Synthesis, Characterization and Feasibility of a Gelatin Methacryloyl Hydrogel for Naringenin Release—Effect on Osteoblasts In Vitro

Failures in oral implant installation may be associated with elevated concentrations of matrix metalloproteinases (MMPs). The overexpression of these enzymes leads to extensive extracellular matrix degradation, delaying or impairing tissue repair. Moreover, their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs), are often insufficient to counteract pathologically elevated MMP levels. To address this, various MMP-regulating strategies have been explored, including the use of flavonoids such as naringenin (NA), a citrus-derived compound with promising anti-inflammatory effects and MMP downregulation. Additionally, surface modifications of titanium (Ti) implants can enhance tissue response and improve osseointegration. This study aimed to characterize and evaluate the effects of Ti surface modification through alkali treatment and NA-laden gelatin methacryloyl (GelMA) coating on osteoblast (Ob) functions related to peri-implant repair in vitro. Ti discs were alkalinized using 5 M sodium hydroxide (NaOH) at 60°C for 24 h. GelMA hydrogel (15% w/v) containing 0% (control) or 1% NA (w/w) was prepared and applied as a coating. The coatings were characterized for morphology, swelling, degradation, and NA release profile. SAOS-2 osteoblasts (HTB-85) were then cultured on the coated discs, and cell adhesion, viability, and synthesis of MMP-2, MMP-9, TIMP-1, and TIMP-2 were assessed. Data were analyzed by one- or two-way ANOVA and Student's t-test/post hoc tests (α = 0.05). Scanning electron microscopy confirmed successful coating, with the GelMA+NA 1% group showing a more uniform and porous surface compared to GelMA alone. Both formulations displayed similar swelling capacity and degradation profiles over 21 days (p > 0.05). NA release was sustained for 14 days, peaking at 15 h. Cell viability and adhesion were comparable between groups (p > 0.05). Osteoblasts cultured on GelMA and exposed to the inflammatory stimulus tumor necrosis factor-alpha (TNF-α) showed increased synthesis of MMP-2, MMP-9, TIMP-1, and TIMP-2. However, cells cultured on GelMA+NA 1% exhibited significantly reduced MMP-2 and MMP-9 levels compared to GelMA under TNF-α stimulation (p < 0.05), with no significant changes in TIMP-1 or TIMP-2. In summary, Ti surface modification through alkali treatment followed by GelMA/NA coating was cytocompatible, showed controlled degradability, sustained NA release, and downregulated MMP synthesis in osteoblasts. These results suggest its potential as a promising strategy to modulate MMPs, which may help mitigate excessive matrix degradation and favor peri-implant tissue repair.