Ceramic-Inspired Moldable Osteogenic Paste For Alveolar Bone Regeneration

Aim or purpose: Current alveolar bone defect treatments rely on coagulation-dependent stabilization, limiting efficacy in patients with clotting disorders. This study aimed to develop a ceramic-inspired osteogenic (CIO) hydrogel for moldable, rapid-curing, and coagulation-independent bone regeneration. Materials and methods: CIO hydrogel composed of gelatin methacrylate (GelMA), nanoclay (Laponite), and synthetic apatite was tested in New Zealand albino rabbits (male, 2.5-3 kg) and cynomolgus monkeys (male, 5 kg) with critical-sized cranial/alveolar defects. Ethics approvals: JGLI-20230710 (rabbits) and PL21-0613-1 (monkeys). Hydrogel rheology, mechanical strength, cytocompatibility, and osteogenic differentiation were assessed via SEM, FTIR, rheometry, and CCK-8/ALP assays. Bone regeneration was evaluated using micro-CT, histology (H&E, Masson’s trichrome), and biochemical analysis over 6 months. Results: CIO hydrogel exhibited shear-thinning behavior (15 s UV curing), enhanced compressive strength (1.5-fold vs. GelMA-L, p<0.001), and promoted MSC proliferation/osteogenesis (ALP activity: 3.2-fold vs. control, p<0.001). In rabbits, CIO achieved 82% BV/TV vs. 28% in controls (p<0.01). Monkey alveolar defects showed regenerated bone with comparable BMD (1.12±0.15 g/cm³) and trabecular structure (Tb.Th: 0.21±0.03 mm) to autologous bone (p>0.05). Conclusions: The CIO hydrogel enables moldable, rapid stabilization of bone grafts, overcoming coagulation limitations and restoring complex alveolar defects. Preclinical results validate its safety and efficacy, supporting future clinical translation for personalized bone regeneration.