周期性微区功能结构构建及其调控成骨分化研究

发布时间：2018-06-05 16:19

本文选题：成骨 + 二氧化钛　；参考：《华南理工大学》2016年博士论文

【摘要】：骨组织与材料的界面处存在复杂的生理微环境,为提高植入体界面处的骨再生,大量研究利用硬度、微纳米拓扑结构以及表面官能团等材料的固有性能模拟细胞外基质的微环境调控干细胞成骨分化和诱导骨组织再生,但模拟骨内电生理微环境调控成骨分化的研究较少。骨内电生理微环境源于胶原纤维的压电响应特性及其空间多级排列特性。因此,模拟骨的电生理微环境,对电活性生物材料进行微区功能设计,对调控成骨分化和骨再生具有重要的科研价值和临床意义。本研究针对电活性生物材料仿生微区构建开展如下工作:(1)利用二氧化钛的半导体特性,在医用钛表面构建周期性微区二氧化钛异质结构。该微区异质结构由两种具有不同载流子密度的n型二氧化钛半导体周期性平行排列组成,可形成内建周期性微区静电场。体外细胞实验证明二氧化钛异质结构仿生微区静电场样品具有良好的生物相容性,且在不加入成骨诱导液的条件下就能通过微区电刺激促进骨髓间充质干细胞成骨分化,体内动物植入实验进一步证实其具有诱导骨再生的作用。本研究对于开发新型仿生微区电特性生物材料具有启发作用。(2)利用激光诱导微区相变技术构建微区压电响应型铌酸钾钠植入体,模拟骨内胶原纤维的压电响应特性。由于微区压电响应型植入体的微区电性不同,将在其表面产生空间特异性微区电场,模拟骨内电生理微环境。体外实验表明微区压电响应型植入体具有良好的生物相容性,并显著促进骨髓间充质干细胞的铺展。且在无成骨诱导液加入的条件下,植入体表面细胞碱性磷酸酶活性增加。动物体内植入实验也表明该微区压电响应型结构可以成倍提高植入体界面的骨再生能力。本研究成功构建仿生微区压电响应性植入体,该研究思想为植入体设计提供了新的思路。(3)本研究进一步提出利用微区压电响应型植入体材料表面形成的微区电场破坏细菌呼吸链,杀灭细菌的设想。首先通过调控极化参数实现对微区压电响应型植入体表面微区电场强度的有效调控。研究表明高微区电场强度的植入体可破坏细菌细胞膜,起到完全杀灭细菌的目的。实验结果也表明微区电场未影响活性氧产生,但可以显著促进巯基氧化。最终提出微区压电响应型植入体造成细菌定向迁移至质子耗散区引起细菌内质子失衡的杀菌机理。构建具有良好生物相容性且兼具抗菌性能的骨植入材料可实现成骨性和抗菌性的统一,具有重大临床意义。(4)钛表面空间可控的拓扑结构信号可以提高骨再生的效率。本研究利用选区激光辐照在水热处理纳米针状膜层表面构建缓冲区。该微区功能结构对类骨磷灰石沉积和蛋白吸附具有区域选择性,且避免了纳米针状膜层对成骨细胞增殖造成的抑制作用。细胞实验证实该微区功能结构可加速成骨细胞体外分化和钙结节沉积,且钙结节成分更接近于骨磷灰石成分。体内植入实验证明该功能微区结构可以诱导骨再生。
[Abstract]:There is a complex physiological microenvironment at the interface of bone tissue and material. In order to improve the bone regeneration at the implant interface, a large number of studies have been made to simulate the osteogenesis of the stem cells and induce the regeneration of bone tissue by using the intrinsic properties of the material such as the hardness, the micro nano topology and the surface functional groups to simulate the osteogenesis of the stem cells and the induction of bone tissue regeneration. There are few studies on the regulation of osteogenic differentiation in the microenvironment. The electrophysiological microenvironment in bone originates from the piezoelectric response characteristics and the spatial multilevel arrangement of the collagen fibers. Therefore, the simulation of the electrophysiological microenvironment of the bone and the microfunctional design of the electroactive biomaterials have important scientific and clinical significance for the regulation of osteogenesis and bone regeneration. In this study, the following work is carried out for the biomimetic microarea construction of electroactive biomaterials: (1) using the semiconductor properties of titanium dioxide to construct a periodic microzone titanium dioxide heterostructure on the surface of medical titanium. The microstructure of the microregion is composed of two kinds of N type TiO 2 semiconductors with different carrier density. In vitro cell experiments have proved that the bionic microzone electrostatic field samples of titanium dioxide heterostructure have good biocompatibility, and the bone marrow mesenchymal stem cells can be divided into bone by micro area electrical stimulation without the inclusion of osteogenic inducer, and the animal implantation experiments in vivo further confirm that This study has an enlightening effect on the development of a new biomimetic biomimetic biomimetic biomaterial. (2) the piezoelectric response type of potassium niobate implant was constructed by laser induced microphase transition technology to simulate the piezoelectric response characteristics of the collagen fibers in the bone. In the same way, the space specific microelectric field will be produced on the surface to simulate the electrophysiological microenvironment in the bone. In vitro experiments show that the micropiezoelectric responsive implants have good biocompatibility and significantly promote the spread of bone marrow mesenchymal stem cells. And the alkaline phosphatase activity of the implant surface cells under the non osteogenic inducer added. In vivo implantation experiments in animal body also show that the piezoelectric responsive structure of the microregion can double the bone regeneration ability of the implant interface. This study successfully constructed a biomimetic micro piezoelectric responsive implant, which provides a new idea for the design of the implant. (3) this study further proposed the use of micropiezoelectric responsive implants. The microelectric field formed by the surface of the material destroys the bacterial respiration chain and destroys the bacteria. First, the effective control of the micro area electric field intensity of the microzone piezoelectric responsive implant is realized by controlling the polarization parameters. The research shows that the implanted body of the high micro electric field strength can destroy the bacterial cell membrane, and the aim of killing bacteria completely is the experimental junction. The results also show that the micro area electric field does not affect the production of reactive oxygen species, but it can significantly promote the oxidation of sulfhydryl groups. Finally, it is suggested that the micropiezoelectric responsive implants cause the bactericidal mechanism of bacterial endoplasmic disequilibrium caused by the directional migration of bacteria to the proton dissipative region. The unity of sexual and antibacterial properties is of great clinical significance. (4) the spatial controllable topological structure signal of the titanium surface can improve the efficiency of bone regeneration. The inhibitory effect of the nanoscale membrane on osteoblast proliferation was avoided. Cell experiments confirmed that the functional structure of the microregion could accelerate the differentiation of osteoblasts and the deposition of calcium nodules, and the calcium nodule composition was closer to the bone apatite. In vivo implantation experiments proved that the functional microstructure could induce bone regeneration.
【学位授予单位】：华南理工大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R68;R318.08

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