Ultrasound-controlled MXene-based Schottky heterojunction improves anti-infection and osteogenesis properties. Theranostics The current clinical treatment of osteomyelitis is limited by the emergence of drug-resistant bacteria, which often leads to the failure of traditional antibiotic treatment and large bone defects. Sonodynamic therapy (SDT) is a new strategy that is widely used to overcome the problem of bacterial resistance to antibiotic therapy as well as poor tissue penetration using near-infrared light in photodynamic therapy (PDT). Therefore, it is necessary to develop a new sonosensitizer that can kill bacteria and promote bone repair. Herein, we developed a sonosensitizer, porphyrin metal-organic framework (HNTM), with a Schottky junction modified by TiC nanosheets (HN-TiC) for highly efficient sonodynamic therapy of osteomyelitis and bone regeneration. TiC greatly improves the acoustic catalytic performance by rapidly transferring the charge carriers generated by HNTM under ultrasound (US) irradiation, which killing drug-resistant bacteria through the generation of large amounts of reactive oxygen species (ROS). And HN-TiC shows excellent 99.75% antibacterial effectiveness against MRSA. In addition, HN-TiC generates a sonocurrent under low-intensity US to promote the repair of bone defects for a long time period. Mechanistic research using CCK-8 and RNA-seq showed that HN-TiC nanocomposites can promote the proliferation of stem cells by regulating the cell cycle, DNA replication, and apoptosis. In addition, after low-intensity US irradiation, HN-TiC promotes osteogenic differentiation via some key signaling pathways, including the calcium, Wnt, and TGF-beta signaling pathways, according to the Kyoto Encyclopedia of Genes and Genomes (KEGG). In a MRSA-infected rat tibial osteomyelitis model, HN-TiC successfully eliminated the infection and significantly improved bone regeneration under US irradiation. This study indicates that engineered HN-TiC is a distinctive nanocomposite for successful osteomyelitis treatment. 10.7150/thno.81511

MXene-Functionalized Ferroelectric Nanocomposite Membranes with Modulating Surface Potential Enhance Bone Regeneration. ACS biomaterials science & engineering Rapid and effective bone defect repair remains a challenging issue for clinical treatment. Applying biomaterials with endogenous surface potential has been widely studied to enhance bone regeneration, but how to regulate the electric potential and surface morphology of the implanted materials precisely to achieve an optimal bioelectric microenvironment is still a major challenge. The aim of this study is to develop electroactive biomaterials that better mimic the extracellular microenvironment for bone regeneration. Hence, MXene/polyvinylidene fluoride (MXene/PVDF) ferroelectric nanocomposite membranes were prepared by electrospinning. Physicochemical characterization demonstrated that TiCT MXene nanosheets were wrapped in PVDF shell layer and the surface morphology and potential were modulated by altering the content of MXene, where uniform distribution of fibers and enhanced electric potential can be obtained and precisely assembled into a natural extracellular matrix (ECM) in bone tissue. Consequently, the MXene/PVDF membranes facilitated cell adhesion, stretching, and growth, showing good biocompatibility; meanwhile, their intrinsic electric potential promoted the recruitment of osteogenic cells and accelerated the differentiation of osteoblast. Furthermore, 1 wt % MXene/PVDF membrane with a suitable surface potential and better topographical structure for bone regeneration qualitatively and quantitatively promoted bone tissue formation in a rat calvarial bone defect after 4 and 8 weeks of healing. The fabricated MXene/PVDF ferroelectric nanocomposite membranes show a biomimetic microenvironment with a sustainable electric potential and optimal 3D topographical structure, providing an innovative and well-suited strategy for application in bone regeneration. 10.1021/acsbiomaterials.2c01174

