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Graphical abstract Highlights • Sr, Zn, and Sr/Zn-codoped HA porous scaffolds were prepared by combing an ion-exchange and a foaming method. • The ion-exchange method realized multi-ion doping of HA while protecting the intrinsic physiochemical and bioactive properties of HA. • A joint experimental-computational investigation proved doping of Sr/Zn into HA; doped HA have high crystallinity. • The Ca(II) substitution was more favored in the Sr and Zn-doped HA. • Sr/Zn codoped HA scaffolds exhibited both good osteoinductivity and excellent antibacterial properties. Abstract The porous scaffold of hydroxyapatite (HA) is highly promising for application in clinics owing to its interconnected porous structure, excellent mechanical properties, biocompatibility, and biological activity; however, the effectiveness of its antibacterial properties and osteoinductivity limits its wide usage. In the present study, strontium (Sr), zinc (Zn), and Sr/Zn-codoped porous scaffolds of HA were prepared by an ion-exchange method and a foaming method. The results based on the density functional theory (DFT) and experimental methods suggested that Sr and Zn were successfully doped into the HA lattice structure, thereby changing the lattice parameters of HA. Sr-doped, Zn-doped, and codoped porous HA scaffolds promoted the proliferation of bone marrow stromal cells (BMSCs), and Sr-doped and codoped porous HA scaffolds promoted BMSC differentiation. In addition, Zn-doped and codoped porous HA scaffolds exhibited excellent antibacterial properties. In short, the codoped HA porous scaffolds, prepared using the simple, facile, and mild ion-exchange, and foaming methods, had good biocompatibility, osteoinductivity, and antibacterial properties, which could effectively inhibit microbial infection and promote bone tissue regeneration in the process of bone repair. Moreover, they are hopeful to be good bone replacement material in clinical application. [ABSTRACT FROM AUTHOR]