Advances in copper-containing biomaterials for managing bone-related diseases

Bone-related diseases pose a major challenge in contemporary society, with significant implications for both health and economy. Copper, a vital trace metal in the human body, facilitates a wide range of physiological processes by being crucial for the function of proteins and enzymes. Numerous studies have validated copper's role in bone regeneration and protection, particularly in the development and expansion of bone collagen. Owing to copper's numerous biological advantages, an increasing number of scientists are endeavoring to fabricate novel, multifunctional copper-containing biomaterials as an effective treatment strategy for bone disorders. This review integrates the current understanding regarding the biological functions of copper from the molecular and cellular levels, highlighting its potential for bone regeneration and protection. It also reviews the novel fabrication techniques for developing copper-containing biomaterials, including copper-modified metals, calcium phosphate bioceramics, bioactive glasses, bone cements, hydrogels and biocomposites. The fabrication strategies and various applications of these biomaterials in addressing conditions such as fractures, bone tumors, osteomyelitis, osteoporosis, osteoarthritis and osteonecrosis are carefully elaborated. Moreover, the long-term safety and toxicity assessments of these biomaterials are also presented. Finally, the review addresses current challenges and future prospects, in particular the regulatory challenges and safety issues faced in clinical implementation, with the aim of guiding the strategic design of multifunctional copper-based biomaterials to effectively manage bone-related diseases.