Bioactive Materials最新文献

{"title":"Angiogenesis in rheumatoid Arthritis: Pathological characterization, pathogenic mechanisms, and nano-targeted therapeutic strategies","authors":"Fang Zhao ,&nbsp;Zeyu Hu ,&nbsp;Gejing Li ,&nbsp;Min Liu ,&nbsp;Qiong Huang ,&nbsp;Kelong Ai ,&nbsp;Xiong Cai","doi":"10.1016/j.bioactmat.2025.04.026","DOIUrl":"10.1016/j.bioactmat.2025.04.026","url":null,"abstract":"<div><div>Angiogenesis is critical from early development through the progression of life-threatening diseases. In rheumatoid arthritis (RA), angiogenesis is markedly heightened and undergoes aberrant changes that exacerbate the progression of synovitis. However, the intricate mechanisms underlying these changes remain poorly understood. Despite the development of numerous anti-angiogenic agents, their clinical efficacy is often compromised by adverse effects and the emergence of adaptive resistance, leading to disease relapse or progression. Nanomedicine has gained significant attention owing to its excellent biocompatibility, precise biological targeting, and enhanced therapeutic outcomes. Anti-angiogenic nanoagents have shown transformative potential in treating cancer and retinal diseases. Nevertheless, a comprehensive review addressing the fundamental mechanisms of anti-angiogenic nanoagents in RA has yet to be undertaken. Herein, this review provides an in-depth description of the unique structural and functional aspects of pathological angiogenesis in RA and its negative consequences. The mechanisms of pro-angiogenic mediators contributing to RA angiogenesis are further explored. Subsequently, biological activities of nanomedicines for the treatment of RA are summarized. Finally, the cutting-edge developments in the anti-angiogenic nanoagents of RA engineered based on these mechanisms and bioactivities are outlined. A helpful introduction to anti-angiogenic strategies for treatment of RA, which may offer novel perspectives for the development of nanoagents, is opening a new horizon in the fight against RA.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 603-639"},"PeriodicalIF":18.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899939","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":"Enhanced sequential osteosarcoma therapy using a 3D-Printed bioceramic scaffold combined with 2D nanosheets via NIR-II photothermal-chemodynamic synergy","authors":"Guangyu Jian ,&nbsp;Si Wang ,&nbsp;Xinlu Wang ,&nbsp;Qinyi Lu ,&nbsp;Xingyu Zhu ,&nbsp;Shucheng Wan ,&nbsp;Shan Wang ,&nbsp;Dize Li ,&nbsp;Chao Wang ,&nbsp;Qingqing He ,&nbsp;Tao Chen ,&nbsp;Jinlin Song","doi":"10.1016/j.bioactmat.2025.04.029","DOIUrl":"10.1016/j.bioactmat.2025.04.029","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma (OS) is a malignant tumor originating from primitive mesenchymal cells, characterized by rapid metastasis, high invasiveness, and significant mortality. The primary challenges in OS management include the effective elimination of residual tumor cells to prevent recurrence and the repair of extensive bone defects caused by surgical intervention.</div></div><div><h3>Objective</h3><div>This study aims to develop an innovative biomimetic 3D-printed bioactive glass ceramic (BGC) scaffold modified with two-dimensional nanosheets to address both tumor ablation and bone tissue repair.</div></div><div><h3>Materials and methods</h3><div>The nanosheets were constructed via ellagic acid (EA) and ruthenium (Ru) coordination, leveraging the non-topological adhesion properties of catechol in EA to deposit the nanosheets onto the BGC scaffold (EARu-BGC). The therapeutic effects of EARu-BGC were evaluated <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Results</h3><div>EARu-BGC sequentially responds to the local microenvironment during OS treatment. During the tumor ablation phase, EARu-BGC induced ferroptosis through the synergistic effects of photothermal and chemodynamic therapy, achieving over 90 % tumor cell ablation and significantly inhibiting tumor volume and weight. In the bone tissue repair phase, EARu-BGC exhibited adaptive ROS scavenging and facilitated a pro-healing microenvironment, promoting osteogenic differentiation. The gradual degradation of the BGC scaffold provided essential minerals and space for new bone formation. In vivo experiments demonstrated that EARu-BGC significantly enhanced osteogenesis, increasing the trabecular number to 1.51 ± 0.15/mm and reducing trabecular separation to 1.50 ± 0.04 mm.