp) scaffolds are among the most extensively studied materials for this application. However, HAp has been reported to be too weak to treat such defects and, therefore, has been limited to non-load-bearing applications. To capitalize the advantages of HAp and at the same time overcome the drawbacks nanocrystalline HAp (nHAp) is combined with various types of bioactive polymers to generate highly porous biocomposite materials that are used for osteoconduction in the field of orthopedic surgery. In this study we have reviewed nanosized HAp-based highly porous composite materials used for bone tissue engineering, introduced various fabrication methods to prepare nHAp/polymer composite scaffolds, and characterized these scaffolds on the basis of their biodegradability and biocompatibility through in vitro and in vivo tests. Finally, we provide a summary and our own perspectives on this active area of research.     

Manufacturing of individual biodegradable bone substitute implants using selective laser melting technique

The additive manufacturing technique selective laser melting (SLM) has been successfully proved to be suitable for applications in implant manufacturing. SLM is well known for metal parts and offers direct manufacturing of three-dimensional (3D) parts with high bulk density on the base of individual 3D data, including computer tomography models of anatomical structures. Furthermore, an interconnecting porous structure with defined and reproducible pore size can be integrated during the design of the 3D virtual model of the implant. The objective of this study was to develop the SLM processes for a biodegradable composite material made of β-tricalcium phosphate (β-TCP) and poly(D, L)-lactide (PDLLA). The development of a powder composite material (β-TCP/PDLLA) suitable for the SLM process was successfully performed. The microstructure of the manufactured samples exhibit a homogeneous arrangement of ceramic and polymer. The four-point bending strength was up to 23 MPa. The X-ray diffraction (XRD) analysis of the samples confirmed β-TCP as the only present crystalline phase and the gel permeations chromatography (GPC) analysis documented a degradation of the polymer caused by the laser process less than conventional manufacturing processes. We conclude that SLM presents a new possibility to manufacture individual biodegradable implants made of β-TCP/PDLLA.     

Melt-Versus Solution-Extrusion Additive Manufacturing of Poly(methyl methacrylate) Medical Implant Prototypes

The development of tailored additive manufacturing (AM) approaches is resulting in novel strategies for engineering the macro/microstructural details of potential medical devices made of biocompatible polymers. The aim of this work is the employment of a multifunctional AM machine for fabricating poly(methyl methacrylate) (PMMA) constructs with a predefined shape and porous architecture, by either melt- or solution-extrusion AM. In particular, PMMA porous scaffolds are manufactured by employing fused filament fabrication (FFF) or computer-aided wet-spinning (CAWS). The comparative characterization of the two developed PMMA implant prototypes demonstrates significant differences in terms of porous structure, polymer surface topography, material composition, glass transition temperature, and mechanical properties. As a consequence, FFF-printed PMMA samples support a faster in vitro proliferation of a murine fibroblast cell line in comparison to PMMA scaffolds by CAWS. The results achieved encourage further research on the developed processing protocols, aimed at the development of tailored PMMA implants for personalized surgery applications.     

A numerical investigation into the influence of the properties of cobalt chrome cellular structures on the load transfer to the periprosthetic femur following total hip arthroplasty

Stress shielding of the periprosthetic femur following total hip arthroplasty is a problem that can promote the premature loosening of femoral stems. In order to reduce the need for revision surgery it is thought that more flexible implant designs need to be considered. In this work, the mechanical properties of laser melted square pore cobalt chrome molybdenum cellular structures have been incorporated into the design of a traditional monoblock femoral stem. The influence of incorporating the properties of cellular structures on the load transfer to the periprosthetic femur was investigated using a three dimensional finite element model. Eleven different stiffness configurations were investigated by using fully porous and functionally graded approaches. This investigation confirms that the periprosthetic stress values depend on the stiffness configuration of the stem. The numerical results showed that stress shielding is reduced in the periprosthetic Gruen zones when the mechanical properties of cobalt chrome molybdenum cellular structures are used. This work identifies that monoblock femoral stems manufactured using a laser melting process, which are designed for reduced stiffness, have the potential to contribute towards reducing stress shielding.     

增材制造骨科植入型医疗器械的发展现状及应用

目的介绍国内外增材制造骨科医疗器械的发展及应用情况,并对基于增材制造技术的定制式骨科植入型医疗器械发展方向进行讨论,以期能为相关研究人员提供参考。方法结合增材制造技术在医疗器械领域的发展现状,简要说明其普遍存在的问题,并对增材制造技术的个性化骨科植入型医疗器械的发展方向进行讨论。结果增材制造是一种通过材料的逐层累加以实现零部件自由成型的加工生产工艺。近年来,增材制造技术因其可实现复杂结构等优势在医疗器械领域,尤其是骨科植入物方面得到了广泛应用,不仅为产品生产提供了一种新的加工工艺,也为医疗产业带来了便利。结论迄今为止,国内外已有多种基于增材制造技术的骨科医疗器械在临床上得到广泛应用,利用增材制造技术完成复杂的医疗器械结构的设计与制造,用于满足特殊需求的治疗案例也越来越多,基于增材制造技术的定制式骨科植入型医疗器械也逐步成为医学研究的热点之一。     

Three different strategies to obtain porous calcium phosphate cements: comparison of performance in a rat skull bone augmentation model

