Bioactive Materials最新文献

{"title":"Zwitterionic multifunctional coatings with strong hydration for ureteral stents to inhibit infectious encrustation","authors":"Yucong Wu ,&nbsp;Zhenqing Li ,&nbsp;Xiufang Wen ,&nbsp;Yanping Zhong ,&nbsp;Haoyan Chen ,&nbsp;Lei Qian ,&nbsp;Jiawei Li ,&nbsp;Sujuan Yan ,&nbsp;Peng Yu ,&nbsp;Ye Tian ,&nbsp;Haoyu Jin ,&nbsp;Zhengao Wang ,&nbsp;Jinxia Zhai ,&nbsp;Chengyun Ning","doi":"10.1016/j.bioactmat.2025.08.015","DOIUrl":"10.1016/j.bioactmat.2025.08.015","url":null,"abstract":"<div><div>In the complex urinary environment, an effective method is needed to combat ureteral stent encrustation. Herein, recognizing that the adsorption of mineral salts is the initial step in the encrustation process, we utilized the barrier effect of hydration layers to inhibit encrustation. Through molecular dynamics simulations, sulfobetaine methacrylate can form a hydration layer, which repels encrustation ions in a simulated urinary environment, preventing attachment. Then, we developed a multifunctional zwitterionic polymer coating on the polyurethane stent (PU/ATS) by employing UV-initiated free radical polymerization combined with a dip-coating technique. The hydration layer endows the coating with superhydrophilicity and excellent lubricity, effectively resisting 96.1 % and 83.5 % of encrustation in 30 days and 90 days of urine flow simulation and significantly reducing the bacteria adhesion. PU/ATS demonstrated improved anti-encrustation and anti-biofilm performance under infected conditions compared to the Bard® InLay Optima® stent. Moreover, in the rat bladder encrustation model, the PU/ATS reduced encrustation by 99.6 % (no infected) and by 86.7 % (infected) without organ damage. Therefore, the PU/ATS, by leveraging the hydration layer mechanism as an effective barrier, provides a practical and highly promising solution to combat encrustation and its associated urological complications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 57-73"},"PeriodicalIF":18.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107342","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":"Preclinical research models for evaluating the biocompatibility of bioresorbable metallic cardiovascular stents: A comparative review","authors":"Samuel Hansen ,&nbsp;Thuy Anh Bui ,&nbsp;Xiaoxue Xu ,&nbsp;Kristine McGrath","doi":"10.1016/j.bioactmat.2025.09.004","DOIUrl":"10.1016/j.bioactmat.2025.09.004","url":null,"abstract":"<div><div>Cardiovascular stents are widely used to treat atherosclerosis by relieving vascular obstruction and providing structural support after coronary angioplasty. Bioresorbable metallic stents represent a promising alternative to conventional corrosion-resistant stents, which are linked to late-stage complications such as in-stent restenosis and thrombosis. Due to the diversity of stent materials and designs, rigorous evaluation of their interactions with the vascular environment in relevant preclinical models is essential before clinical translation. However, current studies employ highly variable in vitro cell systems, in vivo animal models, and experimental assays to assess biocompatibility, making it difficult to draw definitive conclusions about candidate designs. This review outlines the current landscape of bioresorbable metallic stents, critically examines the strengths and limitations of preclinical models described in the literature and in international guidelines, and provides recommendations to guide future research in this rapidly evolving field.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"54 ","pages":"Pages 871-885"},"PeriodicalIF":18.0,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057149","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":"Biomimetic dynamic nanomedicine SrHCF: Lattice self-reconstruction based on Fe2+ response to achieve synergistic “ferrous chelation-antioxidation-calcium antagonism-inflammation inhibition” quadruple treatment of CIRI","authors":"Tingli Xiong ,&nbsp;Shuya Wang ,&nbsp;Xiaojing Shi ,&nbsp;Ruishi Li ,&nbsp;Wenxuan Zheng ,&nbsp;Weimin Qi ,&nbsp;Min Liu ,&nbsp;Lin Dai ,&nbsp;Qiong Huang ,&nbsp;Kelong Ai","doi":"10.1016/j.bioactmat.2025.08.030","DOIUrl":"10.1016/j.bioactmat.2025.08.030","url":null,"abstract":"<div><div>Revascularization has revolutionized the treatment of ischemic stroke (IS), but its efficacy is limited by cerebral ischemia-reperfusion injury (CIRI). CIRI involves the dynamic interaction of multidimensional pathological mechanisms such as ferroptosis, calcium