【作者】 张其翼；

【导师】 陈继镛；

【作者基本信息】 四川大学 ， 生物医学工程， 2003， 博士

【摘要】 各种原因所致的骨缺损在临床上十分常见，骨缺损治疗尤其是大范围和负重骨缺损修复，一直是临床上亟待解决的难题。目前，骨缺损修复方法包括：自体、同种异体。异种骨移植以及各种骨替代材料应用；自体骨移植势必造成供区损伤，而且难以获得与缺损骨形态完全一致的供体；同种异体或异种骨移植存在免疫排斥及潜在传染疾病的可能，经过去除有机质或脱钙处理的骨，机械性能差，不能满足临床应用要求；虽然，应用组织工程化人工骨进行骨缺损修复的研究已经取得了一些进展，有可能在不远的将来应用于临床，但目前，组织工程化人工骨的应用尚不现实。所以，各种骨替代材料的应用仍是目前骨缺损修复的最主要手段。 理想的骨替换材料应满足组成、结构、外形的仿真，功能的恢复和生物力学相容性等条件。而到目前为止，所有的骨替换材料(包括陶瓷、高分子、金属及复合材料)都各有其优缺点。以羟基磷灰石为代表的磷酸钙类生物陶瓷材料与自然骨的无机成分类似，不仅生物相容性好，而且容易成形，可达到形态的精确匹配，并具有良好的骨传导性。特别是，自上世纪80年代末期，不外加生长因子的磷酸钙陶瓷可以在软组织中诱导骨生成以来，磷酸钙陶瓷的骨诱导性已被许多学者证实并在国际上得到广泛接受。目前，磷酸钙陶瓷材料骨诱导性已成为生物材料研究的一大热点。但它的缺点是不兼备生物力学相容性。虽然它已被广泛用于骨缺损的修复或替代，但因其韧性低，在生理环境中抗疲劳性差，易碎裂而仅限于非负重骨的骨缺损修复。当它们用于负重骨的修复时，往往会因为机械强度差可致植入失败。另一方面，钛已经被广泛地应用于临床作为骨修复材料，大量研究表明钦具有良好的生物相容性。金属钦植于骨内后可实现骨融合式愈合;与其他金属材料相比，它的弹性模量更接近骨，有利于骨界面力的传导;具有足够的强度和韧性，能够承受人体的机械作用力。但是却缺乏骨诱导能力。 因此，充分利用磷酸钙陶瓷和金属钦各自的优点制作的覆盖磷酸钙陶瓷涂层的钦及钦合金被用作骨替换材料具有广泛的前景。为使植入体兼具生物活性和生物力学性能，一方面通过对其所用基底钦进行合理的几何构型设计使其与人体骨缺损处匹配，最大限度的减少应力屏蔽，实现生物力学相容性;同时多孔结构有利于组织长入，对细胞的粘附、增殖和分化，以及形貌和基因表达都有着不同的影响，再通过对其表面赋予磷酸钙陶瓷涂层可提高其生物活性，促进植入体和骨组织的牢固结合。 涂层材料是生物医学材料的一类，尤其是钦及钦合金表面喷涂轻基磷灰石涂层已在临床有着广泛的应用。本文系统地研究了不同后处理的等离子喷涂涂层在体外的溶解特性、生物矿化能力，研究表明等离子喷涂涂层经不同气氛和温度的处理，得到不同组成和结晶度的涂层，处理过程中温度对提高结晶度至关重要，而水汽有利于晶粒的长大。将涂层浸泡于SBF、Tris一HCI溶液中，钙离子的溶解以表面粒子交换为主，因而与晶粒大小密切相关;磷酸根离子的溶解则主要与晶粒结构，晶粒的溶解度以及溶液活度积与溶度积之比相关。当溶液中的离子浓度足够时，矿化发生，表面生成类骨磷灰石层。类骨磷灰石的形貌与涂层的溶解性有关，溶解度大的涂层，形成的成核位点较多，晶体生长受限，形成网状结构;而溶解度小的涂层，形成的成核位点较少，晶体生长较充分，形成大颗粒的表面结构。在更接近体液环境的动态条件下，对形成类骨磷灰石的能力以及形成类骨磷灰石的形貌差异进行了研究。结果表明，体外涂层表面类骨磷灰石的生长方式和微结构随浸泡条件的不同而不同，静态时，晶体生长没有择优取向，且所选的两种涂层所形成的类骨磷灰石在形貌上的差异不是特别大;然而在动态时，由于溶液的不断更新而使界面离子浓度稳定维持在一较低水平，故晶体生长表现出的择优取向，而呈现出不同的生长方式和显著的形貌差异。动态浸泡方式模拟了人体的体液的交换流量，因而显示的结果更接近于体内的情况。通过设计体外浸泡模型以考察等离子喷涂涂层在多孔环境下的生物学活性。研究表明在多孔的条件下更容易形成类骨磷灰石，在数量和形貌_!:都与1卜多孔条件卜存在旅异，多孔条件更有利与类骨磷灰石的形成。 墓于此，;乍结合多孔磷酸钙陶瓷在生物活性方面的优良性能所提供的模板作用，本文将作为骨林换材料的钦通过几何构型的设计而达到剪裁其力学性能和l生物学性能的作用，从而可以史好的满足对植入体生物学和力‘笋卜}:能匹配的要求。首次采用钦粉发泡烧结的方法制备了具有优良孔结构的多孔钦，L亥法川-通过工艺控制实现对孔隙率和孔径分布的控制，从而实现对植入体力学性能和多孔结构的控制。为了提高材料的生物学性能，采用多种涂层技术在多孔钦表面制备磷灰石涂层，基于所用钦基底的多孔特征，采用的涂层方法均为在液相中进行，使得即使在具有异形多孔结构的材料_}几也能实现均匀涂覆。 溶胶一凝胶法采用湿化学方法制备膜和涂层的有效方法。其优点在一于可很好地控制涂层的化学组成，得?更多还原

