Biomaterials最新文献

{"title":"STING-activating layered double hydroxide nano-adjuvants for enhanced cancer immunotherapy","authors":"Lirui Jia ,&nbsp;Yang Qin ,&nbsp;Xin Li ,&nbsp;Hongzhuo Liu ,&nbsp;Zhonggui He ,&nbsp;Yongjun Wang","doi":"10.1016/j.biomaterials.2025.123294","DOIUrl":"10.1016/j.biomaterials.2025.123294","url":null,"abstract":"<div><div>Cancer vaccines represent a promising therapeutic strategy in oncology, yet their effectiveness is often hampered by suboptimal antigen targeting, insufficient induction of cellular immunity, and the immunosuppressive tumor microenvironment. Advanced delivery systems and potent adjuvants are needed to address these challenges, though a restricted range of adjuvants for human vaccines that are approved, and even fewer are capable of stimulating robust cellular immune response. In this work, we engineered a unique self-adjuvanted platform (MLDHs) by integrating STING agonists manganese into a layered double hydroxide nano-scaffold, encapsulating the model antigen ovalbumin (OVA). The MLDHs platform encompasses Mn-doped MgAl-LDH (MLMA) and Mn-doped MgFe-LDH (MLMF). Upon subcutaneous injection, OVA/MLDHs specifically accumulated within lymph nodes (LNs), where they were internalized by resident antigen-presenting cells. The endosomal degradation of MLDHs facilitated the cytoplasmic release of antigen and Mn²⁺, promoting cross-presentation and triggering the STING pathway, which in turn induced a potent cellular immune response against tumors. Notably, OVA/MLMF induced stronger M1 macrophage polarization and a more potent T-cell response within tumor-infiltrating lymphocytes compared to OVA/MLMA, leading to significant tumor regression in B16F10-OVA bearing mice with minimal adverse effects. Additionally, combining MLMF with the vascular disrupting agent Vadimezan disrupted the tumor's central region, typically resistant to immune cell infiltration, further extending survival in tumor-bearing mice. This innovative strategy may show great potential for improving cancer immunotherapy and offers hope for more effective treatments in the future.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123294"},"PeriodicalIF":12.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of urinary extracellular vesicles in delivering functional proteins and modulating gene expression for genetic kidney disease","authors":"Yi Huang ,&nbsp;Ali Osouli ,&nbsp;Hui Li ,&nbsp;Megan Dudaney ,&nbsp;Jessica Pham ,&nbsp;Valeria Mancino ,&nbsp;Taranatee Khan ,&nbsp;Baishali Chaudhuri ,&nbsp;Nuria M. Pastor-Soler ,&nbsp;Kenneth R. Hallows ,&nbsp;Eun Ji Chung","doi":"10.1016/j.biomaterials.2025.123296","DOIUrl":"10.1016/j.biomaterials.2025.123296","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) is a widespread health concern, impacting approximately 600 million individuals worldwide and marked by a progressive decline in kidney function. A common form of CKD is autosomal dominant polycystic kidney disease (ADPKD), which is the most inherited genetic kidney disease and affects greater than 12.5 million individuals globally. Given that there are over 400 pathogenic <em>PKD1/PKD2</em> mutations in patients with ADPKD, relying solely on small molecule drugs targeting a single signaling pathway has not been effective in treating ADPKD. Urinary extracellular vesicles (uEVs) are naturally released by cells from the kidneys and the urinary tract, and uEVs isolated from non-disease sources have been reported to carry functional polycystin-1 (PC1) and polycystin-2 (PC2), the respective products of <em>PKD1</em> and <em>PKD2</em> genes that are mutated in ADPKD. uEVs from non-disease sources, as a result, have the potential to provide a direct solution to the root of the disease by delivering functional proteins that are mutated in ADPKD. To test our hypothesis, we first isolated uEVs from healthy mice urine and conducted a comprehensive characterization of uEVs. Then, PC1 levels and EV markers CD63 and TSG101 of uEVs were confirmed via ELISA and Western blot. Following characterization of uEVs, the <em>in vitro</em> cellular uptake, inhibition of cyst growth, and gene rescue ability of uEVs were demonstrated in kidney cells. Next, upon administration of uEVs <em>in vivo</em>, uEVs showed bioavailability and accumulation in the kidneys. Lastly, uEV treatment in ADPKD mice (<em>Pkd1</em>^{<em>fl/fl</em>}<em>;Pax8-rtTA;Tet-O-Cre</em>) showed smaller kidney size, lower cyst index, and enhanced PC1 levels without affecting safety despite repeated treatment. In summary, we demonstrate the potential of uEVs as natural nanoparticles to deliver protein and gene therapies for the treatment of chronic and genetic kidney diseases such as ADPKD.