Elsevier

Applied Surface Science

Volume 436, 1 April 2018, Pages 653-661
Applied Surface Science

Full Length Article
Layered titanates with fibrous nanotopographic features as reservoir for bioactive ions to enhance osteogenesis

https://doi.org/10.1016/j.apsusc.2017.12.027Get rights and content

Highlights

  • Higher pH conditions enhance the loading efficiency of bioactive ions in titanates.

  • Bioactive ions release doesn’t compromise the structural integrity of the surface layer.

  • Bioactive ions together with nanotopographic features enhanced the osteogenic activity.

Abstract

In this study, an osteogenic environment was constructed on Ti alloy implants by in-situ formation of nanosized fibrous titanate, Na2Ti6O13, loaded with bioactive ions, i.e. Sr, Mg and Zn, to enhance surface bioactivity. The bioactive ions were loaded by ion exchange with sodium located at inter-layer positions between the TiO6 slabs, and their release was not associated with the degradation of the structural unit of the titanate. In-vitro cell culture experiments using MC3T3-E1 cells proved that both bioactive ions and nanotopographic features are critical in promoting osteogenic differentiation of the cells. It was found that the osteogenic functions of the titanate can be modulated by the type and amount of ions incorporated. This study points out that nanosized fibrous titanate formed on the Ti alloy can be a promising reservoir for bioactive ions. The major advantage of this approach over other alternatives for bioactive ion delivery using degradable bioceramic coatings is its capacity of maintaining the structural integrity of the coating and thus avoiding structural deterioration and potential mechanical failure.

Introduction

The construction of an osteogenic microenvironment is critical to enhance osseointegration of bone replacement materials [[1], [2]]. Due to the well-documented importance of bioactive ions in osteogenesis, it has been a highly attractive to utilize them in modern bone biomaterial design. Among bioactive ions, strontium (Sr), magnesium (Mg), and zinc (Zn) have been proved to promote new bone formation and widely used in chemical modification of bone biomaterials [[3], [4], [5], [6], [7], [8], [9], [10]]. Sr, a trace element chemically close to calcium, is known to promote new bone formation by enhancing bone-forming cells activity and meanwhile reducing bone-resorbing cells activity [11]. In our previous work, we found that silicates containing Sr significantly accelerated bone formation at bone fracture sites [12]. One of the most common approaches to endow the implant surface with an ability to release bioactive ions is to coat biodegradable mineral materials composed of the desired ions onto the implant [[13], [14], [15]]. Ions can be released upon the degradation of the mineral materials, however, the structural integrity of the surface coating is inevitably compromised, incurring the possibility of mechanical loss and even delamination of the coating. In addition, to preserve the long-term stability of the implant, the degradation rate of the surface coating is required to perfectly coordinate with the rate of the new bone formation. This is, however, beyond the capabilities of current techniques.

To overcome the side effects caused by the degradation of the surface coating while making the best use of the bioactive ions, we herein propose to use a chemical stable material with an ability to selectively release bioactive ions. For this aim, we selected sodium titanate nanofibers, in-situ formed on Ti alloy discs, as a reservoir for bioactive ions. Titanates exhibits excellent chemical and thermal stability, being widely used in water treatment and photocatalysis [[16], [17]]. More recently, Ciofani et al. that barium titanate promoted the osteogenic differentiation of mesenchymal stem cells [18]. They consist of an array of three TiO6 zig-zag octahedron that share edges to form a chain where sodium ions reside in the inter-layer position between the TiO6 slabs [[19], [20], [21]]. The alkali metal or alkali earth metal ions in titanates are exchangeable with other cations [[20], [21], [22], [23], [24]], making them a potential ideal reservoir for bioactive ions, such as Sr [[16], [25]]. Due to the chemical stability of the TiO6 slabs in titanates, the release of Sr is not accompanied by the degradation of the titanate. Therefore, titanates have great potential to perform a selective release of bioactive ions while maintaining the structural integrity of the implant surface. Moreover, recent studies proved that engineered nanotopography can facilitate cell adhesion, promote proliferation, initiate intracellular signaling, provide contact guidance and mediate stem cell differentiation [[26], [27], [28], [29]]. Titanates formed by hydrothermal methods normally exhibit nanofiber and nanoflake-shapes [[30], [31]], which makes them particularly appealing in the surface modification of orthopaedic implants, as they can mimic the nanotopography of extracellular matrix (ECM). Based on the above-mentioned merits of titanates, we are interested in exploration of their potential for enhancing osseointegration.

Section snippets

In situ formation of titanate nanostructure

Commercially available Ti–6Al–4V discs (Baoji Junhang Metal Material Co., Ltd. Shanxi, China) with a diameter of 15mm and a thickness of 1mm were used. Prior to use in any procedure, both kinds of discs were pre-washed with diluted acid solution containing 20 mL pure water (H2O), 0.02 mL 48% hydrofluoric acid (HF), and 0.13 mL 48% nitric acid HNO3. Then, discs were ultrasonically washed with millipore pure water in an ultrasonic bath. To produce titanate nanofibers on the Ti alloys, the

Results and discussion

We firstly used conventional hydrothermal treatments in NaOH solution to in-situ form titanate nanofibers on Ti alloy discs. As shown in Fig. 1, the nanotopography can be modulated by adjusting the concentration of NaOH solution and treatment temperatures, which directly influences the subsequent ion exchange efficiency. Cluster flowers were formed on the Ti alloy by low temperature of alkali treatment (60 °C, Fig. 1A and B). With the increase of alkali treatment temperature, nanotopography is

Conclusions

In this study, layered sodium titianates with fibrous nanostructures were applied as a nano-reservoir for bioactive ions (M2+), which can be Sr2+, Mg2+ and Zn2+ etc. to enhance the osseointegration of bone implants. At higher pH conditions, the ions were uploaded as [M (OH)] +, instead of M2+, thus increasing the upload efficiency. Zn2+ is more readily to be uploaded compared to Sr2+ and Mg2+, while Mg2+ is the least. The Sr-loaded titanate surface significantly enhances bone-related gene

Acknowledgments

The authors would like to acknowledge funding support from Shenzhen Science and Technology Research Funding (JSGG20151030140325149, JCYJ20150630114942256, JCYJ20160531171344016 and JCYJ20170413161800287), Chinese Postdoctoral Science Foundation (2017M612761) and National Natural Science Foundation (31700835), Guangdong Provincial Science and Technology Project (2017A010103014) and Shenzhen Peacock Innovation Team grant (Grant 110811003586331).

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      As a result, large amount and various types of metal ions can be incorporated at desirable combination and ratio by controlling ion concentration and pH of the solution in the second solution treatment [152–156]. When Sr2+ and Mg2+ ions that are known for their promotion in new bone formation were incorporated in the sodium titanate (Na2Ti6O13) formed on Ti-6Al-4V by NaOH hydrothermal treatment and subsequent MgCl2 or SrCl2 solution treatment, an increase of ALP and upregulation of osteogenic gene expression of Runx-2, OPN, OCN on MC3T3-E1 preosteoblast cells were observed [156]. Yamaguchi et al. reported that Sr- or Mg-containing calcium hydrogen titanate were formed on Ti by soaking the metal in a mixed solution of 50 mM CaCl2 + 50 mM SrCl2 or 40 mM CaCl2 + 60 mM MgCl2 [154,155].

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    These authors contributed equally to this work.

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