Alkaline “Nanoswords” Coordinate Ferroptosis-like Bacterial Death for Antibiosis and Osseointegration

Abstract

Ferroptosis is an iron-dependent cell death and is associated with cancer therapy. Can it play a role in resistance of postoperative infection of implants, especially with an extracellular supplement of Fe ions in a non-cytotoxic dose? To answer this, "nanoswords" of Fe-doped titanite are fabricated on a Ti implant surface to resist bacterial invasion by a synergistic action of ferroptosis-like bacteria killing, proton disturbance, and physical puncture. The related antibiosis mechanism is explored by atomic force microscopy and genome sequencing. The nanoswords induce an increased local pH value, which not only weakens the proton motive force, reducing adenosine triphosphate synthesis of Staphylococcus aureus, but also decreases the membrane modulus, making the nanoswords distort and even puncture a bacterial membrane easily. Simultaneously, more Fe ions are taken by bacteria due to increased bacterial membrane permeability, resulting in ferroptosis-like death of bacteria, and this is demonstrated by intracellular iron enrichment, lipid peroxidation, and glutathione depletion. Interestingly, a microenvironment constructed by these nanoswords improves osteoblast behavior in vitro and bone regeneration in vivo. Overall, the nanoswords can induce ferroptosis-like bacterial death without cytotoxicity and have great promise in applications with clinical implants for outstanding antibiosis and biointegration performance.

Layer-by-Layer Assembly of CeO2 Nanoparticle/Bovine Serum Albumin Films for Bone Regeneration

“…However, ALP is an early indicator of osteoblast differentiation, and the activity of ALP will be decreased when the cell enters the period of mineralization. 54 Here, the slight decrease of ALP activity in the control group after 7 days of induction treatment was mainly attributed to the mineralization of some osteoblasts. On the other hand, calcium nodule, a calcified osteoblast matrix produced in mineralization stage, can accurately reflect the osteogenic mineralization condition.…”

“…Under both induced mineralization and oxidative mineralization conditions, CeO 2 NP-based drug-loaded coating exhibited good promoting effects for ALP activity, which may be related to the osteogenic induction effect of the introduced BAI drugs. However, ALP is an early indicator of osteoblast differentiation, and the activity of ALP will be decreased when the cell enters the period of mineralization . Here, the slight decrease of ALP activity in the control group after 7 days of induction treatment was mainly attributed to the mineralization of some osteoblasts.…”

Metal ions: the unfading stars of bone regeneration—from bone metabolism regulation to biomaterial applications

“…This was accompanied by an orderly lamellar structure of mature bone matrix and neoangiogenesis. In another intriguing study, Xue et al 275 proposed a Fe-based “nanosword” that was highly biocompatible and could fully utilize the powerful bactericidal effect of iron, which showed promising prospects in the field of infected bone defect treatment (Fig. 10d).…”

“…Copyright © 2021 Elsevier. (d) The "nanosword" leverages the potent antibacterial effect of ferrous ions and its physical piercing behavior to efficiently eradicate bacteria, thereby combating bone tissue infections 275. Copyright © 2023 American Chemical Society.…”

Injectable Self-Harden Antibiofilm Bioceramic Cement for Minimally Invasive Surgery

“…The material could kill the S. aureus bacteria by inducing ferroptosis-like bacterial death and destroying bacteria by physically puncturing bacteria with the nanosword-like topography . Moreover, Li et al and Uskokovic et al both found that iron-doped brushite cement has antibacterial activity against E.…”