Magnesium-based composite scaffolds for therapeutic delivery in bone tissue engineering: Current advances and emerging frontiers

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 Mg²⁺ 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.