Aug 2026· Biomaterials· Vol 337, pp.
124519
· 0 citations· 74 references
Medicine
TL;DR
In vivo validation confirms a 90% tumor inhibition rate alongside robust biosafety, offering a novel self-powered paradigm for integrated therapy and repair post-osteosarcoma surgery.
Abstract
Postoperative treatment of osteosarcoma faces the dual challenges of tumor recurrence and extensive bone defect repair, necessitating the development of a synergistic strategy capable of simultaneously eliminating residual tumor cells and promoting bone regeneration. Existing prosthetic implants are often limited by their singular functionality, leading to issues such as high recurrence rates and non-union. This study innovatively constructs a functional titanium alloy scaffold system synergistically driven by a biodegradable "shell-like" triboelectric nanogenerator (BS-TENG). The BS-TENG efficiently converts natural joint movement into electricity. Within the acidic tumor microenvironment, this electrical output accelerates the breakdown of the scaffold's MgxFe1-xS2 coating, leading to the localized release of H2S gas and Fe2+ ions. The H2S upregulates HMOX1 protein expression, which synergizes with heightened Fe2+ levels to induce intense lipid peroxidation, thereby activating a selective ferroptosis cascade in osteosarcoma cells and drastically lowering their survival. In physiological conditions, the scaffold shows excellent biocompatibility. Concurrent electrical stimulation and controlled Mg2+ release significantly boost alkaline phosphatase activity and calcium nodule formation, effectively promoting bone regeneration. In vivo validation confirms a 90% tumor inhibition rate alongside robust biosafety, offering a novel self-powered paradigm for integrated therapy and repair post-osteosarcoma surgery.
A novel functionalized 3D-printed scaffold with NIR-II responsiveness (BGS/I-LDH@MgO2), designed to simultaneously address the dual needs of inhibiting osteosarcoma recurrence and promoting bone regeneration, demonstrates excellent anti-tumor and osteogenic properties.
Hong Cheng, Tao Wang, Hanji Huang et al.· Bioactive Materials· 0 citations
Infected bone defects present a major clinical challenge. Persistent bacterial infection and the inflammatory microenvironment not only directly impede bone healing but also lead to peripheral nerve impairment, which further compromises the regeneration process. While conventional implants offer mechanical support, they lack the multifunctional capacity to simultaneously eradicate infection and orchestrate neuro-coupled bone healing often resulting in implant failure. In this study, black phosphorus quantum dots (BPQDs) were used to endow graphene-like carbon nitride (g-C3N4, CN) with photothermal activity and enhanced piezoelectric properties. Additionally, BP/CN hydrogel was prepared to modify 3D-printed titanium prostheses for the treatment of infectious bone defects. The prosthesis interface constructed achieved a strong antibacterial effect through the synergy of photothermal and sonodynamic therapies. It also promoted Schwann cell transformation towards a repair type and the secretion of neurotrophic factors, thereby promoting peripheral nerve repair and nerve-guided bone regeneration in the defect area. The results showed that the calcium ion-mediated MAPK/JNK signaling pathway plays a key role in the regulation of Schwann cell phenotypic conversion. Thus, this advanced implant design provides an integrated strategy that concurrently addresses infection control, nerve repair, and osteogenesis, offering a promising therapeutic platform for complex bone defect reconstruction.
Zhen Ai, Dan Li, Yujia Tian et al.· Biomaterials· 0 citations
Bone tumor treatment often involves surgical resection, which can lead to critical bone defects requiring structural implants for functional and aesthetic restoration. However, the development of scaffolds capable of accurately eliminating residual tumor cells while simultaneously driving bone defect reconstruction remains a significant clinical challenge. To address this dual need, we engineered a biomimetic, multifunctional porous silicon nitride (Si3N4) scaffold integrated with ultrathin niobium carbide (Nb2C) MXene nanosheets. Specifically, this Nb2C MXene-coated porous Si3N4 scaffold (MPSNS) was created by attaching Nb2C MXene nanosheets onto three dimensional (3D)-printed Si3N4 scaffolds, thereby altering its surface physicochemical properties, improving its biological interactions, and enabling targeted tumor ablation. This scaffold exhibits a highly stable, hydrophilic bio-interface that confers excellent biocompatibility and superior osteoinductive activity. Furthermore, the photothermal conversion properties of the Nb2C MXene nanocoating enable targeted tumor ablation and suppression while concurrently promoting bone defect repair. Collectively, this comprehensive study highlights the transformative potential of integrating Nb2C MXene nanosheets with 3D-printed Si3N4 ceramics. By exhibiting superior mechanical integrity, biocompatibility, osteogenic performance, and photothermal tumoricidal efficacy, the MPSNS establishes a promising advanced biomaterial platform for regenerative medicine.
