摘要/Abstract
摘要： 目的 ·将有机药物与无机粒子相结合并赋予水凝胶以治疗功能，构建可以促进骨缺损再生的有机 -无机双效骨诱导复合水凝胶。方法 ·制备同时负载有机药物维生素 D3以及无机粒子磷酸钙纳米粒的脂质体 (vitamin D3&calcium phosphate nanoparticlesliposomes，VD3&CaP-Lip)，并通过动态光散射粒度分析仪、透射电子显微镜、扫描电子显微镜、高效液相色谱仪对其粒径、电位、形态学以及体外释放特性进行观察；进一步将上述脂质体与甲基丙烯酸酐修饰的明胶 (gelatin-methacrylic，GelMA)水凝胶相结合制备复合水凝胶（ VD3&CaP-Lip@Gel），并通过扫描电子显微镜、高效液相色谱仪、 CCK-8试剂盒、细胞活 /死染色、碱性磷酸酶 (alkaline phosphatase，ALP)活力测定、 ALP染色、茜素红 S染色、茜素红定量分析对该复合水凝胶的形态学、体外释放特性、体外矿化能力、细胞相容性、细胞黏附性以及体外促成骨能力进行观察。结果 ·成功构建了 VD3&CaP-Lip@Gel水凝胶。体外释放结果显示，该复合水凝胶可在局部持续释放维生素 D3约 17 d。形态学观察结果显示，该水凝胶有着良好的形态学特征，在模拟体液中可以促进体外生物矿化。细胞实验结果显示，该复合材料有着良好的细胞相容性以及细胞黏附性；相较于阴性对照组、阳性对照组以及 GelMA组，其具备明显的体外促成骨分化能力。结论 ·所构建具有骨诱导性的有机 -无机双效复合水凝胶可实现药物及纳米粒子的体外局部长期释放，可明显在体外促进成骨分化、加速骨再生过程。
关键词: 水凝胶, 脂质体, 骨再生, 磷酸钙纳米粒
Abstract:
Objective · To construct the dual-functional organic/inorganic composite hydrogel with osteoinductivitycombined organic medicinal therapy with inorganic nanoparticle treatment into make hydrogel more functional in clinical application and more efficient for bone regeneration research. Methods · Liposomes simultaneously loaded with organic drug vitamin D3 and inorganic calcium phosphate nanoparticles were prepared, and dynamic light scattering (DLS), transmission electron microscopy(TEM), scanning electronmicroscopy (SEM), hightperformance liquid chromatography (HPLC) were utilized to explore the particle size, zeta potential, morphology and release property of these composite nanocarriers. Further, composite hydrogels (VD3&CaP-Lip@Gel) with the ability of osteoinductivity were fabricatedincorporating these composite nanocarriers with gelatinmethacrylic (GelMA) hydrogel, and the morphology, drug release property, mineralization, cytocompatibility, cell adhesion and osteogenic differentiation of these compound hydrogels were investigatedSEM, HPLC, CCK-8 kit, live&dead staining, alkaline phosphatase (ALP) activity assay,ALPstaining, alizarin red S staining and alizarin red S quantitative analysis. Results · The VD3&CaP-Lip@Gel was successfully constructed. According to the results of drug release, the hydrogel could continuously release vitamin D3 for 17 days in situ. The results of morphology exhibited that these hydrogels possessed excellent morphological characteristics and could promote mineralization in simulated body fluid (SBF) solution. Comparing with the negative control group, positive control group and GelMA group, the composite hydrogel revealed remarkable capability in cytocompatibility and osteogenic differentiation in vitro experiments. Conclusion · The dual-functional organic/inorganic osteogenetic hydrogel has been successfully constructed with the ability in long-term release of drug and inorganic nanoparticles in situ, which is able to promote bone regeneration in vitro.
Key words: hydrogel, liposome, bone regeneration, calciumphosphate nanoparticle (Cap)
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