Research Paper
Superior biofunctionality of dental implant fixtures uniformly coated with durable bioglass films by magnetron sputtering

https://doi.org/10.1016/j.jmbbm.2015.07.028Get rights and content

Highlights

  • Dental screws biofunctionalized with bioglass (BG) coatings by magnetron sputtering.

  • Mechanical reliability of BG films evaluated by “cold” implantation in pig jaw bone.

  • BG films stimulated strong cellular adhesion and proliferation of human DPSCs.

  • Ability to conserve healthy stem cell pool – key to implants with extended lifetime.

Abstract

Bioactive glasses are currently considered the suitable candidates to stir the quest for a new generation of osseous implants with superior biological/functional performance. In congruence with this vision, this contribution aims to introduce a reliable technological recipe for coating fairly complex 3D-shaped implants (e.g. dental screws) with uniform and mechanical resistant bioactive glass films by the radio-frequency magnetron sputtering method. The mechanical reliability of the bioactive glass films applied to real Ti dental implant fixtures has been evaluated by a procedure comprised of “cold” implantation in pig mandibular bone from a dead animal, followed by immediate tension-free extraction tests. The effects of the complex mechanical strains occurring during implantation were analysed by scanning electron microscopy coupled with electron dispersive spectroscopy. Extensive biocompatibility assays (MTS, immunofluorescence, Western blot) revealed that the bioactive glass films stimulated strong cellular adhesion and proliferation of human dental pulp stem cells, without promoting their differentiation. The ability of the implant coatings to conserve a healthy stem cell pool is promising to further endorse the fabrication of new osseointegration implant designs with extended lifetime.

Introduction

The international dental implants market experienced a continuous growth in the last decade, slightly fading only during the global financial crisis, followed by a strong revival from 2013 to a level rated at 6.4 billion dollars (http://www.marketsandmarkets.com/PressReleases/dental-implants-market.asp, 2015a). Reputed economic research agencies forecast a continuous strong rise in the Compound Annual Growth Rate (CAGR) in coming years: Transparency Market Research—CAGR ~7.3% (http://www.marketsandmarkets.com/PressReleases/dental-implants-market.asp, 2015a) until 2018; TechNavio—CAGR of ~5.4% from 2012 to 2016 (http://www.technavio.com/report/global-dental-implants-market-2012-2016, 2015b); Persistence Market Research—CAGR ~9.7% for the 2014–2020 period (http://www.persistencemarketresearch.com/mediarelease/dental-implants-market.asp, 2015c).

The evolution of dental implants’ market is determined by economical aspects, and changes in cultural perception on health and lifestyle of the society (〈http://www.transparencymarketresearch.com/dental-implants-market.html〉, 〈http://www.dentaleconomics.com/articles/print/volume-100/issue-12/features/trends-in-implant-dentistry.html〉, http://www.dental-tribune.com/articles/business/americas/11737_dental_implants_market_expected_to_double_by_2018.html): (i) life expectancy (the edentation problem becomes more acute with the increase of the population age); (ii) demographics in certain regions of the world; (iii) oral hygiene concerns; (iv) sociological and cultural reasons (in the collective mentality a pleasant appearance enhances the perception of a more dynamic, professional and trustworthy individual); (v) per capita incomes in the emerging economies; (vi) implants’ availability due to an increased number of certified producers; (vii) advanced therapeutic biomedical progress and new technologies advertised through diverse media channels. According to a recent study of the American Association of Oral and Maxillofacial Surgeons (http://www.dentaleconomics.com/articles/print/volume-100/issue-12/features/trends-in-implant-dentistry.html, 2015e), 69% of adults with ages between 35 and 44 in USA have lost at least one tooth due to accidents or dental disease, while by age 74, 26% of adults are edentulous. The American Academy of Implant Dentistry reported that 3 million people have dental implants in USA, and that the number is growing by 500,000 a year (http://www.bluemcare.com/en/blogs/nieuws/good-news-for-bluem-dental-implants-market-expecte/, 2015g). Yet, Europe is the largest dental implants market with a share of ~42% of the global market (http://www.marketsandmarkets.com/PressReleases/dental-implants-market.asp, 2015a), followed by North America, and by the countries with major booming economies and a large population (China, India, Brazil). Such demand stimulates the search for more effective manufacturing processes and implants with superior functionality and fast healing responses.

