A hierarchical Bilayered scaffold for periodontal complex structure regeneration.

The periodontal tissue comprises alveolar bone, cementum, and periodontal ligament (PDL), forming a highly hierarchical architecture. Although current therapies could regenerate the hard tissue well, the simultaneous reconstruction of hard and soft tissue remains a great clinical challenge with the major difficulty in highly orientated PDL regeneration. Using the unidirectional freeze-casting method and biomimetic mineralization technique, we construct a hierarchical bilayer scaffold with the aligned chitosan scaffold with ZIF-8 resembling PDL, and intrafibrillarly mineralized collagen resembling alveolar bone. The hierarchical bilayer scaffold exhibits different geomorphic clues and chemical microenvironments to realize a perfect simulation of the natural periodontal hierarchical architecture. The aligned scaffold with ZIF-8 could induce the fibrogenic differentiation of bone mesenchymal stromal cells (BMSCs), and the mineralized scaffold could induce osteogenic differentiation of BMSCs. The hierarchical bilayer scaffold could simulate periodontal complex tissue, exhibiting great promise for synchronized multi-tissue regeneration of periodontal tissue.