【作者】 李立华；

【导师】 周长忍； Peter Fratzl；

【作者基本信息】 暨南大学 ， 生物医学工程， 2008， 博士

【摘要】 为模拟天然骨组织的结构和成分,本研究以羟基磷灰石(HA)和壳聚糖(CS)为主要材料,利用间接快速原位成型(RP)、冷冻干燥和生物矿化技术制备了一系列具有可控结构、孔隙率和孔径的木垛型多孔复合支架。这些支架包括:HA/CS、HA/CS/PLLA木垛型支架、纳米-微米HA/CS木垛-网络型支架和生物矿化木垛型壳聚糖支架(BMCW)。通过改变材料的组成成分和结构,借助SEM、FTIR、XRD、细胞培养及压缩强度试验,研究了支架的形态、生物相容性和力学性能的变化。结果表明利用RP技术制备支架材料具有整体成型,批量制备,性质均一等特点,降低了平行试验中的个体差异;支架具有相互连通、直径为500μm的大孔及分布不均的微孔结构,以保证细胞接种和粘附以及血管和神经等的长入,大孔孔隙率为50 vol%;支架材料利于前体成骨细胞的分化,接种4周后,成骨细胞不仅沿大孔孔壁形成较厚的细胞复层,也渗透分布在支架细棱的微孔处,并且形成细胞-细胞及细胞-基体相互连接的网络,贯穿整个3D多孔支架;木垛网络型支架更接近于细胞生理环境,有利于真正的三维细胞培养,壳聚糖纤维网络有利于细胞的优先粘附和生长;在不影响支架生物相容性的前提下,纳米/微米级HA的共用,大大提高了支架的力学强度,nano-μm HA木垛-网络型复合支架具有更高的力学性能,压缩强度和压缩模量分别达到0.54±0.02 MPa和6.13±0.60 Mpa,但是粒子易渗出;通过生物矿化技术,以壳聚糖木垛型支架为模板,调控生长HA纳米晶体,在支架内形成了致密的高结晶度HA纳米晶体层,压缩强度和压缩模量分别达到0.54±0.005Mpa和5.47±0.65MPa,同时保证了支架的多孔结构,生物相容性和力学性能,该支架可应用于非承重骨组织工程支架材料。本研究同时探讨了乙醇/水共溶剂体系的矿化技术和矿化机理,此方法可以推广用于纳米HA的批量制备以及其他生物材料的快速矿化,将具有重大的理论和应用价值。更多还原

【Abstract】 To mimic the structure and component of natural bone,a series of hydroxyapatite （HA） and chitosan（CS） composite woodpile scaffolds were designed with rapid prototyping technique（RP）,freeze drying and biomineralization.These bone tissue engineering scaffolds with controlled architecture and porosity were HA/CS and HA/CS/PLLA woodpile,nano-micron HA/CS woodpile-network and biomineralized CS woodpile（BMCW）.The morphology,biocompatibility and mechanical properties were characterized by SEM,FTIR,XRD,cell culture and compression test.Results showed that the scaffolds were produced with the RP technique in batch and the scaffolds had almost the same properties such as mechanical,geometry etc.The composite scaffolds possessed controlled woodpile structure,in which the dimension of one strut as well as the distance between two struts was 500μm,which will be suitable for cell seeding,attachment and rapid vascularisation.Osteoblast grew not only in the macropores but also micropores of the strut and formed thick cell multilayer after four weeks.The cells preferred to grow on the chitosan network in woodpile-network scaffold,which is similar to the real three dimensional physiological environment.Nano HA improved the compression strength and compressive modulus dramatically to 0.54±0.02 MPa and 6.13±0.60 MPa respectively.The BMCW was prepared by mineralization of CS woodpile scaffolds,and the thick nano HA crystal layer with high crystallization deposited in the scaffolds to form nanoscopic hybrid composites, which achieved the compression strength of 0.54±0.005Mpa and modulus of 5.47±0.65 MPa respectively.The rapid and efficient one-pot mineralization approach and ethanol/H₂O co-solvent system can be extended to the mineralization of other materials and will have a very broad application in the future.更多还原