Bioactive Materials最新文献

{"title":"Polydopamine as a biocompatible and precise mitochondrial targeted therapeutic platform for reversing myocardial ischemia-reperfusion injury","authors":"Tianjiao Zhao ,&nbsp;Yunying Huang ,&nbsp;Wensheng Chen ,&nbsp;Weimin Qi ,&nbsp;Jue Wang ,&nbsp;Yingci Xia ,&nbsp;Jia Zhou ,&nbsp;Xingyu Long ,&nbsp;Yayun Nan ,&nbsp;Qiong Huang ,&nbsp;Kelong Ai","doi":"10.1016/j.bioactmat.2025.07.037","DOIUrl":"10.1016/j.bioactmat.2025.07.037","url":null,"abstract":"<div><div>Targeting mitochondria offers a compelling strategy for treating a broad spectrum of major diseases. However, the development of specific and biocompatible mitochondrial delivery vectors remains a key obstacle. In this study, we identified polydopamine (PDA)—a highly biocompatible material with inherent reactive oxygen species (ROS)-scavenging capabilities—as a naturally mitochondria-targeting biomaterial. PDA exhibits strong binding affinity to several critical outer mitochondrial membrane proteins, including the voltage-dependent anion channel and translocases of the outer membrane, conferring it with intrinsic mitochondrial tropism. As a proof-of-concept, we constructed a special channel PDA nanocapsule (CP) to encapsulate the mitochondrial permeability transition pore (mPTP) inhibitor cyclosporine A (CsA), forming CPC. In a myocardial ischemia-reperfusion injury (MIRI) model, intravenously administered CPC selectively accumulated in infarcted myocardium and was highly enriched within cardiomyocyte mitochondria. CPC not only suppressed the mitochondrial ROS burst but also released CsA in a controlled manner via its specialized channels, inhibiting mPTP opening. This intervention prevented cardiomyocyte apoptosis and attenuated the subsequent inflammatory cascade by blocking the cGAS-STING pathway. Remarkably, CPC nearly reversed the pathological effects of MIRI, with efficacy surpassing that of CsA alone. This innovative mitochondrial-targeting approach offers a versatile platform for mitochondrial repair and presents new therapeutic avenues for a range of diseases associated with mitochondrial injury.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"53 ","pages":"Pages 908-931"},"PeriodicalIF":18.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216498","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":"Biocompatibility and immunomodulation of MXenes for targeted delivery of bioactive agents and drugs","authors":"Marzieh Ramezani Farani ,&nbsp;Danial Mirzaee ,&nbsp;Afrooz Hatami ,&nbsp;Krishan Kumar ,&nbsp;Seyed Majid Ghoreishian ,&nbsp;Yun Suk Huh","doi":"10.1016/j.bioactmat.2025.09.038","DOIUrl":"10.1016/j.bioactmat.2025.09.038","url":null,"abstract":"<div><div>MXenes, a burgeoning class of two-dimensional transition metal carbides and nitrides, have emerged as promising candidates for biomedical applications owing to their exceptional physicochemical properties and versatile surface chemistry. This review comprehensively examines the biocompatibility and immunomodulatory behavior of MXenes, with a particular emphasis on their potential in drug delivery systems. We elucidate the critical aspects of MXene–protein interactions, including protein corona formation, cellular uptake pathways, and the influence of surface functionalization on biological interfaces. Special attention is given to the immunological profile of MXenes, exploring their immunogenic potential and immunomodulatory capabilities within therapeutic contexts. Furthermore, we assess the viability of MXenes as nanocarriers for drugs and bioactive compounds, analyzing a wide array of functionalization strategies and stimuli-responsive release mechanisms aimed at enhancing therapeutic efficacy. Despite their immense potential, challenges such as long-term stability, cytotoxicity, and clinical translatability persist. We conclude by outlining these limitations and proposing strategic avenues for future research. This review serves as a vital resource for researchers at the intersection of materials science and biomedicine, particularly those advancing next-generation, two-dimensional nanomaterial-based drug delivery platforms.