Investigation of the Early Healing Response to Dicationic Imidazolium-Based Ionic Liquids: A Biocompatible Coating for Titanium Implants

Abstract

Dicationic imidazolum-based ionic liquids with amino acid anions (IonL) have been proposed as a multifunctional coating for titanium dental implants, as their properties have been shown to address multiple early complicating factors while maintaining host cell compatibility. This study aims to evaluate effects of this coating on host response in the absence of complicating oral factors during the early healing period using a subcutaneous implantation model in the rat. IonLs with the best cytocompatibility and antimicrobial properties (IonL-Phe, IonL-Met) were chosen as coatings. Three different doses were applied to cpTi disks and subcutaneously implanted into 36 male Lewis rats. Rats received two implants: one coated implant on one side and an uncoated implant on the contralateral sides (n = 3 per formulation, per dose). Peri-implant tissue was evaluated 2 and 14 days after implantation with H&E staining and IHC markers associated with macrophage polarization as well as molecular analysis (qPCR) for inflammatory and healing markers. H&E stains revealed the presence of the coating, blood clots, and inflammatory infiltrate at 2 days around all implants. At 14 days, inflammation had receded with more developed connective tissue with fibroblasts, blood vessels in certain doses of coated and uncoated samples with no foreign body giant cells. This study demonstrated that IonL at the appropriate concentration does not significantly interfere with healing and Ti foreign body response. Results regarding optimal dose and formulation from this study will be applied in future studies using an oral osseointegration model.