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.

中文翻译：

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热敏可注射羟丙基甲壳质水凝胶，用于鲑鱼降钙素的持续释放，具有增强的成骨作用和降血钙作用。

药物疗法对主要由骨质疏松症和骨肿瘤引起的高钙血症治疗是调节体内钙平衡的有效方法。作为临床治疗肽，鲑鱼降钙素（sCT）被认为是速效药物，但半衰期短。为了应对这一挑战，我们设计了一种基于羟丙基几丁质（HPCH）的可注射热敏水凝胶，并结合了sCT和透明质酸（HA）（sCT–HA）的复合物，具有高达96.84±7.25％的高缔合效率。该复合水凝胶显示出可调节的生物降解性能。体外sCT释放曲线表明，这种水凝胶可以实现长期持续的sCT释放（28天），并具有相当的结构稳定性。细胞研究表明，与sCT组相比，该多组分水凝胶具有更高的ALP活性（2.10倍），钙表达（2.30倍）和细胞外钙沉积（1.10倍），具有出色的相容性和骨传导潜力。 。体内sCT释放证实，这种水凝胶系统可长达28天实现sCT的持续释放和持续的降血钙作用，并且根据组织学评估（H＆E和IgG染色）没有任何炎症和免疫反应。这些发现表明，这种骨传导性水凝胶系统可以为骨相关疾病的治疗提供有前途的方法。