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 546-567"},"PeriodicalIF":18.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217803","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":"Topology-optimized melt-electrowritten PCL patch for abdominal wall reconstruction","authors":"Yakui Liu,&nbsp;Max von Witzleben,&nbsp;Sarah Duin,&nbsp;Anne Bernhardt,&nbsp;Michael Gelinsky","doi":"10.1016/j.bioactmat.2025.09.026","DOIUrl":"10.1016/j.bioactmat.2025.09.026","url":null,"abstract":"<div><div>Abdominal wall patches are clinically essential for treating abdominal defects or hernias, with mechanical strength representing a critical requirement. Therefore, rational scaffold design and fabrication methods are crucial for achieving optimal performance. This study introduces an innovative approach to the design of scaffolds for abdominal wall repair, using topology optimization and melt electrowriting (MEW). Through topology optimization, we provided a systematic, data-driven basis for scaffold design. We further refined the scaffold structure to enhance print efficiency and continuity, and successfully implemented MEW as fabrication technology, marking its first application in abdominal repair. Mechanical testing revealed that the topology-optimized scaffold achieved abdominal tensile strength of 1.85 ± 0.02 N/cm, 39 % superior to conventional designs. Subsequent biological assessments – including fibroblast proliferation and alignment analyses – showed that collagen coating significantly enhanced cell attachment and proliferation, especially in multi-layer (300 layers) scaffolds, maintaining diameters of 11.34 ± 0.67 μm throughout the depth. Finally, <em>ex vivo</em> porcine abdominal wall tests confirmed clinical mechanical suitability. This work offers a promising direction for future advancements in tissue engineering, particularly in optimizing scaffold structures for biological and mechanical performance.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 529-545"},"PeriodicalIF":18.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217745","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":"Dimensional memory in glioblastoma mechanics: Traction force analysis of cells cultured in 2D versus 3D collagen environments","authors":"Mishal Khan ,&nbsp;Philipp Kollenz ,&nbsp;Maret Fritzenschaft ,&nbsp;Fereydoon Taheri ,&nbsp;Federico Colombo ,&nbsp;Johannes W. Blumberg ,&nbsp;Luise Schlotterose ,&nbsp;Ulrich Sebastian Schwarz ,&nbsp;Aldo Leal-Egaña ,&nbsp;Christine Selhuber-Unkel","doi":"10.1016/j.bioactmat.2025.09.025","DOIUrl":"10.1016/j.bioactmat.2025.09.025","url":null,"abstract":"<div><div>Glioblastoma (GB) is one of the most aggressive and lethal brain tumors, characterized by rapid proliferation, diffuse infiltrative growth, therapeutic resistance, and molecular heterogeneity. A major challenge in studying GB is the lack of <em>in vitro</em> models that accurately replicate the tumor's cellular characteristics observed <em>in vivo</em>, particularly the importance of three-dimensional (3D) models. This study investigated the traction stress exerted by LN229 and T98G human GB cell lines, as well as the HMC3 human microglia cell line, using traction force microscopy. First, cells were cultured on two-dimensional (2D) collagen-coated surfaces and within three-dimensional (3D) collagen-based bioactive matrices. Afterward, these cells were extracted and reseeded on flat polyacrylamide gels coated with collagen type I to perform traction force microscopy, thereby directly probing the mechanical memory imparted by their prior 2D or 3D environments. Our findings reveal that GB cells exert substantially higher traction stresses when cultured on 2D collagen-coated surfaces compared to those cultured in 3D bioactive matrices. This underscores the relevance of