Phosphorylated chitosan as a hydrosoluble additive for bioactive calcium carbonate cements: Elaboration, setting mechanism, and handling properties

Chitosan is extensively used in the biomedical field owing to its biocompatibility and degradability. However, its limited solubility hinders its use as an effective additive in bone mineral cements. This study aimed to synthesize water-soluble phosphorylated chitosan and introduce it in calcium carbonate cement in view to control the composition, in vitro bioactivity, and physicochemical properties of the cement for bone repair. NMR spectroscopy results showed that chitosan was selectively functionalized (Cs–P) with phosphate groups mainly grafted at the C6 position on the chitosan backbone. For the first time, phosphorylated chitosan was associated with calcium carbonate cement; it was dissolved in a Na2CO3 solution (liquid phase of the cement) used as a setting accelerator. The quantitative XRD analysis at different time points revealed that the dissolution-recrystallization mechanism involved in the paste setting and hardening was different than for the reference cement: composite cement including 2.5 wt% Cs–P was mainly composed of vaterite (74 wt%) stabilized by Cs–P and some magnesian calcite (26 wt%). We pointed out the pivotal role of the calcium-binding ability of Cs–P phosphate groups and also of magnesium in controlling the cement setting mechanism and properties and its evolution in SBF. Interestingly, this composite cement also exhibited good physicochemical and handling properties: short initial (17 min) and final (28 min) setting times, high injectability (95%), enhanced anti-washout resistance of the paste, and a compressive strength compatible with implantation in non-load bearing bone defects. The in vitro evolution of the composite cement in SBF solution revealed some apatite formation on the cement surface and a high resorption rate (>20% at 28 days) owing to the solubility of the vaterite polymorph, making this composite cement a promising resorbable and bioactive ceramic able to be implanted through a minimally invasive technique.