Strategic incorporation of metal ions in bone regenerative scaffolds: multifunctional platforms for advancing osteogenesis.

Bone serves as a critical structural framework, enabling movement and protecting internal organs. Consequently, maintaining skeletal health is a pivotal objective in bone tissue engineering. Bioactive metal ions, such as magnesium, strontium, zinc and copper, play essential roles in bone metabolism by participating in key physiological processes that sustain bone health and support regeneration. Recent studies indicate that these ions enhance the physicochemical properties and biological performance of bone tissue engineering materials, thereby facilitating osseointegration through diverse mechanisms. Specifically, magnesium promotes osteogenic differentiation; strontium inhibits osteoclast activity; zinc exhibits antibacterial properties; and copper facilitates vascularization for osteogenesis. Therefore, incorporating bioactive metal ions has emerged as a prevalent strategy in bone tissue engineering to address orthopedic disorders. This review systematically summarizes the roles of magnesium, strontium, zinc and copper in bone repair and regeneration. It provides an in-depth analysis of engineered materials incorporating these ions, with a focus on their applications and modifications across various material types. Furthermore, we explore the synergistic effects of combining these metal ions in bone tissue engineering, emphasizing their enhanced biological properties. By synthesizing recent research findings, this review aims to provide new insights and potential breakthroughs in leveraging bioactive metal ions for advancing treatments of orthopedic diseases.