Engineering a proper immune response following biomaterial implantation is essential to bone tissue regeneration. Herein, a biomimetically hierarchical scaffold composed of deferoxamine@poly(ε‐caprolactone) nanoparticles (DFO@PCL NPs), manganese carbonyl (MnCO) nanosheets, gelatin methacryloyl hydrogel, and a polylactide/hydroxyapatite (HA) matrix is fabricated to augment bone repair by facilitating the balance of the immune system and bone metabolism. First, a 3D printed stiff scaffold with a well‐organized gradient structure mimics the cortical and cancellous bone tissues; meanwhile, an inside infusion of a soft hydrogel further endows the scaffold with characteristics of the extracellular matrix. A Fenton‐like reaction between MnCO and endogenous hydrogen peroxide generated at the implant‐tissue site triggers continuous release of carbon monoxide and Mn2+, thus significantly lessening inflammatory response by upregulating the M2 phenotype of macrophages, which also secretes vascular endothelial growth factor to induce vascular formation. Through activating the hypoxia‐inducible factor‐1α pathway, Mn2+ and DFO@PCL NP further promote angiogenesis. Moreover, DFO inhibits osteoclast differentiation and synergistically collaborates with the osteoinductive activity of HA. Based on amounts of data in vitro and in vivo, strong immunomodulatory, intensive angiogenic, weak osteoclastogenic, and superior osteogenic abilities of such an osteoimmunity‐regulating scaffold present a profound effect on improving bone regeneration, which puts forward a worthy base and positive enlightenment for large‐scale bone defect repair.
We developed dual biologically responsive nanogapped gold nanoparticle vesicles loaded with immune inhibitor and carrying an anticancer polymeric prodrug for synergistic concurrent chemo-immunotherapy against primary and metastatic tumors, along with guided cargo release by photoacoustic (PA) imaging in the second near-infrared (NIR-II) window. The responsive vesicle was prepared by self-assembly of nanogapped gold nanoparticles (AuNNPs) grafted with poly(ethylene glycol) (PEG) and dual pH/GSH-responsive polyprodug poly(SN38-co-4-vinylpyridine) (termed AuNNP@PEG/PSN38VP), showing intense PA signal in the NIR-II window. The effect of the rigidity of hydrophobic polymer PSN38VP on the assembled structures and the formation mechanism of AuNNP@SN38 Ve were elucidated by computational simulations. The immune inhibitor BLZ-945 was encapsulated into the vesicles, resulting in pH-responsive release of BLZ-945 for targeted immunotherapy, followed by the dissociation of the vesicles into single AuNNP@PEG/PSN38VP. The hydrophilic AuNNP@PEG/PSN38VP nanoparticles could penetrate deep into the tumor tissues and release the anticancer drug SN38 under the reductive environment. A PA signal in the NIR-II window in the deep tumor region was obtained. The BLZ-945-loaded vesicle enabled enhanced PA imaging-guided concurrent chemo-immunotherapy efficacy, inhibiting the growth of both primary tumors and metastatic tumors.
Smart assemblies have attracted increased interest in various areas, especially in developing novel stimuli-responsive theranostics. Herein, commercially available, natural tannic acid (TA) and iron oxide nanoparticles (Fe O NPs) are utilized as models to construct smart magnetic assemblies based on polyphenol-inspired NPs-phenolic self-assembly between NPs and TA. Interestingly, the magnetic assemblies can be specially disassembled by adenosine triphosphate, which shows a stronger affinity to Fe O NPs than that of TA and partly replaces the surface coordinated TA. The disassembly can further be facilitated by the acidic environment hence causing the remarkable change of the transverse relaxivity and potent "turn-on" of fluorescence (FL) signals. Therefore, the assemblies for specific and sensitive tumor magnetic resonance and FL dual-modal imaging and photothermal therapy after intravenous injection of the assemblies are successfully employed. This work not only provides understandings on the self-assembly between NPs and polyphenols, but also will open new insights for facilely constructing versatile assemblies and extending their biomedical applications.
Bone Repair In article number 2202044, Jiayong Dai, Jianxun Ding, Huanghao Yang, and co‐workers develop an osteoimmunity‐regulating biomimetically hierarchical scaffold to improve large‐scale bone‐defect regene ration through alleviating inflammation, enhancing neovascularization, stimulating osteogenesis, and inhibiting osteoclasts, facilitating the balance of the immune system and bone metabolism and augmenting bone repair.
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