纳米化表面钛合金内植物的界面组织学和生物力学评价

背景：假体松动是造成人工关节置换失败和翻修的主要原因之一。材料表面处理能够促进假体和骨组织界面的骨整合,提高假体的稳定性。 目的：研究纳米化表面钛合金(Ti6A14V)內植物在动物体内的骨整合情况。 方法：基于严重塑性变形原理制备纳米化表面钛合金。在比格犬股骨髁间植入普通表面、羟基磷灰石表面和纳米化表面钛合金内植物,置入后3个月取材,处死前行影像学观察,处死后取带有内植物的股骨髁制作不脱钙骨组织磨片,行Van Gieson苦味酸一品红染色,观察内植物和骨组织界面组织学情况,并进行骨动力学参数计算。同时行推出实验,比较不同表面内植物和骨组织界面生物力学情况。 结果与结论：影像学检查,见内植物和骨组织结合良好;界面组织学可见羟基磷灰石表面和纳米化表面钛合金与骨界面有大量成熟骨小梁直接结合,两者界面骨结合率相似(P > 0.05),但都优于普通表面钛合金(P < 0.01);推出实验显示羟基磷灰石表面和纳米化表面钛合金內植物和骨组织的结合力相似(P > 0.05),但都优于普通表面钛合金(P < 0.001)。提示严重塑性变形原理制备的纳米化表面钛合金和羟基磷灰石表面钛合金一样具有成骨诱导活性,能够促进骨整合,具有良好的临床应用前景。     

力学载荷对破骨细胞凋亡的影响及其调节机制

破骨细胞是参与骨代谢的基本功能细胞之一.破骨细胞在骨重建过程中主要承担旧骨组织的破坏和吸收,因此,破骨细胞凋亡的微小变化都可能会改变骨重建的进程.调节破骨细胞凋亡的因素有很多,如雌激素、二磷酸盐等生物化学因素,但力学载荷对于破骨细胞生物学活性影响的研究相对较少.综述了力学载荷对破骨细胞生物学活性的影响以及细胞凋亡与破骨细胞凋亡的调节.     

影响骨整合的因素分析

骨整合即在光镜水平下正常的改建骨和假体之间看不见软组织,假体与骨组织直接接触,其承受的负荷能通过这种直接接触持续不断地传递并分散到骨组织中.当今多数学者倾向于骨整合结合方式.纤维骨性结合是指假体与周围骨质之间不直接接触,而是有一层类似牙周膜的纤维膜相隔.本文主要通过文献资料法以及笔者多年工作经验,针对影响影响假体-骨界面骨整合的因素进行分析总结,希望能促进假体-骨界面骨整合技术的进一步发展.     

不同材料人工关节磨损颗粒对假体--骨界面骨形成影响的比较研究

目的 :观察不同材料人工关节磨损颗粒对假体 -骨界面骨形成的影响 ,进一步探讨其在人工关节无菌性松动中的作用。方法 :以改良“骨收集室”(BHC)植入兔胫骨干骺端为假体 骨界面模型 ,分别在BHC内加入1.5mg/ml(W/V)Ti合金、CoCr合金或UHMWPE颗粒混悬物 10 μl,4周取材。组织学观察成骨情况 ,颗粒分布及其周围的组织细胞学反应。图像分析测量每个视野小梁骨面积与组织总面积的比值 (BA/TTA) ,于各组间比较。结果 :UHMWPE颗粒与CoCr合金颗粒均明显抑制BHC内网织骨形成 ,并有以MΦ为主的炎症反应及纤维组织大量增生 ,组织构成与人体内无菌性松动假体周围界膜接近。Ti合金颗粒则对成骨影响相对较小。各加颗粒组BHC中组织BA/TTA均小于空白对照组 (P <0 .0 1) ,其中又以UHMWPE颗粒与CoCr合金颗粒组最小 (P <0 .0 1) ,而后两者间无显著性差异 (P >0 .0 5 )。结论 :磨损颗粒除可激活MΦ性骨溶解外 ,还可抑制网织骨形成。因此 ,其造成的人工关节假体 骨界面骨重建障碍可能是骨吸收增加和骨形成减少协同作用的结果。     

