Magnesium-containing Medicines

    Magnesium is the fourth most abundant mineral in the human body after calcium, potassium, and sodium. A person weighing 70 kg has about 25 grams of magnesium in their body. Since the early 18th century, magnesium oxide (MgO) and Epsom salt (MgSO4·7H2O) have been used as medicines, commonly treating many diseases. People used them to alleviate health problems such as muscle pain, electrolyte imbalances, constipation, and eclampsia. Currently, magnesium supplements include potassium and magnesium aspartate tablets and magnesium gluconate granules.

    In fact, every cell in the human body contains magnesium and needs it to function normally. Thousands of biochemical reactions occur in the human body every moment, and magnesium is a cofactor in many of these reactions. Magnesium is involved in human activities including:

    Cellular Energy Production: The process of producing energy from carbohydrate and fat metabolism involves numerous magnesium-dependent chemical reactions. Magnesium in cells is mainly found in mitochondria, playing a crucial role in ATP synthesis.

    DNA Synthesis: The most important enzymes in DNA replication and repair cannot function normally without magnesium.

    Protein Synthesis: The process of synthesizing proteins requires various enzymes, and the vast majority of these crucial enzymes need magnesium as their cofactor. Currently, 3,751 human proteins with magnesium binding sites have been identified.

    Regulation of Mineral Concentrations: Magnesium-dependent proteins are also responsible for controlling the movement of different minerals, such as sodium (Na+), potassium (K+), and calcium (Ca2+), in and out of cells. For example, calcium ions enter cells when needed (such as for nerve stimulation and muscle contraction), and when the action is completed, the cell needs magnesium-assisted ion pumps to move calcium ions out of the cell. Without sufficient magnesium, cells cannot restore the original concentrations of sodium, potassium, and calcium. External manifestations include sensitivity to noise, irritability, migraines, spasms, arrhythmia, and increased anxiety.

    Taking large amounts of calcium through dietary supplements to prevent bone loss has become a very common practice. However, simply supplementing calcium not only fails to prevent but may not even slow down bone loss, let alone prevent fractures. Magnesium is one of the key factors helping the body absorb and utilize calcium. Magnesium deficiency may prevent calcium excretion, causing cells to be overstimulated, leading to damage or even death.

Orthopedic Fixation Materials and Vascular Stent Materials

    Currently, there are various magnesium alloy medical products internationally, including plates, rods, tubes, porous foams, composite materials, bone screws, and vascular stents. These products are mainly used as fracture fixation materials, orthopedic materials, dental implant materials, oral restoration materials, and porous scaffold materials for bone tissue engineering.

    Biodegradable magnesium alloys are rapidly developing new medical metal materials, mainly applied in cardiovascular stents and orthopedic implant materials. As magnesium materials implanted in the human body as bone screws or stents, they can automatically dissolve while ensuring body functions, without the need for removal, thus avoiding secondary damage to the body.

Applications in Orthopedics

    Bone tissue has the potential for self-repair and regeneration after trauma. However, this healing process is not only time-consuming but also difficult to fully restore the initial structure and mechanical properties of bone tissue. Therefore, in clinical work, it is often necessary to transplant biomaterials to accelerate the bone healing process and maintain final bone density. As one of the most important trace elements in bone tissue and an indispensable active component in systemic biological activities, magnesium ions are considered to play an important role in bone tissue repair.

    Advantages: Magnesium alloy implants can degrade and be absorbed after damaged bone tissue completes repair, eliminating the need for secondary surgery for removal, significantly reducing patient suffering and treatment costs. Additionally, the density and elastic modulus of magnesium alloys are closer to human bone tissue, which can significantly reduce stress shielding effects, beneficial for bone tissue healing.

    Areas for Improvement: As magnesium alloy implants degrade in the human body, harmful ions are released, posing potential threats to human health. Rapid corrosion rates can produce large amounts of H2, which, when accumulated around the implant or subcutaneously, can cause inflammation and affect bone healing. The degradation rate and mechanical decay of magnesium alloy implants must match the rate of bone healing.

    The earliest clinical medical report of magnesium alloys was in 1878 when Dr. Edward used magnesium wire as a hemostatic ligature. In 1907, Lambotte first used pure magnesium internal fixation plates and gold-plated steel nails to fix tibial fractures, but due to the rapid decomposition of magnesium in the body, it resulted in a large amount of gas produced subcutaneously. From 1938 to 1945, there were reports of pure Mg, Mg-Al-Mn alloy, Mg-10Al alloy, and Mg-Cd alloy used in clinical fracture internal fixation. Among them, magnesium-cadmium alloy was used to fix fractures in 1944, and magnesium-aluminum alloy was used to treat gunshot wounds in 1945. Early clinical studies showed that Mg and magnesium alloys had no significant toxicity and could promote bone healing, but the degradation rate was generally too fast, producing a large amount of gas postoperatively, causing inflammatory stimulation, and failing to provide long-term effective fixation support.

Application in Vascular Stents

    The degradability and appropriate mechanical properties of magnesium alloys allow them to be used in the manufacture of degradable vascular stents. Currently, degradable magnesium alloy stents under study include: AE21, AM60, WE43, magnesium-rhenium-yttrium alloy stents, magnesium-zinc-lithium alloy stents, etc.

    The DREAMS series (AMS-1, DREAMS 1G, DREAMS 2G, DREAMS 3G) from Germany's Biotronik is the earliest and relatively mature magnesium alloy coronary stent. Clinical trials have been ongoing since 2005, and it has now developed to the third generation of magnesium alloy stents, with the first clinical trial in mainland China starting in 2023. The first-generation degradable metal stent AMS-1 uses an alloy of 93% magnesium and 7% rare earth elements, with a thickness of 165 μm without drug coating. AMS-1 degrades rapidly, turning into ions just 60 days after implantation. The rapid degradation also causes the blood vessel to lose support and quickly recoil. Researchers added a paclitaxel coating (7.4 μg/cm²) to AMS-1 and covered the magnesium alloy surface with a layer of polylactic acid to slow down stent degradation. In the subsequent 3-year follow-up, the improved AMS-1 had a target vessel failure rate of only 6.6%, with no cardiac deaths or in-stent thrombosis.

    The second-generation Magmaris is also made of slow-degrading magnesium alloy, with a thickness and width of 150 μm, using a 6-crown 2-link design. To reduce the degradation rate, Magmaris uses square stent struts and side electrolytic polishing technology. Electrolytic polishing also provides the stent with softer edges, making it easier to deliver and beneficial for the hemodynamics around the stent struts.

    The third-generation DREAMS 3G has achieved more technical breakthroughs compared to its predecessor Magmaris, including the use of BIOTRONIK's proprietary BIOmag magnesium alloy material and sirolimus drug coating, maintaining a 12-month degradation time while also considering radial support durability. DREAMS 3G inherits the advantages of its predecessors in terms of safety, with a low rate of target lesion failure during trials and virtually no cases of stent thrombosis.