overload, oxidative stress, and subsequent inflammatory cytokine storm, which make many emerging single-target therapeutic strategies limited in alleviating CIRI. Strategies that simultaneously and synergistically target multiple key pathological factors in CIRI remain highly anticipated but extremely challenging. This study constructed a Sr-substituted Prussian blue (PB)-like nanodrug (SrHCF) as the ultimate multifunctional nanoplatform for the treatment of CIRI. Specifically, SrHCF firstly holds highly active pseudo-superoxide dismutase (SOD)/catalase (CAT) enzymes to effectively eliminate reactive oxygen species (ROS). Secondly, the Fe³⁺-CN-Sr²⁺ coordination network of SrHCF efficiently captures Fe²⁺ and triggers lattice reconstruction to convert it into PB with stronger antioxidant activity and then thirdly, synchronously releases Sr²⁺ to effectively antagonize Ca²⁺. Due to this multi-pathway therapeutic coordination mechanism, SrHCF can simultaneously inhibit neuronal ferroptosis, reduce oxidative stress and prevent calcium overload. These synergistic effects enable SrHCF to protect mitochondria and alleviate endoplasmic reticulum stress, ultimately significantly reducing neuronal death and the inflammatory storm caused by the activation of the cGAS-STING pathway of microglia. This study provides a promising paradigm of multi-target synergistic regulation for CIRI treatment.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 23-41"},"PeriodicalIF":18.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048537","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":"Engineered bacteria and bacteria-derived nanomaterials for cancer therapy: Mechanisms, designs and advances","authors":"Qinzhen Cheng ,&nbsp;Yalan Zhu ,&nbsp;Shiwen Lv ,&nbsp;Jiacheng Shi ,&nbsp;Mingjie Kuang ,&nbsp;Li Wang ,&nbsp;Xiaoyuan Ji","doi":"10.1016/j.bioactmat.2025.09.012","DOIUrl":"10.1016/j.bioactmat.2025.09.012","url":null,"abstract":"<div><div>Bacteria have emerged as powerful and versatile platforms for cancer therapy, leveraging their inherent tumor-targeting capabilities, adaptability to engineering, and ability to interact dynamically with the tumor microenvironment (TME). This review systematically introduces the multimodal mechanisms of action underlying bacteria-based cancer therapeutics, from direct tumor lysis to bacterial tropism and immune modulation in the TME. We summarize engineering strategies for bacteria-based cancer therapy through two principal approaches: biological engineering (genetic reprogramming and biofilm encapsulation) and physicochemical modification (chemical conjugation, physical interaction, and biomineralization coating). This discussion highlights the key applications of live bacteria, including facultative anaerobes (e.g., <em>Salmonella typhimurium</em> (<em>S. typhimurium</em>) and <em>Escherichia coli</em> (<em>E. coli</em>), obligate anaerobes (e.g., <em>Clostridium</em>), and probiotics (e.g., <em>Bifidobacterium</em>), for precision oncotherapy. In addition to whole-cell therapies, we introduce bacterial derivatives such as outer membrane vesicles (OMVs) and membrane-coated nanoparticles as complementary approaches. Finally, we discuss key translational challenges in bacteria-based cancer therapies, including strain optimization, immune-related adverse effects, and manufacturing scalability. This review consolidates current advances in bacterial cancer therapy, offering a design framework to optimize microbial therapeutics. By bridging engineering principles with clinical needs, it provides actionable insights for developing safer, more effective living medicines against cancers.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 1-22"},"PeriodicalIF":18.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047907","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":"An injectable hyaluronic acid–silanol hydrogel containing arginine and puerarin for immune modulation and enhanced diabetic wound healing","authors":"Renwen Wan ,&nbsp;Zhiheng Lin ,&nbsp;Mowen Xu ,&nbsp;Wei Luo ,&nbsp;Hengjie Jia ,&nbsp;Zhufeng Hu ,&nbsp;Zhengyuan Fang ,&nbsp;Junming Sun ,&nbsp;Yisheng Chen ,&nbsp;Shiyi Chen ,&nbsp;Zhiwen Luo ,&nbsp;Lei Yi ,&nbsp;Zhijie Zhao","doi":"10.1016/j.bioactmat.2025.08.040","DOIUrl":"10.1016/j.bioactmat.2025.08.040","url":null,"abstract":"<div><div>Diabetic wound healing is a significant complication of diabetes mellitus, characterized by prolonged healing times, heightened infection risks, and potential amputations, necessitating