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123296"},"PeriodicalIF":12.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective vascular disrupting therapy by lipid nanoparticle-mediated Fas ligand silencing and stimulation of STING","authors":"Rikito Endo ,&nbsp;Tomoki Ueda ,&nbsp;Takumi Nagaoki ,&nbsp;Yusuke Sato ,&nbsp;Nako Maishi ,&nbsp;Kyoko Hida ,&nbsp;Hideyoshi Harashima ,&nbsp;Takashi Nakamura","doi":"10.1016/j.biomaterials.2025.123297","DOIUrl":"10.1016/j.biomaterials.2025.123297","url":null,"abstract":"<div><div>Although recent therapeutic developments have greatly improved the outcomes of patients with cancer, it remains on ongoing problem, particularly in relation to acquired drug resistance. Vascular disrupting agents (VDAs) directly damage tumor blood vessels, thus promoting drug efficacy and reducing the development of drug resistance; however, their low molecular weight and resulting lack of selectivity for tumor endothelial cells (TECs) lead to side effects that can hinder their practical use. Here, we report a novel tumor vascular disrupting therapy using nucleic acid-loaded lipid nanoparticles (LNPs). We prepared two LNPs: a small interfering RNA (siRNA) against Fas ligand (FasL)-loaded cyclic RGD modified LNP (cRGD-LNP) to knock down FasL in TECs and a stimulator of interferon genes (STING) agonist-loaded LNP to induce systemic type I interferon (IFN) production. The combination therapy disrupted the tumor vasculature and induced broad tumor cell apoptosis within 48 h, leading to rapid and strong therapeutic effects in various tumor models. T cells were not involved in these antitumor effects. Furthermore, the combination therapy demonstrated a significantly superior therapeutic efficacy compared with conventional anti-angiogenic agents and VDAs. RNA sequencing analysis suggested that reduced collagen levels may have been responsible for TEC apoptosis. These findings demonstrated a potential therapeutic method for targeting the tumor vasculature, which may contribute to the development of a new class of anti-cancer drugs.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123297"},"PeriodicalIF":12.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI-responsive nanoprobes for visualizing hydrogen peroxide in diabetic liver injury","authors":"Xingyue Fan ,&nbsp;Yue Sun ,&nbsp;Jiaqi Fu ,&nbsp;Hui Cao ,&nbsp;Shiyi Liao ,&nbsp;Cheng Zhang ,&nbsp;Shuangyan Huan ,&nbsp;Guosheng Song","doi":"10.1016/j.biomaterials.2025.123292","DOIUrl":"10.1016/j.biomaterials.2025.123292","url":null,"abstract":"<div><div>Diabetic liver injury has emerged as a significant complication associated with diabetes, warranting increased attention. The generation of hydrogen peroxide (H₂O₂) due to oxidative stress plays a critical role in the onset and progression of this condition. Despite this, there is a scarcity of probes capable of non-invasively, accurately, and reliably visualizing H₂O₂ levels in deep-seated liver in diabetes-induced liver injury. In this study, we introduce a novel H₂O₂-responsive magnetic probe (H₂O₂-RMP), designed for the sensitive imaging of H₂O₂ in the liver injury caused by diabetes. H₂O₂-RMP is synthesized through the co-precipitation of a H₂O₂-responsive amphiphilic polymer, manganese(III) porphyrin (Mn-porphyrin), and iron oxide nanoparticles. When exposed to H₂O₂, the released iron oxide nanoparticles aggregate, resulting in an increased T₂-weighted MR signal intensity. H₂O₂-RMP not only demonstrates a wide dynamic response range (initial r₂ = 9.87 mM^-¹s^-¹, Δr₂ = 7.69 mM^-¹s^-¹), but also exhibits superior selectivity for H₂O₂ compared to other reactive oxygen species. Importantly, H₂O₂-RMP exhibits high sensitivity, with a detection limit for hydrogen peroxide as low as 0.56 μM. Moreover, H₂O₂-RMP has been effectively applied for real-time imaging of H₂O₂ levels in the livers of diabetic model mice with varying degrees of severity, highlighting its potential for visual diagnosis and monitoring the progression of diabetic liver injury.