</div></div><div><h3>Conclusion</h3><div>The EARu-BGC scaffold presents a promising multifunctional platform for OS treatment by effectively balancing antitumor efficacy with bone repair capabilities.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 540-555"},"PeriodicalIF":18.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888170","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":"Microenvironment-responsive living hydrogel containing engineered probiotic for treatment of massive bone defects","authors":"Haoyu Fang ,&nbsp;Yanyi Wang ,&nbsp;Li Li ,&nbsp;Xiaotong Qin ,&nbsp;Daoyu Zhu ,&nbsp;Pei Liu ,&nbsp;Qianhao Yang ,&nbsp;Youshui Gao ,&nbsp;Zhongmin Shi ,&nbsp;Xin Ma ,&nbsp;Chao Zhong ,&nbsp;Yixuan Chen","doi":"10.1016/j.bioactmat.2025.04.020","DOIUrl":"10.1016/j.bioactmat.2025.04.020","url":null,"abstract":"<div><div>Self-activating and microenvironment-responsive biomaterials for tissue regeneration would address the escalating need for bone grafting, but remain challenging. The emergence of microbial living therapeutics offers vast potential in regenerative medicine, as genetically engineered probiotics possess efficient stimuli-responsiveness and tunable biological functions. Here, using elevated endogenous nitric oxide (NO) signals as a biological trigger in bone fracture injuries, a Living Responsive Regenerative Medicine (LRRM) strategy for <em>in situ</em> bone defect repair through real-time controlled release of bone morphogenetic protein-2 (BMP2) is proposed. The <em>Escherichia coli</em> Nissle 1917 (EcN) strain, genetically engineered to sense NO signals and correspondingly produce and secrete BMP2, was firstly encapsulated in gelatin methacryloyl (GelMA) microspheres and then embedded in a bulky hyaluronic acid methacryloyl (HAMA) hydrogel to form a living hydrogel device that circumvents immune attack and prevents bacterial leakage. <em>In vivo</em> multiple bone defect models demonstrated the efficacy of the living hydrogel in enhancing the maturation of bone callus, promoting neovascularization, and facilitating full-thickness bone union. Strategic incorporation of engineered probiotics and the bilayer-structured encapsulation system may emerge as an effective and microenvironment-responsive medicine approach for tissue regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 556-570"},"PeriodicalIF":18.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888171","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":"Construction of vascularized liver microtissues recapitulates angiocrine-mediated hepatocytes maturation and enhances therapeutic efficacy for acute liver failure","authors":"Liuyang Zhu ,&nbsp;Sen Liu ,&nbsp;Zhuangzhuang Yang ,&nbsp;Long Yang ,&nbsp;Yueyue Yang ,&nbsp;Pinsheng Han ,&nbsp;Yu Miao ,&nbsp;Lei Lin ,&nbsp;Lilin Xu ,&nbsp;Yan Li ,&nbsp;Xinyue Li ,&nbsp;Libo Wang ,&nbsp;Tianyu Zhao ,&nbsp;Weiwei Wang ,&nbsp;Zilin Cui ,&nbsp;Ze Wang ,&nbsp;Deling Kong ,&nbsp;Zhongyang Shen ,&nbsp;Yamin Zhang","doi":"10.1016/j.bioactmat.2025.04.030","DOIUrl":"10.1016/j.bioactmat.2025.04.030","url":null,"abstract":"<div><div>Liver failure poses a significant challenge for millions of patients. The use of primary human hepatocytes and the engineering of liver organoids or liver tissue provide promising solutions to mitigate the shortage of donor organs. However, insufficient vascularization and functional immaturity remain major barriers impeding optimal functional recovery after transplantation. In this study, adult stem cells derived from human liver tissues were induced to form liver organoids, which were subsequently co-cultured with vascular organoids generated from human induced pluripotent stem cells in a defined ratio to create vascularized liver microtissues. This approach successfully established a complex vascular network analogous to that found in the liver, effectively recapitulating a more physiologically relevant liver architecture. Mechanistically, this configuration promoted the structural and secretory maturation of liver organoids through paracrine signaling from the vasculature. Following transplantation into the mesentery of mice, the vascularized liver microtissues rapidly established connections with the host vasculature and enhanced secretion of albumin into the bloodstream. Moreover, the transplantation of vascularized liver microtissues could effectively ameliorate liver injury and inflammatory responses, reduce apoptosis while promoting cell proliferation in CCl₄-induced acute liver failure mice. These findings provide a robust platform for investigating the interactions between vessels and liver, and have important implications for liver failure treatment in the field of regenerative medicine.