异种生物骨钉界面的成骨能力

背景：牛皮质骨作为异种皮质骨材料应用最为广泛,但其免疫原性反应严重,从而可能导致内固定失败。 目的：观察3种不同皮质骨螺钉在动物体内的转归,及不同材料骨钉的生物力学性能以及免疫原性反应差异。 方法：脱脂、脱细胞、灭菌及诱导活性修饰处理制备牛皮质骨生物界面螺钉及普通方式处理后的消毒牛骨钉及消毒羊骨钉。再将3种骨钉植入健康18只山羊股骨中段进行生物学性能观察。 结果与结论：Lane组织学评分生物界面骨螺钉>消毒羊骨钉>消毒牛骨钉(P < 0.01)。生物力学实验行初始界面刚度载荷及界面刚度比较,3组差异无显著性意义(P > 0.05);12周时,生物界面骨螺钉>两组消毒钉(P< 0.05);24周时,生物界面骨螺钉>消毒羊骨钉>消毒牛骨钉(P < 0.01)。提示,生物界面骨螺钉的初始力学性能不低于消毒牛骨,且能较长时间保持稳定的力学性能;生物界面骨螺钉具有一定的成骨作用,与宿主骨组织结合后,产生了更强的界面力学性能。     

载荷作用下骨细胞分泌因子对成骨细胞和破骨细胞的调节

骨细胞是骨组织主要的力学感受及转导细胞,它们通过众多突触结构相互连接,形成庞大的骨稳态细胞调控网络,联系着成骨细胞、破骨细胞等骨基质表面细胞。骨细胞通过旁分泌途径影响成骨细胞骨形成和破骨细胞骨吸收来调节骨代谢,维持骨更新。针对骨细胞在受到力学刺激后分泌或释放的一些信号分子或蛋白因子对成骨细胞和破骨细胞生长分化的影响,本文综述近年来关于受力学刺激的骨细胞如何与成骨/破骨细胞进行通讯,为骨细胞生物力学研究提供新思路。     

骨组织工程化培养中成骨细胞力学响应的初步研究

由于骨具有支撑、保护、运动的功能,是承力器官,力学环境对骨组织的发生、发展有着十分重要的影响。活体研究表明:载荷可促进成骨细胞的增殖、分化和细胞外基质的分泌,及骨衬细胞的生物学活动;力学因素显著影响骨细胞生物学活动,包括骨细胞的凋亡;力学环境引起骨内细胞的协同反应,对骨组织变化起整合作用。由于骨组织力学环境如此重要,力学环境就有可能是工程化骨培养中的必要因素。由此,笔者尝试建立三维立体条件下成骨细胞力学响应的模型,研究骨内细胞的力学反应。模型包括支架材料、种子细胞和有力学作用的培养环境。支架材料除具有一般生物支架材料的要求外,还应与天然松质骨有相似的结构和力学性能,这里包括生物衍生松质骨、珊瑚支架等。种子细胞可采用乳鼠分离出的成骨细胞或成骨细胞系,接种在支架上进行培养。载荷直接施加在复合体上,复合体的表观应变被精确控制,可形成与骨活体内相似的力学环境,其中载荷可采用不同形状的波形,如正弦波、方波等。加载应变可达到0～10 000,频率0～100 Hz,大大包括了活体骨组织所受的力学环境。载荷形成细胞的力学环境是以支架材料的表观应变衡量,这正对应活体骨研究的力学指标。     

钛及金刚石涂膜材料颌骨内种植骨界面的超微结构观察

为研究金刚石涂膜作为种植材料在人体内的生物相容性 ,本文将纯钛、金刚石涂膜、不锈钢三种种植材料分别植入鼠下颌骨内 ,通过光镜和扫描电镜 ,观察界面骨形成情况。结果表明 :金刚石涂膜种植体界面的新骨生成启动早 ,植入后四周界面骨结合量明显高于纯钛和不锈钢种植体 ,九周时金刚石涂膜和钛骨界面已与正常骨结构相似 ,充分达到了骨整合。将金钢石涂膜种植体应用于临床 ,可望缩短种植后的无负荷期 ,使患者能早日镶复义齿。不锈钢种植材料不适于临床种植应用     