innovative therapeutic approaches. This study aims to evaluate the efficacy of a novel injectable hydrogel, AP@HA-Si InjGel, which combines hyaluronic acid, silanol, and bioactive compounds to promote wound healing in diabetic patients. Utilizing a combination of in vitro assays, diabetic mouse models, and advanced techniques such as single-cell RNA sequencing, we demonstrated that AP@HA-Si InjGel significantly accelerates wound closure, enhances collagen deposition, and modulates macrophage polarization towards a pro-healing M2 phenotype while suppressing the inflammatory M1 phenotype. The hydrogel exhibited excellent biocompatibility with over 90 % cell viability and significant antioxidant properties, reducing reactive oxygen species accumulation. Histological analysis confirmed that AP@HA-Si InjGel promoted neovascularization and improved extracellular matrix remodeling, thereby enhancing tissue regeneration. Furthermore, single-cell RNA sequencing revealed distinct macrophage subtypes, with an increased proportion of M2 macrophages and a favorable differentiation trajectory towards enhanced wound healing. Overall, these findings highlight the therapeutic potential of AP@HA-Si InjGel as a comprehensive strategy for diabetic wound management, warranting further exploration in clinical settings to address the growing challenge of impaired wound healing in diabetic patients.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"54 ","pages":"Pages 850-870"},"PeriodicalIF":18.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044635","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 naturally derived lipopeptide lipid nanoparticle platform enabling multiple nucleic acids delivery","authors":"Han Xiao ,&nbsp;Bailing Feng ,&nbsp;Dongdong Gao ,&nbsp;Shuangni Shi ,&nbsp;Yiqing Yang ,&nbsp;Yiwei Zhang ,&nbsp;Fengyang Wang ,&nbsp;Qi Yao ,&nbsp;Haiqing Song ,&nbsp;Ying Liu ,&nbsp;Gang Cheng","doi":"10.1016/j.bioactmat.2025.09.007","DOIUrl":"10.1016/j.bioactmat.2025.09.007","url":null,"abstract":"<div><div>Lipid nanoparticles (LNPs) have emerged as versatile platforms for nucleic acid-based therapies. Despite advancements, key challenges remain in achieving tissue-specific delivery while maintaining low toxicity and tunable properties essential for therapeutic applications. Here, we report a novel high-performance LNP platform employing arginine-histidine peptide-dioleoylphosphatidylethanolamine (RmHnC-DOPE) lipopeptides as core components. Through systematic optimization of arginine-to-histidine ratios, we engineered three variants, R3H7C-DOPE, R4H6C-DOPE, and R5H5C-DOPE, enabling payload-specific and tissue-selective delivery of siRNA, mRNA, and plasmid DNA. <em>In vitro</em> evaluation demonstrated superior gene silencing efficiency for R4H6C-DOPE (85.1%) and R5H5C-DOPE (89.5%) compared to benchmark SM-102 LNPs (67.4%), while maintaining &gt;99% cell viability. R5H5C-DOPE exhibited exceptional broad-spectrum delivery, achieving 74.8% and 92.1% transfection efficiency for mRNA and pDNA, respectively. Notably, R3H7C-DOPE showed 11-fold enhanced pDNA expression relative to SM-102. <em>In vivo</em> studies revealed R3H7C-DOPE's superior hepatic targeting, achieving &gt;2-fold greater PCSK9 suppression (14.1 ± 7.3% residual expression at day 28) versus SM-102 (53.8 ± 41.2% at day 7). R5H5C-DOPE demonstrated remarkable extrahepatic targeting with &gt;90% pulmonary localization, effectively overcoming the hepatic tropism of conventional LNPs. Comprehensive safety assessments revealed exceptional biocompatibility of RmHnC-DOPE formulations, with 100% survival rates across mouse strains, contrasting sharply with SM-102-induced severe toxicity and mortality. Long-term studies confirmed sustained tolerability with preserved organ function and minimal inflammatory responses. This versatile platform combines superior biocompatibility, precise tissue targeting, and synthetic accessibility, providing a clinically viable solution for diverse gene delivery applications spanning hepatic silencing and extrahepatic therapeutics.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"54 ","pages":"Pages 829-849"},"PeriodicalIF":18.