Ion substitution Human stem cells Bone biomaterial Calcium phosphate Dicalcium phosphate dihydrate, DCPD (CaHP0 4 •2H 2 O), brushite, is an important calcium phosphate compound encountered in mineralized tissues and used in medicine, especially in bone cernent for mulations. However, the use of DCPD as direct implantable biomaterial has not received dedicated attention. In addition, the possibility to dope DCPD with biologically active ions to modulate its per formances was not systematically explored. We have investigated in depth the doping of DCPD with Mg 2+ , sr2 + , Zn 2+ , Cu 2+ , and Ag + ions. Clear modifications in terms of chemical composition, particl e size, pore distribution, crystal morphology, and affinity for water were pointed out. Then, the samples were cultured with human adipose derived stem cells to explore cytotoxicity and proliferation. Various be haviors were noticed dependent on the incorporated metal ions. Such DCPD compounds associated with bioactive metal ions, and particularly Ag + and Zn 2+ , appear promising as a new family of reactive ma terials for use, as such or in combination, in bone related applications.