Multifunctional ZnO-based nanocomposite hydrogel for treating peri-implantitis

Introduction:: Utilization of dental implants has become very prominent with almost 500,000 patients getting these implants placed annually in US alone. Despite high clinical success, there are implant-associated challenges such as peri-implantitis (PI). PI is a plaque-mediated pathological disease which results in soft tissue inflammation, bone resorption and implant failure. Current treatment strategies

include surgical intervention to support regeneration of the lost tissue while preventing infection. In this study, we propose development of ECM-mimicking, photo-crosslinkable, adhesive nanocomposite hydrogel with multifunctional attributes: bone formation, reducing inflammation and combating infection.


Materials and Methods:: Zinc oxide tetrapods (ZnO-T) were synthesized by flame transport method and characterized to confirm shape and size. Cell-laden hydrogels containing ZnO-T were prepared by encapsulating 5x10⁶cells/ml hBM-MSCs in 5wt% GelMA. Samples were cultured in osteogenic media for 21 days and cell functionality was determined. The anti-inflammatory efficacy of ZnO-T was assessed against mouse bone marrow mononuclear cells primed to M1 pro-inflammatory phenotype via relative gene expression of pro-inflammatory markers. The antibacterial efficacy of the GelMA ± ZnO-T was assessed against Porphyromonas gingivalis using ATP and total biomass. Samples without ZnO-T were used as controls. Statistical significances (p< 0.05) were assessed by one-way ANOVA with Tukey post hoc tests.

Results, Conclusions, and Discussions:: SEM analysis (a) confirmed the tetrahedral nature of ZnO-T. Incorporation of the tetrapods did not alter physico-mechanical properties of the hydrogel (b,c) but significantly upregulated osteogenic differentiation (e). Treatment of M1 macrophages with ZnO-T results in significant reduction of CD80 and TNFα relative to vehicle treated control (d). Antibacterial assessment of different hydrogel
formulations demonstrated the ability of ZnO-T containing systems to inhibit bacterial growth in a dose dependent manner.

In this study we engineered multifunctional ZnO-T nanocomposite hydrogel which can support bone formation while tuning down the inflammatory response and combating infection thus presenting a therapeutic approach to support aseptic bone regeneration for treating PI.

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