Autophagy Regulation in Oral Tissue Regeneration: A Review of Biological Scaffolds and Nanoparticles

Specially designed biological scaffolds have been developed to facilitate oral tissue regeneration through the regulation of autophagy. For instance, a previous study [191] demonstrated the potential of 3D-printed Sr5(PO4)2SiO4 (SPS) bioactive ceramic scaffolds in promoting the regeneration of cartilage and subchondral bone. This was achieved by activating the Wnt and autophagy pathways while inhibiting the hedgehog pathway. Another study [192] showed that strontium-substituted 45S5 bioglass could enhance bone regeneration in osteoporotic bone defects by enhancing autophagy at early stages and activating the Akt-mTOR pathway at later stages.

Recently published research [193] has highlighted the effectiveness of well-designed chitosan nanoparticles loaded with minocycline in protecting against oral pathogens and inducing autophagic activity in cells, without interfering with cytoskeletal organization or increasing cell death. The activation of autophagy further enhances the therapeutic potential of chitosan nanoparticles, which facilitate periodontal tissue regeneration.

Other nanoparticles have also demonstrated size-dependent effects on periodontal tissue regeneration [194], [195]. For example, 13- and 45-nm gold nanoparticles were found to promote osteogenic differentiation of periodontal ligament stem cells by activating autophagy [194], while BMP-2 plasmid encapsulated polyethyleneimine-modified porous silica nanoparticles stimulated autophagy and promoted osteogenesis and bone regeneration in MC3T3-E1 cells [195].

Platelet-rich plasma/fibrin (PRP/PRF) is considered one of the most reliable autologous biomaterials for oral tissue regeneration. Recent studies [197], [198] have shown that PRP/PRF strongly activates autophagy and promotes the expression of LC3B and Beclin-1 in human dental pulp stem cells and periodontal ligament stem cells. Inhibition of autophagy suppresses PRP-induced stem cell proliferation, migration, and osteogenic differentiation, while autophagy activation substantially augments PRP-stimulated stem cell ability.