Cross-talk between biometal ions and immune cells for bone repair

Biometal ions are crucial in the structure and function of living organisms and have extensively been employed to promote bone tissue regeneration. Nevertheless, the biological functions of biometal ions and the underlying mechanisms responsible for their pro-regenerative effects remain incompletely understood, since bone repair is an intricate physiological process involving multiple cell types and signals. Recent accomplishments in the osteoimmunological field have revealed the momentous involvement of the immune system in mediating the therapeutic effects of biometal ions. The inflammatory factors secreted by immune cells contribute to bone cell migration, activation, and proliferation. This review summarizes the immune system and its constituent cells, followed by the current perspective on immunomodulation during bone healing. Next, the physicochemical and physiological properties of various biometal ions, including lithium, sodium, potassium, magnesium, calcium, strontium, vanadium, iron, cobalt, copper, and zinc, are thoroughly reviewed. In addition, the interactions between biometal ions, immune cells, and bone tissue are discussed, aiming to provide insights into the prospective development of novel approaches to bone tissue regeneration by harnessing the therapeutic potential of these biometal ions.