Naringenin-polyethylene glycol coating of titanium enhances biological seal-related functions of gingival fibroblasts under inflammatory challenge

The formation and maintenance of a biological seal between the peri-implant soft tissue and the titanium (Ti) abutment are critical for preventing peri-implant disease and ensuring implant longevity. However, this seal is fragile and prone to breakdown, particularly under inflammatory conditions. This study aimed to investigate the potential of a polyethylene glycol (PEG) coating associated to a bioactive flavonoid naringenin (NA) to enhance human gingival fibroblast (HGF) functions related to biological sealing on Ti surfaces. Initially, the effects of NA (10 µg/mL) on HGF proliferation, adhesion, and collagen synthesis were assessed under tumor necrosis factor alpha (TNF-α)-induced inflammatory challenge. Subsequently, Ti discs were coated with PEG or PEG incorporated with 10 µg/mL (v/v) of NA, and their surface morphology, chemical composition, and NA release profiles were evaluated. HGF responses, including viability, adhesion/spreading, matrix metalloproteinases (MMPs) and collagen production, were analyzed on the coated discs in the presence or absence of TNF-α-challenge. The results demonstrated that NA enhanced critical cellular processes underlying biological seal formation, including cell proliferation, adhesion, and collagen synthesis, while Ti discs were successfully coated with PEG-NA, which enabled rapid NA release. Moreover, the Ti/PEG-NA coating improved HGF viability and collagen synthesis while reducing TNF-α-induced MMP-2 and MMP-9 production. These in vitro findings underscore the potential of the PEG-NA coating to modulate HGF adhesion and metabolism, representing a promising strategy to enhance soft tissue integration and, consequently, long-term implant stability.