Titanium (Ti) has become the material of choice for developing long-term implantable devices due to its superior chemical and mechanical properties. 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. Imidazolium-based ionic liquid (IonL) coatings with amino acid-based anions are known to be biocompatible, therefore, to harness the constructive inflammatory influence of DAMPs, HMGB1 can be immobilized via an IonL coating on the Ti implant surface that can modulate healing toward repair and osseointegration. Here we use GPU-enabled molecular dynamics (MD) simulations to study this novel immunomodulatory approach and provide a molecular-scale understanding of IonL-HMGB1-TiO₂ interactions under physiologically relevant conditions. MD simulations in different IonLs and in water were performed on GPUs using the CUDA-accelerated NAMD software package. We first investigated the IonL-solid interface in detail to explain the stability of the IonL coatings on the TiO₂surface. HMGB1 was observed to bind directly and irreversibly to the TiO₂ surface in water. In contrast, a well-structured, strongly bound IonL coating formed on the TiO₂ surface effectively blocks HMGB1 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 it from direct adsorption to the TiO₂ surface. After implantation, when 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 protein surface 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.

Danieli Rodrigues

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