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123292"},"PeriodicalIF":12.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrid cell membrane coating orchestrates foreign-body reactions, anti-adhesion, and pro-regeneration in abdominal wall reconstruction","authors":"Lingbing Yang ,&nbsp;Pu Wang ,&nbsp;Yilin Zhang ,&nbsp;Jin Zhou ,&nbsp;Xuewei Bi ,&nbsp;Zhiyong Qian ,&nbsp;Sen Hou ,&nbsp;Linhao Li ,&nbsp;Yubo Fan","doi":"10.1016/j.biomaterials.2025.123289","DOIUrl":"10.1016/j.biomaterials.2025.123289","url":null,"abstract":"<div><div>Tension-free synthetic meshes are the clinical standard for hernia repair, but they often trigger immune response-mediated complications such as severe foreign-body reactions (FBR), visceral adhesions, and fibrotic healing, increasing the risk of recurrence. Herein, we developed a hybrid cell membrane coating for macroscale mesh fibers that acts as an immune orchestrator, capable of balancing immune responses with tissue regeneration. Cell membranes derived from red blood cells (RBCs) and platelets (PLTs) were covalently bonded to fiber surfaces using functionalized-liposomes and click chemistry. The fusion of clickable liposomes with cell membranes significantly improved coating efficiency, coverage uniformity, and <em>in vivo</em> stability. Histological and flow cytometric analyses of subcutaneous implantation in rats and mice demonstrated significant biofunctional heterogeneity among various cell membrane coatings in FBR. Specifically, the RBC-PLT-liposome hybrid cell membrane coating markedly mitigated FBR, facilitated host cell infiltration, and promoted M2-type macrophage polarization. Importantly, experimental results of abdominal wall defect repairs in rats indicate that the hybrid cell membrane coating effectively prevented visceral adhesions, promoted muscle regenerative healing, and enhanced the recruitment of Pax7⁺/MyoD⁺ muscle satellite cells. Our findings suggest that the clickable hybrid cell membrane coating offers a promising approach to enhance clinical outcomes of hernia mesh in abdominal wall reconstruction.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123289"},"PeriodicalIF":12.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"M1-macrophage membrane-camouflaged nanoframeworks activate multiple immunity via calcium overload and photo-sonosensitization","authors":"Yinjing Shen ,&nbsp;Nuo Yu ,&nbsp;Wenjing Zhao ,&nbsp;Shining Niu ,&nbsp;Pu Qiu ,&nbsp;Haiyan Zeng ,&nbsp;Zhigang Chen ,&nbsp;Wei Men ,&nbsp;Dong Xie","doi":"10.1016/j.biomaterials.2025.123287","DOIUrl":"10.1016/j.biomaterials.2025.123287","url":null,"abstract":"<div><div>Immunotherapy is a powerful weapon for inhibiting tumor metastasis, while its efficacy is significantly compromised in immunosuppressive tumor microenvironment (TME). To reverse TME, this work has developed biomimetic nanoframeworks with calcium overload and photo-sonosensitization capacity to activate multiple immunities for metastasis inhibition. The biomimetic nanoframeworks were prepared by the assembly of Ca²⁺ ions and Protoporphyrin IX (PpIX) into nanoframeworks (Ca-PpIX), and the encapsulation of M1 macrophage membrane (Ca-PpIX@M). They exhibit pH-dependent Ca²⁺ ions release, ¹O₂ generation and photothermal conversion under external near-infrared light and ultrasound stimuli. The Ca²⁺-overload and elevated ¹O₂ cause oxidative stress within cells, leading to efficient mitochondrial dysfunction. Successively, the mitochondrial dysfunction induces a reduction in adenosine triphosphate (ATP) levels to inhibit the HSP90 expression, improving photothermal ablation's efficacy. The photo-sonosensitization has the ability to repolarize macrophages with the ratio of M1/M2 macrophage increasing from 0.25 to 2.45, which is better than monoactivation. Importantly, the Ca-PpIX@M also can induce the process of immunogenic cell death, resulting in the maturation of dendritic cells (30.2 %) and activation of cytotoxic (12.4 %) and helper T cells (19.7 %), thereby enhancing antitumor immunity <em>in vivo</em>. As a result, tumor growth and metastasis have been significantly inhibited. This work offers insights into developing biomimetic nanoframeworks to reverse TME for activating multiple immunity.