基于微流控技术的海藻酸钠微球可控制备与性能

Controllable Preparation and Properties of Sodium Alginate Microspheres Based on Microfluidics

对海藻酸钠(SA)进行氧化,并利用碳二亚胺法使其接枝细胞黏附肽,制得改性海藻酸钠(ROSA)。以ROSA为原料,采用微流控技术可控制备单分散性良好的水凝胶微球。利用倒置光学显微镜、激光共聚焦显微镜等对微球表面形貌及生物相容性进行表征。结果表明:制备出的海藻酸钠微球粒径均一、结构规整,在体外环境4周内完全降解,可有效控释负载的重组人骨形态发生蛋白-2(rhBMP-2),易与细胞黏附,生物相容性良好。

In order to improve the degradability and biocompatibility of sodium alginate(SA),SA was oxidized with sodium periodate and then grafted with cell adhesion peptide by carbodiimide water method.Modified sodium alginate(ROSA)was used as the material to prepare monodispersible water-in-oil droplets by the shear action of continuous relatively dispersed phase in microfluidic technology.After the release of calcium ions in the droplets,the droplets were crosslinked into homogeneous hydrogel microspheres.The structural of SA before and after modification were detected by infrared spectroscopy(FT-IR)and X-ray photoelectron spectroscopy(XPS).The surface morphology and biocompatibility of the microspheres were characterized by inverted optical microscopy and laser confocal microscopy.The most suitable hydrogel microspheres for subsequent biomedical applications were obtained by systematically studying the effect of the fabrication technique on the microsphere properties,and adjusting the flow rates of the dispersed and continuum phases,the degree of oxidation and the mass fraction of the SA.Results showed that the formation of aldehyde group and the detection of nitrogen in ROSA proved the success of the SA material modification.The size of the hydrogel microspheres could be controlled at(50.4±1.3)μm,the coefficient of variation was less than 5%,the monodispersion was good,and the structure shape was regular.The microspheres were completely degraded within 4 weeks in vitro and could effectively control the release of the loaded recombinant human bone morphogenetic protein-2(rhBMP-2).The microspheres showed no obvious cytotoxicity to rat bone marrow mesenchymal stem cells(rBMSCs),and their adhesion to rBMSCs was significantly enhanced,showing good biocompatibility.