Thermo-reversible hydrogels have been widely studied in biomedical research fields, because of their potential performance in drug delivery and tissue engineering. In this study, a novel thermo-sensitive methylcellulose (MC) hydrogel based on calcium phosphate nanoparticles (CaP NPs) was prepared by in situ formation process in which precursor salts induced a salt-out effect in the MC solution. Based on the Hofmeister series, CaCl₂, Na₂HPO₄, and NaH₂PO₄ precursor salts with a good salt-out effect were used as the precursor salts for CaP NPs. The gelation of MC solution was accelerated by the salt addition, and its effect varied with the salt type. When CaP precursor salts with two different Ca/P ratios (0.8/1 and 1.6/1) were added into the MC solution, more elastic MC hydrogel was formed at 1.6/1 Ca/P ratio. The CaP NPs were rectangular in shape (40–50 nm), and evenly distributed in the MC gel. The X-ray diffraction (XRD) observation indicates that dicalcium phosphate dehydrate (DCPD) and octacalcium phosphate (OCP) were synthesized at 0.8/1 Ca/P ratio, whereas DCPD was synthesized at 1.6/1 Ca/P ratio. This indicates that the CaP NPs with different crystalline phases were in situ synthesized in accordance with the Ca/P ratio and pH condition (pH 7.4, 9.0). Moreover, the DCPD and OCP crystalline phases were converted to the hydroxyapatite (HAP) crystalline phase, as the pH was changed to alkaline region. Therefore, the resulting MC composite hydrogel containing HAP NPs will be suitable for bone regeneration as an injectable hydrogel.

由于热可逆水凝胶在药物输送和组织工程中的潜在性能，因此已在生物医学研究领域进行了广泛研究。在这项研究中，通过原位形成盐的前体盐在MC溶液中引起盐析作用的原位制备方法，制备了一种基于磷酸钙纳米颗粒（CaP NPs）的新型热敏甲基纤维素（MC）水凝胶。基于Hofmeister系列，CaCl ₂，Na ₂ HPO ₄和NaH ₂ PO ₄具有良好盐析效果的前体盐用作CaP NP的前体盐。盐的加入促进了MC溶液的凝胶化，其作用随盐的种类而变化。当将具有两种不同Ca / P比（0.8 / 1和1.6 / 1）的CaP前体盐添加到MC溶液中时，以1.6 / 1 Ca / P比形成更具弹性的MC水凝胶。CaP NP呈矩形（40–50 nm）形状，并均匀分布在MC凝胶中。X射线衍射（XRD）观察表明，磷酸二氢钙脱水物（DCPD）和磷酸八钙（OCP）以0.8 / 1 Ca / P比合成，而DCPD以1.6 / 1 Ca / P比合成。这表明具有不同结晶相的CaP NP处于原位根据Ca / P比和pH条件（pH 7.4，9.0）合成。此外，随着pH值更改为碱性区域，DCPD和OCP晶相转变为羟基磷灰石（HAP）晶相。因此，所得的包含HAP NP的MC复合水凝胶将适合作为注射水凝胶用于骨再生。