Table 1.

Summary of studies incorporating different ions within metal biomaterials.

Type of ion incorporated	Type of biomaterial	Ion incorporation methodology	Content of ion incorporated	Ion release rate or amount of ion released	Effect on osteogenesis	References
Copper	317L-Cu stainless steel	Ion doping	4.5 wt% of total 317L	0.067 μM per hour	↑ ALP activity ↑ COL1, OPN, Runx-2 ↑ Proliferation ↑ Bone formation	Ren et al., 2015
	317L-Cu stainless steel	Ion doping	4.5 wt% of total 317L	0.137ng/cm2/day	↑ ALP and LOX activity ↑ Runx-2, COL1 and OPN expression ↑ Fracture healing	Wang L. et al., 2017
Zinc	Pure zinc rods	Integrated within metal composition	100% Zinc matrix	N/A	↑ ALP staining and activity ↑ Mineralization ↑ ALP, COL1, OPN expression	Zhu et al., 2017
	Zinc ion implanted titanium	Bioactive coating	N/A	1.83–3.98 μM#	↑ ALP activity ↑ Mineralization	Jin et al., 2014
	Zinc incorporated TiO2 coating	Bioactive coating	Atomic concentration of zinc: 7.38–15.75 %	3.82–15.30 μM*	↑ ALP activity ↑ OCN, ALP, Col I, OCN, Runx2 expression ↑ Mineralization	Qiao et al., 2014
Boron	B-containing coatings on Ti substrates	Surface treatment	0.02 M Na2B4${\text{O}}_{7^{-}}$10H2O	3.7 μM#	↑ ALP activity	Ying et al., 2018
Lithium	Lithium coating on titanium scaffolds	Surface coating	0.02 M LiCl	0.43–1.44 μM*	↑ ALP, OPN, OCN, COL1, Runx2 expression ↑ Bone ingrowth ↑ Mineralization	Liu et al., 2018

^#Total amount released at the end of the experiment.

^*The minimum and the maximum amount released during the experiment (based on cell culture media change timepoints).

BMSC, bone mesenchymal stem cells (hBMSC, human; rBMSC, rat); ALP, alkaline phosphatase activity; COL1, collagen type I; OPN, osteopontin; Runx-2, Runt-related transcription factor 2; LOX, lysyl oxidase; OCN, osteocalcin.

↑increase.