Development of a Three-dimensional Smart Electroconductive Hydrogel as an Advanced Strategy for Peri-implant Infection Control

Abstract

Despite the growing advances in dental implants for the rehabilitation of missing teeth, the increasing incidence of peri-implant diseases reflects the limitation of current therapies in controlling biofilm and stimulating bone regeneration. Thus, the present study aims to develop a new multifunctional strategy for the control of peri-implant infections by creating an injectable electroconductive hydrogel of gelatin methacryloyl (GelMA) loaded with polypyrrole (PPy) and zinc (Zn), and to evaluate its physicochemical, mechanical, microbiological, immunomodulatory, and biological properties. In this work, injectable GelMA hydrogels will be used as an osteogenic three-dimensional platform to be loaded with zinc oxide, which has shown excellent performance in bacteria elimination and immunomodulatory properties. Additionally, to elevate the biomaterial to a more intelligent level, the incorporation of the conductive polymer PPy will allow for both bone formation and biofilm elimination through electrical stimulation (ES). For this purpose, hydrogels with different formulations of PPy + Zn will be developed and characterized regarding their composition, morphology, mechanical, and electrical properties. Computational simulations will be employed to optimize their physicochemical properties. Subsequently, the effect of ES and hydrogel on ionic release, reactive oxygen species generation, cytocompatibility, and antimicrobial activity will be evaluated. The viability, proliferation, differentiation, and mineralization of cells will be tested in vitro in murine pre-osteoblastic cells. Immunomodulatory effects will be investigated through macrophage polarization assays. Furthermore, the in vitro antimicrobial activity of the hydrogels will be tested against polymicrobial biofilms. To confirm the in vitro antimicrobial effect, the antimicrobial action of the hydrogels in oral environment conditions (in situ) will be evaluated. Quantitative data will be subjected to appropriate statistical analysis with a significance level of 5%. By enhancing the 3D porous architecture of GelMA hydrogel with the antibacterial/immunomodulatory effect of zinc and the broad-spectrum antimicrobial and osteogenic activity of PPy activated by ES, it is expected that the proposed innovative smart biomaterial in this study has the potential to be considered a promising and intelligent treatment modality for the control of peri-implant infections. (AU)