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123287"},"PeriodicalIF":12.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Force-electric biomaterials and devices for regenerative medicine","authors":"Shuncheng Yao ,&nbsp;Xi Cui ,&nbsp;Chao Zhang ,&nbsp;Wenguo Cui ,&nbsp;Zhou Li","doi":"10.1016/j.biomaterials.2025.123288","DOIUrl":"10.1016/j.biomaterials.2025.123288","url":null,"abstract":"<div><div>There is a growing recognition that force-electric conversion biomaterials and devices can convert mechanical energy into electrical energy without an external power source, thus potentially revolutionizing the use of electrical stimulation in the biomedical field. Based on this, this review explores the application of force-electric biomaterials and devices in the field of regenerative medicine. The article focuses on piezoelectric biomaterials, piezoelectric devices and triboelectric devices, detailing their categorization, mechanisms of electrical generation and methods of improving electrical output performance. Subsequently, different sources of driving force for electroactive biomaterials and devices are explored. Finally, the biological applications of force-electric biomaterials and devices in regenerative medicine are presented, including tissue regeneration, functional modulation of organisms, and electrical stimulation therapy. The aim of this review is to emphasize the role of electrical stimulation generated by force-electric conversion biomaterials and devices on the regulation of bioactive molecules, ion channels and information transfer in living systems, and thus affects the metabolic processes of organisms. In the future, physiological modulation of electrical stimulation based on force-electric conversion is expected to bring important scientific advances in the field of regenerative medicine.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123288"},"PeriodicalIF":12.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supramolecular assembly of multi-purpose tissue engineering platforms from human extracellular matrix","authors":"Bruno Ladeira ,&nbsp;Maria Gomes ,&nbsp;Kongchang Wei ,&nbsp;Catarina Custódio ,&nbsp;João Mano","doi":"10.1016/j.biomaterials.2025.123270","DOIUrl":"10.1016/j.biomaterials.2025.123270","url":null,"abstract":"<div><div>Recapitulating the biophysical and biochemical complexity of the extracellular matrix (ECM) remains a major challenge in tissue engineering. Hydrogels derived from decellularized ECM provide a unique opportunity to replicate the architecture and bioactivity of native ECM, however, they exhibit limited long-term stability and mechanical integrity. In turn, materials assembled through supramolecular interactions have achieved considerable success in replicating the dynamic biophysical properties of the ECM. Here, we merge both methodologies by promoting the supramolecular assembly of decellularized human amniotic membrane (hAM), mediated by host-guest interactions between hAM proteins and acryloyl-β-cyclodextrin (AcβCD). Photopolymerization of the cyclodextrins results in the formation of soft hydrogels that exhibit tunable stress relaxation and strain-stiffening. Disaggregation of bulk hydrogels yields an injectable granular material that self-reconstitutes into shape-adaptable bulk hydrogels, supporting cell delivery and promoting neovascularization. Additionally, cells encapsulated within bulk hydrogels sense and respond to the biophysical properties of the surrounding matrix, as early cell spreading is favored in hydrogels that exhibit greater susceptibility to applied stress, evidencing proper cell-matrix interplay. Thus, this system is shown to be a promising substitute for native ECM in tissue repair and modelling.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123270"},"PeriodicalIF":12.