加工机械可调和生物活性金属支架的生物医学应用
Summary
Bioactive and mechanically reliable metal scaffolds have been fabricated through a method which consists of two processes, dynamic freeze casting for the fabrication of porous Ti, and coating and densification of the Ti scaffolds. The densification process is simple, effective and applicable to the fabrication of functionally graded scaffolds.
Abstract
Biometal systems have been widely used for biomedical applications, in particular, as load-bearing materials. However, major challenges are high stiffness and low bioactivity of metals. In this study, we have developed a new method towards fabricating a new type of bioactive and mechanically reliable porous metal scaffolds-densified porous Ti scaffolds. The method consists of two fabrication processes, 1) the fabrication of porous Ti scaffolds by dynamic freeze casting, and 2) coating and densification of the porous scaffolds. The dynamic freeze casting method to fabricate porous Ti scaffolds allowed the densification of porous scaffolds by minimizing the chemical contamination and structural defects. The densification process is distinctive for three reasons. First, the densification process is simple, because it requires a control of only one parameter (degree of densification). Second, it is effective, as it achieves mechanical enhancement and sustainable release of biomolecules from porous scaffolds. Third, it has broad applications, as it is also applicable to the fabrication of functionally graded porous scaffolds by spatially varied strain during densification.
Introduction
而金属生物材料已被广泛用作由于其优异的机械强度和韧性，1-3承重植入物和内固定装置，他们涉及两个关键的挑战：1）机械失配，因为金属是比生物体组织硬得多，从而导致不希望的损害到周围组织和2）低的生物活性，往往导致界面差与生物组织，往往挑起异物反应 （如炎症或血栓形成）。已经提出了促进骨向内生长的结构4-6多孔金属支架，改善骨-植入物接触，而应力屏蔽效果，因为它们降低的刚性抑制7-9此外，各种表面改性已经应用于提高金属植入物的生物活性;这些修改包括涂层将金属表面与生物活性分子（例如，生长的fac器）或药物 （如万古霉素，四环素）10-12但是，存在的问题，如多孔金属支架降低机械性能，降低的硬度和快速释放的生物活性涂层的层仍然没有得到解决。13-16
特别是，钛（Ti）和Ti的合金是一体的，因为它们的优异的机械性能，化学稳定性的最流行biometal系统，以及良好的生物相容性。13,17-19其泡沫形的应用也引起越来越多的关注，因为在3D多孔网络促进除了骨样的机械性能的骨向内生长。20-22已作出努力通过开发新的制造技术，包括聚合海绵的复制，金属粒子，快速成型（RP）的方法的烧结来提高机械性能，并为了控制孔的各种特征空间保持器的方法（例如，孔隙分数，形状，大小，分布，和连接）和材料性质（例如，金属相和杂质）23-25 最近，水性金属浆料的冻结铸造已经获得了相当大的注意，以产生机械增强的Ti形式具有良好对准孔结构通过利用在凝固过程中的单向冰枝晶生长;然而，所造成的金属粉末与水接触氧污染需要特别小心，以尽量减少钛支架的脆化。14,15
因此，我们开发了对制造生物活性和机械可调多孔钛支架的新方法。25支架最初有超过50％的孔隙率多孔结构。所制造的多孔支架涂覆有生物活性分子，然后进行压缩使用期间的最后的孔隙率，机械性能和药物释放行为由APPLI分别控制一个机械压力机编辑应变。致密多孔钛种植体，尽管低刚度比得上骨（3-20 GPA）2由于被覆层的一者所示低孔隙率具有良好的强度，致密多孔钛的生物活性显著改善。因为引起的致密化过程中的独特扁平孔结构。此外，涂布的生物活性分子被视为被逐渐从支架释放时，保持其功效为长时间。
在这项研究中，我们介绍了我们建立的方法来制作致密多孔钛支架的生物医学应用的潜在用途。该协议包括动态凝固的铸造金属浆料和多孔支架的致密化。首先，为了制造多孔钛支架具有良好的延展性的动态冷冻铸造方法被引入，如图1A。钛粉末分散在液体莰;然后，通过降低温度，液相固化，从而在钛粉末网络和固体莰晶体之间的相分离。接着，将固化的Ti-莰生坯进行烧结，其中的Ti粉末缩合的连续钛支柱，和莰相完全除去，得到多孔结构。该涂层和致密化过程用所获得的多孔支架受雇于，变化的致密化和初始孔隙的程度。被覆层和它的释放行为进行观察和使用绿色荧光蛋白（GFP）包被的多孔钛具有和不致密化相比，GFP-涂覆致密的Ti定量。最后，提出并通过改变多孔支架的内层和外层部分的致密化的程度表现出功能梯度的Ti支架具有两个不同的多孔结构。
Protocol
Representative Results
Discussion
而biometal系统已被广泛地用于生物医学应用，特别是，作为承重材料，高刚度和金属的低生物活性已被视为重大的挑战。在这项研究中，我们建立了一个新的金属系统，致密多孔金属支架具有仿生机械性能以及生物活性表面与可持续释放行为的制造方法。我们的制作方法的主要优点包括：1）在前面的动态冷冻的铸造方法没有变化，我们已经开发，28 2）中的一个参数度的控制致密化-实现机…
Divulgazioni
The authors have nothing to disclose.
Acknowledgements
This research was supported by the Technology Innovation Program (Contract grant No. 0037915, WPM Biomedical Materials-Implant Materials) and Industrial Strategic Technology Development Program (Contract grant No. 10045329, Development of customized implant with porous structure for bone replacement), funded by the Ministry of Trade, industry & Energy (MI, Korea), and BK21 PLUS SNU Materials Division for Educating Creative Global Leaders (Contract grant No. 21A20131912052).
Materials
| Titanium powder | Alfa Aesar | #42624 | -325 mesh, 99.5% (metals basis) |
| Camphene | SigmaAldrich | #456055 | 95%, C10H16 |
| KD-4 | Croda | | Hypermer, polymeric dispersant |
| Phosphate Buffer Solution (PBS) | Welgene | ML 008-01 | |
| Green Fluorescent Protein (GFP) | Genoss Co. | – | >98% purity, 1mg/ml |
| Ball mill oven | SAMHENUG ENERGY | SH-BDO150 | |
| Freeze dryer | Ilshin Lab. | PVTFD50A | |
| Cold isostatic pressing (CIP) machine | SONGWON SYSTEMS | CIP 42260 | |
| Vaccum furnace | JEONG MIN INDUSTRIAL | JM-HP20 | |
| electical chaege machine | FANUC robocut | 0iB | External use |
| Press machine | CG&S | AJP-200 | |
| Confocal laser scanning spectroscopy (CLSM) | Olympus | FluoView FV1000 | External use |
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