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 525-539"},"PeriodicalIF":18.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888173","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":"Harnessing advanced computational approaches to design novel antimicrobial peptides against intracellular bacterial infections","authors":"Yanpeng Fang ,&nbsp;Duoyang Fan ,&nbsp;Bin Feng ,&nbsp;Yingli Zhu ,&nbsp;Ruyan Xie ,&nbsp;Xiaorong Tan ,&nbsp;Qianhui Liu ,&nbsp;Jie Dong ,&nbsp;Wenbin Zeng","doi":"10.1016/j.bioactmat.2025.04.016","DOIUrl":"10.1016/j.bioactmat.2025.04.016","url":null,"abstract":"<div><div>Intracellular bacterial infections pose a significant challenge to current therapeutic strategies due to the limited penetration of antibiotics through host cell membranes. This study presents a novel computational framework for efficiently screening candidate peptides against these infections. The proposed strategy comprehensively evaluates the essential properties for the clinical application of candidate peptides, including antimicrobial activity, permeation efficiency, and biocompatibility, while also taking into account the speed and reliability of the screening process. A combination of multiple AI-based activity prediction models allows for a thorough assessment of sequences in the cell-penetrating peptides (CPPs) database and quickly identifies candidate peptides with target properties. On this basis, the CPP microscopic dynamics research system was constructed. Exploration of the mechanism of action at the atomic level provides strong support for the discovery of promising candidate peptides. Promising candidates are subsequently validated through <em>in vitro</em> and <em>in vivo</em> experiments. Finally, Crot-1 was rapidly identified from the CPPsite 2.0 database. <strong>Crot-1</strong> effectively eradicated intracellular MRSA, demonstrating significantly greater efficacy than vancomycin. Moreover, it exhibited no apparent cytotoxicity to host cells, highlighting its potential for clinical application. This work offers a promising new avenue for developing novel antimicrobial materials to combat intracellular bacterial infections.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 510-524"},"PeriodicalIF":18.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879208","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":"Cryopreservable, scalable and ready-to-use cell-laden patches for diabetic ulcer treatment","authors":"Bangrui Yu ,&nbsp;Lanlan Peng ,&nbsp;Wenjun Dang ,&nbsp;Ying Fu ,&nbsp;Zhijie Li ,&nbsp;Jinteng Feng ,&nbsp;Heng Zhao ,&nbsp;Tian Wang ,&nbsp;Feng Xu ,&nbsp;Martin L. Yarmush ,&nbsp;Haishui Huang","doi":"10.1016/j.bioactmat.2025.04.024","DOIUrl":"10.1016/j.bioactmat.2025.04.024","url":null,"abstract":"<div><div>Stem cell-laden hydrogel patches are promising candidates to treat chronic ulcers due to cells’ long-lasting and dynamic responses to wound microenvironment. However, their clinical translations are prohibited by the cryopreservation difficulty due to their weak mechanical strength and slow biotransport capability, and by the morphological mismatch between clinical ulcers and pre-fabricated patches. Here we report a stem cell-laden alginate-dopamine hydrogel patch that can be readily cryopreserved, processed, and scaled toward clinical usages. This cell-hydrogel patch not only maintains cell viability and structure integrity during cryopreservation, but also can be directly utilized without centrifugation or incubation post cryopreservation. In addition, this tissue-adhesive hydrogel patch enables close wound contact and fast cellular response, and its scalable and flexible structure enables assembly for large or irregularly shaped ulcers. Therefore, it accelerates ulcer healing and reduces scar formation <em>via</em> continuous, versatile, self-adjusting paracrine of imbedded, cryopreserved stem cells. These findings highlight its potential for scalable clinical applications in chronic wound management and pave the way for broader adoption of ready-to-use regenerative therapies.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 461-474"},"PeriodicalIF":18.