3D printing of TiC-MXene-incorporated composite scaffolds for accelerated bone regeneration. Biomedical materials (Bristol, England) Grafting of bone-substitute biomaterials plays a vital role in the reconstruction of bone defects. However, the design of bioscaffolds with osteoinductive agents and biomimetic structures for regeneration of critical-sized bone defects is difficult. TiCMXene-belonging to a new class of 2D nanomaterials-exhibits excellent biocompatibility, and antibacterial properties, and promotes osteogenesis. However, its application in preparing 3D-printed tissue-engineered bone scaffolds for repairing bone defects has not been explored. In this work, TiCMXene was incorporated into composite scaffolds composed of hydroxyapatite and sodium alginate via extrusion-based 3D printing to evaluate its potential in bone regeneration. MXene composite scaffolds were fabricated and characterized by SEM, XPS, mechanical properties and porosity. The biocompatibility and osteoinductivity of MXene composite scaffolds were evaluated by cell adhesion, cell counting kit-8 test, quantitative real-time polymerase chain reaction, alkaline phosphatase activity and alizarin red S tests of bone mesenchymal stem cells (BMSCs). A rat calvarial defect model was performed to explore the osteogenic activity of the MXene composite scaffolds. The results showed the obtained scaffold had a uniform structure, macropore morphology, and high mechanical strength.experimental results revealed that the scaffold exhibited excellent biocompatibility with BMSCs, promoted cell proliferation, upregulated osteogenic gene expression, enhanced alkaline phosphatase activity, and promoted mineralized-nodule formation. The experimental results confirmed that the scaffold effectively promoted bone regeneration in a model of critical-sized calvarial- bone-defectand promoted bone healing to a significantly greater degree than scaffolds without added TiCMXene did. Conclusively, the TiCMXene composite 3D-printed scaffolds are promising for clinical bone defect treatment, and the results of this study provide a theoretical basis for the development of practical applications for tissue-engineered bone scaffolds. 10.1088/1748-605X/ac5ffe

Mild Photothermal-Stimulation Based on Injectable and Photocurable Hydrogels Orchestrates Immunomodulation and Osteogenesis for High-Performance Bone Regeneration. Small (Weinheim an der Bergstrasse, Germany) A photoactivated bone scaffold integrated with minimally invasive implantation and mild thermal-stimulation capability shows great promise in the repair and regeneration of irregularly damaged bone tissues. Developing multifunctional photothermal biomaterials that can simultaneously serve as both controllable thermal stimulators and biodegradable engineering scaffolds for integrated immunomodulation, infection therapy, and impaired bone repair remains an enormous challenge. Herein, an injectable and photocurable hydrogel therapeutic platform (AMAD/MP) based on alginate methacrylate, alginate-graft-dopamine, and polydopamine (PDA)-functionalized Ti3C2 MXene (MXene@PDA) nanosheets is rationally designed for near-infrared (NIR)-mediated bone regeneration synergistic immunomodulation, osteogenesis, and bacterial elimination. The optimized AMAD/MP hydrogel exhibits favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro. The proper immune microenvironment provided by AMAD/MP could further modulate the balance of M1/M2 phenotypes of macrophages, thereby suppressing reactive oxygen species-induced inflammatory status. Significantly, this multifunctional hydrogel platform with mild thermal stimulation efficiently attenuates local immune reactions and further promotes new bone formation without the addition of exogenous cells, cytokines, or growth factors. This work highlights the potential application of an advanced multifunctional hydrogel providing photoactivated on-demand thermal cues for bone tissue engineering and regenerative medicine. 10.1002/smll.202300111

Piezoresistive MXene/Silk fibroin nanocomposite hydrogel for accelerating bone regeneration by Re-establishing electrical microenvironment. Bioactive materials The electrical microenvironment plays an important role in bone repair. However, the underlying mechanism by which electrical stimulation (ES) promotes bone regeneration remains unclear, limiting the design of bone microenvironment-specific electroactive materials. Herein, by simple co-incubation in aqueous suspensions at physiological temperatures, biocompatible regenerated silk fibroin (RSF) is found to assemble into nanofibrils with a β-sheet structure on MXene nanosheets, which has been reported to inhibit the restacking and oxidation of MXene. An electroactive hydrogel based on RSF and bioencapsulated MXene is thus prepared to promote efficient bone regeneration. This MXene/RSF hydrogel also acts as a piezoresistive pressure transducer, which can potentially be utilized to monitor the electrophysiological microenvironment. RNA sequencing is performed to explore the underlying mechanisms, which can activate Ca/CALM signaling in favor of the direct osteogenesis process. ES is found to facilitate indirect osteogenesis by promoting the polarization of M2 macrophages, as well as stimulating the neogenesis and migration of endotheliocytes. Consistent improvements in bone regeneration and angiogenesis are observed with MXene/RSF hydrogels under ES . Collectively, the MXene/RSF hydrogel provides a distinctive and promising strategy for promoting direct osteogenesis, regulating immune microenvironment and neovascularization under ES, leading to re-establish electrical microenvironment for bone regeneration. 10.1016/j.bioactmat.2022.08.025