高孔隙强韧化仿生骨基元人工骨合成及成骨转化机制研究

The development of Nano artificial bone and the mechanism of its bone formation is a hotspot at home and abroad. In the past National Natural Science Foundation research, we found nanometer hydroxyapatite ( nano-hydroxyapatite, nHA ) similar to the shape and size of bone tissue can be directly involved in the process of osteogenesis during new bone formation in vivo. This research, on the basis of the former natural science fundation, was guided by the principle of bionics. Using the lastest nano self-assembly method, we synthetized the nHA / collagen bone elementary unit particles- - a minimal unit of bone tissue. The structure, hydroxyapatite whisker and the size of collagen bundles of the matrix collagen particles and its arrangement in collagen forms are similar to that in natural bone. And it's also alike in terms of physical and chemical and biological effects. At the same time, according to the natural bone structure, with nHA / collagen matrix element as a raw material, we used computer-controlled automatic forming technology for the synthesis of highly porous nHA / collagen matrix biomimetic artificial bone. The artificial bone not only has the similar element composition to the natural bone, but also has a similar shape, structure, porosity, pore size, distribution of the bone gradient and biomechanical strength. Meanwhile we will explore the biology properties and the mechanism of bone formation of nHA / collagen matrix artificial bone in vivo and develop bionic nano artificial bone suitable for clinical application. We hope there will be at last a intact theoretical system ready for clinical use.

人工骨强韧化和成骨机理研究一直是国内外研究热点。在既往承担的基金研究中发现与骨组织中大小形状相近的纳米羟基磷灰石（nHA）具有骨转化能力。本课题在前期承担的国家自然基金基础上，依据仿生学原理改进纳米自组装法合成nHA /胶原粒，其组成相、nHA和胶原束大小、nHA在胶原中排列均与自然骨相近且具相似的理化和生物学特性。采用高精度CT和生物力学机采集自然骨高精三维数据及相关联生物力学数据构建数据库，以此数据库为基础据临床需求设计调整合成人工骨参数，以nHA/胶原为原料，计算机控制自动成形技术合成强韧化高孔隙nHA/胶原基仿生人工骨，使其与自然骨有相似基元组成、相似形状、三维结构、孔隙率、骨质分布梯度、并有可控孔径大小、高韧性和生物力学强度，进而克服现有人工骨低孔隙率、易碎和血管不易长入的缺点。同时探索nHA/胶原基人工骨体内成骨转化机制，构建符合临床要求的仿生纳米人工骨并为其临床应用奠定基础。

项目背景：近年来随着材料学和计算机辅助技术的发展，利用复合材料在组成和结构上仿生自然骨构建组织工程骨成为研究和开发的热点和焦点。尤其是通过对骨生理和病理成骨机理研究的深入，发现正常骨是由纳米羟基磷灰石和I型胶原纤维通过特定的排列和化学健的连接组成，是羟基磷灰石纳米晶须和I型胶原纤维组成的微基元系统的集合。探索构建基于纳米羟基磷灰石/胶原骨基元的个体化仿生人工骨将为临床大段骨缺损，尤其是负重部位大段骨缺损重建和修复提供重要的新思路。 .主要研究内容和结果、关键数据：依据仿生学原理采用纳米自组装法合成了骨组织最小组成单位-nHA/COL基元微粒，并通过X射线衍射、傅里叶红外光谱仪（FTIR）等分析证实该基元微粒在组成相、羟基磷灰石晶须和胶原束大小、nHA在胶原中排列形式均与自然骨相近，并具有相似的理化和生物学效应。建立了正常成人四肢管状骨和腰椎椎体骨的骨质数据库，根据统计学规律和人工骨的特性进一步优化人工骨参数设计；利用熔融沉积快速成型三维重建技术构建了nHA/COL等仿生基元的高孔隙强韧化仿生人工骨。该人工骨不仅具有与自然骨相似的基元组成，还具有相似三维空间结构分布和较好的力学强度。并且通过对该仿生人工骨的生物学特性检测及体内大段骨缺损修复研究证实其是一种适用于负重部位大段骨缺损个体化修复的骨移植体，同时探索了基于nHA仿生人工骨生物学性能和体内成骨转化机制。.科学意义：该人工骨的设计和规模化制造技术能够满足临床松质骨填充植骨和皮质骨承重部位解剖和功能重建要求的仿生人工骨的需求。解决了有机无机复合人工骨多重仿生构建和智能化个体化构建难题以及现有人工骨存在的强度、脆性与弹性模量难以协调的矛盾。