Effect of Ionic Liquid Coatings on Early Healing and Osseointegration of Titanium Implants




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Although titanium (Ti) dental implants are known to achieve high success rates and osseointegration in vivo, a higher incidence of implant failures have been recently reported. Implant failures are caused by several factors; however, the nature and intensity of the inflammatory response at the titanium-tissue interface determines the healing outcome of an implant. Surface modifications performed on titanium implants have attempted to directly address both patient and external factors that interfere with constructive inflammation, but often do not address multiple complications that impact osseointegration while maintaining regenerative healing. Dicationic imidazolium-based ionic liquids (IonL) have demonstrated low toxicity, antimicrobial, lubricant, and anticorrosive activities in vitro making them a potential candidate as a multifunctional dental implant coatings. However, the biological response to these coatings in vivo is unknown. The goal of this dissertation was to evaluate the effect IonLs have on inflammation, healing, and osseointegration of titanium dental implants. This research is divided into three aims (i) to investigate the biocompatibility of IonL in a subcutaneous model, (ii) to define and validate success criteria for an oral implantation model and (iii) to investigate the impact of IonL on early healing and osseointegration in an oral implantation model. In each aim a combination of clinical evaluation, histopathology, immunohistochemistry, molecular analysis, and MicroCT was used to track inflammation and healing from 2-30 days (d) in the Lewis rat. In aim 1, an initial evaluation of both IonL-Phe and IonL-Met indicated that IonL appeared in peri-implant tissues and increased acute inflammation at 2d compared to uncoated Ti. At 14d, inflammation receded with more developed peri-implant tissue in coated and uncoated samples with no foreign body giant cells. IonL was no longer observed at 14d, suggesting elution or resorption by macrophages. This aim demonstrated that medium dose IonL-Phe does not significantly interfere with Ti foreign body response in an aseptic environment. In aim 2, a new pre-clinical oral implantation model defined an appropriate baseline for successful Ti osseointegration. Healing was similar to other rodent models: hematoma and acute inflammation at 2d, initial bone formation at 7d, advanced bone formation and remodeling at 14d, and bone maturation at 30d. Overall, this model resulted in a 78.5% osseointegration success rate (>60% bone-to-implant contact (BIC)), similar to human osseointegration. Therefore, This model combines the advantages of a rodent model while maximizing BIC, making it an excellent candidate for evaluation of IonLs. Following aim 2, a pilot in vivo assessment determined medium dose IonL-Phe demonstrated the best histogical response and BIC for the remaining evaluation. In aim 3, IonL-Phe-coated and uncoated cpTi screws were implanted into several demographic groups of rats to represent biological variations that could affect healing. Molecular and histological analysis indicated IonL heightened acute inflammation compared to uncoated Ti. However, the coating was released/resorbed by 7 days and did not negatively affect subsequent bone remodeling in all demographics. Overall, IonL-Phe coating did not disturb oral Ti osseointegration and may provide additional control over the healing environment in scenarios known to be challenged by bacteria, such as peri-implantitis



Engineering, Materials Science, Biology, General, Health Sciences, Dentistry