Ferric oxide nanosheet-engineered Mg alloy for synergetic osteosarcoma photothermal/chemodynamic therapy

Osteosarcoma(OS)is a malignant tumor with a high rate of recurrence.Recently,biodegradable Mg-based implants have become a new therapeutic platform for bone-related diseases.However,poor biosafety and deficient intelligent tumor-killing ability of Mg-based implants are still the main challenges for the pre-cise treatment of OS.Herein,based on the excellent catalytic and photothermal conversion properties of nanozyme ferric oxide(Fe_(3)O_(4)),a novel two-step hydrothermal method for in situ preparation of Fe_(3)O_(4)nanosheets on the surface of plasma electrolytic oxidation(PEO)-treated Mg alloy using Mg-Fe layered double hydroxides(Mg-Fe LDH)as precursor was proposed.Compared with Mg alloy,there were no obvious corrosion cracks on the surface of Fe_(3)O_(4)nanosheets-coated Mg alloy(Fe_(3)O_(4)-NS)immersed in 0.9 wt.%NaCl for 14 days,which demonstrated the corrosion resistance of Mg alloy was significantly enhanced.Cytocompatibility experiments and hemolysis assay confirmed the great biocompatibility of Fe_(3)O_(4)-NS,especially,hemolysis ratio was lower than 1%.Meanwhile,Fe_(3)O_(4)-NS presented excellent cat-alytic oxidation capacity in the presence of H_(2)O_(2),and its temperature can significantly increase from 27℃to approximately 56℃under NIR irradiation.Therefore,intelligent responsive Fe_(3)O_(4)nanosheets-engineered Mg-based implants demonstrated excellent antitumor properties in vivo and in vitro due to their photothermal and chemodynamic synergetic effects.This study provides a novel approach for the preparation of Fe_(3)O_(4)coatings on the surface of Mg alloys and a new strategy for the treatment of OS.

Shifting focus from bacteria to host neutrophil extracellular traps of biodegradable pure Zn to combat implant centered infection

The widespread use of orthopedic implants to support or replace bones is increasingly threatened by the risk of incurable bacterial infections,impenetrable microbial biofilms,and irreversible antibiotic resistance.In the past,the development of anti-infective biomaterials focused solely on direct antibacterial properties while ignoring the host’s immune response.Inspired by the clearance of infection by the innate neutrophil response and partici-pation in anti-infectious immunity of Zn ions,we report an innovative neutrophil extracellular traps(NETs)strategy,induced by biodegradable pure Zn,which achieved therapeutic efficacy toward biomaterial-related infections.Our in vitro and in vivo data showed that pure Zn was favorable for NETs formation by promoting the release of DNA fibers and granule proteins in a reactive oxygen species(ROS)-dependent manner,thereby retraining and degrading bacteria with an efficiency of up to 99.5%.Transcriptome analysis revealed that cytoskeletal rearrangement and toll-like receptor(TLR)signaling pathway were also involved in Zn-induced NETs formation.Furthermore,the in vivo results of a Staphylococcus aureus(S.aureus)-infected rat model veri-fied that pure Zn potentiated the bactericidal capability of neutrophils around implants,and promoted osseointegration in S.aureus-infected rat femurs.This antibacterial immunity concept lays a foundation for the development of other antibacterial biomaterials and holds great promise for treating orthopedic infections.

Mg(OH)_(2)nanosheets on Ti with immunomodulatory function for orthopedic applications

Macrophages play a vital role for guiding the fate of osteogenesisrelated cells.It is well known that nano-topography and bioactive ions can directly enhance osteogenic behavior.However,the effects of nano-structure combined with bioactive ions release on macrophage polarization and the following osteogenesis and angiogenesis are rarely reported.Herein,Mg(OH)_(2)films with nano-sheet structures were constructed on the surface of Ti using hydrothermal treatment.The film presented nanosheet topography and sustained release of Mg ions.The results of in vitro culture of bone marrow-derived macrophages(BMDMs),including PCR,western blot and flow cytometry suggested that the nano-Mg(OH)_(2)films were more favorable for macrophages polarizing to tissue healing M2 phenotype.Moreover,air-pouch model confirmed that the nano-Mg(OH)_(2)film coated Ti would induce milder inflammation and thinner fibrous layer in vivo,compared with untreated Ti.Furthermore,macrophages-conditioned culture mediums were collected from nano-Mg(OH)_(2)coated Ti group was superior for the osteogenic behaviors of mice bone marrow stem cells and the angiogenic behaviors of human umbilical vein endothelial cells.With harmonious early inflammatory response and subsequently improved osteogenesis and angiogenesis,the nano-Mg(OH)_(2)coated Ti is promising for orthopedic applications.

Black Mn-containing layered double hydroxide coated magnesium alloy for osteosarcoma therapy, bacteria killing, and bone regeneration

Osteosarcoma (OS) tissue resection with distinctive bactericidal activity, followed by regeneration of bone de-fects, is a highly demanded clinical treatment. Biodegradable Mg-based implants with desirable osteopromotive and superior mechanical properties to polymers and ceramics are promising new platforms for treating bone-related diseases. Integration of biodegradation control, osteosarcoma destruction, anti-bacteria, and bone defect regeneration abilities on Mg-based implants by applying biosafe and facile strategy is a promising and challenging topic. Here, a black Mn-containing layered double hydroxide (LDH) nanosheet-modified Mg-based implants was developed. Benefiting from the distinctive capabilities of the constructed black LDH film, including near-infrared optical absorption and reactive oxygen species (ROS) generation in a tumor-specific microenvi-ronment, the tumor cells and tissue could be effectively eliminated. Concomitant bacteria could be killed by localized hyperthermia. Furthermore, the enhanced corrosion resistance and synergistic biofunctions of Mn and Mg ions of the constructed black LDH-modified Mg implants significantly facilitated cell adhesion, spreading and proliferation and osteogenic differentiation in vitro, and accelerated bone regeneration in vivo. This work offers a new platform and feasible strategy for OS therapeutics and bone defect regeneration, which broadens the biomedical application of Mg-based alloys.