protein-based bioactive materials, such as collagen scaffolds, in replicating <em>in vivo</em> tumor microenvironments to study GB behavior. Single-cell nanoindentation and focal adhesions quantification were performed to offer mechanistic insights into glioblastoma and microglia cells. Interestingly, in addition to notable differences in traction stresses between cells cultured in 2D and 3D collagen environments, glioblastoma showed significant variation based on the cell type in terms of single-cell stiffness and focal adhesion metrics. These findings underscore the importance of complementary biophysical assays and realistic 3D bioactive matrices when studying GB mechanics <em>in vitro</em>.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 515-528"},"PeriodicalIF":18.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217746","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":"Cell-instructive microfibers enable programmable alignment of bioprinted hMSC","authors":"A. Neuhäusler ,&nbsp;N. Kötting ,&nbsp;L. Keuper ,&nbsp;N. Lindner ,&nbsp;E. Schätzlein ,&nbsp;A. Blaeser","doi":"10.1016/j.bioactmat.2025.09.027","DOIUrl":"10.1016/j.bioactmat.2025.09.027","url":null,"abstract":"<div><div>Biofabrication of hierarchical tissues with features ranging various size ranges and controllable anisotropy remains a challenge in 3D-bioprinting. To overcome this hurdle, the application of multi-functional microfibers acting as cell-instructive bioink additive, recently gained particular attention. In this work, we investigate a microfluidic spinning process for the fabrication of collagen microfibers with adjustable diameters ranging from 5 to 50 μm. The thread was collected on a rotating winder and fragmented into microfibers of defined length (60–300 μm). By integrating microfiber fragments into an agarose-hyaluronan hydrogel, fine-tuning of its viscosity range (10–1000 mPa∗s), and thus the precise control of the extruded strands’ diameter (0.3–1.4 mm) was achieved. While remaining strong shear-thinning behavior (n-value 0.6), E-modulus and yield stress were decreased in fiber-filled hydrogel, hinting at an interaction of agarose polymer chains with microfibers. Remarkably, the orientation of collagen microfibers could be directed either parallel or orthogonal to the printing path. This allows the biofabrication of hydrogel structures with adjustable domains of defined anisotropy. Finally, the fibers showed excellent biofunctionality both in 2D and 3D. Besides a high degree of alignment of individual cells along the microfiber axis (&gt;80 % of cells), hMSCs built a dense, branched network in 3D. Moreover, PC12 and C2C12 were successfully differentiated in 2D and 3D. Specifically, neurite length was higher on smaller fiber diameters, even spanning non-adjacent clusters. Elongated, multi-nuclei myotubes were formed, indicating C2C12 differentiation. In summary, the work demonstrates the great potential of 3D-bioprinting in cross-scale organization of fragmented collagen microfibers.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 503-514"},"PeriodicalIF":18.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217747","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":"Spermidine reduces peri-implant inflammation and fibrosis to nurture osseointegration","authors":"Qiming Liu ,&nbsp;Qianqian Wu ,&nbsp;Tingting Cao ,&nbsp;Rundong Miao ,&nbsp;Chenyu Wang ,&nbsp;Jiawei Zhang ,&nbsp;Xue Gao ,&nbsp;Li Wang ,&nbsp;Guoxin Shi ,&nbsp;Jinyu Lai ,&nbsp;Runjiao Yang ,&nbsp;Xianshu Piao ,&nbsp;Jiaao Yu ,&nbsp;Jincheng Wang ,&nbsp;Song Liang ,&nbsp;Shuqing Kou ,&nbsp;Thomas M. Roberts ,&nbsp;Bingdi Wang ,&nbsp;Zhenning Liu","doi":"10.1016/j.bioactmat.2025.09.036","DOIUrl":"10.1016/j.bioactmat.2025.09.036","url":null,"abstract":"<div><div>Medical implants of exogenous materials often induce foreign body response (FBR) in hosts, which is characterized by inflammation and fibrosis. Herein, composite scaffolds with interpenetrating hard and soft phases