Infection microenvironment-triggered nanoparticles eradicate MRSA by thermally amplified chemodynamic therapy and M1 macrophage.

It is of great significance to develop a novel approach to treat bacterial infections, as the frequent misuse of antibiotics leads to the serious problem of bacterial resistance. This study proposed antibiotic-free antibacterial nanoparticles for eliminating methicillin-resistant Staphylococcus aureus (MRSA) based on a multi-model synergistic antibacterial ability of chemodynamic therapy (CDT), photothermal effect, and innate immunomodulation. Specifically, a polydopamine (PDA) layer coated and Ag nanoparticles loaded core-shell structure Fe3O4 nanoparticles (Fe3O4@PDA-Ag) is prepared. The Fe3O4 catalyzes H2O2 present in acidic microenvironment of bacterial infection into more toxic reactive oxygen species (ROS) and synergizes with the released Ag ions to exert a stronger bactericidal capacity, which can be augmented by photothermal action of PDA triggered by near-infrared light and loosen the biofilm by photothermal action to promote the penetration of ROS and Ag ion into the biofilm, result in disrupting biofilm structure along with killing encapsulated bacteria. Furthermore, Fe3O4@PDA-Ag exerts indirect antibacterial effects by promoting M1 macrophage polarizing. Animal models demonstrated that Fe3O4@PDA-Ag effectively controlled MRSA-induced infections through photothermal enhanced CDT, Ag+ releasing, and macrophage-mediated bactericidal properties. The acid-triggered antibacterial nanoparticles are expected to combat drug-resistant bacteria infection.

Cu-Sr Bilayer Bioactive Glass Nanoparticles/Polydopamine Functionalized Polyetheretherketone Enhances Osteogenic Activity and Prevents Implant-Associated Infections through Spatiotemporal Immunomodulation.

Key factors contributing to implantation failures include implant-associated infections (IAIs) and insufficient osseointegration of the implants. Polyetheretherketone (PEEK) is widely used in orthopedics, yet its clinical applications are restricted due to its poor osteogenic and antibacterial properties as well as inadequate immune responses. To overcome these drawbacks, a novel spatiotemporal immunomodulation approach is proposed, chelating Cu-Sr bilayer bioactive glass nanoparticles (CS-BGNs) onto the PEEK surface via polydopamine (PDA). The CS-BGNs possess a bilayer core-shell structure where copper is distributed in the outer layer and strontium is clustered in the inner layer. The results show that CS-BGNs/PDA functionalized PEEK demonstrates a controlled and sequential release of Cu2+ and Sr2+ . In the early stage, Cu2+ from the outer layer releases rapidly, while Sr2+ from the inner layer releases in the late stage. This well-ordered release pattern modulates the phenotypic transition of macrophages, which induces M1 polarization in the early stage and M2 polarization in the late stage. Combined with the direct effects of Cu2+ and Sr2+ , the spatiotemporal immunomodulation not only benefits the early antibacterial and tissue-healing process, but also promotes the long-term process of osseointegration, providing new perspectives on the design of novel immunomodulatory biomaterials.

Influence of porosity on osteogenesis, bone growth and osteointegration in trabecular tantalum scaffolds fabricated by additive manufacturing.

Porous tantalum implants are a class of materials commonly used in clinical practice to repair bone defects. However, the cumbersome and problematic preparation procedure have limited their widespread application. Additive manufacturing has revolutionized the design and process of orthopedic implants, but the pore architecture feature of porous tantalum scaffolds prepared from additive materials for optimal osseointegration are unclear, particularly the influence of porosity. We prepared trabecular bone-mimicking tantalum scaffolds with three different porosities (60%, 70% and 80%) using the laser powder bed fusing technique to examine and compare the effects of adhesion, proliferation and osteogenic differentiation capacity of rat mesenchymal stem cells on the scaffolds in vitro. The in vivo bone ingrowth and osseointegration effects of each scaffold were analyzed in a rat femoral bone defect model. Three porous tantalum scaffolds were successfully prepared and characterized. In vitro studies showed that scaffolds with 70% and 80% porosity had a better ability to osteogenic proliferation and differentiation than scaffolds with 60% porosity. In vivo studies further confirmed that tantalum scaffolds with the 70% and 80% porosity had a better ability for bone ingrowh than the scaffold with 60% porosity. As for osseointegration, more bone was bound to the material in the scaffold with 70% porosity, suggesting that the 3D printed trabecular tantalum scaffold with 70% porosity could be the optimal choice for subsequent implant design, which we will further confirm in a large animal preclinical model for better clinical use.

