Multifunctional therapeutic ion-doped bioactive glasses for enhanced bone regeneration, immunomodulation, and antibacterial applications

One of the major challenges of tissue engineering is developing biomaterials that simultaneously promote tissue regeneration and prevent bacterial infections. Bioactive glasses (BGs) have a well-established reputation for inducing angiogenesis and osteogenesis in hard-tissue applications but often exhibit insufficient antibacterial efficacy to prevent biofilm formation under clinically relevant conditions. The incorporation of various therapeutic inorganic ions into BGs has emerged as a promising strategy to overcome this limitation and enhance biological responses, including osteogenesis, angiogenesis, immunomodulation, antioxidant activity, and antimicrobial properties. This review systematically categorizes dopants based on their chemical nature, highlighting their specific biological and antimicrobial effects. For each ion, the proposed mechanisms by which they promote bone regeneration, angiogenesis, immunomodulation, and antibacterial activity are discussed. Additionally, the review addresses advanced applications of doped and co-doping BGs in theragnostic and theragenerative therapies, including selective cytotoxicity toward cancer cells, bio-labelling imaging capabilities, photothermal properties, and hemostatic functions. By integrating current findings on doped BG compositions, surface morphologies, and their interactions with immune and bone cells, this review provides a detailed framework for designing next-generation multifunctional BG-based biomaterials. These materials hold significant potential to overcome existing limitations in antibacterial capacity and mechanical properties, thereby advancing clinical outcomes in bone tissue engineering and implantology.