人工活性骨内部结构建模方法的探索

骨内部结构是影响人工活性骨制造的一个重要因素。在分析骨组织结构和人工骨内部结构应具备条件的基础上，建立了一种人工骨内部微细结构的简化模型，并利用Visual C 及Open GL实现了建模方法。对该建模方法进行改进，可进一步提高对模型中骨单位和微孔的数量、大小及其分布的控制，以满足制造人工活性骨的需求。     

人工活性骨内部结构建模方法的探索

骨内部结构是影响人工活性骨制造的一个重要因素。在分析骨组织结构和人工骨内部结构应具备条件的基础上,建立了一种人工骨内部微细结构的简化模型,并利用VisualC++及OpenGL实现了建模方法。对该建模方法进行改进,可进一步提高对模型中骨单位和微孔的数量、大小及其分布的控制,以满足制造人工活性骨的需求。     

三种仿生人工骨内部微细结构的对比研究

提出一种采用基于快速成形的立体编织技术来制造纤维增强复合材料仿生人工骨的方法，制造的三种仿生人工骨内部的纤维分别被铺设成螺旋、正交和同心结构，其中正交结构和同心结构人工骨的内部纤维可以被精确地安置在设计位置上，根据犬桡骨缺损修复实验过程中的X光片、组织切片和成分对比等内容，研究了人工骨内部不同的纤维结构对促进成骨和人工骨降解的影响，研究发现，在骨修复初期三种仿生人工骨都能提供一定的机械性能，但是随着时间的推移，螺旋结构人工骨的降解量最小，同心结构人工骨的成骨量最高，说明由壳聚糖、骨形态发生蛋白和磷酸钙盐等制成的纤维增强型人工骨具有良好的骨传导和骨诱导作用，其中同心结构人工骨具有最佳的成骨作用，其内部纤维结构相对最优。     

基于快速成形的β-磷酸三钙人工骨结构设计及制造

提出一种以计算机辅助设计(CAD)和光固化快速成形技术为基础的人工骨间接制造方法．应用CAD准确设计和控制人工骨内部结构，通过光固化快速成形技术制造相应的树脂模具，在模具中填充β-TCP生物陶瓷，经过烘干和热分解去模，获得了与设计相符的β-TCP生物陶瓷人工骨，该方法克服了传统人工骨构造方法中内部微管道结构不可控的缺点，为构造更有利于细胞-组织长入和成活的人工骨内部空间结构开辟了新路，实验证明，从人工骨的结构设计到最终的烧结成型，整个过程均是可控的，而且按照设计准则所构造的生物陶瓷人工骨内部空间结构，有助于促进其活化。     

生物活性梯度涂层的结构与动物实验

采用先进的表面技术复合制备生物活性梯度涂层材料。通过与rhBMP-2生物组装获得具有骨诱导功能的复合人工骨材料，这种材料在植入动物体内3周后即可形成大量的新生骨细胞和骨组织，新生骨组织沿着涂层的微孔长入，与涂层结合紧密。16周后新生骨组织矿化均匀，形成比较成熟的、排列有序的层板编织骨。作为对比研究的金属钛合金植入体与骨组织结合的界面中只是形成大片的纤维组织，而未见新生骨组织。     

图像处理技术在人工骨三维仿生设计中的应用

基于图像的人工骨三维仿生设计,包括两方面内容:在对图像数字化处理分析的基础上进行的人工骨外部结构三维重建和内部微观结构仿生设计.由此能够设计出具有与人体实际骨外部形状极其相似的人工骨.图像处理包括图像预处理、图像分割、三维可视化三个功能子集.     

生物压电陶瓷复合种植材料的制备与性能研究

研究了一种新型的人工生物压电陶瓷复合种植材料－ＨＡＢＴ生物压电陶瓷。对该种材料的压电性能、力学性能、热学性能、化学性能和生物学性能进行了初步考察和动物试验。结果表明，该材料既具有与人体组织相近的生物相容性和力学相容性，又具有相似于人体自然骨的压电性。该材料还能诱导骨组织的生长，符合生物安全性检测要求。     

生物活性压电陶瓷在植骨材料的研究进展

目前临床上的植骨材料在使用中有着一定的局限性,例如生物活性不足、骨折不愈合、成骨量有限、材料降解速度与组织生长不匹配等问题.研究具备成骨性能的新型生物活性骨修复材料是目前骨组织工程领域研究的热点和重点之一.介绍了CaTiO3、BaTiO3基无铅压电陶瓷、[(K,Na)NbO3]基(KNN基)无铅压电陶瓷及LiNbO3作为植骨材料的研究进展.生物压电陶瓷有着较好的细胞相容性和组织相容性,具有成为骨替代物的潜力.     

