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 2 implants: 1 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 *

Effects of Titanium Corrosion Products on In Vivo Biological Response: A Basis for the Understanding of Osseointegration Failures Mechanisms

“…In the context of this early inflammation and considering the nature of both connective tissues, the subcutaneous model is viable to understand the general features of the inflammatory response and/or FBR to the corroded biomaterial. However, titanium implantation follows a well-orchestrated inflammatory response that ultimately leads to bone apposition in osseointegration model (Davies, 2003;Wheelis et al, 2021), while in connective tissue, it leads to a well-organized capsule with no evidence of FBGC (Biguetti et al, 2019;Wheelis et al, 2020). Thus, the gradual differentiation of bone cells and bone deposition is another sophisticated step that required additional investigation in this study.…”

“…When Ti is compared with copper, the resulting connective tissue capsule around copper displayed a higher amount of macrophages and FBGC and higher levels of proinflammatory cytokines (Suska et al, 2003). In previous studies, cpTi disk implantation in subcutaneous tissue was followed by a mild and transitory inflammatory response (Biguetti et al, 2019;Wheelis et al, 2020), and a well-tolerated response has also been shown with modified Ti alloys (silver thiolate-modified Ti) (Tîlmaciu et al, 2015). Accordingly, our results from control cpTi groups implanted in subcutaneous tissue demonstrated a constructive and mild inflammation along with gradual deposition and remodeling of the collagenous matrix in subcutaneous tissue, with no evidence of FBGC formation (Figure 3).…”

“…Next, control and corroded cpTi disks were implanted in the subcutaneous tissue of mice. Interestingly, the reaction of soft tissue surrounding metallic implants has been previously evaluated comparing Ti-based biomaterials with different type of materials (Suska et al, 2003) or coatings (Wheelis et al, 2020) in rats, modified Ti alloys (silver thiolatemodified Ti) (Tîlmaciu et al, 2015), and pharmacologic treatments following cpTi-disk implantation in mice (Biguetti et al, 2019). When Ti is compared with copper, the resulting connective tissue capsule around copper displayed a higher amount of macrophages and FBGC and higher levels of proinflammatory cytokines (Suska et al, 2003).…”

“…RT-PCR array reactions were performed as previously described . Extraction of the total RNA from mouse tissues and complementary DNA synthesis were performed following methods previously described for oral osseointegration and subcutaneous implantation (Biguetti et al, 2019;Wheelis et al, 2021;Wheelis et al, 2020). The total RNA was extracted by using RNeasy kit (Qiagen Inc., Valencia, CA, United States), and the integrity of RNA samples was checked by 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA, United States).…”

Biobanked human foreskin epithelial cell sheets reduce inflammation and promote wound healing in a nude mouse model

“…CD68-positive cells were mostly expressed in macrophages and a large amount of macrophages infiltration in the early stage of transplantation would lead to collagen deposition and scar formation. Many studies have shown that reducing macrophage infiltration or regulating macrophage polarization can reduce inflammatory response and promote tissue repair [ 26 ]. On the other hand, we detected more P63 positive cells in the cryopreserved ECSs, which was conducive to epithelial regeneration.…”