Functionalization of titanium substrate with multifunctional peptide OGP-NAC for the regulation of osteoimmunology

Abstract

The immune response to an orthopedic implant is closely related to the nearby bone metabolism balance. To modify titanium (Ti) substrates and accordingly regulate the balance between osteoclast activation and osteoblast differentiation, a multifunctional peptide OGP-NAC was synthesized via conjugating an osteogenic growth peptide (OGP) with N-acetylcysteine (NAC). Then, the synthesized peptide was employed to functionalize Ti substrates and the response of both osteoblasts and osteoclasts was investigated in vitro. The results showed that OGP-NAC was successfully prepared and immobilized onto Ti substrate surfaces. Thereafter, studies on introducing RAW 264.7 cells (one kind of monocyte macrophage responsible for immune responses) to osteoclasts demonstrated that the peptide modified Ti surface could inhibit RAW 264.7 cells from secreting important inflammatory cytokines (TNF-α and IL-1β), and suppress the activation of MAPK, NF-κB and NFAT c1, which are important transcription factors for osteoclastogenesis. Meanwhile, the modified surface promoted osteoblast spreading, proliferation and differentiation. The study offers a feasible strategy to mediate the balance between osteoclast activation and osteoblast differentiation, having great potential for improving osseointegration of an orthopedic implant.