Alginate hydrogels are frequently used in 3D bioprinting and tissue repair and regeneration. Establishing the structure–property–performance correlation of these materials would benefit significantly from high-resolution structural characterization in aqueous environments from the molecular level to continuum. This study overcomes technical challenges and enables high-resolution atomic force microscopy (AFM) imaging of hydrated alginate hydrogels in aqueous media. By combining a new sample preparation protocol with extremely gentle tapping mode AFM imaging, we characterized the morphology and regional mechanical properties of the hydrated alginate. Upon cross-linking, basic units of these hydrogel materials consist of egg-box dimers, which assemble into long fibrils. These fibrils congregate and pile up, forming a sponge-like structure, whose pore size and distribution depend on the cross-linking conditions. At the exterior, surface tension impacts the piling of fibrils, leading to stripe-like features. These structural features contribute to local, regional, and macroscopic mechanics. The outcome provides new insights into its structural characteristics from nanometers to tens of micrometers, i.e., at the dimensions pertaining to biomaterial and hydrogel–cell interactions. Collectively, the results advance our knowledge of the structure and mechanics from the nanometer to continuum, facilitating advanced applications in hydrogel biomaterials.

中文翻译：

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水性介质中海藻酸盐水凝胶材料的高分辨率原子力显微镜研究


海藻酸盐水凝胶经常用于 3D 生物打印和组织修复和再生。建立这些材料的结构-性能-性能相关性将大大受益于从分子水平到连续体的水环境中的高分辨率结构表征。这项研究克服了技术挑战，并能够对水性介质中的水合海藻酸盐水凝胶进行高分辨率原子力显微镜 （AFM） 成像。通过将新的样品制备方案与极其温和的轻敲模式 AFM 成像相结合，我们表征了水合藻酸盐的形态和区域机械特性。交联后，这些水凝胶材料的基本单元由蛋盒二聚体组成，蛋盒二聚体组装成长原纤维。这些原纤维聚集并堆积，形成海绵状结构，其孔径和分布取决于交联条件。在外部，表面张力会影响原纤维的堆积，导致条纹状特征。这些结构特征有助于局部、区域和宏观力学。该结果为其从纳米到数十微米的结构特征提供了新的见解，即与生物材料和水凝胶-细胞相互作用有关的尺寸。总的来说，这些结果将我们对结构和力学的了解从纳米推进到连续体，促进了水凝胶生物材料的高级应用。