An OGP binding protein complex-mimicking peptide hydrogel for dental pulp regeneration

The regeneration of the dentin-pulp complex remains a critical challenge in oral regenerative medicine. Osteogenic growth peptide (OGP) has garnered significant attention due to its theoretical ability to promote the differentiation of human dental pulp stem cells (hDPSCs). However, its clinical potential is limited by rapid diffusion and susceptibility to enzymatic degradation within the tissue microenvironment. Inspired by the natural OGP-OGP binding protein (OGPBP) system, this study reports an OGPBP complex-mimicking peptide hydrogel (Gel Nap-OGP) for dental pulp regeneration. Gel Nap-OGP is obtained via ultraviolet-triggered co-assembly of two rationally designed peptides: an OGP mimetic peptide Nap-Phe-Phe-Glu-Tyr-Gly-Phe-Gly-Gly-OH (NapFFEOGP(10-14)) and an OGPBP mimetic peptide Nap-Phe-Phe-Glu-Lys(acrylamide)-Lys(acrylamide)-OH (NapFFEK(aa)K(aa)). The resulting hydrogel nanofiber network loads NapFFEOGP(10-14) through dynamic non-covalent interactions, effectively preventing the peptide from enzymatic degradation and facilitating its controlled release. In vitro studies demonstrate that Gel Nap-OGP maintained favorable cytocompatibility without significantly affecting hDPSC proliferation, while enhancing osteogenic/odontogenic differentiation, as indicated by increased expression of RUNX2, ALP, and DSPP. Furthermore, in vivo experiments confirm its excellent biosafety, along with its ability to enhance mineralized tissue formation in an ectopic renal capsule model. RNA sequencing analyses further reveal that Gel Nap-OGP can modulate gene expression programs related to classical osteogenic/odontogenic signaling pathways. We anticipate that this biomimetic peptide hydrogel could be applied for dental pulp regeneration in clinical settings in the future.