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Xi Fu,1 Pin Liu,1 Dingyun Zhao,2 Bo Yuan,1 Zhanwen Xiao,1 Yong Zhou,2 Xiao Yang,1 Xiangdong Zhu,1 Chongqi Tu,2 Xingdong Zhang1 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People’s Republic of China; 2Department of Orthopaedics, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaCorrespondence: Xiangdong ZhuNational Engineering Research Center for Biomaterials, Sichuan University, No. 29 Wangjiang Road, Chengdu 610064, People’s Republic of ChinaTel +86 28 8547 0770Email zhu_xd1973@scu.edu.cnChongqi TuDepartment of Orthopaedics, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, People’s Republic of ChinaTel +86 28 8542 2570Email tcqbonetumor@163.comBackground: Angiogenic and osteogenic activities are two major problems with biomedical titanium (Ti) and other orthopedic implants used to repair large bone defects.Purpose: The aim of this study is to prepare hydroxyapatite (HA) coatings on the surface of Ti by using electrochemical deposition (ED), and to evaluate the effects of nanotopography and silicon (Si) doping on the angiogenic and osteogenic activities of the coating in vitro.Materials and Methods: HA coating and Si-doped HA (HS) coatings with varying nanotopographies were fabricated using two ED modes, ie, the pulsive current (PC) and cyclic voltammetry (CV) methods. The coatings were characterized through scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectrometer (XPS), and atomic force microscopy (AFM), and their in vitro bioactivity and protein adsorption were assessed. Using MC3T3-E1 pre-osteoblasts and HUVECs as cell models, the osteogenic and angiogenic capabilities of the coatings were evaluated through in vitro cellular experiments.Results: By controlling Si content in ∼ 0.8 wt.%, the coatings resulting from the PC mode (HA-PC and HS-PC) and CV mode (HA-CV and HS-CV) had nanosheet and nanorod topographies, respectively. At lower crystallinity, higher ionic dissolution, smaller contact angle, higher surface roughness, and more negative zeta potential, the HS and PC samples exhibited quicker apatite deposition and higher BSA adsorption capacity. The in vitro cell study showed that Si doping was more favorable for enhancing the viability of the MC3T3-E1 cells, but nanosheet coating increased the area for cell spreading. Of the four coatings, HS-PC with Si doping and nanosheet topography exhibited the best effect in terms of up-regulating the expressions of the osteogenic genes (ALP, Col-I, OSX, OPN and OCN) in the MC3T3-E1 cells. Moreover, all leach liquors of the surface-coated Ti disks promoted the growth of the HUVECs, and the HS samples played a more significant role in promoting cell migration and tube formation than the HA samples. Of the four leach liquors, only the two HS samples up-regulated NO content and expressions of the angiogenesis-related genes (VEGF, bFGF and eNOS) in the HUVECs, and the HS-PC yielded a better effect.Conclusion: The results show that Si doping while regulating the topography of the coating can help enhance the bone regeneration and vascularization of HA-coated Ti implants.Keywords: electrochemical deposition, hydroxyapatite, silicon, coating, morphology, MC3T3-E1 cells, HUVECs