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.
Patients
often face the challenge of antibiotic-resistant bacterial
infections and lengthy tissue reconstruction after surgery. Herein,
human hair-melanosome derivatives (HHMs), comprising keratins and
melanins, are developed using a simple “low-temperature alkali
heat” method for potentially personalized therapy. The mulberry-shaped
HHMs have an average width of ∼270 nm and an average length
of ∼700 nm, and the negatively charged HHMs can absorb positively
charged Lysozyme (Lyso) to form the HHMs-Lyso composites through electrostatic
interaction. These naturally derived biodegradable nanostructures
act as exogenous killers to eliminate methicillin-resistant Staphylococcus aureus (MRSA) infection with a high antibacterial
efficacy (97.19 ± 2.39%) by synergistic action of photothermy
and “Lyso-assisted anti-infection” in vivo. Additionally, HHMs also serve as endogenous regulators of collagen
alpha chain proteins through the “protein digestion and absorption”
signaling pathway to promote tissue reconstruction, which was confirmed
by quantitative proteomic analysis in vivo. Notably,
the 13 upregulated collagen alpha chain proteins in the extracellular
matrix (ECM) after HHMs treatment demonstrated that keratin from HHMs
in collagen-dependent regulatory processes serves as a notable contributor
to augmented wound closure. The current paradigm of natural material–tissue
interaction regulates the cell–ECM interaction by targeting
cell signaling pathways to accelerate tissue repair. This work may
provide insight into the protein-level pathways and the potential
mechanisms involved in tissue repair.
Global multidrug‐resistant (MDR) bacteria are spreading rapidly and causing a great threat to human health due to the abuse of antibiotics. Determining how to resensitize MDR bacteria to conventional inefficient antibiotics is of extreme urgency. Here, a low‐temperature photothermal treatment (PTT, 45 °C) is utilized with red phosphorus nanoparticles to resensitize methicillin‐resistant Staphylococcus aureus (MRSA) to conventional aminoglycoside antibiotics. The antibacterial mechanism is studied by the proteomic technique and molecular dynamics (MD) simulation, which proves that the aminoglycoside antibiotics against MRSA can be selectively potentiated by low‐temperature PTT. The catalytic activity of 2‐aminoglycoside phosphotransferase (APH (2″))—a modifying enzyme—is demonstrated to be obviously inhibited via detecting the consumption of adenosine triphosphate (ATP) in the catalytic reaction. It is also found that the active site of aspartic acid (ASP) residues in APH (2″) is thermally unstable from the results of molecular dynamics simulation. Its catalytic ability is inhibited by preventing the deprotonating procedure for the target OH of gentamycin. The combined therapy also exhibits great biocompatibility and successfully treats MRSA infections in vivo. This low‐temperature PTT strategy has the potential to be an exogenous‐modifying enzyme inhibitor for the treatment of MDR bacterial infection.
In article number https://doi.org/10.1002/adhm.201801465 by Wenbo Jiang, Shuilin Wu, Yongqiang Hao, and co‐workers, HA/Ag/CS coatings are designed to prevent biofilm formation and enhance osteoinductivity of Ti implants. Organic chelators CS and PDA are used to reduce the rapid silver ion release from AgNPs. Due to the double chelating effect of PDA and CS, the coating exhibits excellent antibacterial effects with good osteogenic performance and longitudinal biocompatibility.
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