Understanding of dopant-induced osteogenesis and angiogenesis in calcium phosphate ceramics.

General trends in synthetic bone grafting materials are shifting towards approaches that can illicit osteoinductive properties. Pharmacologics and biologics have been used in combination with calcium phosphate (CaP) ceramics, however, they have recently become the target of scrutiny over safety. The importance of trace elements in natural bone health is well documented. Ions, for example, lithium, zinc, magnesium, manganese, silicon, strontium, etc., have been shown to increase osteogenesis and neovascularization. Incorporation of dopants (trace metal ions) into CaPs can provide a platform for safe and efficient delivery in clinical applications where increased bone healing is favorable. This review highlights the use of trace elements in CaP biomaterials, and offers an insight into the mechanisms of how metal ions can enhance both osteogenesis and angiogenesis.