Calcium Peroxide Nanoparticles‐Embedded Coatings on Anti‐Inflammatory TiO₂ Nanotubes for Bacteria Elimination and Inflammatory Environment Amelioration

Abstract

materials and therapies for skin wound repair. [1][2][3] Pathogenic bacteria such as Staphylococcus aureus can adhere to the surface of implants to avoid death from the sterilization procedure, or are present in adjacent tissues prior to implantation. [4] If the bacterial contamination cannot be treated and effectively removed from the site, the surviving bacteria will recover and rapidly re-colonize, which may give rise to tissue damage and inflammation. [5,6] Although more and more antibiotics have been approved by FDA to treat malignant bacterial infections and generally exhibit sufficient antibacterial activity, the fast emergence of multi-drug resistant bacteria still reminds us to prevent the excessive use of antibiotics. Other commonly used antibacterial strategies, such as photothermal treatment and sonodynamic therapy, always bring potential side effects on surrounding cells/tissues. Accordingly, the development of an ideal antibacterial component will be a long-term and arduous striving goal.Medical-grade titanium is one of the main types of metal implants used, due to its high biocompatibility and its ability to safely sustain extensive contact with soft tissues such as gum, muscle, and skin. [7][8][9] Currently, titanium implants are treated with antibacterial coatings to avoid potential bacterial infections, [10] such as surface modifications with antibiotics, anti-bacterial metallic Implant-associated bacterial infections significantly impair the integration between titanium and soft tissues. Traditional antibacterial modifications of titanium implants are able to eliminate bacteria, but the resulting proinflammatory reactions are usually ignored, which still poses potential risks to human bodies. Here, a dual drug-loading system on titanium has been developed via the adhesion of a catechol motif-modified methacrylated gelatin hydrogel onto TiO 2 nanotubes. Then synthesized CaO 2 nanoparticles (NPs) are embedded into the hydrogel, and interleukin-4 (IL-4) is loaded into the nanotubes to achieve both antibacterial and anti-inflammatory properties. The dual drug-loading system can eliminate Staphylococcus aureus (S. aureus) rapidly, attributed to the H 2 O 2 release from CaO 2 NPs. The potential cytotoxicity of CaO 2 NPs is also remarkably reduced after being embedded into the hydrogel. More importantly, with the gradual release of IL-4, the dual drug-loading system is capable of modulating pro-inflammatory reactions by inducing M2 phenotype polarization of macrophages. In a subcutaneous infection model, the S. aureus contamination is effectively resolved after 2 days, and the resulting pro-inflammatory reactions are also inhibited after 7 days. Finally, the damaged tissue is significantly recovered. Taken together, the dual drug-loading system exhibits great therapeutic potential in effectively killing pathogens and inhibiting the resulting pro-inflammatory reactions.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/smll.202102907.

Immunomodulatory biomaterials for implant-associated infections: from conventional to advanced therapeutic strategies

“…Similarly, He et al constructed a dual drug-loading system on titanium implants by adhering catechol-motif-modified methacrylated gelatin (GelMA) hydrogel to TiO 2 nanotubes [ 234 ]. The formation of porous TiO 2 nanotubes on the Ti surface by anodic oxidation not only enhanced the adhesion between the hydrogel coating and the Ti substrate, but also served as a storage reservoir for sequential drug release.…”

Bismuth Quantum Dot (Bi QD)/Polydimethylsiloxane (PDMS) Nanocomposites with Self-Cleaning and Antibacterial Activity for Dental Applications

“…The disk diffusion measurement of the pure 0D Bi QDs with different concentrations can be seen in Figure S3 and Table S1 . The result shows that the mean diameter ( d ) distinctly increased with the concentration of the pure 0D Bi QDs, demonstrating that the pure 0D Bi QDs indeed have high antibacterial activity, similar to Ag nanoparticles (NPs) [ 39 ], N-doped TiO 2 NPs [ 40 ], and Ca-doped SiO 2 NPs [ 41 ], and can further improve the antibacterial efficiency under light illumination due to the excellent photothermal effect [ 22 , 24 , 42 ]. The antimicrobial activity of the Bi QD/PDMS nanocomposites with different concentrations of 0D Bi QDs on the S. mutans culture is shown in Figure 5 .…”

Fabrication of a New Hyaluronic Acid/Gelatin Nanocomposite Hydrogel Coating on Titanium-Based Implants for Treating Biofilm Infection and Excessive Inflammatory Response

“…Finally, we hypothesized that the constructed natural hydrogel coating serves as a drug reservoir in the delivery system. Moreover, the constructed polymer coating not only alleviated the toxicity of the antibacterial agent but also improved biocompatibility and the degree of matching with the mechanical properties of human bones . We anticipate that the developed system might effectively treat biofilm infection, alleviate OS, and promote bone repair in vivo.…”