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Ti-based functionally graded porous structure for dual drug delivery system

机译:钛基功能梯度多孔结构,用于双重药物输送系统

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Statement of Purpose: Although porous metal scaffolds are widely used, there are still demands for gradient porous structure which mimics the structure of real bone. By mimicking bone structure, reduced "stress shielding effect" is expected. In this study, intrinsic ductility of porous titanium scaffold by dynamic freeze casting was used to fabricate gradient porous structure. After shaping two different forms, they were assembled into a single scaffold by unidirectional compressing (z-axis) to make gradient porous structure. Another advantage of porous scaffolds besides biomimicking is their ability to load and release drugs. Through two body combination after drug loading, different release behavior can be achieved for each part. Methods: Commercial pure titanium was mixed with camphene and oligomeric polyester dispersant in an Al mold and the Al mold was rotated at a speed of 30 rpm at 44°C for 12 h. After densifying the specimen using CIP process, the resulting green body was freeze dried in vacuum chamber to remove the camphene.. Heat treatment was done in vacuum system at 1300°C for 2 h. After sintering, it was machined into a rod and a ring shape with different heights and the different combination of rod and ring are referred to as positive and negative as shown in Fig. 1. Rod and ring with different height are compressed along the z-axis into one scaffold. The morphology of scaffolds was observed by micro CT. Green Fluorescent Protein (GFP) was loaded in the negative scaffold and the release behavior was observed by confocal laser scanning microscopy (CLSM). Results and Discussion: Spherical pore shape became irregular shape with decreasing porosity because of unidirectional compressing (Fig. 1). After compressing, porosity and pore size decreased dramatically. As combined specimens have decreased porosity part, mechanical properties were significantly increased, resulting from the densified part which can endure more load, while maintaining the stiffness under 15 GPa, which is in the range of elastic modulus of bone (Fig. 2). In addition, after 7 d of release in Phosphate Buffer Saline (PBS), larger amount of GFP remained in dense region in the negative scaffold as showin in Fig.3. indicating that densified porous structure prolonged release of growth factors. Conclusions: Functionally graded porous titanium scaffold was successfully fabricated by unidirectional compressing. As combined structure has less porous part, mechanical properties were enhanced significantly. Also prolonged release of drug was achieved for densified part. Thus, drug-loaded functionally graded porous titanium scaffolds have a potential to be used for dental and orthopedic implant with its enhanced mechanical properties and prolonged drug release behavior. Figure 1. Schematic images, optical images after unidirectional compressing, and micro CT images of positive scaffold (A), and negative scaffold (B). Figure 2. Mechanical properties of homogeneous 70% porous Ti scaffold and combined scaffolds. Figure 3. Surface images of GFP loaded combined scaffolds before and after 7-days release test for porous and dense parts.
机译:目的说明:尽管多孔金属支架被广泛使用,但仍然需要模仿真实骨骼结构的梯度多孔结构。通过模拟骨骼结构,可以降低“应力屏蔽效果”。在这项研究中,通过动态冷冻铸造的多孔钛支架的固有延展性被用来制造梯度多孔结构。将两种不同的形状成型后,通过单向压缩(z轴)将它们组装成单个支架,以制成梯度多孔结构。除生物模拟外,多孔支架的另一个优势是其负载和释放药物的能力。通过药物加载后的两个身体结合,可以实现每个部分不同的释放行为。方法:在Al模具中将商用纯钛与with烯和低聚聚酯分散剂混合,并在44℃下以30 rpm的速度旋转Al模具12 h。使用CIP工艺将样品压实后,将得到的生坯在真空室中冷冻干燥以除去remove烯。在真空系统中于1300°C进行2 h的热处理。烧结后,将其加工成具有不同高度的杆和环,如图1所示,将杆和环的不同组合称为正负。如图1所示,将不同高度的杆和环沿z-轴压缩。轴成一个脚手架。通过微型CT观察支架的形态。将绿色荧光蛋白(GFP)加载到阴性支架中,并通过共聚焦激光扫描显微镜(CLSM)观察释放行为。结果与讨论:由于单向压缩,球形孔隙形状随着孔隙率的降低而变为不规则形状(图1)。压缩后,孔隙率和孔径显着降低。由于组合试样的孔隙率降低,致密化的零件可以承受更大的载荷,同时保持其刚度在15 GPa以下(处于骨骼的弹性模量范围内),从而使机械性能显着提高(图2)。另外,在磷酸盐缓冲盐水(PBS)中释放7天后,阴性支架中的致密区域中保留了大量的GFP,如图3所示。表明致密的多孔结构延长了生长因子的释放。结论:通过单向压缩成功制备了功能梯度多孔钛支架。由于组合结构具有较少的多孔部分,因此机械性能得到了显着增强。对于致密的部分,还实现了药物的延长释放。因此,载有药物的功能梯度多孔钛支架具有增强的机械性能和延长的药物释放性能,有望用于牙科和整形外科植入物中。图1.示意图,单向压缩后的光学图像以及正支架(A)和负支架(B)的微CT图像。图2.均质的70%多孔Ti脚手架和组合脚手架的机械性能。图3.在多孔和致密部分的7天释放测试之前和之后,加载GFP的组合支架的表面图像。

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