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Development of hybrid materials with molecular structure of organic-inorganic co-network is a promising method to enhance the stability and mechanical properties of biopolymers. Chitosan-silica hybrid nanocomposite scaffolds loaded with mangiferin, a plant-derived active compound possessing several bioactivities, were fabricated using the sol-gel synthesis and the freeze-drying processes. Investigation on the physicochemical and mechanical properties of the fabricated scaffolds showed that their properties can be improved and tailored by the formation of 3-dimensional crosslinked network and the addition of ZnO nanoparticles. The scaffolds possessed porosity, fluid uptake, morphology, thermal properties and mechanical strength suitable for bone tissue engineering application. Investigation on the biomineralization and cell viability indicated that the inclusion of bioactive mangiferin further promote potential …