Magnesium Ion Applications in Bone Tissue Engineering

Magnesium ions have emerged as versatile agents in bone tissue engineering, harnessed for their capacity to promote osteogenesis, modulate immune responses and support vascularisation. As a biodegradable metal, magnesium releases Mg²⁺ in situ, creating a dynamic microenvironment that stimulates osteoblast proliferation, differentiation and extracellular matrix mineralisation. Beyond direct effects on bone cells, Mg²⁺ regulates the local immune milieu by influencing macrophage phenotype, thereby establishing a pro-osteogenic niche. Concurrently, magnesium enhances angiogenesis, ensuring adequate nutrient and oxygen supply to regenerating tissue. Biomaterial platforms—ranging from alloys and composites to hydrogels and ion-enriched scaffolds—are engineered to control release kinetics, mechanical properties and degradation rates, optimising the balance between bone formation and scaffold resorption. Key challenges include preventing excessive alkalinity, tailoring ion concentrations to avoid inhibitory effects and integrating magnesium-based constructs with host tissue. Collectively, advances in magnesium-ion delivery offer promising routes to address critical-sized defects, non-union fractures and osteoporosis-related injuries, with broad implications for orthopaedic and maxillofacial reconstruction.

Research from Nature Portfolio

Recent studies have demonstrated that divalent metal cations can stimulate skeleton interoception, a sensory feedback loop whereby prostaglandin E₂ released from macrophages activates calcitonin gene-related peptide-positive nerve fibres to reduce sympathetic tone and promote new bone formation. This neuro-immune axis highlights a previously underappreciated pathway through which Mg²⁺ augments osteogenesis. A pivotal investigation further elucidated the biphasic influence of magnesium ions on bone healing: in early inflammation, Mg²⁺ influx via the TRPM7 channel in monocyte-derived macrophages drives epigenetic changes that foster a pro-osteogenic immune microenvironment, whereas prolonged exposure impairs hydroxyapatite deposition and delays maturation. These insights have reshaped our understanding of dose- and time-dependent effects of Mg²⁺ in regenerative strategies.

Magnesium Ion Applications in Bone Tissue Engineering publication trend

The graph below shows the total number of articles in magnesium ion applications in bone tissue engineering across all publications each year (not limited to Nature Index journals).

Technical terms

Osteogenesis: The process of new bone formation mediated by osteoblasts and their precursors.

Angiogenesis: The growth of new blood vessels from pre-existing vasculature to support tissue regeneration.

TRPM7: A magnesium-permeable ion channel and kinase that regulates Mg²⁺ influx and downstream signalling in immune and bone cells.

Skeleton interoception: A neuro-immune circuit in which bone-derived signals are conveyed to the central nervous system to modulate bone remodelling.

Hydroxyapatite: A calcium phosphate mineral analogous to bone matrix, commonly used as a scaffold material for bone repair.

Biomaterial: An engineered substance designed to interact with biological systems for therapeutic or diagnostic purposes, here used as magnesium-based scaffolds or coatings.

References

1. TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration. Nature Communications (2021).
2. A Magnesium‐Enriched 3D Culture System that Mimics the Bone Development Microenvironment for Vascularized Bone Regeneration. Advanced Science (2019).
3. Magnesium and Osteoporosis: Current State of Knowledge and Future Research Directions. Nutrients (2013).
4. Divalent metal cations stimulate skeleton interoception for new bone formation in mouse injury models. Nature Communications (2022).
5. Effect of magnesium ion on human osteoblast activity. Brazilian Journal of Medical and Biological Research (2016).
6. Regulation of Magnesium Matrix Composites Materials on Bone Immune Microenvironment and Osteogenic Mechanism. Frontiers in Bioengineering and Biotechnology (2022).
7. Double-edged effects caused by magnesium ions and alkaline environment regulate bioactivities of magnesium-incorporated silicocarnotite in vitro. Regenerative Biomaterials (2021).
8. In Vitro and In Vivo Applications of Magnesium-Enriched Biomaterials for Vascularized Osteogenesis in Bone Tissue Engineering: A Review of Literature. Journal of Functional Biomaterials (2023).