With the ever-deeper understanding of nano-bio interactions and the development of fabrication methodologies of nanomaterials, various therapeutic platforms based on nanomaterials have been developed for next-generation oncological applications, such as osteosarcoma therapy. In this work, a black phosphorus (BP) reinforced 3D-printed scaffold is designed and prepared to provide a feasible countermeasure for the efficient localized treatment of osteosarcoma. The in situ phosphorus-driven, calcium-extracted biomineralization of the intra-scaffold BP nanosheets enables both photothermal ablation of osteosarcoma and the subsequent material-guided bone regeneration in physiological microenvironment, and in the meantime endows the scaffolds with unique physicochemical properties favoring the whole stepwise therapeutic process. Additionally, a corrugated structure analogous to Haversian canals is found on newborn cranial bone tissue of Sprague-Dawley rats, which may provide much inspiration for the future research of bone-tissue engineering.

The residual of malignant tumor cells and lack of bone‐tissue integration are the two critical concerns of bone‐tumor recurrence and surgical failure. In this work, the rational integration of 2D Ti3C2 MXene is reported with 3D‐printing bioactive glass (BG) scaffolds for achieving concurrent bone‐tumor killing by photonic hyperthermia and bone‐tissue regeneration by bioactive scaffolds. The designed composite scaffolds take the unique feature of high photothermal conversion of integrated 2D Ti3C2 MXene for inducing bone‐tumor ablation by near infrared‐triggered photothermal hyperthermia, which has achieved the complete tumor eradication on in vivo bone‐tumor xenografts. Importantly, the rational integration of 2D Ti3C2 MXene is demonstrated to efficiently accelerate the in vivo growth of newborn bone tissue of the composite BG scaffolds. The dual functionality of bone‐tumor killing and bone‐tissue regeneration makes these Ti3C2 MXene‐integrated composite scaffolds highly promising for the treatment of bone tumors, which also substantially broadens the biomedical applications of 2D MXenes in tissue engineering, especially on the treatment of bone tumors.

Background Osteoarthritis (OA) is the most common joint disease and is the leading cause of chronic disability among older people. Chondrocyte death and extracellular matrix (ECM) degradation was involved in OA pathogenesis. Ferroptosis was an iron-dependent cell death associated with peroxidation of lipids. Here, we proved that ferroptosis exists in OA and identified glutathione peroxidase 4 (GPX4) as an important regulator of OA.Methods Ferroptosis-related alterations were analyzed in human OA and undamaged cartilage. Expression of GPX4 was examined in 55 paired human OA samples. Ferrostatin-1 (Fer-1) and Deferoxamine (DFO) were used to treat OA, in vitro and in vivo. Alterations of GPX4-mediated signaling pathway were identified by RNA-seq analysis. AAV-Gpx4-shRNA were used to downregulate GPX4 expression in vivo.Findings Transcriptomic, biochemical, and microscopical analyses indicated that ferroptosis was closely associated with OA. Expression of GPX4 in the OA cartilage from 55 OA patients were significantly lower than undamaged cartilage. Fer-1 and DFO could protect OA in a necroptosis-independent manner, suggesting that ferroptosis exists in OA prog. Importantly, GPX4 downregulation could increase the sensitivity of chondrocytes to oxidative stress and aggravate ECM degradation through the MAPK/NFkB pathway. Furthermore, downregulation of GPX4 expression by AAV-Gpx4 shRNA aggravated OA in vivo.Interpretation Ferroptosis contributes to OA pathogenesis and GPX4 was the intersection of two mechanisms in regulating OA progression: ferroptosis and ECM degradation.