Figure 8.

Tuning the cobalt dose range is a promising strategy to resolve the controversies about the orthopedic applications of cobalt. The cobalt-induced bone regeneration is the outcome of the cooperation of osteoimmune, skeletal, and vascular systems. For the multimodal effects of cobalt, appropriate regulation of these multiple systems ultimately yields the optimal bone regeneration effect. In contrast, overactivation of a single system did not always benefit the artificial regeneration effect. An optimal bone regeneration effect was achieved in the 1 ppm cobalt group with a good balance of the osteogenesis/osteoclastogenesis system, a moderate immune response, and superior proangiogenic effects.