Dual-Setting Magnesium Phosphate Bone Cement with Improved Handling Through the Integration of Chitosan-Derived Hydrogels

Magnesium phosphate cements (MPCs) are promising bone substitutes, but rapid setting, high exothermicity, and poor handling limit their clinical application. This study developed a dual-setting MPC by integrating chitosan-derived hydrogels into the cement matrix. Zinc ion-crosslinked carboxymethyl chitosan (CMCS) and thermosensitive chitosan/β-glycerophosphate (CS/GP) hydrogels were initially evaluated as modifiers of borax-containing (0.5% B) MPC formulations, after which the CS/GP formulation was further optimized by varying the CS (1.0/1.5%) and GP (5.6%/8.0%) concentrations. The effects of these modifications on setting behavior, physicochemical characteristics, mechanical performance, biodegradation, and cytocompatibility were systematically investigated. The B/CS/GP systems prolonged setting time, reduced the reaction temperature, moderated pH evolution, and markedly improved qualitative injectability and cohesion. XRD, FTIR, and SEM confirmed preservation of the characteristic phase composition, chemical structure, and microstructure. All formulations maintained favorable mechanical properties and supported osteoblast viability above the threshold. Among the investigated groups, the cement containing 0.5% B, 1.5% CS, and 5.6% GP exhibited the most balanced performance, combining improved handling characteristics with enhanced compressive strength. These findings demonstrate that the integration of CS-derived hydrogels, particularly the thermosensitive CS/GP system, provides a promising strategy for developing injectable dual-setting MPCs with improved handling characteristics without compromising their fundamental physicochemical and biological properties.