Cryogenically direct-plotted alginate scaffolds consisting of micro/nano-architecture for bone tissue regeneration

Alginate, which can be derived from brown seaweed, is a well-known anionic linear polysaccharide. Alginate has been used extensively for tissue regeneration because it accelerates epithelialization and granular tissue formation, as well as encapsulating various growth factors due to its rapid gelation in calcium chloride. Although alginate is a good candidate as a natural tissue engineering material, difficulties in processing and its low mechanical properties as a porous structure remain important limitations. In previous work, we introduced multi-layered scaffolds using natural biomaterials, mainly collagen and chitosan, which were fabricated using a cryogenic direct-plotting process. The fabricated scaffolds showed good cellular activities; however, problems with regards to mechanical properties remained due to the presence of micropores. To overcome this limitation, we developed a new fabrication process that resulted in alginate scaffolds consisting of micropores in the shell and nanopores in the core region of a single strut. These alginate scaffolds exhibited good structural stability and a Young's modulus that was increased tenfold in the dry state in comparison to alginate scaffolds with a homogeneous micropore structure. The hierarchical scaffold showed highly viable cells in vitro, as well as sufficient alkaline phosphatase activity and calcium mineralization for bone tissue regeneration in comparison to a control alginate scaffold, which was fabricated using a conventional freeze-drying method. These results suggest that alginate scaffolds with a hierarchical structure have potential for use in hard tissue regeneration.