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044636","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":"Sulfated chitosan enhances BMP-2-mediated spinal fusion via skeletal stem cell rejuvenation in aging","authors":"Xiaogang Wang ,&nbsp;Dongao Huang ,&nbsp;Luli Ji ,&nbsp;Yuanman Yu ,&nbsp;Fuwei Zhu ,&nbsp;Jing Wang ,&nbsp;Changsheng Liu","doi":"10.1016/j.bioactmat.2025.08.044","DOIUrl":"10.1016/j.bioactmat.2025.08.044","url":null,"abstract":"<div><div>Spinal degenerative diseases in elderly patients often require spinal fusion, but outcomes are limited by an aging microenvironment and stem cell dysfunction or depletion. In this study, we developed a bone morphogenetic protein-2 (BMP-2)/sulfated chitosan (SCS)/calcium phosphate cement (CPC) composite scaffold to enhance spinal fusion in aged mice. BMP-2/SCS significantly improved spinal fusion success rates (83.3 %) compared to BMP-2 alone (16.7 %) and high-dose BMP-2 (50 %). The BMP-2/SCS group promoted robust new bone formation and H-type vessel development, facilitating vascular-bone coupling in the fusion region. Mechanistically, SCS suppressed BMP-2-induced osteoclast overactivation and reduced MMP-9 secretion, leading to vertebral skeletal stem cell (vSSC) rejuvenation. Rejuvenated vSSCs primarily differentiated into the osteogenic bone/cartilage lineage while stromal lineage differentiation was suppressed. In contrast, co-administration of BMP-2 and alendronate sodium abolished BMP-2-mediated increases in vSSC numbers, vSSC rejuvenation, and bone integration, highlighting the indispensable role of osteoclast activity in BMP-2-induced bone regeneration. Collectively, this study demonstrates that BMP-2/SCS scaffolds effectively reverse age-related deficiencies by creating a rejuvenated bone microenvironment, promoting vascular-bone coupling, and enhancing osteogenesis, offering a promising strategy to improve spinal fusion outcomes in elderly patients.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"54 ","pages":"Pages 797-812"},"PeriodicalIF":18.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026999","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":"Regulating SLC7A11/GSH/GPX4 axis by glucose dyshomeostasis to simultaneously promote disulfidptosis, cuproptosis and ferroptosis","authors":"Mengsi Zhang ,&nbsp;Hao Zheng ,&nbsp;Hao Jin ,&nbsp;Xuanqi Zhu ,&nbsp;Shuwei Liu ,&nbsp;Yang Chen ,&nbsp;Hao Zhang ,&nbsp;Songling Zhang","doi":"10.1016/j.bioactmat.2025.09.003","DOIUrl":"10.1016/j.bioactmat.2025.09.003","url":null,"abstract":"<div><div>As one of the key targets of tumor metabolic therapy, glucose dyshomeostasis by disrupting glucose metabolism possesses the potential to reverse therapeutic resistance of a variety of regulated cell deaths (RCDs), but the functional pathways are not fully revealed and employed. Herein, we demonstrate that the intervention on SLC7A11/GSH/GPX4 antioxidant axis by glucose dyshomeostasis can simultaneously promote disulfidptosis, cuproptosis and ferroptosis, which is verified by employing glucose oxidase (GOx)-modified copper-apigenin (CuAp) network nanoshuttles (CuAp@GOx NSs) in ovarian tumor therapy. Ap and GOx can jointly induce glucose dyshomeostasis respectively by inhibiting glucose transporter 1-mediated glucose uptake upstream, and consuming massive glucose downstream. As a result of glucose dyshomeostasis, the NADPH supplement is downregulated, which further disrupts SLC7A11/GSH/GPX4 antioxidant axis. This simultaneously boosts disulfidptosis by facilitating cystine accumulation, cuproptosis by attenuating GSH-mediated Cu⁺ inactivation, and ferroptosis by downregulating GPX4 expression. Owing to the combination of disulfidptosis, cuproptosis and ferroptosis, CuAp@GOx NSs exhibit good efficacy in treating ovarian tumor model. This work proposes an alternative strategy for tumor therapy based on glucose dyshomeostasis, which mainly targets the RCDs relating to SLC7A11/GSH/GPX4 axis.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"54 ","pages":"Pages 744-758"},"PeriodicalIF":18.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026950","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":"Immunomodulatory copper-based polyphenol nanozyme for diabetic infectious wound healing via NIR amplified cuproptosis bacteriostat in synergy with ferroptosis inhibition anti-inflammation","authors":"Huyang Gao ,&nbsp;Juan Luo ,&nbsp;Xixi Chen ,&nbsp;Yaohui Huang ,&nbsp;Mengxue Mo ,&nbsp;Qianyu Luo ,&nbsp;Yan Liu ,&nbsp;Binbin Zou ,&nbsp;Yanjun Lei ,&nbsp;Zhengzhao Li ,&nbsp;Linhai Huang ,&nbsp;Xiaolin Huang ,&nbsp;Peng Liang ,&nbsp;Meihua Lin ,&nbsp;Jingju Huang ,&nbsp;Hongsheng Lu ,&nbsp;Hualin Huang ,&nbsp;Huile Gao ,&nbsp;Jianfeng Zhang ,&nbsp;Junyu Lu ,&nbsp;Ming Gao","doi":"10.1016/j.bioactmat.2025.08.042","DOIUrl":"10.1016/j.bioactmat.2025.08.042","url":null,"abstract":"<div><div>Diabetic