Titanium (Ti) based materials, first introduced in clinical practice in the ’40s (Bothe et al., 1940, Nakajima and Okabe, 1996), have a dominant share of the dental implants market due to a set of relevant properties: (i) corrosion resistance and compatibility in biological environments; (ii) excellent mechanical properties and reduced mass density. A smaller market share appertains to implants fabricated from another bioinert material: zirconia (e.g. CeraRoot®).

The osseointegration of Ti dental implants can be enhanced by two main surface engineering approaches: (i) topographical and physico-chemical modifications (via machining, grit-blasting, acid-etching, anodic oxidation, laser processing (Ballo et al., 2011, Bosco et al., 2012), cold-plasma treatment (Yoshinari et al., 2011) or photofunctionalization (Suzuki et al., 2013); (ii) chemical alterations (by addition of growth factors (Gaviria et al., 2014, Le Guehennec et al., 2007) or by coating with a continuous, mechanical resistant bioactive layer (Bosco et al., 2012, Gaviria et al., 2014, Le Guehennec et al., 2007).

The bioactive materials, including bioglasses/glass–ceramics and calcium phosphate-based bioceramics, possess unique biologic qualities (Hench, 1991, Zhao et al., 2011). When in contact with the physiological environment they stimulate bony tissue repair and lead to the creation of a strong bond between the surrounding tissue and the medical device (Hench, 1991, Bachar et al., 2013, Li et al., 2014, Shen et al., 2015, Kapoor et al., 2015). Dental implants are currently coated with hydroxyapatite [HA, Ca10(PO4)6(OH)2] or biphasic calcium phosphates (CaP) [HA+β-Ca3(PO4)2] layers deposited by plasma spraying (Ong and Chan, 2000). Their share from the global market is not large, but is in a continuous rise (Bosco et al., 2012, Gaviria et al., 2014). However, plasma spraying technology is quite expensive and produces thick coatings susceptible to delamination, containing hardly reproducible residual phases with unpredictable biological behaviour, due to thermal stresses and/or compositional gradients induced by the high/transient temperatures involved (Epinette and Manley, 2004, Miyazaki and Kawashita, 2013). Moreover, delamination debris (in form of chips/cutting blades) is prone to inflict serious injuries/wounds in the implantation site.

Bioglasses (BG) are osteoproductive and possess the highest index of bioactivity, reflected in their ability to form a strong and enduring bond with the living tissues in a very short time. The first compositional system – 45S5 Bioglass® (wt%: SiO2—45, Na2O—24.5, CaO—24.5, P2O5—6) – was patented in the early ’70s by Hench, 1991, 2006). Nowadays, 45S5 Bioglass® and S53P4 BonAlive® (wt%: SiO2—53, Na2O—23, CaO—20, P2O5—4) formulations, are considered the bioactive glass gold standards, being currently the only melt-quenched BGs accepted by the USA Food and Drug Administration for use in clinical practice (Massera et al., 2012, Vallittu et al., 2015). However, the significant mismatch in the thermal expansion coefficients (CTE) of these classical BG systems (~15–17×10−6 °C−1) and Ti and its medical grade alloys (~9.2×10−6 °C−1), limits their use to applications bearing low biomechanical loads such as: bone fillers, scaffolds, auricular implants, treatment or repair of eye shelf or frontal sinus (Karlsson and Hupa, 2008, Fagerlund et al., 2012, Jones, 2013, Jones and Clare, 2012, Hench, 2013). The high Na2O content and the related fast degradation rate of 45S5 Bioglass® and S53P4 BonAlive® might be inappropriate for durable implant coatings. However, in some cases remnants of S53P4 were still observed after several year post-implantation (Lindfors et al., 2010, Massera et al., 2014).

