The Preparation, Characterization And Pro-angiogenesis Property Of Copper-doped Calcium Silicate(Cu-CS) Bioceramic

Angiogenesis/vascularization is critical during tissue regeneration. During tissue regeneration, new blood networks should be formed to provide enough oxygen and nutrients for the growth of cells. Previously, bioglass had been proved to enhance angiogenesis. Recently, our studies have demonstrated that cacium silicate(CS) can promote endothelial cells to form capillary networks, and silicon ion in CS extracts played a dominating role. In addition, it has been reported that copper ions at low concentration can induce and stabilize hypoxia microenvironment, and further facilitate VEGF expression production to activate downstream angiogenesis signal pathway. But copper ion release behavior of soluabe copper salt is uncontrollable, which may cause cell toxicity.On basis of the pro-angiogenesis effects of Cu and Si ions, we assume that combination of Cu ions and Si ions can achieve synergy pro-angiogenesis effect. Then, we determined non-toxic and pro-agiogenic concentration range of copper ion for HUVEC. A copper doped cacilum silicate Cu-CaSi O3(Cu-CS) bioceramic was then designed and synthesized. Results showed that the ion extracts of Cu-CS have better stimulatory effect on capillary network formation of co-cultured HUVEC in HUVEC-HDF co-culture system than single CS ion extracts or copper ions, indicating that Cu and Si ions have synery effect to promote angiogenesis. Finally, mechanism hypothesis of the stimulatory effects of Cu-CS on vascularization of HUVEC-HDF co-culture system has been proposed.