【Abstract】 Bone defects are common in clinic. Therapy to bone defects, especially defects in load-bearing position or large bone defects has been a long-standing problem. Up to date, commonly used bone defect repairing technologies include allograft, autograft, heterograft and the application of bone substitute. Autograft will result in new wound and bone defects in other locus and it is also very difficult to obtain bone in the exact shape of the defect. Allograft and heterograft may cause immune rejection and infectious diseases. Organic substance-free or decalcified bone lacks biomechanical strength and thus, is not ideal for clinic application. Although some progress has been made in the research of application of tissue engineering bone substitute for bone defect repairing and it may be used in the future, but until now, it is not feasible for clinical application. Therefore, the application of bone substitutes is the major means for bone defect repairing.Ideal bone grafting materials must satisfy some requirements such as imitation in composition, structure and shape to natural bone, functional restoration and compatibility in biomechanics. Up to date, all developed bone substitute materials (including ceramics, polymers, metals and composites) have their own advantages and disadvantages. Hydroxyapatite, which represents calcium phosphate ceramics family, is similar in composition with natural bone. It is biocompatible, osteoconductive and easy to fabricate to the exact shape as required. Especially, since the discovery of osteogenesis when Ca-P materials were implant in soft tissue at the end of the 80’s of the last century, osteoinductivity of porous calcium phosphate ceramics has been well accepted all over the world. Recently, osteoinductivity of calcium phosphate ceramics has attracted much research interests. However, the biomechanical property of calcium phosphate ceramics is not ideal. Although it has been widely applied as bone substitute, it is limited to be used in non-load-bearing part due to its toughness and shortages in anti-fatigue property. When it is used in load-bearing position, the implantation always fails due to its biomechanics. On the other hand, titanium has been widely used in clinic as bone substitute and has been confirmed to be excellent in biocompatibility. When implanted in bone, titanium implant can be integrated inbone well. While compared with other metals, its elastic module is closer to bone and thus, it facilitates stress conduction between bone-titanium interfaces. Moreover, it has sufficient mechanical strength and elasticity to support human body. Unfortunately, it lacks osteoinductivity.Having combined the advantages of calcium phosphate ceramics and titanium, calcium phosphate ceramics coated titanium and titanium alloy have good prospect. To obtain both bioactivity and biomechanics, titanium substrates can be geometrically designed to fit the bone defects to avoid stress-shielding. On the other hand, because its porous structure facilitates the tissue ingrwoth and osteoblast adhesion, proliferation differentiation and gene expression, calcium phosphate ceramics coating could enhance the bioactivity of the implant and bone-implant integration.Coated materials are important parts of biomedical materials, especially, titanium and titanium alloys coated with hydroxyapatite have broad applications in clinic. This study systematically studied the solubility, biomineralization of plasma sprayed calcium phosphate coatings after different post-treatment methods. Result showed that after plasma-sprayed coatings were post-treated with different atmosphere and temperature, coatings with different composition and crystallinity can be obtained. In the process of post-treatment, temperature was crucial to the increase of crystallinity while water vapor is advantageous to the growth of crystal particle size. When the coatings were immersed in SBF and Tris-HCl solution, the dissolution of Ca ions occurred through ion exchange on the particle surface and thus, was strongly rel更多还原