Cell response to plasma electrolytic oxidation surface-modified low-modulus β-type titanium alloys
Graphical abstract
Introduction
In order to optimise the osseointegration of implanted biomaterials, an in-depth understanding of the physical and chemical characteristics of the bone–implant interface is required, since attributes such as surface topography and chemistry play an important role in cell attachment, spreading and proliferation as well as the initial inflammatory response [[1], [2], [3]]. The mechanisms underpinning the interactions between the implant and the surrounding cells are still the subject of considerable interest and debate; however, several studies have shown that osseointegration can be improved by modifying the surface roughness of the implanted biomaterial [2,[4], [5], [6]]. Following implantation, the surface of the implant comes into contact with a number of proteins and cell types, including neutrophils, monocytes, macrophages, stromal cells and osteoblasts, which is in turn affected by the surface physicochemical properties of the implant material such as roughness, wettability, and porosity. Therefore, the cell behaviour at the bone–implant interface is influenced by the biomaterial surface characteristics [7,8] which, in turn, influence the outcome of the implantation procedure [9].
Metals are probably still the materials most frequently used in orthopaedic surgery for bone interfacing applications including fracture fixation, and reconstructions of damaged tissue in patients with degenerative and inflammatory conditions of bone and joints. Thus, metallic biomaterials must exhibit specific properties such as biological compatibility, enhanced mechanical performance and superior corrosion resistance [10,11]. Titanium and titanium alloys are of particular interest due to the passive titanium oxide layer that forms readily on their surface when exposed to the atmosphere providing corrosion resistance and chemical stability [12,13]. This native oxide layer is thin (approximately 2–7 nm) and bioinert, but its ability to induce apatite formation is dependent on the surface properties of the oxide layer, rather than on the bulk titanium itself [14]. Several methods have been used to introduce a bioactive layer to promote long-term osseointegration [[15], [16], [17], [18]]. Plasma electrolytic oxidation (PEO), also called anodic spark oxidation or micro-arc oxidation, has been shown over the last decade to be a highly effective methods to produce a bioactive surface with a rough and porous structure. The coating layer produced using PEO has been shown extensively to enhance the bioactivity and osseointegration of commercially pure α-Ti (CP α-Ti) dental implant materials, e.g. TiUnite® (Nobel Biocare) [[19], [20], [21]], BioSpark™ (Keystone Dental) [[22], [23], [24], [25], [26], [27]], and Ticer® (ZL Microdent) [28,29].
A wide variety of low-modulus β-type titanium alloys have been developed for potential use in load-bearing orthopaedic applications to ameliorate the effects of stress shielding on bone [[30], [31], [32], [33]]; however, the applicability of PEO treatment to low-modulus titanium alloys in a long term in vitro study has not yet been investigated. Hence, we considered that knowledge transfer of the PEO technique from CP α-Ti to low-modulus β-type titanium alloys would be a valuable assessment for orthopaedic research. The aim of this work was to explore the effect of PEO-treated near β- and β-type titanium alloys compared with PEO-treated CP α-Ti and (α + β)-Ti6Al4V on foetal human osteoblasts (fHOb) and investigate the early inflammatory response using CD14+ monocytes.
Section snippets
PEO coating preparation
Coatings were produced on four different titanium and titanium alloy substrates: CP α-Ti (Ti-TEK Ltd., Birmingham, UK), (α + β)-Ti6Al4V (Ti-TEK Ltd., Birmingham, UK), near β-Ti13Nb13Zr (Xi’an Saite Metal Materials Development Co., Ltd., Xi’an, Shaanxi, China), and β-Ti45Nb (ATI WahChang, Huntsville, USA). CP α-Ti and (α + β)-Ti6Al4V are the most commonly used substrate materials in dentistry and orthopaedics, respectively, and these served as commercial reference materials for comparison with
Osteoblast metabolic activity: a prolonged time course with osteogenic stimuli
Metabolic activity increased with time on all substrates. Fig. 1(a–d) shows a time-dependent reduction of alamarBlue® on low-modulus near β-Ti13Nb13Zr and β-Ti45Nb alloys together with CP α-Ti and (α + β)-Ti6Al4V control materials treated using different PEO processing times (tPEO: 0, 2, 5 and 30 min). A characteristic lag-log growth phase was observed from day 0 to day 6, after which cells reached confluency and a plateau phase was observed. After day 9, metabolic activity increased during a
Discussion
In the present study, we examined the behaviour of fHOb in a prolonged 26-day cell culture experiment on PEO-treated titanium and titanium alloys (tPEO: 0, 2, 5 and 30 min). The alloys were CP α-Ti, (α + β)-Ti6Al4V and the low-modulus materials near β-Ti13Nb13Zr and β-Ti45Nb. In particular, we aimed to determine whether the application of PEO technology could be extended to low-modulus titanium alloys without hindering the osteoblast response or provoking an inflammatory response. The study
Conclusions
PEO surface modification of low-modulus near β-Ti13Nb13Zr and β-Ti45Nb alloys showed comparable cellular behaviour in a long-term culture to CP α-Ti and (α + β)-Ti6Al4V control substrates. The study also provided evidence of apatite mineral deposition on PEO-treated low-modulus alloys, without an undue inflammatory response. This suggests that PEO application can be successfully extended to modify the surface of low-modulus β-type titanium alloys offering lower stress shielding without impeding
Acknowledgments
This work was supported by funding from the European Commission Seventh Framework Programme (FP7/2007-2013) under the grant agreement No. 264635 (BioTiNet—ITN). Dr. Roger Brooks acknowledges funding support from the National Institute for Health Research.
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2021, Materials Science and Engineering CCitation Excerpt :At this stage, the surface wettability and chemical composition play crucial roles [73]. Some studies have suggested that PEO-coated implants are a suitable surface for protein adsorption, and PEO-TPMS scaffolds are advantageous at this stage [74]. The second stage is the primary attachment of cells by focal adhesion on the surface [75] and consequent cell network generation due to contractile forces [76].