Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Cavendish Laboratory, Department of Physics, University of Cambridge, J J Thomson Avenue, Cambridge, CB3 0HE, UK.
Sci Rep. 2021 Mar 23;11(1):6673. doi: 10.1038/s41598-021-85199-1.
Microcapsules and microgels consisting of macromolecular networks have received increasing attention due to their biomedical and pharmaceutical applications. Protein microgels and in particular silk-based microcapsules have desirable properties due to their biocompatibility and lack of toxicity. Typically such structures formed through emulsion templating are spherical in geometry due to interfacial tension. However, approaches to synthesis particles with more complex and non-spherical geometries are sought due to their packing properties and cargo release characteristics. Here, we describe a droplet-microfluidic strategy for generating asymmetric tubular-like microgels from reconstituted silk fibroin; a major component of native silk. It was determined using fluorescence microscopy, that the shear stress within the microchannel promotes surface protein aggregation, resulting in the asymmetric morphology of the microgels. Moreover, the structural transition that the protein undergoes was confirmed using FTIR. Crucially, the core of the microgels remains liquid, while the surface has fully aggregated into a fibrillar network. Additionally, we show that microgel morphology could be controlled by varying the dispersed to continuous phase flow rates, while it was determined that the radius of curvature of the asymmetric microgels is correlated to the wall shear stress. By comparing the surface fluorescence intensity of the microgels as a function of radius of curvature, the effect of the shear stress on the amount of aggregation could be quantified. Finally, the potential use of these asymmetric microgels as carriers of cargo molecules is showcased. As the core of the microgel remains liquid but the shell has gelled, this approach is highly suitable for the storage of bio-active cargo molecules such as antibodies, making such a delivery system attractive in the context of biomedical and pharmaceutical applications.
由于在生物医学和制药方面的应用，由高分子网络组成的微胶囊和微凝胶受到了越来越多的关注。由于其生物相容性和无毒特性，蛋白质微凝胶，尤其是丝素基微胶囊，具有理想的特性。通常，通过乳液模板形成的这种结构由于界面张力而在几何形状上是球形的。然而，由于其堆积特性和货物释放特性，人们正在寻求合成具有更复杂和非球形几何形状的颗粒的方法。在这里，我们描述了一种从重组丝素蛋白（天然丝的主要成分）生成不对称管状微凝胶的液滴微流控策略。使用荧光显微镜确定，微通道内的剪切应力促进了表面蛋白质的聚集，从而导致微凝胶的不对称形态。此外，使用 FTIR 证实了蛋白质经历的结构转变。至关重要的是，微凝胶的核心仍然是液体，而表面已完全聚集形成纤维状网络。此外，我们表明可以通过改变分散相与连续相的流速来控制微凝胶的形态，而确定不对称微凝胶的曲率半径与壁剪切应力相关。通过比较微凝胶的表面荧光强度与曲率半径的关系，可以定量确定剪切应力对聚集量的影响。最后，展示了这些不对称微凝胶作为货物分子载体的潜在用途。由于微凝胶的核心仍然是液体但外壳已经凝胶化，因此这种方法非常适合储存生物活性货物分子，如抗体，因此这种输送系统在生物医学和制药应用中具有吸引力。
