Full Length ArticleLayered titanates with fibrous nanotopographic features as reservoir for bioactive ions to enhance osteogenesis
Graphical abstract
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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These authors contributed equally to this work.