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of NanoBiT-Nanobody-based FGL1 biosensors for early assisted diagnosis of esophageal cancer","authors":"Lingyun Li ,&nbsp;Zhongyun Lan ,&nbsp;Huarui Qiao ,&nbsp;Xiangjing Meng ,&nbsp;Ziyang Shi ,&nbsp;Wanting Zhang ,&nbsp;Yi'ang Wang ,&nbsp;Zengchao Sun ,&nbsp;Qianqian Cui ,&nbsp;Lu Wang ,&nbsp;Siyu Zhou ,&nbsp;Fangzheng Hu ,&nbsp;Daizhou Zhang ,&nbsp;Yuanyuan Dai ,&nbsp;Hao Chen ,&nbsp;Yong Geng","doi":"10.1016/j.biomaterials.2025.123286","DOIUrl":"10.1016/j.biomaterials.2025.123286","url":null,"abstract":"<div><div>Esophageal cancer (EC) is one of the most common causes of cancer-related mortality due in part to challenges in early diagnosis. Biomarker identification is crucial for improved early screening and treatment strategies for patients. Firstly, we employed serum proteomics techniques to screen for potential biomarkers in 15 early-stage EC patients and 5 healthy individuals. Among the differentially expressed proteins, FGL1 emerged as a promising candidate (AUC = 0.974) for early detection of EC. Subsequently, we developed NanoBiT-conjugated dual nanobodies (NBNB) sensors for robust and quantitative signal detection in fetal bovine serum (FBS) in 30 min or less, with a limit of detection (LoD) of 11.38 pM. In a case–control study recruiting 96 EC patients and 99 control samples, testing serum samples with the developed NBNB sensors revealed significantly elevated serum level of FGL1 in all-stage EC patients (AUC = 0.7880) and early-stage EC patients (AUC = 0.8286). Additionally, the combined diagnostic performance of FGL1 and CEA in EC samples is notably enhanced (AUC = 0.8847). These findings propose FGL1 as a novel and promising target for the early-stage EC diagnosis and treatment selection. Furthermore, we applied the assay to patients across six types of cancer, suggesting FGL1 as a potential pan-cancer marker. This study introduces a rapid, easy-to-use, cost-effective, reliable, universal, and high-throughput alternative to meet the growing demand for cancer biomarker testing in both academic and clinical settings.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123286"},"PeriodicalIF":12.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metal-free antioxidant nanozyme incorporating bioactive hydrogel as an antioxidant scaffold for accelerating bone reconstruction","authors":"Yang Yang ,&nbsp;Qianrui Zeng ,&nbsp;Chaoyue Zhao ,&nbsp;Jie Shi ,&nbsp;Wanmeng Wang ,&nbsp;Yunkai Liang ,&nbsp;Changyi Li ,&nbsp;Qingxin Guan ,&nbsp;Bo Chen ,&nbsp;Wei Li","doi":"10.1016/j.biomaterials.2025.123285","DOIUrl":"10.1016/j.biomaterials.2025.123285","url":null,"abstract":"<div><div>Oxidative stress at bone defect sites mediates inflammation and even osteoblast apoptosis, severely hindering the repair process. While current antioxidant bone tissue engineering (BTE) scaffolds lack broad-spectrum reactive oxygen species (ROS) scavenging capability and structure-activity elucidation. Herein, we report a three-dimensional nitrogen-doped carbon antioxidant nanozyme (ZIFC) derived from metal-organic frameworks, which exhibits cascading superoxide dismutase- and catalase-like activities, along with the ability to scavenge other harmful free radicals. Through the experimental studies and theoretical calculations, we reveal that the catalase-like activity arises from the synergistic catalytic interaction between graphitized pyridinic nitrogen and its adjacent carbon atom. Moreover, hybrid double network hydrogel integrated with ZIFC is utilized to construct composite scaffold (Gel/ZIFC) by 3D printing. <em>In vivo</em> transcriptome analysis confirms that Gel/ZIFC can rapidly activate antioxidant defense system and suppress local inflammation under oxidative stress microenvironment, thereby protecting cells from oxidative damage. Subsequently, owing to the unique osteoinductive property of carbon nanomaterials and the osteoconductive property of 3D-printed scaffold, Gel/ZIFC composite scaffold exhibits desirable bone repair efficacy. The elucidation of structure-activity relationship and therapeutic mechanism provides new insights and guidance for devising antioxidant BTE scaffolds, and demonstrates their feasibility for clinical application.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123285"},"PeriodicalIF":12.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}