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Fabrication of Mechanically Tunable and Bioactive Metal Scaffolds for Biomedical Applications

Biometal systems have been widely used for biomedical applications, in particular, as load-bearing materials. However, major challenges are high stiffness ...

Korea Institute of Industrial Technology

Complications following lumbar transforaminal epidural injection are frequently related to inadvertent vascular injection of corticosteroids. Several methods have been proposed to reduce the risk of vascular injection. The generally accepted technique during epidural steroid injection is intermittent fluoroscopy. In fact, this technique may miss vascular uptake due to rapid washout. Because of the fleeting appearance of vascular contrast patterns, live fluoroscopy is recommended during contrast injection. However, when vascular contrast patterns are overlapped by expected epidural patterns, it is hard to distinguish them even on live fluoroscopy.

Accuracy of live fluoroscopy to detect intravascular injection during lumbar transforaminal epidural injections.

Highly porous titanium with aligned large pores up to 500 μm in size, which is suitable for scaffold applications, was successfully fabricated using the reverse freeze casting method. In this process we have newly developed, the Ti powders migrated spontaneously along the pre-aligned camphene boundaries at a temperature of 45.5°C and formed a titanium-camphene mixture with an aligned structure; this was followed by freeze drying and sintering. As the casting time increased from 24 to 48 h, the initial columnar structures turned into lamellar structures, with the porosity decreasing from 69 to 51%. This reduction in porosity caused the compressive yield strength to increase from 121 to 302 MPa, with an elastic modulus of the samples being in the range of 2-5 GPa. In addition, it was demonstrated that reverse freeze casting can also be successfully applied to various other raw powders, suggesting that the method developed in this work opens up new avenues for the production of a range of porous metallic and ceramic scaffolds with highly aligned pores.

Reverse freeze casting: a new method for fabricating highly porous titanium scaffolds with aligned large pores.

This paper reports a new approach to fabricating biocompatible porous titanium with controlled pore structure and net-shape. The method is based on using sacrificial Mg particles as space holders to produce compacts that are mechanically stable and machinable. Using magnesium granules and Ti powder, Ti/Mg compacts with transverse rupture strength (~85 MPa) sufficient for machining were fabricated by warm compaction, and a complex-shape Ti scaffold was eventually produced by removal of Mg granules from the net-shape compact. The pores with the average size of 132-262 μm were well distributed and interconnected. Due to anisotropy and alignment of the pores the compressive strength varied with the direction of compression. In the case of pores aligned with the direction of compression, the compressive strength values (59-280 MPa) high enough for applications in load bearing implants were achieved. To verify the possibility of controlled net-shape, conventional machining process was performed on Ti/Mg compact. Compact with screw shape and porous Ti scaffold with hemispherical cup shape were fabricated by the results. Finally, it was demonstrated by cell tests using MC3T3-E1 cell line that the porous Ti scaffolds fabricated by this technique are biocompatible.

Fabrication of porous titanium scaffold with controlled porous structure and net-shape using magnesium as spacer.

Porous Ti has been widely investigated for orthopedic and dental applications on account of their ability to promote implant fixation via bone ingrowth into pores. In this study, highly aligned porous Ti scaffolds coated with a bone morphogenetic protein (BMP)-loaded silica/chitosan hybrid were produced, and their bone regeneration ability was evaluated by in vivo animal experiments. Reverse freeze casting allowed for the creation of highly aligned pores, resulting in a high compressive strength of 254 ± 21 MPa of the scaffolds at a porosity level of ∼51 vol %. In addition, a BMP-loaded silica/chitosan hybrid coating layer with a thickness of ∼1 μm was uniformly deposited on the porous Ti scaffold, which enabled the sustained release of the BMP over a prolonged period of time up to 26 days. The cumulative amount of the BMP released was ∼4 μg, which was much higher than that released from the specimen without a hybrid coating layer. In addition, the bone regeneration ability of the porous Ti scaffold with a BMP-loaded silica/chitosan coating layer was examined by in vivo animal testing using a rabbit calvarial defect model and compared with those of the as-produced porous Ti scaffold and porous Ti scaffold with a silica/chitosan coating layer. After 4 weeks of healing, the specimen coated with a BMP-loaded silica/chitosan hybrid showed a much higher bone regeneration volume (∼36%) than the as-produced specimen (∼15%) (p < 0.005) and even the specimen coated with a silica/chitosan hybrid (∼25%) (p < 0.05).

Highly aligned porous Ti scaffold coated with bone morphogenetic protein-loaded silica/chitosan hybrid for enhanced bone regeneration.

This paper proposes dynamic freeze casting as a new manufacturing technique for producing porous Ti scaffolds with a uniform porous structure and good ductility. In this method, Ti/camphene slurries with various initial Ti contents (15, 20, and 25 vol.%) were frozen at 44 °C for 12 h in rotation, which allowed for the extensive growth of camphene crystals and the uniform construction of walls made of Ti particles. All the fabricated samples showed spherical-like pores surrounded by dense Ti walls that were uniformly formed after sintering at 1300 °C for 2 h in a vacuum. The porosity decreased from 71 to 52 vol.% with an increase in Ti content from 15 to 25 vol.%, whereas the pore size decreased from 362 to 95 μm. On the other hand, the compressive strength and stiffness increased considerably from 57±4 to 183±6 MPa and from 1.3±0.5 to 5.0±0.8 GPa, respectively, due to the decrease in the porosity of the samples.

Dynamic freeze casting for the production of porous titanium (Ti) scaffolds.

Metals have been used as biostructural materials because of outstanding mechanical reliability. However, low bioactivity and high stiffness in biological environments have been major issues of metals, causing stress shielding effects or foreign body reactions after implantation. Therefore, in this study, densified porous titanium has been introduced to achieve comparable mechanical properties to hard tissues and bioactivity that promote a better interface between the implant and bone. Porous titanium scaffolds were successfully fabricated through dynamic freezing casting, and were densified, controlling the degree of densification by applied strain. During densification, structural integrity of porous titanium was well maintained without any mechanical deterioration, exhibiting good pore connectivity and large surface area. Densified porous titanium possesses two important features that have not been achieved by either dense titanium or porous titanium: 1) mechanical tunability of porous scaffolds through densification that allows scaffolds to be applied ranging from highly porous fillers to dense load-bearing implants and 2) improved bioactivity through bioactive coating that is capable of sustainable release through utilizing high surface area and pore connectivity with controllable tortuosity. This simple, but effective post-fabrication process of porous scaffolds has great potential to resolve unmet needs of biometals for biomedical applications.

Novel strategy for mechanically tunable and bioactive metal implants.

Blends of ductile Ti metal with polyetheretherketone (PEEK) polymer were studied with regard to their mechanical properties and in vitro biocompatibility. PEEK/Ti composites with various Ti contents, ranging from 0 vol % to 60 vol %, were produced by compression molding at 370°C. In all composites produced, regardless of the initial Ti content, Ti particles were well distributed in the PEEK matrix. Addition of Ti led to a significant increase in mechanical properties of PEEK. Specifically, an increase in Ti content enhanced compressive strength and stiffness, while preserving ductile fracture behavior. In addition, the use of Ti for reinforcement of PEEK provided the composites with improved in vitro biocompatibility in terms of the attachment, proliferation, and differentiation of MC3T3-E1 cells. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.

Hyun-Do Jung

Liquid Processing & Casting Technology R&D Group

Korea Institute of Industrial Technology

Fabrication of Mechanically Tunable and Bioactive Metal Scaffolds for Biomedical Applications