A systematic review of the interaction and effects generated by antimicrobial metallic substituents in bone tissue engineering

Metallic elements are one of the key components of human physiology, which are required for basic cellular and extracellular functions. Herein, we provide insight into the bioactive metallic dopants silver (Ag), zinc (Zn), copper (Cu), magnesium (Mg) and ceria (Ce), which provide resistance against human pathogenic bacteria, and summarise the pathways for their generated effects crucial for osteogenic activity in an antibacterial environment and bone regeneration. Although most of these elements interact with genetic material, resulting in denaturation to produce apoptosis of pathogenic cells, some create adverse effects in the cellular matrix, which interfere with normal cellular metabolism and inhibit cellular activity, reducing the further growth and formation of bacterial colonies. Furthermore, although remarkable antibacterial activity has been recorded, bacterial cells have developed pathways and transporter proteins that remove the excess of these antibacterial elements from the cellular matrix. Thus, a discussion of these reported pathways as limitations is presented to find more novel modes of administration of these elements since they show good biocompatibility and are non-cytotoxic at certain release concentrations. As a cofactor of several enzymes, it is worth noting that some of these elements not only help in the metabolism of bone, but also activate the genetic pathways that regulate the formation of and maintain the factors that support new bone. The choice of incorporating these materials in ionic or nanoparticle form depends on the target substrate since they exhibit different mechanisms of action and even produce selective effects depending on their physical properties.