Fabrication and in vitro biological activity of functional pH-sensitive double-layered nanoparticles for dental implant application

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Abstract
Sufficient bone mass plays a vital role in dental implant fixation and durability. However, bone deficiency is common clinically, and peri-implant infection causes alveolar bone to further resorb. Therefore, inhibiting bone resorption and promoting peri-implant bone regeneration are highly desirable. For this purpose, functional pH-sensitive double-layered nanoparticles were fabricated for application on dental implant surface. These double-layered nanoparticles were composed of a poly(L-lactic acid) inner layer and a chitosan outer shell. Recombinant human bone morphogenetic protein-2-loaded poly(L-lactic acid) nanoparticles were prepared by the emulsification-solvent evaporation method. Osteoprotegerin was conjugated to the chitosan backbone via a pH-sensitive hydrazone bond. The release profile consisted of an initial fast release and a more continuous slow release for at least 30 days. Moreover, the cumulative osteoprotegerin release increased significantly with decreasing pH (p < 0.05). The results from biological studies indicated that the double-layered nanoparticles could inhibit the generation of osteoclasts, recruit bone marrow-derived mesenchymal stem cells (BMSCs), and promote BMSCs to differentiate into osteoblasts. Meanwhile, the inhibitory effect on osteoclasts increased with decreasing pH (p < 0.05). It can be concluded that the pH-sensitive double-layered nanoparticles, which had a significant effect on inhibiting bone resorption and promoting bone regeneration, are ideal nanoparticles to be applied on dental implant surface.
Funding Information
  • Natural Science Foundation of Jiangsu Province (BK20170115)
  • China Japan Sasakawa Medical Fellowship
  • National Natural Science Foundation of China (51371006, 81901046)

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