采用立体编织工艺构造人工骨仿生微结构

为了实现人工骨植入体内的有效活化,应用立体编织法制作人工骨的微管结构.以CAD设计人工骨的微结构,用三维立体编织技术将可吸收手术缝合线编织成人工骨微结构支架的负型,为控制人工骨的微管尺寸,在缝线上涂敷Ⅰ型胶原蛋白,在编织物内充填自固化磷酸钙骨水泥(CPC),固化后形成含有微孔结构的人工骨.实验表明,缝线的降解速度高于CPC的降解速度,能够早期在人工骨内部形成相互导通的微管道结构,这不仅有利于骨生长,还可以促进人工骨的活化,同时还具有一定的力学强度,可望用于骨缺损的修复.     

钙、磷、硅玻璃塑固人工骨

通过钙、磷、硅玻璃塑固人工骨的研究得到一种具有一定机械强度，化学稳定性好，具有好的生物相容性和生物活性的塑固人工骨，硬化时间在２～３０ｍｉｎ内。     

Engineered polycaprolactone – magnesium hybrid biodegradable porous scaffold for bone tissue engineering

In this paper, we describe the fabrication of a new biodegradable porous scaffold composed of polycaprolactone(PCL) and magnesium(Mg)micro-particles. The compressive modulus of PCL porous scaffold was increased to at least 150% by incorporating 29% Mg particles with the porosity of 74% using Micro-CT analysis. Surprisingly, the compressive modulus of this scaffold was further increased to at least 236% when the silane-coupled Mg particles were added. In terms of cell viability, the scaffold modified with Mg particles significantly convinced the attachment and growth of osteoblasts as compared with the pure PCL scaffold. In addition, the hybrid scaffold was able to attract the formation of apatite layer over its surface after 7 days of immersion in normal culture medium, whereas it was not observed on the pure PCL scaffold. This in vitro result indicated the enhanced bioactivity of the modified scaffold. Moreover, enhanced bone forming ability was also observed in the rat model after 3 months of implantation. Though bony in-growth was found in all the implanted scaffolds. High volume of new bone formation could be found in the Mg/PCL hybrid scaffolds when compared to the pure PCL scaffold. Both pure PCL and Mg/PCL hybrid scaffolds were degraded after 3 months. However, no tissue inflammation was observed. In conclusion, these promising results suggested that the incorporation of Mg micro-particles into PCL porous scaffold could significantly enhance its mechanical and biological properties. This modified porous bio-scaffold may potentially apply in the surgical management of large bone defect fixation.     

Fabrication and characterization of a PAM modified PHBV/BG scaffold

In order to improve the bioactivity and mechanical strength of the scaffold used in bone repair simultaneously, a novel porous PAM-poly （β-hydroxybutyrate-co-β-hydroxyvalerate） （PHBV）/bioactive glass （BG） scaffold was prepared by photo-initiated polymerization. PAM was used to improve the hydrophilicity of PHBV matrix while the BG particles were added to increase the bioactivity and strength of the matrix synchronously. The grafted amide group and Si-O moieties from acrylamide and the added BG were confirmed by Fourier Transform Infrared Spectrometry （FTIR）. The micromorphology of the scaffolds before and after grafting was observed by scanning electron microscopy （SEM）. The resulting images demonstrate that the PAM-PHBV/BG scaffold has a well connected pore structure and appropriate pore size which may be convenient for cells to grow and discharge metabolites. The specific gravity method was used to evaluate the pore property of the scaffold and the result shows that the scaffold has an average porosity up to 82.0%. Mercury intrusion porosimetry （MIP） indicated that the pores of PAM-PHBV/BG scaffold were mainly distributed between 75 and 150 μm. The compressive strength test was adopted to evaluate the mechanical property of the scaffold. The result shows that the PAM-PHBV/BG scaffold has a relatively high compressive strength （0.91 MPa） when compared with the pure PHBV scaffold. Besides, the properties of the pure PHBV scaffold, PHBV/BG scaffold were also evaluated. The newly prepared PAM-PHBV/BG scaffold may be worthy of further studying as a bone repair material.     

Haversian bone-mimicking bioceramic scaffolds enhancing MSC-macrophage osteo-imunomodulation

The interaction between immune cells and bone forming cells plays a vital role in maintaining the homeostasis of the skeletal system, and is regulated by the three-dimensional structure of tissues. Whether the construction of biomaterials can activate or reproduce this spatial “cross-talk” between immune cells and bone forming cells in bone natural formation process is a prerequisite for successful fracture healing and bone regeneration. Herein, a bone marrow mesenchymal stem cells(MSCs)/macroph...     

