Magnesium-based biodegradable implants Free

Life expectancy has increased considerably over the past 50 years. In line with this, the market for implantable medical devices – which is catered by an international and innovation-driven industrial sector – is booming due to upward trends in medical conditions and patient activity, changing patient treatment approaches and technical advances. For instance, the demand for cardiac implants quadrupled, for orthopedic implants doubled and for all other implants tripled between 1997 and 2007.²  With growing expectations on the quality of life, the associated healthcare costs and need to control these have turned into a pressing societal issue, especially in regions with an aging population.

Current (metallic) materials for biomedical implants are essentially neutral in the body. Such non-degradable, biopassive implants either remain in place (with the risk of loosening, fracturing and tissue inflammation) or are explanted after healing (implying additional surgical risk, patient discomfort and costs). Degradable or absorbable materials that are under development meet these drawbacks in part as they do need less repeated invasive surgery, since once absorbed they leave behind only the healed natural tissue. Apart from magnesium, other materials that are being considered are certain types of polymers and iron. Further trends are toward implants and coatings that are also vehicles for drug delivery (bioactive devices), for instance, to repress inflammation and aid the healing process. Biodegradable materials are of particular interest here, as bioactive substances may be incorporated that gradually release on dissolution of the implant in the body.

As for magnesium, its biocompatibility including its decomposition in the body (corrosion in the electrolytic environment), non-toxicity to the human body and its functional role in the physiological system render it as an attractive candidate for degradable implants. Its mechanical properties – notably strength and modulus of elasticity – and its density are quite similar to natural bone and hence, of interest for hard-tissue engineering applications.

Pioneering work in this field goes back to the end of the nineteenth century and indicated a significant reduction in healing time and acceleration in mineralization of bone fractures, while no toxic effects were observed.³  The rapid degradation of the magnesium implant and formation of hydrogen gas in the associated corrosion process, however, posed a problem and the interest shifted in favor of stainless steel and titanium. It was not before the late 1970s that the corrosion resistance of magnesium alloys was substantially improved by the use of specific alloying elements and high-purity alloys, so that hydrogen formation was suppressed as well. Most recently, the use of magnesium for medical applications has seen a growing research interest, also because of its perceived osteoconductive activity favoring bone apposition.⁴ 

Figure 1 illustrates the steep increase since 2005 in the number of published research works on the subject. Acknowledging that the outcome of such a basic literature search is merely indicative, the trend is undeniable; yet, it is also obvious that the magnitude of the research in this particular field is still modest as compared with the overall magnesium and/or biomedical research efforts. Research efforts thus have steadily increased as of late, and numerous research groups from around the globe are currently engaged in this multidisciplinary field of study. With an emphasis on China, Germany, the USA and Australia, the first-mentioned country appears to be especially active.⁵ 

Meanwhile, the possibilities and limitations have been explored and with this the challenges and needs for development have become apparent. The current state-of-the-art can concisely be assessed in terms of its so-called technology readiness level (TRL). Within this methodology, the maturity of evolving technologies prior to incorporating them into (sub)systems or regular practice is rated from TRL1 (basic principles observed and reported) to TRL9 (system adequacy proven in practice). In this view, magnesium-based materials for biomedical applications would have to be rated TRL3–5, meaning that research and development are directed to the demonstration of technical feasibility (proof of concept) and validation in a laboratory setting and relevant simulated or somewhat realistic environments. Cardiovascular implants seem to be a bit ahead of orthopedic implants in this respect.

If and to what extent magnesium implants will become common practice still remains to be seen. At the time of writing of this editorial, an early generation of magnesium drug-eluting coronary stents is being clinically studied in Europe. A favorable outcome of this milestone study will be a positive signal to the stakeholders that this is a viable route for the development of degradable implants, which will in turn trigger further research and development. Efforts to bring such products to the market are vast but can be leveraged by the high societal and commercial stakes. Eventual success will also depend on any breakthroughs with competing biodegradable materials, notably with polymers in view of mechanical performance and with iron in view of the tuning of corrosion rate and release of corrosion products.

The preamble of this themed issue has been the Magnesium-based Biodegradable Implants Symposium that was organized by Candan Tamerler (University of Washington) and Wim Sillekens (now European Space Agency) at the occasion of the TMS 142nd Annual Meeting on March 3–7th 2013, in San Antonio, TX, USA. The symposium comprised over 30 oral presentations including keynote addresses by Frank Witte (now Charité – Universitätsmedizin Berlin), Jörg Löffler (ETH Zürich) and Jag Sankar (North Carolina A&T State University). Several presenters at this symposium have contributed to this Emerging Materials Research (EMR) issue as well with a written account of their work, while the open call for papers has yielded the complementary half of the papers.

This themed issue consists of one review paper, five research papers and two short communications that are accordingly arranged as follows:

• Singh and Choudhary review an important aspect of biodegradation, namely, the interaction between corrosion and mechanical failure of the implant material (e.g. stress–corrosion cracking), and show that tailored and specific experimental data on this are still scarce, yet also identify contributing (microstructural) factors and outline approaches to prevent premature failure.

• Maier et al. focus on a class of magnesium alloys (containing rare earths as alloying elements) that appear to be of particular interest for the targeted applications and for these demonstrate that mechanical and corrosive properties can be adjusted (and thus optimized versus each other), among others by heat treatment.

• Seitz et al. rely on the same class of rare earth–containing alloys and demonstrate the use of a representative alloy (with a favorable combination of corrosion resistance and mechanical properties including ductility and biocompatibility) as a stenting material within air-ducting tubuli for a veterinary application.

• Schille et al. discuss the use of zone coulometry and ion-release analysis as evaluation tools for studying biocorrosion of several experimental (manganese free) magnesium alloys and show among others that these tests can be instrumental in evaluating their degradation in electrolytes.

• Yang and Gray-Munro introduce their study into the application of biomimetic calcium phosphate coatings on a magnesium alloy and on the basis of in vitro corrosion testing and surface characterization conclude that overall dissolution of the magnesium substrate can almost be blocked, but also that coating performance depends strongly on (and thus can be controlled by) coating bath composition.

• Niederlaender et al. report about a screening of several magnesium alloy classes with respect to their cytocompatibility using endothelial cell lines and primary human endothelial cells (the latter being closer to the clinical situation) and found distinct differences not only between the individual alloys but also between the cell types.

• Smith et al. touch on the issue of how specific alloying additions and heat-treatment processing affects the cytocompatibility as tested with indirect cell-culture assays as an upbeat for biomaterial design for the alloy class at hand.

• White et al. address the development of plasma electrolytic oxidation as a surface treatment technique to enhance the corrosion resistance and the hardness and wear resistance of prospective magnesium-based implants that have to rely on these attributes.

With this, the themed issue offers a representative sample of the topical research that will hopefully contribute to advancing the field by disseminating results of the concerned research groups, as well as by providing inspiration to all others concerned for the next steps in the research on and the development of magnesium-based biodegradable implants. Thanks to all those who have contributed to realizing this EMR issue, including the authors, the reviewers and, in particular, the Managing Editor Sohini Banerjee for her guidance throughout the process.