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874374","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":"Sequential simulation of regeneration-specific microenvironments using scaffolds loaded with nanoplatelet vesicles enhances bone regeneration","authors":"Wenshuai Li ,&nbsp;Qichen Shen ,&nbsp;Tong Tong ,&nbsp;Hongsen Tian ,&nbsp;Xiaowei Lian ,&nbsp;Haoli Wang ,&nbsp;Ke Yang ,&nbsp;Zhanqiu Dai ,&nbsp;Yijun Li ,&nbsp;Xianhua Chen ,&nbsp;Qingqing Wang ,&nbsp;Dan Yang ,&nbsp;Feng Wang ,&nbsp;Feng Hao ,&nbsp;Linfeng Wang","doi":"10.1016/j.bioactmat.2025.04.018","DOIUrl":"10.1016/j.bioactmat.2025.04.018","url":null,"abstract":"<div><div>Bone regeneration is a complex and coordinated physiological process, and the different stages of this process have corresponding microenvironments to support cell development and physiological activities. However, biological scaffolds that provide different three-dimensional environments during different stages of bone regeneration are lacking. In this study, we report a novel composite scaffold (NPE@DCBM) inspired by the stages of bone regeneration; this scaffold was composed of a fibrin hydrogel loaded with nanoplatelet vesicles (NPVs), designated as NPE, and decellularized cancellous bone matrix (DCBM) microparticles. Initially, the NPE rapidly established a temporary microenvironment conducive to cell migration and angiogenesis. Subsequently, the DCBM simulated the molecular structure of bone and promoted new bone formation. <em>In vitro</em>, the NPVs regulated lipid metabolism in bone marrow mesenchymal stem cells (BMSCs), reprogramed the fate of BMSCs by activating the PI3K/AKT and MAPK/ERK positive feedback pathways, and increased BMSC functions, including proliferation, migration and proangiogenic potential. <em>In vivo</em>, NPV@DCBM accelerated bone tissue regeneration and repair. Initially, the NPE rapidly induced angiogenesis between DCBM microparticles, and subsequently, BMSCs differentiated into osteoblasts with DCBM microparticles at their core. In summary, the design of this composite scaffold that sequentially mimics different bone regeneration microenvironments may provide a promising strategy for bone regeneration, with clinical translational potential.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 475-493"},"PeriodicalIF":18.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874379","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":"Harnessing the power of physicochemical material property screening to direct breast epithelial and breast cancer cells","authors":"Lisa E. Tromp ,&nbsp;Rik de Jong ,&nbsp;Torben A.B. van der Boon ,&nbsp;Alejandro Reina Mahecha ,&nbsp;Ruud Bank ,&nbsp;Jan de Boer ,&nbsp;Patrick van Rijn","doi":"10.1016/j.bioactmat.2025.04.003","DOIUrl":"10.1016/j.bioactmat.2025.04.003","url":null,"abstract":"<div><div>Understanding cell-material interactions is crucial for advancing biomedical applications, influencing cellular behavior and medical device performance. Material properties can be manipulated to direct cell responses, benefiting applications from regenerative medicine to implantable devices such as silicone breast implants. Knowledge about the interaction differences between healthy and cancer cells with implants may guide implant design to more precisely influence cell adhesion and proliferation of healthy cells while inhibiting cancer cells, tailoring outcomes to specific cellular responses. To show-case this potential, breast epithelial cells and breast cancer cells were investigated regarding their interaction with a broad range of combined physicochemical properties. This study employed a silicone-based high-throughput screening method utilizing Double Orthogonal Gradients (DOGs) to investigate the influence of topography, stiffness, and wettability on breast epithelial cells (MCF10a) and breast cancer cells (MCF7). Results show distinct cellular responses, including decreased proliferation rates in both MCF10a and MCF7 cells with the introduction of surface topography and the dominant influence of wettability on cell adhesion, proliferation, and cluster formation. The screening identified specific regions of interest (ROIs) where MCF10a cell proliferation outperformed MCF7 cells and that topography inhibits cluster formation (tumorigenesis), offering potential prospects for the creation of novel implant surfaces.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 494-509"},"PeriodicalIF":18.