Fengqian Li,1,* Wen Wu,2,* Li Xiang,1 Gan Weng,1 Hua Hong,3 Hong Jiang,4 Jun Qian31Department of Pharmacy, Shanghai Xuhui Dahua Hospital, 2Department of Orthopaedics, Ninth People’s Hospital, School of Medicine, Shanghai Jiaotong University, 3Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, 4School of Materials Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China*Co-first authors contributed equally to this workAbstract: Nanoporous magnesium–zinc–silicon (n-MZS) xerogels with a pore size of ~4 nm, a surface area of 718 cm2/g, and a pore volume of 1.24 cm3/g were synthesized by a sol–gel method. The n-MZS xerogels had high capacity to load vancomycin hydrochloride (VH) and human bone morphogenetic protein-2 (rhBMP-2), after soaking in phosphate buffered saline (PBS) for 24 hours (1.5 and 0.8 mg/g, respectively). Moreover, the n-MZS xerogels exhibited the sustained release of VH and rhBMP-2 as compared with magnesium–zinc–silicon (MZS) xerogels without nanopores (showing a burst release). The VH/rhBMP-2/n-MZS system not only exhibited a good antibacterial property but also promoted the MG63 cell proliferation and differentiation demonstrating good bactericidal activity and cytocompatibility. The results suggested that n-MZS with larger surface area and high pore volume might be a promising carrier for loading and sustained release of VH and rhBMP-2. Hence, the VH/rhBMP-2/n-MZS system might be one of the promising biomaterials for osteomyelitis treatment and bone repair.Keywords: nanoporous xerogels, sustained release, drugs, osteomyelitis, bone regeneration, bactericidal activity, cytocompatibility