Among the biomaterials used for the development of long-term implantable devices, titanium has become the material of choice due to its superior chemical and mechanical properties. In recent years, immunomodulation has been studied as an emerging approach to regulate inflammatory events caused by implant placement to improve osseointegration and promote healing. Surgical trauma following implantation results in the release of DAMPs (Damage Associated Molecular Patterns) like High Mobility Group Box 1 (HMGB1) protein, which can trigger immune inflammation due to cell stress, or tissue damage. Imidazolium-based ionic liquid (IonL) coatings with amino-acid- based anions are known to be biocompatible and cleared by immune cells within two weeks. Therefore, to harness the constructive inflammatory influence of DAMPs, HMGB1 is immobilized via an IonL coating on the surface of titanium implants which can modulate healing towards repair and osseointegration. Here we use molecular dynamics computer simulations to provide a molecular scale understanding of the IonL-HMGB1-Ti interactions, binding mechanisms and possible molecular arrangements under physiologically relevant conditions. We investigate the structural and dynamic properties of the IonL-solid interface in detail to explain the stability of the IonL coating on the surface. We observe that HMGB1 interacts with the TiO2 surface through IonL-mediated forces. In contrast, HMGB1 was observed to bind directly and irreversibly to the TiO2 surface in water. The well-structured strongly bound IonL coating formed on the TiO2 surface effectively blocks HMGB1 from binding directly to the surface. Additionally, some IonL cations and anions bind to oppositely charged amino acids on the protein surface will help immobilize the protein and further protect the protein from direct adsorption to the TiO2 surface. Once the coating is in contact with water, the considered IonLs dissolve in water and facilitate the transition of the protein from the IonL phase to the aqueous phase. When the protein is released over time, the adsorbed IonL molecules leave the surface of the protein and the binding sites of HMGB1 to its receptors were found to be accessible. These findings will allow the development of a unique surface strategy to improve the clinical outcome of titanium-based implant systems.

Immunomodulatory surface approach for titanium implants

ACS Fall 2021

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