Investigating Adsorption of Enamel Matrix Derivative (EMD) at Implant Relevant Interfaces

Abstract

Dental implants are widely used as a treatment to restore lost teeth, the success rate is high 95% (Tricio et al., 1995; Bahat, 2000; Jemt, 2008), however, there are some conditions where failure can occur such as peri-implantitis. The success of this treatment is based on the contact and bone bridge that forms between the implant surface and surrounding bone, which is known as osseointegration. The titanium (Ti) dental implant is the most common material used because it has high biocompatibility and appropriate mechanical properties. Several surface modifications on the Ti dental implant surface have been applied to improve treatment outcome; physicochemical and topographical modifications have improved efficacy of the osseointegration. The degree of osseointegration is in part modulated by the cellular response in the initial phase of healing. Recently, the use of bioactive agents on the dental implant surface to enhance the cellular response and bone formation has been investigated. Enamel matrix derivative (EMD) is a bioactive agent and Emdogain®, a commercial preparation, produced by Straumann®, is used to regenerate the periodontal tissues including bone. Despite EMD proven efficacy clinically, the mechanism of action is not fully understood. Investigating the EMD interactions and properties at a molecular level can enhance the understanding of its capability, efficacy and expand its use with a dental implant. This project aims to investigate the EMD interactions and properties as a bioactive coating at a molecular level through study the adsorption on Ti surfaces to optimize delivery doses. Also, an aim to investigate the osteogenic cellular response to this coating. The adsorption mass and rate were quantified by quartz crystal microbalance (QCM). EMD was adsorbed on Ti under different concentrations, temperatures, and neutral pH. The results showed that EMD adsorption mass increased as the concentration increase until a specificlimit, the concentration 0.1 mg/ml, and the well-attached adsorption mass does not increase at higher concentrations. This indicates that EMD molecules at this concentration can aggregate, acquire a specific size and properties that allow them to be adsorbed on the Ti surface forming a dense and stable coating. EMD adsorbed equally at 25°C and 37°C separately, suggesting similar adsorption behaviour under these conditions. Thus, changing the working temperature on the adsorbed EMD layer from 25°C to 37°C has no significant effect. This promotes the potential clinical application of EMD on the dental implant surface before implantation within the jawbone. Experiments were conducted under neutral pH to enhance EMD aggregation, adsorption and reduce the intermolecular electrostatic repulsion interactions. The adsorption rate of EMD on Ti surfaces was very rapid and increased with raising the EMD concentration, indicating the high affinity and short time to form the coating. The osteogenic cellular response was examined on the Ti coated with EMD 0.1 mg/ml, with two cell lines MG-63 and MC3T3-E1. The results showed that EMD coating on Ti surfaces did not influence cell response however, and importantly, it does not suppress or affects the cells negatively and this occurs with both cell lines. This can be related to multiple factors that can mediate cell activity such as cell type or surface properties. This work contributes to the understanding of EMD interactions with Ti. Further future work is required to recognize and standardise the use of EMD as a coating in dental implant research. This will provide a better understanding of the EMD interactions and the mechanism of action.