Long‐Term Prevention of Bacterial Infection and Enhanced Osteoinductivity of a Hybrid Coating with Selective Silver Toxicity

Abstract

mechanical properties and biocompatibility. However, despite the dramatic improvements in implant design and perioperative management over the past decades, implant-related infection and limited longevity remain challenges for surgeons and materials scientists. In the United States, 4.3% of orthopedic implants are reported as being infected, with the annual cost of implant-related infection being expected to exceed $1.62 billion by 2020. [1] Implant-related infection comprises a complex biological process including bacterial adhesion and biofilm formation, with the latter constituting the main cause of implant failure owing to the associated antibiotic resistance and immune evasion. [2] In addition, the osseointegration between host bone and implant represents another crucial factor for achieving the long-term survival time of implants. Moreover, rapid bone-implant osseointegration may allow host cells to occupy the implant surface earlier than bacteria, a key factor to prevent bacterial adhesion and biofilm formation. [3] Therefore, an ideal implant for orthopedics and dentistry application should exhibit both anti-biofilm and osseointegration properties.Antibacterial and osteogenic design is required for ideal orthopedic implants. The excellent antimicrobial performance of silver nanoparticles (AgNPs) has attracted interest for the treatment of implant-related infections. However, the dose-dependent cytotoxicity of silver and its negative impact on bone implants restrict the further use of AgNPs coatings. Therefore, a hybrid coating containing polydopamine (PDA), hydroxyapatite (HA), AgNPs, and chitosan (CS) is prepared. Organic chelators CS and PDA that have promising biocompatibility are used to prevent the rapid release of silver ions from the AgNPs coating. The double chelating effect of PDA and CS significantly reduces silver ion release from the hybrid coating. The coating exhibits excellent anti-biofilm efficiency of 91.7%, 89.5%, and 92.0% for Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli, respectively. In addition, the coating can significantly stimulate osteogenic differentiation of MC3T3-E1 cells and promote bone-implant osseointegration in vivo as compared to that in the control group. The longitudinal biosafety of the coating is confirmed in vivo by histological evaluation and blood tests. The results of this study indicate that the hybrid coating exhibits antibacterial properties as well as allow bone-implant osseointegration, thereby providing insight into the design of multifunctional implants for long-term orthopedic applications.

Nanomaterials as Promising Alternative in the Infection Treatment

“…In addition, the coating can significantly stimulate osteogenic differentiation of MC3T3-E1 cells and promotes bone-implant osseointegration in vivo. Therefore, the hybrid coating exhibits antibacterial properties as well as allowing bone-implant osseointegration, thereby providing insights into the design of multifunctional implants for long-term orthopedic applications [97].…”

In Vitro Biological Characterization of Silver-Doped Anodic Oxide Coating on Titanium

“…The following functionalization strategies have already been applied to increase antibacterial potential: drug-loaded surfaces [ 10 ], silver-implanted surfaces [ 11 ], polymer-functionalized surfaces [ 12 ], anodized/oxidized/ion-implanted surfaces [ 13 , 14 ], UV-activated surfaces [ 15 ], nanoscale surfaces [ 16 ], etc. A systematic review by J. Grischke et al concluded that highly modified surfaces enhance antimicrobial activity compared to that of commercial, pure titanium [ 8 ], but some research proved the significant cell toxicity of these surfaces [ 17 , 18 ], which limits the clinical application of new surfaces. Despite biocompatibility and effectiveness, production simplicity and adequate final cost are required for mass-production implants.…”

Biofunctional Elements Incorporated Nano/Microstructured Coatings on Titanium Implants with Enhanced Osteogenic and Antibacterial Performance

“…[50,[165][166][167][168] The dual chelating effect of PDA and chitosan has been demonstrated to significantly reduce Ag ion release with excellent antibacterial effect toward S. aureus, S. epidermidis, and E. coli (Figure 12). [171] The pH level at the peri-implant during bacterial infection is reduced to as low as 5.5. A pH-sensitive coating consisting of AgNPs and acetal linker has been fabricated and the Ag ion is released at low pH when bacterial infection occurs.…”