Bone infection site targeting nanoparticle-antibiotics delivery vehicle to enhance treatment efficacy of orthopedic implant related infection.

Orthopedic implants account for 99% of orthopedic surgeries, however, orthopedic implant-related infection is one of the most serious complications owing to the potential for limb-threatening sequelae and mortality. Current antibiotic treatments still lack the capacity to target bone infection sites, thereby resulting in unsatisfactory therapeutic effects. Here, the bone infection site targeting efficacy of D6 and UBI29-41 peptides was investigated, and bone-and-bacteria dual-targeted nanoparticles (NPs) with D6 and UBI29-41 peptides were first fabricated to target bone infection site and control the release of vancomycin in bone infection site. The results of this study demonstrated that the bone-and-bacteria dual-targeted mesoporous silica NPs exhibit excellent bone and bacteria targeting efficacy, excellent biocompatibility and effective antibacterial properties in vitro. Furthermore, in a rat model of orthopedic implant-related infection with methicillin-resistant Staphylococcus aureus, the growth of bacteria was evidently inhibited without cytotoxicity, thus realizing the early treatment of implant-related infection. Hence, the bone-and-bacteria dual-targeted molecule-modified NPs may target bacteria-infected bone sites and act as ideal candidates for the therapy of orthopedic implant-related infections.

3D Printing for Bone-Cartilage Interface Regeneration.

Due to the vasculature defects and/or the avascular nature of cartilage, as well as the complex gradients for bone-cartilage interface regeneration and the layered zonal architecture, self-repair of cartilage and subchondral bone is challenging. Currently, the primary osteochondral defect treatment strategies, including artificial joint replacement and autologous and allogeneic bone graft, are limited by their ability to simply repair, rather than induce regeneration of tissues. Meanwhile, over the past two decades, three-dimension (3D) printing technology has achieved admirable advancements in bone and cartilage reconstruction, providing a new strategy for restoring joint function. The advantages of 3D printing hybrid materials include rapid and accurate molding, as well as personalized therapy. However, certain challenges also exist. For instance, 3D printing technology for osteochondral reconstruction must simulate the histological structure of cartilage and subchondral bone, thus, it is necessary to determine the optimal bioink concentrations to maintain mechanical strength and cell viability, while also identifying biomaterials with dual bioactivities capable of simultaneously regenerating cartilage. The study showed that the regeneration of bone-cartilage interface is crucial for the repair of osteochondral defect. In this review, we focus on the significant progress and application of 3D printing technology for bone-cartilage interface regeneration, while also expounding the potential prospects for 3D printing technology and highlighting some of the most significant challenges currently facing this field.

Smart Nanomaterials for Treatment of Biofilm in Orthopedic Implants.

Biofilms refer to complex bacterial communities that are attached to the surface of animate or inanimate objects, which highly resist the antibiotics or the host immune defense mechanisms. Pathogenic biofilms in medicine are general, chronic, and even costly, especially on medical devices and orthopedic implants. Bacteria within biofilms are the cause of many persistent infections, which are almost impossible to eradicate. Though some progress has been made in comprehending the mechanisms of biofilm formation and persistence, novel alternative compounds or strategies and effective anti-biofilm antibiotics are still lacking. Smart materials of nano size which are able to respond to an external stimulus or internal environment have a great range of applications in clinic. Recently, smart nanomaterials with or without carriage of antibiotics, targeting specific bacteria and biofilm under some stimuli, have shown great potential for pathogenic biofilm and resident bacteria eradication. First, this review briefly summarizes and describes the significance of biofilms and the process of biofilm formation. Then, we focus on some of the latest research studies involving biofilm elimination, which probably could be applied in orthopedic implants. Finally, some outstanding challenges and limitations that need to be settled urgently in order to make smart nanomaterials effectively target and treat implant biofilms are also discussed. It is hoped that there will be more novel anti-biofilm strategies for biofilm infection in the prospective future.