Silver-quercetin-loaded honeycomb-like Ti-based interface combats infection-triggered excessive inflammation via specific bactericidal and macrophage reprogramming

• Published in: Bioactive materials Vol. 43; pp. 48 - 66
• Main Authors: Yang, Ning, Wu, Ting, Li, Meng, Hu, Xianli, Ma, Ruixiang, Jiang, Wei, Su, Zheng, Yang, Rong, Zhu, Chen
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.01.2025; KeAi Publishing Communications Ltd; KeAi Publishing; KeAi Communications Co., Ltd
• Subjects: Antibacterial activity; Antibiotics; Bacteria; Bacterial infections; Biocompatibility; Biofilms; Bone implants; Bone marrow; Cell differentiation; Coliforms; Differentiation (biology); Dopamine; Drug resistance; E coli; Ethanol; Fourier transforms; Fractures; Homeostasis; Hybridization; Inflammation; Macrophage polarization homeostasis; Macrophages; Mechanical properties; Mesenchymal stem cells; Morphology; Nanoparticles; NF-κB protein; Orthopedics; Osseointegration; Osteoclastogenesis; Osteointegration; Permeability; Porous titanium; Protective coatings; Quercetin; Scanning electron microscopy; Silver; Silver nanoparticles; Spectrum analysis; Staphylococcus infections; Stem cells; Surgical implants; Titanium; China; Osteointegration; Macrophage polarization homeostasis; Porous titanium; Silver nanoparticles; Quercetin
• ISSN: 2452-199X; 2097-1192; 2452-199X
• DOI: 10.1016/j.bioactmat.2024.09.012

Excessive inflammation caused by bacterial infection is the primary cause of implant failure. Antibiotic treatment often fails to prevent peri-implant infection and may induce unexpected drug resistance. Herein, a non-antibiotic strategy based on the synergy of silver ion release and macrophage reprogramming is proposed for preventing infection and bacteria-induced inflammation suppression by the organic-inorganic hybridization of silver nanoparticle (AgNP) and quercetin (Que) into a polydopamine (PDA)-based coating on the 3D framework of porous titanium (SQPdFT). Once the planktonic bacteria (e.g., Escherichia coli, Staphylococcus aureus) reach the surface of SQPdFT, released Que disrupts the bacterial membrane. Then, AgNP can penetrate the invading bacterium and kill them, which further inhibits the biofilm formation. Simultaneously, released Que can regulate macrophage polarization homeostasis via the peroxisome proliferators-activated receptors gamma (PPARγ)-mediated nuclear factor kappa-B (NF-κB) pathway, thereby terminating excessive inflammatory responses. These advantages facilitate the adhesion and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), concomitantly suppressing osteoclast maturation, and eventually conferring superior mechanical stability to SQPdFT within the medullary cavity. In summary, owing to its excellent antibacterial effect, immune remodeling function, and pro-osteointegration ability, SQPdFT is a promising protective coating for titanium-based implants used in orthopedic replacement surgery. Schematic illustration of the design, synthesis, and biomedical applications of SQPdFT. SQPdFT is prepared by the organic-inorganic hybridization of silver nanoparticles (AgNPs) and quercetin (Que) into a polydopamine (PDA)--based coating on the 3D framework of porous titanium. Released Que can disrupt the bacterial membrane of the invading planktonic bacteria. The broken bacterial membrane can elevate the membrane permeability of AgNPs, which can further kill bacteria to inhibit biofilm formation. Importantly, released Que can terminate excessive inflammatory responses via PPARγ/NF-κB pathway-mediated regulation of macrophage polarization homeostasis. In the medullary cavity, SQPdFT has exceptional bone homeostasis repair capacity and superior mechanical stability. [Display omitted] •A novel nano-sliver/quercetin hybrid biocoating (SQPdFT) was developed.•The antibacterial performance is markedly superior to that of nano-silver coatings.•SQPdFT effectively restores bone homeostasis disrupted by excessive inflammation.•SQPdFT exhibits excellent biocompatibility and biosafety.