Background: Calcium phosphate cements (CPCs) are moldable microporous materials widely used for filling bone voids and defects. Introducing macro-porosity into the structure of these cements can enhance the biological functions and the rate of bone formation. 
Methods: In this study, CPCs with different morphologies (non-porous and porous forms) were used as bone fillers. Different amounts of the porogen were used to obtain different macropore diameters. Bone marrow–derived mesenchymal stem cells (MSCs) were obtained from the tibial shaft of Wistar rats. MSC proliferation was assessed using the MTT assay. Real time PCR and analysis of gene expression for genes relevant to osteogenic differentiation of cells loaded on the samples were carried out. For in vivo evaluations, circular holes were created in the proximal epiphysis of the rabbit tibia bone. The holes were filled with non-porous and macroporous CPCs, and histomorphological evaluation was performed at 4 and 8 weeks after the operation. 
Results: The results demonstrated that porous CPC was able to increase alkaline phosphatase activity and the expression of bone-related proteins (osteocalcin, osteopontin, and osteonectin) in MSCs cultured on the surfaces of cements. For in vivo evaluations, circular holes were created in the proximal epiphysis of the rabbit tibia bone. The holes were filled with non-porous and macroporous CPCs and histomorphologically evaluated at 4 and 8 weeks after the operation. The results revealed that, Wwhen the hole was filled with non-porous CPC, a layer of connective tissue with immature woven bone was formed at the surface of the implant without any resorption phenomenon. However, when the defect was filled with porous CPC (average pore diameter of 200 µm), the major part of the cement was resorbed and the resorbed cement was replaced by mature bone trabecula and unmineralized osteoid tissue.
Conclusion: The creation of macroporous cement could significantly improve the osteogenic ability and the active resorption rate of the cement, further associated with bone replacement by the host tissues.