Molecular-Level Understanding of the Influence of Ions and Water on HMGB1 Adsorption Induced by Surface Hydroxylation of Titanium Implants

Abstract

<div><div><div><p>Due to its excellent chemical and mechanical properties, titanium has become the material of choice for orthopedic and dental implants to promote rehabilitation via bone anchorage and osseointegration. Titanium osseointegration is partially related to its capability to form a TiO<sub>2</sub> surface layer and its ability to interact with key endogenous proteins immediately upon implantation, establishing the first bone-biomaterial interface. Surgical trauma caused by implantation results in the release of High Mobility Group Box 1 (HMGB1) protein, which is a prototypic DAMP (Damage Associated Molecular Pattern) with multiple roles in inflammation and tissue healing. To develop different surface strategies that improve the clinical outcome of titanium-based implants by controlling their biological activity, a molecular-scale understanding of HMGB1-surface interactions is desired. Here, we use molecular dynamics (MD) computer simulations to provide direct insight into the HMGB1 interactions and the possible molecular arrangements of HMGB1 on fully hydroxylated and non-hydroxylated rutile (110) TiO<sub>2</sub> surfaces. The results establish that HMGB1 is most likely to be adsorbed directly onto the surface regardless of surface hydroxylation, which is undesirable because it could affect its biological activity by causing structural changes to the protein. The hydroxylated TiO<sub>2</sub> surface shows a greater affinity for HMGB1 than the non-hydroxylated surface. The water layer on the non-hydroxylated TiO<sub>2</sub> surface prevents ions and the protein from directly contacting the surface. However, it was observed that if the ionic strength increases, the total number of ions adsorbed on the two surfaces increases, and the protein’s direct adsorption ability decreases. These findings will help to understand the HMGB1-TiO<sub>2</sub> interactions upon implantation, as well as the development of different surface strategies by introducing ions or ionic materials to the titanium implant surface to modulate its interactions with HMGB1 to preserve biological function.</p></div></div></div>

Exogenous Protein Delivery of Ionic Liquid-Mediated HMGB1 Coating on Titanium Implants

“…2 Rutile is a thermodynamically stable form of titanium dioxide crystalline polymorph. 3 The rutile (110) surface is the most stable crystalline phase, and the implants with rutile phase exhibit better biocompatibility and osseointegration than the anatase phase implant. 3,4 The bulk of the material used for the implantable device determines its mechanical properties, while its surface characteristics, such as topography and chemical composition, guide favorable biological interactions between the implant and the host tissue.…”

Enhanced Antibacterial Ability and Bioactivity of Polyetherketoneketone Modified with LL-37

“…These results confirmed the enhanced osteogenic activity of the LL-37-modified PEKK, especially the P-P-LH group. Bone induction is considered to be crucial for bone implant material, 45 but whether LL-37 can promote osteogenic differentiation of cells to enhance material osteoinductivity remains controversial. 25,26,46 In this study, we found that the P-P-LH group significantly increased ALP activity (Figure 5A,B), promoted ECM mineralization (Figure 5C), and enhanced osteogenic differentiation of hWJ-MSCs at the gene (Figure 6) and protein levels (Figure 7).…”

Histone Tail Electrostatics Modulate E2-E3 Enzyme Dynamics: A Gateway to Regulate Ubiquitination Machinery

“…The protein chains were terminated with ACE (acetylated) and NME (amidated) patches. The systems were solvated with TIP3P water 48 and explicitly neutralized using 150 mM KCl that extended at least 10 Å from the solute 49 , creating systems of ∼400,000 atoms (Figure S2). The overall solvation box of 149.37 × 169.28 × 194.35 Å 3 (Figure S2) was made periodic in all three directions.…”

“…Histograms were generated using CPPTRAJ where the population sum was normalized to 1.0 to present the results of all MD trials (for WT and mutants) as normalized probability distributions. Contact frequency calculations were performed using an in-house TCL code 49,57 and energy decomposition analysis (EDA) was used to calculate non-bonded inter-molecular interaction energies (Coulomb and vdW interactions) between selected residues using a FORTRAN90 program 58–60 .…”

“…Contact frequency calculations were performed using an in-house TCL code 49,57 and energy decomposition analysis (EDA) was used to calculate non-bonded inter-molecular interaction energies (Coulomb and vdW interactions) between selected residues using a FORTRAN90…”