• Mg-based scaffolds orchestrate bone regeneration via ionic and therapeutic cues. • Controlled Mg²⁺ release synergizes with therapeutic agents to enhance bone repair. • The scaffold’s design and composition regulate degradation and bioactive release. • This review emphasizes Mg-based systems as dual ion-drug platforms for bone repair. • Bridges preclinical reports, challenges in clinical translation, and future trends. Critical-sized bone defects present significant challenges in orthopedic medicine, requiring innovative strategies that go beyond conventional treatments. Magnesium (Mg)-based scaffolds have gained attention as a new way to provide structural support and deliver different therapeutic agents. The synergistic action of bioactive Mg ions (Mg²⁺) with incorporated therapeutic agents enables coordinated stimulation of immunomodulation, angiogenesis, antimicrobial activity, and osteogenesis, thereby enhancing bone regeneration. This review critically evaluates the fabrication techniques of Mg-based scaffolds and highlights their influence on scaffold architecture, degradation behavior, and release kinetics. The synergistic release of Mg 2+ and therapeutic agents, such as osteogenic growth factors, polyphenols, and antimicrobials, from the scaffolds through corrosion-triggered, diffusion- and degradation-controlled, and multi-stimuli-responsive controlled delivery and their coordinated action for bone regeneration are briefly summarized. Even though there have been significant improvements, challenges persist in achieving controlled degradation, predictable release profiles, and long-term mechanical stability. This review emphasizes the necessity of advanced design strategies and standardized evaluations to fully exploit the therapeutic potential of Mg-based composite scaffolds in bone regeneration.
Babu et al. (Sun,) studied this question.