Fabrication of reinforced scaffolds for bone regeneration remains a significant challenge. The weak mechanical properties of the chitosan (CS)-based composite scaffold hindered its further application in clinic. Here, to obtain hydroxyethyl CS (HECS), some hydrogen bonds of CS were replaced by hydroxyethyl groups. Then, HECS-reinforced polyvinyl alcohol (PVA)/biphasic calcium phosphate (BCP) nanoparticle hydrogel was fabricated via cycled freeze-thawing followed by an biomineralization treatment using a cell culture medium. The synthesized hydrogel had an interconnected porous structure with a uniform pore distribution. Compared to the CS/PVA/BCP hydrogel, the HECS/PVA/BCP hydrogels showed a thicker pore wall and had a compressive strength of up to 5-7 MPa. The biomineralized hydrogel possessed a better compressive strength and cytocompatibility compared to the untreated hydrogel, confirmed by CCK-8 analysis and fluorescence images. The modification of CS with hydroxyethyl groups and biomineralization were sufficient to improve the mechanical properties of the scaffold, and the HECS-reinforced PVA/BCP hydrogel was promising for bone tissue engineering applications.Copyright © 2020 American Chemical Society.