Stimulation of articular cartilage repair by exploiting biologically active mineral ions: A discussion of the state of the art

Articular cartilage, once damaged by trauma or diseases such as osteoarthritis, has a limited capacity for self-repair due to its avascular nature. Repairing this tissue remains a clinical challenge, further complicated by its high mechanical loading, hierarchical architecture, and specialized ionic environment. Current clinical treatments often yield inferior repair tissue and can cause donor-site morbidity. Cartilage tissue engineering (CTE) seeks to overcome these limitations by generating functional tissue in vitro, typically using growth factors to regulate cell migration, proliferation, chondrogenic differentiation, and extracellular matrix synthesis. However, growth factors are unstable, costly, and may cause side effects. Recently, ionic medicine has emerged as a promising alternative, harnessing the biological activity of mineral ions to modulate cellular processes similar to growth factors. This review summarizes the state of the art in ion-releasing biomaterials for cartilage repair, with particular emphasis on systems delivering silicon, lithium, magnesium, strontium, copper, zinc, cobalt, manganese, molybdenum, cerium, europium, and vanadium. In addition, less commonly studied ions, such as boron, iron, and selenium, that are relevant to cartilage biology but have not yet been systematically incorporated into biomaterials, are reviewed. Subsequently, the effects of these ions are comparatively analyzed and classified as either stimulative or protective. In addition, the synergistic and antagonistic interactions among simultaneously released ions are discussed. Furthermore, ion-releasing biomaterial systems employed in CTE are classified and evaluated. Overall, evidence suggests that ionic medicine holds considerable promise as a valuable alternative to growth factor- and surgery-based approaches for articular cartilage repair.