纳米仿生骨组织材料的生理响应及生物矿化

利用溶胶－凝胶法合成了两种具有纳米结构的新型高生物活性骨修复及骨组织工程支架材料，并利用体外实验方法（In Vitro)以及X－射线衍射（XRD），扫描电子显微镜（SEM），红外光谱（FTIR），氮气吸附－解吸（BET）和等离子发射光谱（ICP）等技术对材料的显微结构及其在模拟生理溶液（SBF）中的降解过程，表面反应产物及生物矿化机理进行了研究，研究表明：两种溶胶－凝胶材料均具有较高的生物活性；由于化学组成不同，它们在SBF溶液中的离子扩散规律及生物矿化行为有所不同。     

Incorporation of Sphingosine 1-Phosphate Loaded Mesoporous Silica Nanoparticles into Poly( L-lactic acid ) Nanofibrous Scaffolds for Bone Tissue Engineering

Controlled release of the functional factors is the key to improve clinical therapeutic efficacy during the tissue repair and regeneration.The three-dimensional(3D)scaffold can provide not only physical properties such as high strength and porosity but also an optimal environment to enhance tissue regeneration.Sphingosine1-phosphate(S1P),an angiogenic factor,was loaded into mesoporous silica nanoparticles(MSNs)and then incorporated into poly(L-lactic acid)(PLLA)nanofibrous scaffold,which was fabricated by thermally induced phase separation(TIPS)method.The prepared scaffolds were examined by attenuated total reflection Fourier transform infrared spectroscopy(ATR-FTIR),scanning electron microscopy(SEM),and transmission electron microscopy(TEM)and compressive mechanical test.The ATR-FTIR result demonstrated the existence of MSNs in the PLLA nanofibrous scaffold.The SEM images showed that PLLA scaffold had regular pore channel,interconnected pores and nanofibrous structure.The addition of MSNs at appropriate content had no visible effect on the structure of scaffold.The compressive modulus of scaffold containing MSNs was higher than that of the scaffold without MSNs.Furthermore,fluorescein isothiocyanate(FITC)was used as model molecule to investigate the release behavior of S1P from MSNsincorporated PLLA(MSNs/PLLA)nanofibrous scaffold.The result showed that the composite scaffold largely reduced the initial burst release and exhibited prolonged release of FITC than MSNs.Thus,these results indicated that S1P-loaded composite nanofibrous scaffold has potential applications for bone tissue engineering.     

聚苯乙烯薄膜三维培养肝细胞的实验研究

采用三维聚苯乙烯薄膜作为细胞培养支架,在体外进行大鼠肝细胞的三维培养,并与常规二维肝细胞培养进行比较.分析了细胞的生长状态及肝细胞功能,包括细胞存活率、白蛋白分泌功能、尿素合成功能及葡萄糖消耗功能.结果显示:三维细胞增殖活力均始终明显高于二维;在显微镜下观察,可看到三维支架表面黏附生长的肝细胞逐渐增多,有肝细胞黏附成团,且肝细胞保持着良好的形态学结构.研究表明,三维培养的肝细胞其增殖生长和代谢功能都优于同样条件下的二维培养,三维聚苯乙烯薄膜可以作为体外肝细胞培养支架,在生物人工肝培养体系中具有应用前景.     

海藻酸盐复合凝胶在骨组织工程中的研究进展

骨组织工程支架是以修复缺损的骨并恢复其功能为目的而开发出的人工支架。海藻酸盐是世界上含量最丰富的海洋生物高分子聚合物,其在骨组织工程材料中的应用已被大量研究报道。虽然海藻酸盐作为骨组织支架材料具有优异的生物相容性、良好的生物可降解性和无免疫原性等优点,但是仍存在机械强度较弱、缺乏细胞特异性结合位点、支架结构在生理环境中易被破坏等缺点,严重限制其在骨组织工程中的应用。目前,研究者已经研究出几大类海藻酸盐复合支架材料,这些材料均表现出优异的力学性能和生化性能,因此,海藻酸盐复合支架材料可能在骨组织修复和再生方面具有较高的应用价值。本文主要针对海藻酸盐复合支架材料在骨组织工程中的应用作简要概述。     

纳米HAP/CPP/PLLA骨组织工程支架复合材料降解特性

现有支架材料的降解速率与骨细胞生长、繁殖速率不匹配,在降解过程中支架材料的强度、刚度衰减速率与成骨速率不匹配,支架材料在体内降解的酸性副产物会引起炎症反应.为克服以上困难,采用溶媒浇铸、颗粒滤取与气体发泡相结合的方法制备出纳米HAP/CPP/PLLA骨组织工程支架复合材料;选用生理盐水作为模拟体液进行降解实验,测试该支架复合材料的降解性能,用扫描电子显微镜对其在不同降解时期的微观结构进行观察.结果表明:纳米HAP/CPP/PLLA支架复合材料在降解过程中具有三维、连通、微孔网状结构,并具有良好的降解性能和生物相容性,是比较理想的骨组织工程支架材料.     

溶胶凝胶法合成含镁磷酸三钙生物陶瓷涂层

用溶胶凝胶法在钛合金基体上经600℃烧结合成了含镁β-磷酸三钙生物陶瓷涂层.试验结果表明,CO32-被合成于磷酸三钙晶体结构之中,形成了B型替换,即CO32-部分替换了PO43-在晶体结构中的位置;模拟体液中,这种涂层的表面可以形成明显的新生类骨层,显示出很好的生物活性,有望在医疗实践中作为人工骨质材料得到广泛应用.