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The use of medical devices has hit an all-time high, with the global industry currently valued at $200 million and strong growth predictions through to 2023.1 These devices include surgical implants, which cover a broad range of applications such as artificial joints, lap-bands, stents, and pacemakers, with the goal of supporting tissue regeneration and providing optimal healing, allowing a patient to return to full health in an acceptable time frame.

Within this industry, the use of bioresorbable implants is increasing, competing with the more traditional titanium implants. Recent developments within the bioresorbable implants market includes magnesium alloys, which offer new, revolutionary solutions, demonstrating both biocompatibility and biosafety. Magnesium alloys present opportunities across the medical device market from orthopedic implants to veterinary applications. Most recently the alloys have progressed to use in cardiovascular stents, known as scaffolds. The alloys are now being used in a commercially available CE marked product (see the sidebar, “Developing the Magmaris Magnesium Scaffold”).

A New Opportunity: Bioresorbable Materials

Top: The monolithic magnesium screws (a); the anodized magnesium screw (b), the PLLA screw (c). Bottom: the first two screws (d and e made from magnesium) stayed intact, whereas the PLLA (f) fractures at four weeks after implantation. (Credit: Marukawa et al. 2015).

Bioresorbable materials are advantageous for use throughout the medical device market because they offer a steady resorption rate and can help achieve optimum healing within the body. Polymer materials have been used as a bioresorbable option for a few years; however, magnesium alloys now offer an improved alternative. In comparison with the relatively low strength of polymers, magnesium demonstrates a tensile strength that is much closer to that of natural bone. This means that these alloys are much more suited for use in load-bearing mechanical medical devices. Magnesium is also a naturally occurring element in the body, with proven biocompatibility.

Magnesium’s biocompatibility means that the body can remove magnesium degradation products. Studies of blood following the use of magnesium implants within the body revealed that resorption caused little change to the composition, with no disorder to the liver or kidneys.2 Furthermore, magnesium is needed for effective heart, muscle, nerve, bone, and kidney function and the World Health Organization (WHO) recommends that adults need between 280 and 300 mg of magnesium per day.3

Developing the Magmaris Magnesium Scaffold

The full Magmaris® scaffold created by Biotronik, which uses SynerMag® magnesium alloy as the key structural backbone of the scaffold.

Cardiovascular disease is the deadliest, yet also the most common disease in the world. Because of this, many revolutionary new procedures are being pioneered for its cure. Coronary angioplasties are known as the most advanced solution, and these involve minimally invasive insertion of a stent into the coronary artery.

Magnesium Elektron, a global developer of magnesium technology, and Biotronik, a manufacturer of cardio medical devices, partnered to develop a cardiovascular stent that resorbs over time. This bespoke new technology was launched following a decade long research program in which SynergMag® 410, a magnesium alloy system, was created as the critical backbone to Biotronik’s Magmaris scaffold. The Magmaris magnesium scaffold was launched in the summer of 2016 by Biotronik, and it is now the world’s first clinically proven magnesium-based resorbable scaffold to obtain a CE mark.

Patients have been treated successfully with Magmaris in Germany, Belgium, Denmark, the Netherlands, Switzerland, Spain, Brazil, New Zealand, and Singapore since its launch. The first patient in Australasia has recently been treated with the Magmaris stent, when it was found that the patient had 90 percent of his heart vessels blocked, causing ongoing angina and chest pain.

The SynerMag® Technology Centre.

During the development project, Magnesium Elektron invested $2.5 million in establishing a dedicated manufacturing facility, incorporating state-of-the-art laboratories, casting extrusion, and heat-treatment facilities. It achieved ISO 13485 certification for this purpose-built SynerMag Technology Centre, which was used during the development of the SynerMag 410 alloy. The ISO 13485 certification means that the material produced is manufactured in line with international standards for biomedical use, which helps to increase the speed of medical device production for manufacturers by ultimately reducing time and costs associated with internally assessing materials brought in. This helps to smooth out processes and simplify the device manufacturer’s role.