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874380","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":"A novel CD44-targeting aptamer recognizes chemoresistant mesenchymal stem-like TNBC cells and inhibits tumor growth","authors":"Alessandra Caliendo ,&nbsp;Simona Camorani ,&nbsp;Luis Exequiel Ibarra ,&nbsp;Gabriella Pinto ,&nbsp;Lisa Agnello ,&nbsp;Sandra Albanese ,&nbsp;Antonietta Caianiello ,&nbsp;Anna Illiano ,&nbsp;Rosaria Festa ,&nbsp;Vincenzo Ambrosio ,&nbsp;Giosuè Scognamiglio ,&nbsp;Monica Cantile ,&nbsp;Angela Amoresano ,&nbsp;Monica Fedele ,&nbsp;Antonella Zannetti ,&nbsp;Laura Cerchia","doi":"10.1016/j.bioactmat.2025.04.027","DOIUrl":"10.1016/j.bioactmat.2025.04.027","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) represents a significant therapeutic challenge owing to the scarcity of targeted medicines and elevated recurrence rates. We previously reported the development of the nuclease-resistant RNA sTN58 aptamer, which selectively targets TNBC cells. Here, sTN58 aptamer was employed to capture and purify its binding target from the membrane protein fraction of cisplatin-resistant mesenchymal stem-like TNBC cells. Mass spectrometry in conjunction with aptamer binding assays across various cancer cell lines identified CD44 as the cellular target of sTN58. By binding to CD44, sTN58 inhibits the invasive growth and hyaluronic acid-dependent tube formation in chemoresistant TNBC cells, where CD44 serves as a key driver of tumor cell aggressiveness and stem-like plasticity. Moreover, in vivo studies demonstrated the aptamer's high tumor targeting efficacy and its capacity to significantly inhibit tumor growth and lung metastases following intravenous administration in mice with orthotopic TNBC. Overall, our findings reveal the striking potential of sTN58 as a targeting reagent for the recognition and therapy of cancers overexpressing CD44.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 443-460"},"PeriodicalIF":18.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867912","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":"Association between serum Copper-Zinc-Selenium mixture and multiple health outcomes","authors":"Yufei Wang ,&nbsp;Yiwen Sun ,&nbsp;Tianyang Jie ,&nbsp;Minqi Wang ,&nbsp;Shutao Zhang ,&nbsp;Hongtao Yang ,&nbsp;Weiyan Jian ,&nbsp;Dai Dai ,&nbsp;Ruida Xu ,&nbsp;Bing Yue ,&nbsp;Xinhua Qu","doi":"10.1016/j.bioactmat.2025.04.004","DOIUrl":"10.1016/j.bioactmat.2025.04.004","url":null,"abstract":"<div><h3>Background</h3><div>Metallic biomaterials have transformed modern medicine, with copper (Cu), zinc (Zn), and selenium (Se) emerging as critical components in medical applications. The study of the single and synergistic effects of serum metal concentrations on human health can provide valuable insights for future clinical transformation of biodegradable alloys.</div></div><div><h3>Methods</h3><div>We evaluated 2381 NHANES 2011–2016 participants to study individual and combined effects of these metals on health outcomes. Multivariable logistic regression, restricted cubic splines, and piecewise linear regression were used to examine linear, nonlinear, and threshold relationships. Overall metal mixture effects were assessed using weighted quantile sum (WQS) and Bayesian kernel-machine regression (BKMR).</div></div><div><h3>Results</h3><div>Elevated serum Cu levels were significantly associated with an increased risk of osteoarthritis. When Serum Cu ≥ 99.48 μg/dL, each 1-unit increase in Ln Cu raised diabetes risk 4.55-fold. For Se ≥ 122.74 μg/L, each 1-unit increase in Ln Se led to a 29.96-fold rise in diabetes prevalence, for Se &lt; 157.56 μg/L it increased heart attack risk 165.19-fold. Furthermore, mixtures of Cu, Se, and Zn were positively associated with diabetes, hypertension, and heart attack risks; each unit increase in the mixture corresponded to a 23 % rise in diabetes and a 15 % rise in hypertension prevalence.</div></div><div><h3>Conclusions</h3><div>Serum Cu levels ≥99.48 μg/dL are significantly linked to diabetes risk, while serum Se levels ≥122.74 μg/L are associated with diabetes risk and levels &lt;157.56 μg/L with elevated heart attack risk. Serum metal mixtures containing Cu, Se and Zn were significantly and positively associated with risk of diabetes, hypertension and heart attack.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 432-442"},"PeriodicalIF":18.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864469","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}