A thermo-sensitive injectable hydroxypropyl chitin hydrogel for sustained salmon calcitonin release with enhanced osteogenesis and hypocalcemic effects

Pharmacotherapy towards hypercalcemia treatment mainly caused by osteoporosis and bone tumor is an effective method to regulate in vivo calcium equilibrium. As a clinical therapeutic peptide, salmon calcitonin (sCT) is considered as a quick-acting medicine but it is limited by the short half-life. To address this challenge, we designed an injectable thermo-sensitive hydrogel based on hydroxypropyl chitin (HPCH) and incorporated the complex of sCT and hyaluronic acid (HA) (sCT-HA) with high association efficiency up to 96.84 +/- 7.25%. This composite hydrogel showed a tunable biodegradable property. In vitro sCT release profiles revealed that this hydrogel can achieve long-term sustained sCT release (28 days) with considerable structure stability. The cellular study illustrated outstanding compatibility and osteoconductive potential of this multi-component hydrogel according to the higher ALP activity (2.10-fold), calcium expression (2.30-fold) and extracellular calcium deposition (1.10-fold) compared to that of the sCT group. In vivo sCT release confirmed that this hydrogel system realized sustained sCT release and a continuous hypocalcemic effect for as long as 28 days, and there were no inflammation and immune responses according to the histological evaluations (H&E and IgG staining). These findings demonstrate that this osteoconductive hydrogel system can provide a promising method for therapy of bone related disease.