NIR-II-activated supramolecular LDH nanoarchitecture integrated with 3D-printed bioactive glass for hypoxia-resistant photodynamic osteosarcoma therapy and bone regeneration
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.
Abstract
The clinical management of osteosarcoma faces critical challenges, including postoperative recurrence and metastasis of residual tumor cells, chemotherapy resistance, and impaired self-repair capacity due to extensive bone defects following tumor resection. Herein, we develop 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. This scaffold consists of 3D-printed bioactive glass scaffold (BGS) and MgO2-modified ZnAl-layered double hydroxides (ZnAl-LDHs) intercalated with 5-iodo-isophthalic acid (I-IPA). Under NIR-II irradiation, the scaffold effectively triggers a photodynamic therapy (PDT) effect to eliminate osteosarcoma cells. Notably, the incorporation of MgO2 enables oxygen release within the tumor microenvironment, alleviating hypoxia and enhancing PDT efficacy for superior antitumor performance. Furthermore, the degradation of ZnAl-LDHs and MgO2 releases Mg2+ and Zn2+ ions and generates a mildly alkaline microenvironment, which collectively facilitate the osteogenic differentiation of bone marrow mesenchymal stem cells and accelerate the process of bone healing. This functionalized 3D-printed scaffold demonstrates excellent anti-tumor and osteogenic properties, showing great promise for the treatment of osteosarcoma-associated bone defects.
Resection of bone-metastatic tumors is often accompanied by severe bone erosion and structural defects. Three‐dimensional (3D) printed hydrogel scaffolds with tailorable architectures and mechanical robustness are increasingly employed to restore bone integrity after tumor removal. Here, a 3D-printed sodium alginate/GelMA hydrogel scaffold is engineered to remodel the local microenvironment for simultaneous tumor ablation and bone repair, aiming to overcome the persistent challenge of functionally modifying hydrogel scaffolds to achieve both effective tumor eradication and bone regeneration. The scaffold encapsulates dendritic cell-derived exosomes loaded with the STING agonist Cyclic dinucleotide (Dex-CDN), together with methacrylated osteogenic growth peptide (OGP-MA), while a dopamine–manganese coordination nanozyme (DM) forms a mussel‐inspired catalytic coating on the surface. Under the acidic tumor milieu, DM exhibits peroxidase‐like activity to trigger Fenton reactions, deplete glutathione, and induce oxidative stress–mediated tumor cell death. Under physiological conditions, DM displays superoxide dismutase‐ and catalase‐like activities, scavenging reactive oxygen species and maintaining redox homeostasis to promote osteogenesis. Sustained Dex‐CDN release activates STING signaling and elicits potent antitumor immunity, whereas OGP‐MA triggers BMP/Smad‐mediated osteogenic differentiation. This integrated scaffold unites catalytic therapy, immune activation, and osteoinduction, offering a promising strategy for localized tumor control and bone regeneration following bone metastatic tumor resection.
Jiachen He, Jianjun Wu, Lin Wang et al.· Advanced Composites and Hybr...· 0 citations
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.
Botao Lu, Zeyu Chen, Shichao Yan et al.· Biomaterials· 0 citations
Infected bone defects remain a significant clinical challenge due to bacterial colonization-induced persistent inflammation, oxidative stress, and local acidification, which collectively impair bone regeneration. Conventional approaches, including antibiotic therapy and bone grafting, are often insufficient to concurrently eradicate infection and promote tissue repair. Herein, we report a multifunctional GelMA-Au@Pt@CaP (GAPCP) hydrogel that integrates second near-infrared window (NIR-II, 1000-1700 nm) photothermal antibacterial activity, nanozyme-mediated antioxidant catalysis, and programmable Ca2+/PO₄3- release to enable synergistic antibacterial and osteogenic therapy. Upon 1064 nm laser irradiation, the Au@Pt nanozyme achieves efficient bacterial ablation and biofilm disruption via photothermal effects. The calcium phosphate (CaP) layer provides responsive ion delivery to enhance osteogenic differentiation and mineralization. Concurrently, the porous Pt shell catalyzes H₂O₂ decomposition under acidic conditions, mitigating oxidative stress and hypoxia. GAPCP scavenges intracellular reactive oxygen species, promotes macrophage polarization toward an anti-inflammatory M2 phenotype, and enhances angiogenic and osteogenic activities in vitro. In an infected calvarial defect model, GAPCP combined with NIR-II irradiation achieves simultaneous antibacterial, anti-inflammatory and bone regenerative outcomes. Transcriptomic analysis reveals that these effects are associated with the coordinated regulation of inflammatory signaling, ion transport, and angiogenesis pathways. This work establishes a NIR-II-responsive multifunctional hydrogel platform that couples infection eradication with microenvironment remodeling to drive bone regeneration, providing a promising strategy for treating infected bone defects.
Kaiwen Chang, Peiyu Lin, Ke Xue et al.· Biomaterials Advances· 0 citations
The postoperative repair of bone tumors remains a significant clinical challenge requiring urgent solutions, and this holds particularly true for regenerating large bone defects, completely removing residual tumor cells, and effectively preventing and controlling postoperative infections. The efficacy of traditional single treatments is limited, as they generally target only one of these challenges. To overcome this dilemma, this study designed a multifunctional composite nanoscaffold by applying Ta4C3 MXenes nanosheets to the surface of a 3D printed nano-hydroxyapatite (nHA)/methacrylated silk fibroin (MASF) composite scaffold through in situ anchoring. 3D printing technology fabricated a porous hierarchical architecture matching the target bone defect, which provides a suitable three-dimensional microenvironment for bone cell adhesion, proliferation, and differentiation. The main inorganic component of natural bone, nHA, was included to promote bone tissue mineralization. Additionally, with good biocompatibility and degradability, MASF acts as the organic matrix and facilitates the stable loading of the Ta4C3 MXenes nanosheets. To be more specific, the introduction of Ta4C3 MXenes nanosheets endows the scaffold with excellent photothermal conversion capabilities, enabling the generation of precise and controllable local high temperatures upon near-infrared light irradiation. This property allows it to efficiently kill residual tumor cells through thermal ablation while also exhibiting excellent broad-spectrum antibacterial activity through its thermal effects. This implantable material integrates bone defect repair, tumor clearance, and anti-infection functions, thereby effectively solving the limitations of traditional single therapies. It also provides new ideas for the clinical treatment of tumor-related bone defects and exhibits great application prospects.
Liu Yang, Kenan Sun, Shihao Deng et al.· Journal of Biological Engine...· 0 citations