Modularized bioceramic scaffold/hydrogel membrane hierarchical architecture beneficial for periodontal tissue regeneration in dogs

BACKGROUND: Destruction of alveolar bone and periodontal ligament due to periodontal disease often requires surgical treatment to reconstruct the biological construction and functions of periodontium. Despite significant advances in dental implants in the past two decades, it remains a major challenge to adapt bone grafts and barrier membrane in surgery due to the complicated anatomy of tooth and defect contours. Herein, we developed a novel biphasic hierarchical architecture with modularized functions and shape based on alveolar bone anatomy to achieve the ideal outcomes. METHODS: The integrated hierarchical architecture comprising of nonstoichiometric wollastonite (nCSi) scaffolds and gelatin methacrylate/silanized hydroxypropyl methylcellulose (GelMA/Si-HPMC) hydrogel membrane was fabricated by digital light processing (DLP) and photo-crosslinked hydrogel injection technique respectively. The rheological parameters, mechanical properties and degradation rates of composite hydrogels were investigated. L-929 cells were cultured on the hydrogel samples to evaluate biocompatibility and cell barrier effect. Cell scratch assay, alkaline phosphatase (ALP) staining, and alizarin red (AR) staining were used to reveal the migration and osteogenic ability of hydrogel membrane based on mouse mandible-derived osteoblasts (MOBs). Subsequently, a critical-size one-wall periodontal defect model in dogs was prepared to evaluate the periodontal tissue reconstruction potential of the biphasic hierarchical architecture. RESULTS: The personalized hydrogel membrane integrating tightly with the nCSi scaffolds exhibited favorable cell viability and osteogenic ability in vitro, while the scratch assay showed that osteoblast migration was drastically correlated with Si-HPMC content in the composite hydrogel. The equivalent composite hydrogel has proven good physiochemical properties, and its membrane exhibited potent occlusive effect in vivo; meanwhile, the hierarchical architectures exerted a strong periodontal regeneration capability in the periodontal intrabony defect models of dogs. Histological examination showed effective bone and periodontal ligament regeneration in the biomimetic architecture system; however, soft tissue invasion was observed in the control group. CONCLUSIONS: Our results suggested that such modularized hierarchical architectures have excellent potential as a next-generation oral implants, and this precisely tuned guided tissue regeneration route offer an opportunity for improving periodontal damage reconstruction and reducing operation sensitivity.