3D-Bioprinted Photothermal Scaffold Enhanced Alveolar Bone Regeneration in Rats

Objectives: The aim of this study was to develop a 3D-printed photothermal scaffold and to determine its osteogenic effect on alveolar bone regeneration.
Methods: To achieve this, a scaffold composed of alginate and PVA incorporating Fe₃O₄ nanoparticles was developed and 3D printed. The physicochemical characterization and photothermal profile analysis of the scaffold with different Fe₃O₄ concentrations were conducted. The osteogenic effect of the photothermal scaffold was evaluated using osteoblast cultures subjected to NIR laser application for 2 minutes, twice a week, over 14 days. In an exodontia model, the first upper molars of Wistar rats were extracted. Later, the scaffold was inserted intra-alveolarly, and NIR laser therapy was applied for 2 minutes, twice a week, over 30 days. Subsequently, the animals were euthanized, and the maxillae were collected for analysis of bone microarchitecture, metabolism, and quality.
Results: The physicochemical characterization revealed that Fe₃O₄ scaffolds at 350 µg/ml demonstrated good printability, swelling capability and degradability. Under 100 mW radiation for 2 minutes, the scaffold reached a temperature of 41.36 ± 2.4°C. In vitro studies showed that mild photothermal therapy (MPT) stimulated osteoblast proliferation and alkaline phosphatase activity. In vivo, the scaffold subjected to MPT increased the number of osteoblasts (75%) and blood vessels (50%) within the alveolus, and enhanced bone quality and strength (p<0.05) while attenuating inflammatory infiltration. Improved bone regeneration was linked to the activation of the Wnt signaling pathway, with increased gene expression of wnt10b and beta-catenin and a reduction in DKK-1, compared to the non-photothermal scaffold.
Conclusions: In summary, this study demonstrated that the 3D-printed photothermal scaffold exhibited superior physical properties, promoted enhanced cell viability and alkaline phosphatase activity, and improved bone regeneration, showing great potential for personalized bone regeneration treatments.