Jun Yuan, Haiyang Song, Quan Li et al.· ACS Applied Materials and In...· 0 citations
Magnesium-based biomaterials show great potential in bone regeneration due to their inherent biocompatibility, osteogenic activity, and ability to modulate the immune microenvironment. However, their rapid degradation rate remains a critical barrier to clinical translation. To address these challenges, we developed a magnesium hydride-gelatin methacryloyl (MgH2-GelMA) composite with sustained release of hydrogen gas and magnesium ions, featuring a bone-mimetic organic-inorganic hybrid network. First, magnesium hydride microcrystals were coated with an inorganic silica layer to mitigate degradation; subsequently, the coated particles were embedded within an organic GelMA hydrogel matrix. The composite achieves controlled co-release of magnesium ions (Mg2+) and hydrogen gas (H2). The released Mg2+ directly stimulates the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts, accelerating osteogenesis. Concurrently, Mg2+ and H2 synergistically induce polarization of bone marrow-derived macrophages (BMDMs) toward an anti-inflammatory phenotype. During the active inflammatory phase, this polarization modulates the immune microenvironment and establishes a pro-regenerative local niche. This study not only elucidates a novel ion-gas synergistic mechanism but also provides innovative insights and theoretical foundations for advancing artificial bone materials from passive biomimetic replacement to active regenerative modulation.
Rui Huang, Zhonghua Yang, Miao Wang et al.· Journal of Biomedical Materi...· 0 citations
High-intensity focused ultrasound (HIFU) has emerged as a game-changing breast-conserving therapeutic modality owing to its dual functions of non-invasive tumor ablation and immunity activation. However, its low focal gain in the target region results in residual tumor tissue after ablation. Inspired by the exceptional acoustic response of bone tumor to HIFU, we developed bone-derived hydroxyapatite (HA)-mineralized metal-organic frameworks (designated as AZSH MOFs) as sonosensitizer that co-encapsulated Zn2+, hypoxic-activated prodrug AQ4N, and STING agonist SR-717 for acoustic-immunological synergistic therapy. AZSH MOFs enabled targeted delivery of HA to mimic bone tumor-like acoustic environment, markedly amplified HIFU energy deposition in the breast tumor tissue, and thus achieved more thorough ablation and local hypoxic. The exacerbated hypoxic selectively activated AQ4N to trigger immunogenic cell death. Meanwhile, Zn2+ with SR-717 upregulated stimulator of interferon genes (STING) pathway to promote intratumoral infiltration of immune cells, and ultimately relieved the immunosuppressive tumor microenvironment. Thus, AZSH MOFs not only improve ablation efficiency of HIFU but also treat residual tumor via enhanced multilevel immune activation, offering valuable insights to facilitate the extensive clinical application of HIFU technology.
Xiaomei Xie, Qi Wang, Hanlin Song et al.· Materials Today Bio· 0 citations
Osteosarcoma, the most common primary malignant bone tumor in adolescents, has a poor prognosis due to high rates of metastasis, recurrence, and chemoresistance, necessitating novel treatments. Herein, a biomimetic nanoplatform CFCM/VK3 was engineered to exploit synergistic iron-copper interference against osteosarcoma. This platform comprises an optimized CuFe2O4 nanoparticle core with superior Fenton-like activity, glutathione depletion capacity, and near-infrared photothermal properties, combined with vitamin K3 (VK3) as an endogenous H2O2 generator specifically activated by tumor-overexpressed quinone oxidoreductase 1 (NQO1). The core is cloaked with K7M2 osteosarcoma cell membranes to enable homologous targeting and immune evasion. After tumor-specific uptake, the acidic microenvironment activates VK3 to generate H2O2 and liberates iron and copper ions. This initiates a self-reinforcing cascade wherein iron-driven oxidative stress impairs mitochondrial ATP synthesis, and the resultant energy shortage traps copper inside cells, thereby amplifying the toxicity of both ions. Critically, the cooperative action of iron and copper simultaneously activates two regulated cell death pathways: iron‑dependent lipid peroxidation leads to ferroptosis and copper‑induced aggregation of lipoylated proteins triggers cuproptosis. Near-infrared irradiation further accelerates these catalytic reactions and provides photothermal ablation. The CFCM/VK3 nanoplatform demonstrates significant tumor suppression and excellent biosafety in an osteosarcoma mouse model, establishing a new paradigm of metal-ion interference therapy that leverages the mutual dependency between iron and copper for self-amplifying antitumor effects.
Unknown authors· Colloids and Surfaces B: Bio...· 0 citations
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