To read more about how Biotronik brought its product to market in partnership with Magnesium Elektron, access the case study at here.

Magnesium alloys can be designed to degrade in a tailored manner to match the needs of specific implants in a range of applications. The advantage of the degradation or resorption process of a magnesium implant is that it allows for new bone to grow inward. This contrasts with other bioresorbable materials such as polymers, which, as well as taking longer to degrade, have the potential to intake water during degradation, leading to a loss in structural integrity as well as size.4

Magnesium Alloys for Use in Medical Devices

Medical implants can be used in a range of applications, such as vascular stents and bone repair. Traditional permanent implants are common and typically made from titanium or stainless steel; however, they often require a secondary operation for removal.5 On the other hand, bioresorbable materials, including magnesium alloys, allow for optimal healing before resorbing into the body as the surrounding tissue replaces the implant. Bioresorbable implants can also provide matching resorption kinetics to the healing period. This bioresorbability prevents the need for secondary surgical procedures, which can be costly and stressful for patients.

A recent study looked at the use of magnesium implants in osteosynthesis in comparison with PLLA polymers.6 This study, conducted by Marukawa et al., was done in the tibia of beagles, using Magnesium Elektron’s SynerMag® alloy to evaluate the effectiveness. The study discovered that 100 percent of the PLLA screws were broken within the time frame. In comparison, only one in 24 of the SynerMag magnesium screws broke. It also found that four out of six PLLA screws loosened within four weeks, whereas all magnesium screws remained tight. This finding demonstrates both the strength and obvious mechanical benefits of magnesium, which can be used in high-load-bearing areas. The study also found magnesium to have good biocompatibility.

Conclusion

Magnesium is proven to be an advantageous alternative to other bioresorbable materials, suitable for use in many different applications. Not only is the element naturally occurring in the body, but magnesium alloys also have proven biocompatibility. Furthermore, magnesium promotes new bone growth, and it does not take on water, which would cause a loss in its integral shape during degradation. The success of magnesium in the medical device sector so far has led to it being developed for a number of different applications. It also shows great promise for use in the pharmaceutical sector as a drug-delivery device.

Magnesium Elektron has successfully produced magnesium alloys for commercial applications. Its magnesium alloy product, SynerMag, which has already been used successfully as a platform material in the healthcare sector, can be designed to resorb at different rates to suit individual requirements.

This article was written by Paul Lyon, Programmes Technology Manager at Magnesium Elektron, Manchester, UK. For more information, Click Here.

References

  1. Anderson, A. Global Medical Implants Market 2016: Industry Review, Research, Statistics, and Growth to 2021. 2016 (internet) https://www.linkedin.com/ pulse/global-medical-implants-market- 2016-industry-review-growth-anderson.
  2. Zhang E, Xu L, Pan F, Yu G, Yang L, Yang K. In vitro and in vivo evaluation of the surface bioactivity of a calcium phosphate coated magnesium alloy. 2009. Biomaterials, Volume 30, Issue 8, Pages 1512–1523.
  3. Institute of Medicine (IOM). Food and Nutrition Board. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride. Washington, DC: National Academy Press, 1997.
  4. Hofmann D, Entrialgo-Castano M, Kratz K, and Lendlein A. Knowledge-based approach towards hydrolytic degradation of polymer-based biomaterials. 2009. Advanced Materials. 21, 3237–3245.
  5. Bostman O.M. Osteoarthritis of the ankle after foreign-body reaction to absorbable pins and screws. The journal of bone and joint surgery. Vol 80-B No 2. March 1998.
  6. Marukawa E, Masato T, Takahashi Y, Hatakeyama I, sata M, et al. Comparison of magnesium alloys and poly-l-lactide screws as degradable implants in canine fracture model. J biomed Mater Res Part B. 2016. 104B:1282–1289.