【作者】 胥正锋；

【导师】 黄煌渊； 姜建元； 马昕； 吕飞舟；

【作者基本信息】 复旦大学 ， 外科学， 2009， 博士

【摘要】 【目的】:β-磷酸三钙(β-TCP)生物陶瓷是近年来逐渐兴起并应用于临床上的新型生物材料。因其良好的生物相容性、可降解性及骨传导作用,作为骨修复材料已广泛应用于骨科临床,修复因创伤、肿瘤、炎症、骨病等所致的骨缺损等。但以往由于其力学性能弱而只能应用于非负重部位。我们和上海贝奥路公司合作,研制出增强型β-TCP生物陶瓷,将力学性能良好而生物学性能较差的致密陶瓷与生物学性能良好而力学性能较差的多孔陶瓷结合在一起。在获取国人颈椎椎体间隙的三维图像,并利用较多志愿者获取国人颈椎椎体间隙解剖学数据的形态学基础上,通过增强型β-TCP技术,设计研发了增强型β-TCP颈椎椎体间融合器,测量其力学强度等表面特征,并建立山羊颈椎前路手术模型,对其进行初步的动物实验,观察并评估其临床效应,为进一步改进和临床应用提供基础。【方法】:(一)、选取青年男性新鲜尸体标本,排除颈椎畸形,创伤,肿瘤及明显退行性变,解冻后取下头颈部标本,在头部中立位,颈部自然弯曲的体位行64排CT薄层扫描及MRI扫描,然后将颈椎标本以外固定支架固定于相同体位,清除颈椎上下椎体间隙的纤维环,髓核及软骨终板,注射硅胶以获得颈椎椎体间隙的三维模型,并对三维模型进行测量和三维扫描,获得国人颈椎椎体间隙的三维图像。将CT扫描、MRI扫描、硅胶模型直接测量的三种方法所得到的数据进行对比,优选出CT更适合于颈椎椎体间隙的测量。(二)、随机选取符合条件的青年志愿者97人,其中男性63人(21～29岁,平均年龄25.2岁);女性34例(20～29岁,平均年龄24.3岁)。按性别分组分别进行CT扫描。获取国人颈椎椎体间隙的解剖学资料。(三)、在前两部分的形态学基础上,通过增强型β-TCP制造技术,制作出增强型β-TCP颈椎椎体间融合器,测量评估理化性能,力学性能等特性。(四)、取10只20～25kg的2岁成年山羊,雌雄不限,随机分为两组,每组5只山羊:A组为实验组,即β-TCP颈椎椎体间融合器组;B组为对照组,即自体三面皮质骨髂骨组。制作出山羊颈椎前路减压融合模型,每只山羊行颈椎前路单节段椎间盘切除术。切除椎间盘后刮除软骨终板,在减压槽内分别放入β-TCP颈椎椎体间融合器及自体三面皮质骨髂骨。植入后前路加用CervicalLock钢板固定。术后即刻摄颈椎侧位片,饲养动物8周。(五)、8周后处死动物,摄颈椎侧位X线片及CT薄层扫描,并行矢状位重建。术后即刻和术后8周的侧位X线片对比评估手术节段的高度变化;CT扫描评估椎体间融合情况。【结果】:(一)、通过硅胶塑形法获得颈椎椎体间隙的三维模型,从而得到国人颈椎椎体间隙的三维图像,并验证了CT、MRI扫描在颈椎测量的准确性。(二)、国人颈椎椎体间隙前后径值为:男性16.35～19.81mm,女性14.98～17.43mm;左右径值:男性为18.55～22.50mm,女性为16.55～20.69mm;正中矢状面颈椎椎体间隙前缘高度值为:男性7.26～9.03mm,女性5.36～5.98mm;椎体中点高度:男性为8.01～9.24mm,女性为7.65～8.12mm;椎体后缘高度:男性为5.01～5.22mm,女性为4.76～5.03mm。颈椎从上向下,椎体间隙逐渐增大;同节段椎体间隙男性明显比女性大。(三)利用增强型β-TCP技术制作增强型β-TCP颈椎椎体间融合器,整体呈盒状,横截面似梯形,外围为致密部分,中心为多孔部分。宽×深×高约为12mm×9mm×8mm。比单纯的多孔β-TCP力学强度明显增加,能较好的将支撑作用与骨传导作用结合在一起。(四)、山羊颈椎前路椎体间融合模型是研究人类颈椎的较好的动物模型,该模型所获得的实验结果具有较大可信性及准确性。(五)、增强型β-TCP颈椎椎体间融合器组能较好的的维持颈椎椎体间隙高度,术后即刻及术后8周的结果没有统计学差异;两组均能获得椎体间融合,结果没有统计学差异。【结论】:增强型β-TCP颈椎椎体间融合器弹性模量与人体骨骼相近,100%降解,具有良好的应用前景。增强型β-TCP颈椎椎体间融合器可为颈椎椎体间融合提供足够的椎间支撑作用,不亚于自体髂骨的椎间融合效果。增强型β-TCP颈椎椎体间融合器的椎间支撑能力、生物力学性能及椎间融合效果均适合颈椎椎体间融合的应用。更多还原

