Enzyme-triggered peptide assembly boosts dental stem cell osteogenic differentiation by enhancing osteogenic...

Tooth regeneration and bone tissue repair represent significant challenges in oral surgery, and osteogenic differentiation is crucial with respect to dental implant osseointegration and bone healing. Studies have reported that osteogenic growth pentapeptide (OGP5) promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts. Owing to their easy availability and multipotent differentiation capabilities, human dental pulp stem cells (hDPSCs) are promising in the context of regenerative medicine and dental therapeutics. However, research on the effects of OGP5 on the differentiation of hDPSCs remains insufficient, and the short half-life and poor targeting of functional small-molecule peptides limit its application. Our findings indicate that OGP5 facilitates the differentiation of hDPSCs into osteoblasts. To increase the efficiency with which OGP5 can induce the osteogenic differentiation of hDPSCs, an amphiphilic peptide (Pep1) with alkaline phosphatase (ALP)-responsive properties was designed and synthesized. The encapsulation of OGP5 led to the self-assembly of OGP5/Pep1 into spherical nanoparticles, which transformed into nanofibers upon ALP induction. Importantly, Pep1 significantly enhanced the accumulation of OGP5 in hDPSCs, thereby promoting the differentiation of hDPSCs into osteoblasts, thus providing a new perspective that can facilitate the development of bone repair and regenerative medicine.