No abstract

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.

Cancer immunotherapy has achieved promising clinical progress over the recent years for its potential to treat metastatic tumors and inhibit their recurrences effectively. However, low patient response rates and dose-limiting toxicity remain as major dilemmas for immunotherapy. Stimuli-responsive nanoparticles (srNPs) combined with immunotherapy offer the possibility to amplify anti-tumor immune responses, where the weak acidity, high concentration of glutathione, overexpressions of enzymes, and reactive oxygen species, and external stimuli in tumors act as triggers for controlled drug release. This review highlights the design of srNPs based on tumor microenvironment and/or external stimuli to combine with different anti-tumor drugs, especially the immunoregulatory agents, which eventually realize synergistic immunotherapy of malignant primary or metastatic tumors and acquire a long-term immune memory to prevent tumor recurrence. The authors hope that this review can provide theoretical guidance for the construction and clinical transformation of smart srNPs for controlled drug delivery in synergistic cancer immunotherapy.

Massive bleeding and wound infection are the major problems often observed during severe trauma, and achieving rapid hemostasis in cases of high‐dose bleeding in arteries and viscera remains an acute clinical demand. Herein, a mussel‐ and barnacle cement proteins‐inspired dual‐bionic hydrogel is first proposed. Benefiting from abundant phenolic hydroxyl groups, a tough dissipative matrix, removal of interfacial water, as well as dynamic redox balance of phenol‐quinone, the multinetwork hydrogel achieves repeatable robust wet‐tissue adhesiveness (151.40 ± 1.50 kPa), a fast multimodal self‐healing ability, and excellent antibacterial property against both Gram‐positive/negative bacteria. For rabbit/pig models of cardiac penetration holes and femoral artery injuries, the dual‐bionic bioadhesive shows better hemostatic efficiency than commercial gauze due to the synergistic effect of strong wound sealing capability, excellent red blood cell capturing property, and activation of hemostatic barrier membrane. More interestingly, the hydrogel combined with commercial hemostatic sponge presents accelerated wound healing as well as great potential for treating deep‐wound hemorrhage in a battlefield environment. Overall, owing to these unique advantages, the novel tissue‐adhesive hemostat opens up a new avenue to rapid sealing hemostasis and wound healing 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.