多孔结构互补支架体内异位成骨及钴铬合金生物功能化研究

发布时间：2018-04-04 15:55

本文选题：骨诱导　切入点：多孔支架　出处：《西南交通大学》2012年硕士论文

【摘要】：随着社会进步、人民生活水平的不断提高,人民对生物医用材料尤其是植入性生物医用材料的需求越来越高,单一组分和结构的植入材料已不能满足复杂多变的临床需求。一方面,在骨组织领域中,多孔贯通的陶瓷支架有利于组织长入、细胞迁移、营养物质的交换以及血管化过程进行,多孔贯通结构被确认是影响多孔支架修复材料在体内组织工程化的、发挥其骨传导、骨诱导性能的重要因素。虽然多孔贯通支架的宏观孔隙结构与其异位骨诱导特性之间的关系获得了广泛关注,但是这种关系还远未完全揭示。另一方面,对于药物洗脱支架(drag eluting stent, DES),为避免高分子支架不能有效控制药物缓释以及钴铬合金(Co-Cr)表面性能单一且不具备生物活性等弊端,对钴铬合金表面生物功能化以形成具有生物活性载药涂层的需要日益迫切。为此,本研究拟通过构建结构互补的多孔贯通孔隙结构,进一步研究支架多孔结构与异位成骨的关系；同时,通过对钴铬合金表面进行载药修饰改善其表面性能。在研究过程中,通过球粒堆积和颗粒造孔的方法制备了宏观孔隙互补的两种羟基磷灰石(Hydroxyapatite, HA)多孔支架。将两种支架同时植入成年狗的背部肌肉以揭示孔隙互补结构对HA支架异位骨诱导性能的影响。两种支架的高贯通性均利于组织的长入,在支架植入早期(1个月),颗粒造孔支架组织学观察到更明显的钙质沉积层,说明其在植入早期具有更好的组织-材料界面活性；在植入3个月后,球粒堆积支架内发现有新骨生成,而在颗粒造孔支架内并未发现有新骨生成；同时,球粒堆积支架力学性能亦优于颗粒造孔支架。由于球粒堆积支架的外凸弧形孔结构更有利于体液的流动,故有利于蛋白和细胞迁移粘附,导致球粒堆积支架的体内组织工程改建效果优于颗粒造孔支架。实验结果再次表明,支架的孔隙结构对其异位成骨性能有重要影响。论文另一部分研究采用碱热处理和生物模拟矿化在钴铬合金表面形成具有生物活性的钙磷涂层,并作为载体固定西罗莫司,得到一种新的钴铬合金生物功能化的表面涂层,达到药物洗脱系统缓释、控释的目的。首先利用酸蚀处理和碱热处理在合金基体上获得了均匀且利于磷灰石晶体形核、生长的表面。再采用生物模拟的方法,在基体表面形成结合牢固的钙磷涂层,通过滴注法在钙磷涂层表面固定西罗莫司。采用以上工艺固定的药物可在模拟体液中的缓慢释放至少90天,改善了药物洗脱支架的性能。
[Abstract]:With the progress of society and the improvement of people's living standard, the demand for biomedical materials, especially implantable biomedical materials, is getting higher and higher. The single component and structure implant materials can not meet the complex and changeable clinical needs.On the one hand, in the field of bone tissue, porous ceramic scaffolds facilitate tissue growth, cell migration, nutrient exchange, and vascularization.The perforated structure is confirmed to be an important factor affecting the tissue engineering of the porous scaffold in vivo and exerting its bone conduction and osteoinductive properties.Although the relationship between macroporous structure and ectopic osteoinductive characteristics of porous perforated scaffolds has been widely concerned, this relationship is far from fully revealed.On the other hand, for the drug-eluting stents drag eluting stents, in order to avoid the polymer stents can not effectively control the drug release and Cobalt-Chromium alloy Co-Cr surface properties are single and do not have biological activities and so on.The need for biofunctionalization of cobalt-chromium alloy to form bioactive drug-loading coating is becoming more and more urgent.Therefore, the relationship between porous structure and heterotopic osteogenesis of the scaffold was further studied by constructing porous and perforated pore structure with complementary structure, and the surface properties of cobalt-chromium alloy were improved by drug loading modification.During the study, two kinds of hydroxyapatite (HA) porous scaffolds with complementary macroporous pores were prepared by the methods of spherulite accumulation and particle pore-forming.Two scaffolds were simultaneously implanted into the back muscles of adult dogs to reveal the effect of porous complementary structure on the heterotopic bone induction of HA scaffolds.The high permeability of the two scaffolds was beneficial to the growth of the tissue. At the early stage of stent implantation (1 month after implantation, a more obvious calcium deposit layer was observed in the grained scaffold, which indicated that the scaffold had better tissue-material interface activity at the early stage of implantation.After 3 months of implantation, new bone formation was found in the spherical scaffold, but no new bone formation was found in the granular scaffold. At the same time, the mechanical properties of the spherical scaffold were better than those of the granular scaffold.Because the protruding arc-shaped pore structure is more favorable to the flow of body fluid, it is advantageous to the migration and adhesion of protein and cells, which leads to the effect of tissue engineering reconstruction of spherulite stacking scaffold is better than that of granular scaffold.The experimental results show that the pore structure of the scaffold has an important effect on the heterotopic osteogenesis.To achieve the drug elution system slow release, the purpose of controlled release.At first, the homogeneous and suitable apatite crystal nucleation and growth surface were obtained by acid etching and alkali heat treatment on the base of the alloy.Then a solid calcium phosphorus coating was formed on the substrate surface by biological simulation. Sirolimus was immobilized on the surface of calcium phosphorus coating by drip method.The drugs fixed by the above process can be released slowly in simulated body fluid for at least 90 days, which improves the performance of drug-eluting stents.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R318.08

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