激光熔凝一步制备复合生物陶瓷涂层的 生物相容性

在钛合金表面上预涂敷 Ca HPO4 - Ca CO3- Y2 O3混合粉末 ,进行激光同步合成和熔覆 ,获得了以 TC4为基材的生物陶瓷涂层复合材料。将该涂层材料植入成年狗的股骨中进行生物相容性试验研究。结果表明 ,该涂层材料对动物的组织和细胞无毒副作用 ,且涂层有良好的生物相容性 ,有诱导骨生长和不影响成骨细胞与破骨细胞活性的特性。     

唇侧植骨不同种植修复体的三维有限元分析

目的分析植骨和修复体对种植修复体内部结构及周围骨组织应力分布的影响。方法建立由两种唇侧骨质牙槽骨模型支持且分别为钴铬合金烤瓷冠与二氧化锆全瓷冠修复的上颌中切牙种植修复体模型,对其进行力学加载,分析植骨与修复体对植体内部各结构与植体-骨界面应力分布的影响。结果植骨组中固位螺丝唇侧体部处及种植体唇侧骨组织中应力远低于非植骨组,但植骨组种植体颈部处的应力则高于非植骨组。相同骨质条件下,二氧化锆全瓷冠组在固位螺丝唇侧体部处的应力大于钴铬合金烤瓷冠组。结论修复体对种植修复体内部结构及周围骨组织应力分布的影响不大,但植骨影响的唇侧骨质差异可影响固位螺丝体部及植体-骨界面处的应力集中状况。     

Histomorphometric study on the osteocyte lacuno-canalicular network in animals of different species. II. Parallel-fibered and lamellar bones

The shape, size and density of osteocyte lacunae in parallel-fibered and lamellar bone were histomorphometrically analyzed in relation to the organization of the collagen fiber texture and the animal species (frog, sheep, dog, bovine, horse and man). The following parameters were measured under the light microscope (LM) by a computer-assisted image analyzer: 1) shape, size and distribution of osteocyte lacunae; 2) osteocyte lacuno-canalicular density. In close agreement with our previous studies, which includes woven bone, it resulted that in all animals (even in frog) osteocyte lacunae have a rounded globous shape in woven bone and an oval shape in both parallel-fibered and lamellar bone; in the latter, however, they are more flattened, only located in loose lamellae and thus regularly distributed in rows. Osteocyte lacunar density is higher in woven-fibered, intermediate in parallel-fibered and lower in lamellar bone, whereas no correlation seems to exist with the animal species. In conclusion, these results suggest that osteocyte shape, size and density seem to depend mainly on collagen fiber texture rather than on the animal species. The role of osteocyte-recruitment on the spatial organization of collagen fibers in bone tissues is discussed.     

Sexual dimorphism and age dependence of osteocyte lacunar density for human vertebral cancellous bone

The sexual dimorphism in age-related loss of human vertebral cancellous bone is not fully understood and could be related to dimorphism in the bone cell populations. The objective of this study was to investigate age- and gender-related differences in the osteocyte population and its relationship with bone volume fraction for human vertebral cancellous bone. Histomorphometric techniques were used to quantify osteocyte lacunae (a measure of osteocyte population) and bone volume fraction in male and female human T12 vertebrae, the most common site of vertebral fracture. Two measures of osteocyte population [number of osteocytes per bone area (OtLcDn) and number of osteocytes per total area (OtLcN/TA)] and their relationships with age and bone volume fraction were found to be sexually dimorphic. Dimorphism in osteocyte density may explain the dimorphic patterns of bone loss in human vertebrae due to the sensory and signal communication functions that osteocytes perform.     