were fabricated, consisting of titanium alloy and a biomatrix mimicking extracellular matrix. Spermidine-functionalized biomatrix (CST@GOA) not only inhibits inflammatory response and osteoclastogenesis of macrophages, but also fosters migration and osteogenesis of MC3T3-E1 cells. Interestingly, CST@GOA can mitigate acute inflammation and fibrosis, characteristics of FBR, against silicone implanted in rats. Moreover, bone repair experiments in rabbits show that CST@GOA-interpenetrated porous titanium alloy scaffolds attenuate FBR against metal implants and promote osseointegration. Meanwhile, diethylenetriamine, a polyamine resembling spermidine in chemistry, has been used in place of spermidine to enable ‘operando’ comparison in both cell and animal experiments. Proteomic analysis of rabbit bone tissues reveals that spermidine modulates PI3K-Akt pathway by upregulating PTEN, which may play a pivotal role in coordinating downstream signaling of inflammation, autophagy and bone homeostasis. Together, it is demonstrated that spermidine can endow either synthetic polymers or metal implants with <em>anti</em>-FBR activity by regulating host response and nurture peri-implant niche to improve osseointegration of metal implants. Hence, spermidine affords a natural and elegant strategy to alleviate FBR against medical implants.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 466-484"},"PeriodicalIF":18.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217798","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 hydrogel micro-/nanofibers for in situ soft tissue repair and regeneration","authors":"Bingcheng Yi ,&nbsp;Xiaoyu Wang ,&nbsp;Jiajia Yu ,&nbsp;Jiale Diao ,&nbsp;Guangjun Wang ,&nbsp;Shuo Li ,&nbsp;Jiayi Bo ,&nbsp;Xuemei Zhang ,&nbsp;Chunling Zhang ,&nbsp;Carlos F. Guimarães ,&nbsp;Qihui Zhou ,&nbsp;Rui L. Reis","doi":"10.1016/j.bioactmat.2025.09.035","DOIUrl":"10.1016/j.bioactmat.2025.09.035","url":null,"abstract":"<div><div>To effectively harness the regenerative potential of the body and orchestrate cellular responses for <em>in situ</em> tissue repair, the design of biomaterials requires careful consideration of precise modulation of biophysical and biochemical cues. This is essential to maximize the guidance of endogenous cell responses at the injury site. Hydrogel micro-/nanofibers, which integrate the benefits of hydrogel biomaterials and micro-/nanofiber architectures into a unified scaffold, have emerged as innovative biomimetic substrates that closely mimic the physiological characteristics of native extracellular matrix. These substrates exhibit tissue-like polymer networks, rapid responsiveness to microenvironmental changes, and permeability to essential nutrients and oxygen. Their biomimetic attributes facilitate cell recruitment and diffusion for angiogenesis, nutrient diffusion for cell self-renewal, and cell-material interactions for matrix remodeling, thus effectively harnessing the regenerative capacity of the body for tissue-specific regeneration. This review offers an overview of recent advances in hydrogel micro-/nanofiber design and their applications in <em>in situ</em> soft tissue engineering, focusing on: I) the concept and biomimetic characteristics of hydrogel micro-/nanofibers; II) current fabrication strategies, including material selection and preparation methods; and III) research progress in employing hydrogel micro-/nanofibers for <em>in situ</em> soft tissue regeneration, particularly in nerve, skin, cardiovascular, and skeletal muscle tissues. Overall, leveraging the body's regenerative potential through biomimetic hydrogel micro-/nanofibers represents an effective and promising approach for restoring damaged tissues. Additionally, this review provides valuable insights to foster interdisciplinary knowledge exchange and enables the development of prognostic markers for the next generation of hydrogel micro-/nanofibers to accelerate soft tissue regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 485-502"},"PeriodicalIF":18.