Developing adequate biomaterials to engineer cell-scaffold interactions has become a promising way for physically regulating the biological behaviors of cells in the field of tissue engineering. Biopolymeric hydrogels have shown great merits as cellular scaffolds due to their biocompatible and biodegradable characteristics. In particular, the advent of atomic force microscopy (AFM) provides a powerful tool for characterizing native specimens at the micro/nanoscale, but utilizing AFM to investigate the detailed structures and properties of hydrogel scaffolds has been still scarce. In this paper, hybrid natural biopolymers are used to form hydrogel scaffolds which exhibit tunable structural and mechanical properties characterized by AFM peak force tapping imaging, and the applications of the formed hydrogel scaffolds in tissue engineering are studied. AFM morphological images showed that the cross-linking reactions of sodium alginate and gum arabic via calcium cations yielded the porous hydrogel scaffolds. By altering the component ratios, AFM mechanical images showed that the porous and mechanical properties (Young's modulus and adhesion force) of the hydrogel scaffolds were tunable. Next, the nanoscale structural and mechanical dynamics of the fabricated hydrogel scaffolds during the degradation process were revealed by AFM peak force tapping imaging. The experimental results on three different types of cells showed that the fabricated hydrogel scaffolds facilitate the formation of cellular spheroids. The research provides a novel idea to design tunable hydrogel scaffolds based on AFM characterizations for investigating cell-scaffold interactions, which will have potential impacts on tissue engineering.

This work was published on IEEE Transactions on Nanobioscience 18.4(2019):597-610.