infectious wound is usually in the environment of high glucose levels and immune disorder. It always results in high reactive oxygen species (ROS) levels, serious immune dysfunction, and extreme susceptibility to infection, delaying wound healing. Herein, we prepared an immunomodulatory polyphenol metal organic framework nanozyme (CE) combined with near infrared (NIR) irradiation for diabetic infectious wound healing. This nanozyme was formed by the self-assembly of Cu ions and ellagic acid. <em>In vitro</em> experiments confirmed that CE + NIR could efficiently lower the inflammatory factors (IL-6 (50.72 %), IL-1β (61.44 %) and iNOS (57.33 %)) expression, and upregulate anti-inflammatory factor (IL-10 (111.44 %)) expression of lipopolysaccharide induced RAW264.7, decreasing the ROS levels, promoting cellular migration (527.91 %), and accelerating angiogenesis (91.81 %) of high glucose treated L929, together with inhibiting the bacterial growth of <em>E. coli</em> (92.21 %) and <em>MRSA</em> (95.89 %). Transcriptome sequencing results and their related validation experiments demonstrated that CE + NIR achieved antioxidant and anti-inflammation through ferroptosis inhibition. And transcriptomics and metabolomics analysis proved the efficient antibacterial activity of CE + NIR through NIR amplified cuproptosis. Markedly, it also confirmed that the strategy of CE + NIR was helpful to immunoregulation activation via inducing macrophage M2 directional polarization, and immune activating T cells number, thereby restoring immune homeostasis, and accelerating tissue repair. It might offer an efficient strategy of other infectious diseases’ immunotherapy with high efficacy and biosafety.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"54 ","pages":"Pages 759-776"},"PeriodicalIF":18.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026951","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":"Bioengineering an improved three-dimensional vascularized co-culture model for studying Neuron–Microglia interactions","authors":"Yinhe Han ,&nbsp;Lina Guo ,&nbsp;Mingqi Wang ,&nbsp;Zhen Cao ,&nbsp;Xu Zheng ,&nbsp;Xinyu Wang ,&nbsp;Lingling Jin ,&nbsp;Xiaoqing Wei ,&nbsp;Xiuli Wang ,&nbsp;Jie Zhao","doi":"10.1016/j.bioactmat.2025.09.008","DOIUrl":"10.1016/j.bioactmat.2025.09.008","url":null,"abstract":"<div><div>Interactions among neurons, microglia, and endothelial cells (ECs) —the principal components of the neurovascular unit (NVU)—are vital for maintaining central nervous system (CNS) homeostasis and are implicated in numerous neurological disorders. However, mechanistic insights into their crosstalk remain limited due to the lack of physiologically relevant <em>in vitro</em> models. In this study, we present an improved 3D vascularized tri-culture model that integrates human-induced neural stem cells (hiNSCs), human vascular organoids (hVOs), and microglia within a geometrically engineered silk fibroin scaffold. This platform effectively recapitulates critical features of the native CNS microenvironment, including spatial neurovascular patterning and cell-type-specific interactions. Within this model, hVOs significantly promoted neuronal differentiation of hiNSCs, resulting in extended axonal networks and improved neurovascular alignment. Microglial effects were found to be phenotype-dependent: both resting (M0) and pro-inflammatory (M1) microglia inhibited hiNSCs differentiation and vascular development, with M1 cells exerting the strongest suppressive influence. In contrast, anti-inflammatory (M2) microglia displayed the least inhibitory effect and even modestly supported neurovascular maturation. Mechanistic studies revealed that M2 microglia cooperate with hVOs via the stromal cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) signaling axis to promote neuronal differentiation. To our knowledge, this represents the first demonstration of SDF-1/CXCR4-mediated immune-neurovascular interaction within a human tri-culture system. Thereafter, this 3D vascularized co-culture model provides a physiologically relevant <em>in vitro</em> platform to investigate neuroimmune and neurovascular interactions. It holds broad potential for mechanistic studies in neurodevelopment and neurodegeneration, drug evaluation, and the development of regenerative therapies.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"54 ","pages":"Pages 813-828"},"PeriodicalIF":18.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044637","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}