Magnesium phosphate minerals and cements as bone substitute materials

When bone defects surpass a critical threshold in size, they typically necessitate intervention through either autologous bone grafting or the use of synthetic substitutes to maintain structural support and prevent unwanted soft tissue infiltration. Most synthetic bone graft materials currently in use are composed of calcium phosphate compounds, such as hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP). Despite their widespread clinical adoption and long-standing research, these materials still face important limitations, including suboptimal mechanical strength and slow resorption, particularly in the case of HA. Magnesium phosphate (MgP) compounds have emerged as promising alternatives in this context. Their higher solubility compared to calcium phosphates and their encouraging performance in promoting bone regeneration, demonstrated even in large animal studies, suggest their potential as next-generation bone substitutes. This review focuses on the current state of research regarding MgP-based materials for bone repair. It explores fundamental aspects of MgP chemistry, how these materials can be processed into clinically applicable forms such as injectable cements, granules, or porous scaffolds, and examines their effects on bone healing in various preclinical animal models. STATEMENT OF SIGNIFICANCE: Critical-sized bone defects remain a major clinical challenge, and despite decades of research, the synthetic substitutes most widely used today are hindered by limited resorption and suboptimal mechanical performance. Magnesium phosphate based biomaterials have recently emerged as promising next-generation bone substitutes due to their favorable resorption kinetics, high initial mechanical strength, bioactivity, and potential to actively support bone regeneration. This review critically evaluates the current state of knowledge on these materials, covering their chemistry, processing into cements, granules, and scaffolds, and preclinical in vivo outcomes. By integrating findings across different magnesium-based systems, the review highlights both opportunities and remaining challenges for translation into clinical practice.