Incorporating other components (e.g. MgO, CaF2, B2O3, and/or ZnO) into the classical formulations enabled reducing the CTEs mismatch and in vitro degradability, without affecting the osteoinduction capacity (Massera et al., 2012, Jones and Clare, 2012, Goel et al., 2012, Agathopoulos et al., 2006, Tulyaganov et al., 2011, Al-Noaman et al., 2013), suggesting the feasibility of manufacturing mechanically reliable BG implant coatings. Although frantic attempts to accomplish reliable BG coatings (onto almost exclusively flat substrates) by employing either well-established or novel physical and chemical deposition technologies (Sola et al., 2011, Verné, 2012) have been carried out, BG coated Ti implants are not yet available for medical practice.

Scientific articles on alternative methods to coat 3D dental implants (fixtures) are scarce. Recent progresses on coating dental implants with hydroxyapatite and fluorapatite by a new deposition technique—CoBlast were made by Dunne et al. (2015). van Oirschot et al. (2014) deposited HA-BG composite coatings synthesized by magnetron sputtering (the BG composition was not disclosed) and studied their osteointegration efficiency in vivo using Beagle dogs as animal model. The best results were reported for pure HA-coated implants, while pure BG-coatings were excluded from the in vivo study because of their weak adherence to implants. However, mechanically reliable BG coatings deposited onto oral implants by reactive plasma spraying were announced in 2000 by Schrooten and Helsen (2000). Other techniques such as ion beam (Wang et al., 2002) and magnetron sputtering (Stuart et al., 2015, Stan et al., 2011, Popa et al., 2014) have been also explored for depositing BG coatings on flat Ti substrates. Mistry et al. (2011) compared the performance of air microplasma sprayed HA and enamelled S53P4 BG coatings in clinical trials. Their results indicated that HA and BG implant coatings were equally successful in supporting final restorations, but the failure rates of BG coated implants in both arches were less than those of HA coated ones.

In most reviews magnetron sputtering is laconically rated as “expensive” and “line-of-sight” (able to coat only flat fixtures) (Bosco et al., 2012, Surmenev, 2012). This reductive vision neglects some of its unique features: (i) a certain quantity of source material (i.e. cathode target) can be used for numerous deposition sessions making this technique cheaper than most of the physical deposition methods; (ii) the translation/rotation of the substrate (i.e. metallic implant/prosthesis) is a facile solution for surpassing the line-of-sight drawback; (iii) the ability to coat large area substrates with pure, dense, uniform, homogenous, and adherent films; (iv) the easiness of process scaling up to an industrial level (e.g. as demonstrated in the past in the decorative and transistor fields) (Wasa et al., 2005).

Recent progresses made by our research team on the BG coatings (Popa et al., 2014, Stan et al., 2010, Stan et al., 2013) encouraged us to apply the optimized deposition regimes to biofunctionalize real dental implants. The aims of this study include: (i) setting a facile way to uniformly deposit, by radio-frequency magnetron sputtering (RF-MS), BG coatings with suitable mechanical resistance and biological behaviour onto dental screws that allow good cellular adhesion and proliferation without intervening in the complex mechanism that is stem cell differentiation; (ii) contributing to the future development of a new generation of implants with superior lifetime and less revision.

Section snippets

Materials

The RF-MS cathode target (110 mm diameter, 3 mm thick) was manufactured by room-temperature (RT) pressing a low sodium containing BG powder (wt%: SiO2—46.06, CaO—28.66, Na2O—4.53, P2O5—6.22, MgO—8.83, and CaF2—5.70) in a titanium holder as described in earlier studies (Stan et al., 2011, Stan et al., 2013, Stan et al., 2009). The BG has suitable thermal features (low CTE (10.44×10−6 °C−1), Tg=600 °C, (Tulyaganov et al., 2011), relatively low degradation rate and proven in vivo osseointegration

Results and discussion

The adhesion of the coating to the metallic implant surface is of critical importance for its successful clinical performance. Information regarding the bonding strength has been provided by pull-out tests performed for films deposited on flat Ti substrates. The mean value for the as-deposited films (63.2±5.2 MPa) increased to 71.4±4.9 MPa (p<0.05) after the thermal treatment at 630 °C (PDHT films). Both values are greater than the limit of 15 MPa imposed by international fabrication standards for

