Novel Co-akermanite (Ca₂CoSi₂O₇) bioceramics with the activity to stimulate osteogenesis and angiogenesis

Both osteogenesis and angiogenesis of bioactive materials play the vital role in the regeneration of large skeletal defects. Silicate-based bioceramics have been suggested to possess osteostimulative and angiogenic activity due to the beneficial effect of the released SiO₄ ^4- ions. Divalent cobalt ions (Co²⁺) have been reported to stimulate angiogenesis due to their hypoxia effect on tissue cells, such as MC3T3-E1 osteoblast-like cells, human bone marrow stromal cells (HBMSCs), human umbilical vein endothelial cells (HUVECs), rat hepatic stellate cells and so on. For these reasons, we supposed that the combination of Co²⁺ ions and silicate-based bioceramics might be able to enhance both osteogenesis and angiogenesis. The aim of this study was to synthesize cobalt-containing silicate bioceramics, Co-akermanite (CAKT, Ca₂CoSi₂O₇), and to investigate their physicochemical properties and biological activity. CAKT powders were, for the first time, synthesized using the sol-gel method and the dense ceramics were prepared by sintering the powder compacts. The effects of ionic products from CAKT bioceramics on the proliferation and alkaline phosphatase (ALP) activity of MC3T3-E1 cells as well as the proliferation and in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs) were systematically studied. The results showed that the released Co, Ca and Si-containing ionic products from CAKT bioceramics at certain concentrations (lower than 3.125 and 25 mg mL^-1) revealed good biocompatibility for both MC3T3-E1 cells and HUVECs. Moreover, the Co, Ca and Si-containing ionic products from CAKT bioceramics at 3.125 and 0.78 mg mL^-1 stimulated ALP activity of MC3T3-E1 cells and significantly enhanced the expression of VEGF and eNOs in HUVECs, as well as the formation of a capillary-like structure of co-cultured HUVECs in human dermal fibroblasts (HDFs) and the HUVEC co-culture model compared with CS bioceramics and culture medium, indicating that Co-containing CAKT bioceramics further enhanced angiogenesis and osteogenesis as compared to CS bioceramics. The results suggest that the combination of ions with different functions could result in a synergetic effect on the stimulation of both osteogenesis and angiogenesis, and CAKT as a bioceramic may be used for enhanced bone regeneration or bone tissue engineering applications.