Preprosthetic surgery has become a routine procedure to obtain sufficient bone quantity and quality for dental implant installation in patients with an initial inadequate bone volume. Although autologous bone onlay or inlay grafting is still the preferred bone augmentation technique, a broad range of synthetic bone substitutes have been developed, for example, calcium phosphate cement (CPC). The introduction of porosity within CPC can be used to increase CPC degradation and bone ingrowth. Therefore, three different strategies to obtain porous CPCs were evaluated in this preclinical study. Instantaneously porous CPC (CPC-IP) was compared with delayed porous CPC in vitro and in vivo. CPC-IP was obtained by the creation of CO? bubbles during setting, whereas delayed porous CPC was obtained after the degradation of incorporated poly(lactic-co-glycolic acid) (PLGA) microspheres. As an additional aspect, delayed porous CPC was created by the incorporation of either hollow or dense degradable PLGA microspheres (CPC-hPLGA and CPC-dPLGA). All CPC compositions showed appropriate clinical handling properties and an interconnected porous structure with a final porosity above 70% (v/v). In vitro degradation studies showed the gradual formation of pores and further CPC-matrix dissolution for CPCs containing PLGA microspheres (dPLGA microspheres > hPLGA microspheres). For in vivo evaluation of the CPCs, an augmentation model was used, allowing a CPC injection into a rigidly immobilized Teflon ring on the rat skull. Histological evaluation after 12 weeks of implantation showed bone formation using all three CPCs. Bone apposition reached volumetric amounts of up to 10% of the augmentation area and a maximum augmentation height of ～1?mm. CPC-IP showed significantly more bone formation and resulted in a superior bone apposition height compared with both CPCs containing PLGA microspheres. No differences in biological performance were observed between the CPCs containing hPLGA and those containing dPLGA microspheres. Further research is necessary to enhance the bone appositional speed and amount of CPCs for bone augmentation procedures before them being used in a potential clinical setting.     

多孔羟基磷灰石生物陶瓷的合成和特性研究进展

人体骨组织的多孔结构，有利于骨组织生长代谢所需物质的交流，并能很好地适应外部应力的变化。合成模拟骨组织多孔结构的生物活性陶瓷材料，用于临床人体骨组织缺失的修复，是组织工程所需要的。将化学沉淀法合成的羟基磷灰石原始粉末与过氧化氢、降乙烯醇、甲基纤维素等孔成孔物质混合，经低温发泡，中温脱碳，高温烧结，可以获得孔径理想，互通性能良好的多孔羟基磷灰石陶瓷。这种陶瓷，在一定程度上具有骨诱导性能，但更重要的是它能够很好的吸附人体骨形成蛋白等骨生长因子，使其具有良好的骨再生能力，从而获得了良好的临床应用性能。本文从临床应用性能的角度，评述了近几年多孔羟基磷灰石生物陶瓷的研究进展。     

3D打印技术在创伤骨科中的应用进展

随着3D打印技术的不断发展,其在创伤骨科领域中的应用越来越广泛,几乎涵盖了人体所有的解剖区域。3D打印技术也被称为"增材制造技术"和"快速成形技术",被认为是"第二次工业革命"。3D打印技术不仅可以打印出患者特异性的解剖实体模型,便于医师对患者复杂的解剖结构及疾病有更好的理解,同时有助于医学教育和手术培训,而且对于一些特殊患者可以制造定制的植入导板及假体,匹配患者的解剖结构,有效解决临床治疗难题。本文就3D打印技术在创伤骨科中的应用进展进行综述。     

Biocompatibility of electrophoretical deposition of nanostructured hydroxyapatite coating on roughen titanium surface: in vitro evaluation using mesenchymal stem cells

A nano hydroxyapatite (HAp) layer was coated on a roughen titanium surface by means of electrophoretic deposition with an acetic anhydride solvent system. The objectives of this current study are to investigate whether nano-HAp can improve mechanical strength at a lower sintering temperature and biocompatibility. Densification temperature was lowered from usual 1000 to 800 degrees C. The coating interfacial bonding strength, phase purity, microstructure, and biocompatibility were investigated. Degradation of HA phase was not detected in XRD. A porous TiO2 layer acts as a gradient coating layer with an intermediate thermal expansion coefficient between hydroxyapatite and titanium that reduces the thermal stress. From SEM image, the coating does not contain any crack. Mesenchymal stem cell (MSC) is the progenitor cell for various tissues in mature animals, which can improve integration of bone tissue into implant. In this in vitro study, rabbit MSCs culture indicated that the HAp/Ti nanocomposite biomaterial had good biocompatibility and bioactivity. Around materials and on its surface cell grew well with good morphology. Proliferation of the MSCs on the nano-HAp coating was higher than its micron counterpart in XTT assay. These properties show potential for the orthopaedic and dental applications.     

不同颅内植入材料对脑损伤修复的影响

背景：有关脑损伤修复移植物选择尚有争议, 迄今还没有一种材料能在理化性质方面完全替代颅骨。 目的：归纳分析不同颅内植入材料对脑损伤修复的影响及其性能评价。 方法：以“颅脑损伤、复合材料、生物材料、损伤修复”为中文关键词,以“Traumatic brain injury,Compound material,Biological material,Damage repair”为英文关键词,采用计算机检索中国期刊全文数据库、PubMed数据库(1993-01/ 2010-11)相关文章。纳入颅脑损伤-损伤修复材料等相关的文章,排除重复研究或Meta分析类文章。 结果与结论：共入选24篇文章进入结果分析。常用的颅骨缺损的修补材料主要有3 大类:自体和异体骨移植、非金属材料、金属代材料。自体和异体骨移植成形不很理想,存在免疫排斥和坏死吸收。以钛网边作为修复材料,应用三维重建技术的数字化颅骨塑形技术,缩短了手术时间、减少了相应并发症,实现了个体化配置修补颅骨缺损,是一种较为理想的颅骨修补材料。钛合金具有良好的生物相容性,强度高,不老化,密度轻,置入后不影响CT/MRI、脑电图等检查,且置入后成纤维细胞可长入钛网的微孔,使钛网与组织融为一体,明显减少并发症的产生,是目前较为理想的修补材料。