Novel Biocement/Honey Composites for Bone Regenerative Medicine

New biocements based on a powdered mixture of calcium phosphate/monetite (TTCPM) modified with the addition of honey were prepared by mixing the powder and honey liquid components at a non-cytotoxic concentration of honey (up to 10% (w/v)). The setting process of the cements was not affected by the addition of honey, and the setting time of ~4 min corresponded to the fast setting calcium phosphate cements (CPCs). The cement powder mixture was completely transformed into calcium-deficient nanohydroxyapatite after 24 h of hardening in a simulated body fluid, and the columnar growth of long, needle-like nanohydroxyapatite particles around the original calcium phosphate particles was observed in the honey cements. The compressive strength of the honey cements was reduced with the content of honey in the cement. Comparable antibacterial activities were found for the cements with honey solutions on Escherichia coli, but very low antibacterial activities were found for Staphylococcus aureus for all the cements. The enhanced antioxidant inhibitory activity of the composite extracts was verified. In vitro cytotoxicity testing verified the non-cytotoxic nature of the honey cement extracts, and the addition of honey promoted alkaline phosphatase activity, calcium deposit production, and the upregulation of osteogenic genes (osteopontin, osteocalcin, and osteonectin) by mesenchymal stem cells, demonstrating the positive synergistic effect of honey and CPCs on the bioactivity of cements that could be promising therapeutic candidates for the repair of bone defects.