Autophagy Modulation: A Key to Optimizing Oral Tissue Regeneration with Biomaterials

Platelet-rich plasma/fibrin (PRP/PRF) is a highly reliable autologous biomaterial for oral tissue regeneration. Recent studies (197, 198) have shown that PRP/PRF strongly activates autophagy and promotes LC3B and Beclin-1 expression in human DPSCs and PDLSCs. Inhibition of autophagy suppresses PRP-induced stem cell proliferation, migration and osteogenic differentiation, while autophagy activation substantially enhances PRP-stimulated stem cell ability.

Biomaterials can also enhance odontogenic differentiation in MSCs by modulating autophagy. One study (199) demonstrated that fluorapatite-modified polycaprolactone nanofibers induce human DPSC differentiation and mineralization by activating the hedgehog, insulin, and Wnt signaling pathways that modulate autophagy. Another similar study (200) reported that autophagy modulates DPSC mineralization on fluorapatite crystal-coated electrospun polycaprolactone scaffolds, with LC3-II protein expression peaking on day 7 of odontogenic/osteogenic differentiation.

However, excessive autophagy induced by biomaterials can impair the regenerative abilities of stem cells. For instance, the widely studied bone tissue engineering nanomaterial graphene oxide (GO) exhibits excellent osteoinduction ability and functionalization. Nevertheless, toxic effects of high concentrations of GO on BMMSCs occur in a dose-dependent manner, evidenced by activation of the mitochondrial apoptotic pathway and autophagy (86).

In conclusion, biomaterials have a positive impact on oral tissue regeneration, with autophagy modulation being an important indicator of their properties. However, excessive autophagy induced by biomaterials can also impair stem cell function, highlighting the need for careful consideration in their use.