Nano–Microscale Models of Periosteocytic Flow Show Differences in Stresses Imparted to Cell Body and Processes

In order to understand how local changes in mechanical environment are translated into cellular activity underlying tissue level bone adaptation, there is a need to explore fluid flow regimes at small scales such as the osteocyte. Recent developments in computational fluid dynamics (CFD) provide impetus to elucidate periosteocytic flow through development of a nano–microscale model to study local effects of fluid flow on the osteocyte cell body, which contains the cellular organelles, and on the osteocyte processes, which connect the cell to the entire cellular network distributed throughout bone tissue. For each model, fluid flow was induced via a pressure gradient and the velocity profile and wall shear stress at the cell-fluid interface were calculated using a CFD software package designed for nano/micro-electro-mechanical-systems device development. Periosteocytic flow was modeled, taking into consideration the nanoscale dimensions of the annular channels and the flow pathways of the periosteocytic flow volume, to analyze the local effects of fluid flow on the osteocyte cell body (within the lacuna) and its processes (within the canaliculi). Based on the idealized model presented in this article, the osteocyte cell body is exposed primarily to effects of hydrodynamic pressure and the cell processes (CP) are exposed primarily to fluid shear stress, with highest stress gradients at sites where the process meets the cell body and where two CP link at the gap junction. Hence, this model simulates subcellular effects of fluid flow and suggests, for the first time to our knowledge, major differences in modes of loading between the domain of the cell body and that of the cell process.     

Determination of bone volume by osteocyte population

During development and growth, biological tissues and organisms can control their size and mass by regulating cell number (Raff, 1992; Conlon and Raff, 1999). Later in life both cell number and organ mass decrease (Buetow, 1985). We demonstrate that the number density of bone cells buried in the calcified matrix (osteocyte lacunar density) predicts extracellular matrix volume for both cancellous and cortical bone in a broad cross-section of the population (males and females, age range 23-91 years, r(2) = 0.98). Our hypothesis is that bone mass is determined by the control of osteocyte number, and that this is a particular instance of the control of organ size through the social controls on cell survival and death (Raff, 1992; Conlon and Raff, 1999).     

Modeling Fluorescence Recovery After Photobleaching in Loaded Bone: Potential Applications in Measuring Fluid and Solute Transport in the Osteocytic Lacunar-Canalicular System

Solute transport through the bone lacunar-canalicular system is essential for osteocyte viability and function, and it can be measured using fluorescence recovery after photobleaching (FRAP). The mathematical model developed here aims to analyze solute transport during FRAP in mechanically loaded bone. Combining both whole bone-level poroelasticity and cellular-level solute transport, we found that load-induced solute transport during FRAP is characterized by an exponential recovery rate, which is determined by the dimensionless Strouhal (St) number that characterizes the oscillation effects over the mean flows, and that significant transport occurs only for St values below a threshold, when the solute stroke displacement exceeds the distance between the source and sink (the canalicular length). This threshold mechanism explains the general flow behaviors such as increasing transport with increasing magnitude and decreasing frequency. Mechanical loading is predicted to enhance transport of all tracers relative to diffusion, with the greatest enhancement for medium-sized tracers and less enhancement for small and large tracers. This study provides guidelines for future FRAP experiments, based on which the model can be used to quantify bone permeability, solute–matrix interaction, and flow velocities. These studies should provide insights into bone adaptation and metabolism, and help to treat various bone diseases and conditions.     

TM种植体骨界面应力分布的有限元分析

背景：种植体形态是决定种植体骨界面应力分布的重要因素之一。探讨顺应人体正常颌骨解剖形态的TM种植体骨界面的应力分布特征对临床医生选择和设计种植体有指导意义。 目的：观察集中荷载作用下TM种植体及其周围骨组织应力分布的特征。 方法：通过逆向工程技术,将二维下颌骨CT图片转化为三维实体模型,并建立3种包含不同锥度的TM种植体真实下颌骨B/2类骨质的有限元模型,利用有限元技术研究两种加载方式下TM种植体骨界面应力分布特征。 结果与结论：垂直加载时,对于锥度较大的TM种植体周边密质骨承受较小的应力;斜向加载时,对于锥度较大的TM种植体周边密质骨和松质骨承受较大的应力;种植体颈部,密质骨上缘与种植体接触处和种植体底部松质骨出现明显应力集中现象,斜向荷载下种植体骨界面的应力分布显著高于垂直荷载下的应力分布。从1/2长度开始变化的TM种植体骨界面在垂直荷载下表现出较好的应力分布特征。     