【Abstract】 [Objective]:In recent years,[3-tricalcium phosphate(β-TCP) bioceramic was more and more popular and became the neotype of biomaterial in clinical medicine. Because of its good capability of biocompatibility,degradation and bone conduction,β-TCP bioceramic was extensively utilized in clinical orthopedics as materials for bone repair,repairing the bone defect caused by trauma,tumor,inflammation and osteopathia.But since its poor mechanical property,the application was restricted to replace non-weight loading part.The absorbable dense/porousβ-TCP bioceramic was designed with the help of Bio-Lu company,combining the dense ceramic which had good mechanical property but poor biocompatibility and the porous ceramic which had good biocompatibility but poor mechanical property.Then the absorbable dense/porousβ-TCP cervical intervertebral fusion cage was invented via the above technique,on the morphological basis of three-dimensional images and large sample anatomic data of Chinese cervical intervertebral space.Besides,we measured the mechanical intensity of the cage,established anterior cervical discectomy goat model, and carried out initial experiments on observation and evaluation of clinical effects, which provided the evidence for clinical application.[Methods]:ⅠSix young male fresh cadavers were chosen which had no cervical vertebrae deformation,trauma,tumor and obviously degeneration.After defrosting, their head and neck were separated from the body and then 64 row thin sheet CT scan and MRI scan were undertaken on the head neutral position and the natural neck curve.Afterwards,the cervical spine specimens were fixed on the same position by the external fixation.All the anulus fibrosus,nucleus and cartilaginous endplate of cervical intervertebral spaces were removed and replaced by injecting silica gel to get the three-dimensional model of cervical intervertebral spaces.The models were measured and scanned so as to get three-dimensional images of Chinese cervical intervertebral spaces.Compared the data from those three methods of CT scan,MRI scan and silica gel model,CT scan was considered as a more suitable method of cervical intervertebral space measurement especially for large samples.Ⅱ.97 qualified young volunteers were chosen randomly,including 63 male(21～29 years old,average age 25.2 years) and 34 female(20～29 years old,average age 24.3 years). They took cervical spine CT scan grouped by gender.By this means,the anatomic data of Chinese cervical intervertebral spaces were gained.Based on the morphological data of the above experiments,the absorbable dense/porousβ-TCP bioceramic cervical intervertebral fusion cage was produced,its physical chemistry property and mechanical property was measured as well.Ⅳ.10 two years old adult goats,20～25kg,male or female,were divided into two groups:5 goats in group A wereβ-TCP bioceramic cervical intervertebral fusion cage group,and the other 5 in group B were autogenic iliac bone group as control.Anterior cervical decompression and fusion goat model was established.After anterior cervical discectomy at single level,cartilaginous end-plate was removed,thenβ-TCP bioceramic cervical intervertebral fusion cage and autogenic iliac bone was implanted separately.At last anterior plate was fixed.Lateral cervical X-ray photo was taken after operation.The goats were raised 8 weeks.Ⅴ.The goats were sacrificed to take lateral cervical X-ray and CT scan.The sagittal reconstruction was established afterwards.X-ray was used to evaluate the change of the operated cervical intervertebral space height.CT scan and reconstruction was to compare intervertebral fusion.[Results]:Ⅰ.The three-dimensional images of Chinese cervical intervertebral space are gained by silica gel moulding which is used to get the three-dimensional model of cervical intervertebral space.The accuracy of CT scan and MRI scan is proven.Ⅱ. The anterioposterior length of Chinese cervical intervertebral space is 16.35～19.81mm in male,14.98～17.43mm in female.It is 18.55～22.50mm in male and 16.55～20.69mm in female from left to right.On midsagittal plane,the height of anterior cervical intervertebral space is 7.26～9.03mm in male and 5.36～5.98mm in female.The height of middle point is 8.01～9.24mm in male,7.65～8.12mm in female.Posterior border is 5.01～5.22mm in male,4.76～5.03mm in female.The intervertebral space is larger and larger from above down and male has larger space than the same level of female.Ⅲ.The absorbable dense/porousβ-TCP bioceramic cervical intervertebral fusion cage’s shape is like a box,has a ladder-shaped cross section,porous in center and dense surrounding.It is about 12mm in width,9mm in depth and 8mm in height.The mechanical intensity of the dense/porous one is significantly augmented than the simply porous so that it is able to perform supportive role and bone conduction better.Ⅳ.The anterior cervical intervertebral fusion model of goat is a good animal model for human cervical spine research.So results from this model is accurate and creditable.Ⅴ.The absorbable dense/porousβ-TCP bioceramic cervical intervertebral fusion cages are able to maintained the height of cervical intervertebral space.And there is no statistical difference of intervertebral fusion rate between these two groups.[Conelusions]:The absorbable dense/porousβ-TCP bioceramic cervical intervertebral fusion cage we designed is absorbable.Its elastic modulus is similar to human bone.It provides enough support for cervical intervertevral fusion,and produces fusion not less than auto-iliac bone at least.In conclusion,the absorbable dense/porousβ-TCP bioceramic cervical intervertebral fusion cage has good supporting ability,biocompatibility,mechanical property and intervertebral fusion effect,which indicates its perspective clinical application in cervical intervertebral fusion.更多还原