Conclusions

Implants with complex 3D architecture could be functionalized by RF-MS with BG thin films, of the SiO2–CaO–Na2O–P2O5–MgO–CaF2 compositional system, eliciting auspicious mechanical and biological properties. The “cold” implantation procedures (performed according to the dental implantology protocols on a pig jaw bone) demonstrated the endurance of the BG films conferred by the high bonding strength. The in vitro biocompatibility studies showed that these BG films allow good cellular adhesion and

Acknowledgments

A.C.P. and G.E.S. are thankful for the financial support of the Romanian National Authority for Scientific Research through the UEFISCDI PN-II-RU-TE-2011-3-0164 (TE49) grant. This work was also supported by the European Regional Development Fund (FEDER) through the COMPETE, by the Portuguese Government through the Portuguese Foundation for Science and Technology (FCT), in the scope of the projects UID/CTM/50011/2013 (Aveiro Institute of Materials, CICECO, www.ciceco.ua.pt).

References (65)

  • J. Massera et al.

    Influence of the partial substitution of CaO with MgO on the thermal properties and in vitro reactivity of the bioactive glass S53P4

    J. Non-Cryst. Solids

    (2012)
  • J. Massera et al.

    Effect of CeO2 doping on thermal, optical, structural and in vitro properties of a phosphate based bioactive glass

    J. Non-Cryst. Solids

    (2014)
  • A.C. Popa et al.

    Nanomechanical characterization of bioglass films synthesized by magnetron sputtering

    Thin Solid Films

    (2014)
  • J. Schrooten et al.

    Adhesion of bioactive glass coating to Ti6Al4V oral implant

    Biomaterials

    (2000)
  • S.B. Shen et al.

    Influence of heat treatment on bond strength and corrosion resistance of sol–gel derived bioglass–ceramic coatings on magnesium alloy

    J. Mech. Behav. Biomed. Mater.

    (2015)
  • G.E. Stan et al.

    Effect of annealing upon the structure and adhesion properties of sputtered bio-glass/titanium coatings

    Appl. Surf. Sci.

    (2009)
  • G.E. Stan et al.

    Bioactive glass thin films deposited by magnetron sputtering technique: the role of working pressure

    Appl. Surf. Sci.

    (2010)
  • G.E. Stan et al.

    Strong bonding between sputtered bioglass–ceramic films and Ti-substrate implants induced by atomic inter-diffusion post-deposition heat-treatments

    Appl. Surf. Sci.

    (2013)
  • B. Stuart et al.

    Preferential sputtering in phosphate glass systems for the processing of bioactive coatings

    Thin Solid Films

    (2015)
  • R.A. Surmenev

    A review of plasma-assisted methods for calcium phosphate-based coatings fabrication

    Surf. Coat. Technol.

    (2012)
  • D.U. Tulyaganov et al.

    Synthesis, processing and characterization of a bioactive glass composition for bone regeneration

    Ceram. Int.

    (2013)
  • P.K. Vallittu et al.

    Fiber glass–bioactive glass composite for bone replacing and bone anchoring implants

    Dent. Mater.

    (2015)
  • L. Varila et al.

    Surface reactions of bioactive glasses in buffered solutions

    J Eur. Ceram. Soc.

    (2012)
  • M. Yoshinari et al.

    Surface modification by cold-plasma technique for dental implants—bio-functionalization with binding pharmaceuticals

    Jap. Dent. Sci. Rev.

    (2011)
  • 〈http://www.marketsandmarkets.com/PressReleases/dental-implants-market.asp〉, 2015a [last accessed...
  • 〈http://www.technavio.com/report/global-dental-implants-market-2012-2016〉, 2015b [last accessed...
  • 〈http://www.persistencemarketresearch.com/mediarelease/dental-implants-market.asp〉, 2015c [last accessed:...
  • 〈http://www.transparencymarketresearch.com/dental-implants-market.html〉, 2015d [last accessed...
  • 〈http://www.dentaleconomics.com/articles/print/volume-100/issue-12/features/trends-in-implant-dentistry.html〉, 2015e...
  • ...
  • 〈http://www.bluemcare.com/en/blogs/nieuws/good-news-for-bluem-dental-implants-market-expecte/〉, 2015g [last accessed:...
  • A.M. Ballo et al.

    Dental implant surfaces—physicochemical properties

  • Cited by (0)

    View full text