机体衰老对骨细胞力学响应的影响

骨骼是一个动态变化的器官,骨细胞的形态、结构和功能随力学刺激大小、方向、形式的不同而发生变化。适当的力学刺激是维持骨形成和骨吸收动态平衡的关键。随着年龄的增加,骨组织衰老会引起包括骨组织微环境、骨细胞形态、骨细胞内信号通路等在内的一系列变化,使骨骼力学响应能力减弱,进而引起骨质疏松等多种疾病。因此,研究衰老如何影响骨细胞的力学响应具有重要意义。重点讨论机体衰老对骨细胞力学响应的影响。     

A review on the wettability of dental implant surfaces II: Biological and clinical aspects

Dental and orthopedic implants have been under continuous advancement to improve their interactions with bone and ensure a successful outcome for patients. Surface characteristics such as surface topography and surface chemistry can serve as design tools to enhance the biological response around the implant, with in vitro, in vivo and clinical studies confirming their effects. However, the comprehensive design of implants to promote early and long-term osseointegration requires a better understanding of the role of surface wettability and the mechanisms by which it affects the surrounding biological environment. This review provides a general overview of the available information about the contact angle values of experimental and of marketed implant surfaces, some of the techniques used to modify surface wettability of implants, and results from in vitro and clinical studies. We aim to expand the current understanding on the role of wettability of metallic implants at their interface with blood and the biological milieu, as well as with bacteria, and hard and soft tissues.     

Micromotion-induced strain fields influence early stages of repair at bone–implant interfaces

Implant loading can create micromotion at the bone–implant interface. The interfacial strain associated with implant micromotion could contribute to regulating the tissue healing response. Excessive micromotion can lead to fibrous encapsulation and implant loosening. Our objective was to characterize the influence of interfacial strain on bone regeneration around implants in mouse tibiae. A micromotion system was used to create strain under conditions of (1) no initial contact between implant and bone and (2) direct bone–implant contact. Pin- and screw-shaped implants were subjected to displacements of 150 or 300 μm for 60 cycles per day for 7 days. Pin-shaped implants placed in five animals were subjected to three sessions of 150 μm displacement per day, with 60 cycles per session. Control implants in both types of interfaces were stabilized throughout the healing period. Experimental strain analyses, microtomography, image-based displacement mapping, and finite element simulations were used to characterize interfacial strain fields. Calcified tissue sections were prepared and Goldner trichrome stained to evaluate the tissue reactions in higher and lower strain regions. In stable implants bone formation occurred consistently around the implants. In implants subjected to micromotion bone regeneration was disrupted in areas of high strain concentrations (e.g. >30%), whereas lower strain values were permissive of bone formation. Increasing implant displacement or number of cycles per day also changed the strain distribution and disturbed bone healing. These results indicate that not only implant micromotion but also the associated interfacial strain field contributes to regulating the interfacial mechanobiology at healing bone–implant interfaces.     

In vivo corrosion of four magnesium alloys and the associated bone response

Degrading metal alloys are a new class of implant materials suitable for bone surgery. The aim of this study was to investigate the degradation mechanism at the bone-implant interface of different degrading magnesium alloys in bone and to determine their effect on the surrounding bone. Sample rods of four different magnesium alloys and a degradable polymer as a control were implanted intramedullary into the femora of guinea pigs. After 6 and 18 weeks, uncalcified sections were generated for histomorphologic analysis. The bone-implant interface was characterized in uncalcified sections by scanning electron microscopy (SEM), element mapping and X-ray diffraction. Results showed that metallic implants made of magnesium alloys degrade in vivo depending on the composition of the alloying elements. While the corrosion layer of all magnesium alloys accumulated with biological calcium phosphates, the corrosion layer was in direct contact with the surrounding bone. The results further showed high mineral apposition rates and an increased bone mass around the magnesium rods, while no bone was induced in the surrounding soft tissue. From the results of this study, there is a strong rationale that in this research model, high magnesium ion concentration could lead to bone cell activation.