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217800","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":"Spatiotemporal-controlled ultrasound-driven Li-PDA@ZnO nanoparticles promote neural stem cell differentiation synergy with biohydrogel repair spinal cord injury","authors":"Dapeng Zhang ,&nbsp;Xiaolong Zhou ,&nbsp;Chenxi Zhao ,&nbsp;Shuwei Han ,&nbsp;Xianzheng Guo ,&nbsp;Haosheng Chen ,&nbsp;Wenzhao Wang ,&nbsp;Wencan Zhang ,&nbsp;Mingzheng Chang ,&nbsp;Qingliang Ma ,&nbsp;Yunhao You ,&nbsp;Mingshan Liu ,&nbsp;Xinyu Liu ,&nbsp;Zhijian Wei ,&nbsp;Xiaohong Kong ,&nbsp;Shiqing Feng","doi":"10.1016/j.bioactmat.2025.07.050","DOIUrl":"10.1016/j.bioactmat.2025.07.050","url":null,"abstract":"<div><div>Neuronal loss following spinal cord injury (SCI) remains a significant barrier to the recovery of neural function. Neural stem cells (NSCs) supplementation offers a promising therapeutic avenue by providing seed cells; however, the differentiation rate of NSCs into neurons is often suboptimal. In this study, lithium was immobilized on the surface of ZnO nanoparticles using a polydopamine coating to synthesize Li-PDA@ZnO nanoparticles. These nanoparticles were designed to induce NSC differentiation into neurons in a spatiotemporal-controlled manner using ultrasound-driven stimulation. Additionally, a biohydrogel system consisting of genipin and collagen was developed to encapsulate NSCs preloaded with endocytosed nanoparticles. The application of ultrasound stimulation to ZnO nanoparticles enhanced the differentiation of NSCs into neurons in a concentration-dependent manner following endocytosis. Li-PDA@ZnO nanoparticles demonstrated improved biocompatibility and further promoted neuronal differentiation, a process mediated by molecular pathways involving ERK and ASCL1. In vivo, the ability of ultrasound-driven nanoparticles to enhance NSC differentiation was validated using a mouse SCI contusion model. Furthermore, the combined nanoparticle-biohydrogel system was evaluated in an SCI transection model, where it was found to reduce local inflammation, enhance neuronal differentiation of NSCs, and increase the proportion of functional neurons. These effects contributed to significant improvements in motor, sensory, and autonomic function recovery following SCI. In summary, spatiotemporal-controlled ultrasound-driven Li-PDA@ZnO nanoparticles effectively enhance the differentiation of NSCs into neurons and, when incorporated into hydrogel systems, represent a novel therapeutic approach for spinal cord injury repair.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 446-463"},"PeriodicalIF":18.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217801","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":"Corrigendum to “Cu(II)-baicalein enhance paracrine effect and regenerative function of stem cells in patients with diabetes”","authors":"Kaijing Liu ,&nbsp;Ruihao Li ,&nbsp;Shusen Wang ,&nbsp;Xue Fu ,&nbsp;Ni Zhu ,&nbsp;Xiaoyu Liang ,&nbsp;Huiyang Li ,&nbsp;Xiaoli Wang ,&nbsp;Le Wang ,&nbsp;Yongjun Li ,&nbsp;Jianwu Dai ,&nbsp;Jing Yang","doi":"10.1016/j.bioactmat.2025.08.006","DOIUrl":"10.1016/j.bioactmat.2025.08.006","url":null,"abstract":"","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 464-465"},"PeriodicalIF":18.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217799","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":"Bacteria microenvironment-responsive missile microneedles modulate immunity and penetrate biofilm for diabetic wound therapy","authors":"Ganghua Yang ,&nbsp;Haowen Kang ,&nbsp;Yuanzheng Zhu ,&nbsp;Hengyu Wu ,&nbsp;Minchen Zhang ,&nbsp;Xinghong Zeng ,&nbsp;Ying Peng ,&nbsp;Wenbing Wan ,&nbsp;Yangyan Yi","doi":"10.1016/j.bioactmat.2025.09.017","DOIUrl":"10.1016/j.bioactmat.2025.09.017","url":null,"abstract":"<div><div>Diabetic wounds, affecting ∼25 % of patients with diabetes, present a therapeutic challenge due to persistent inflammation driven by MCP-1-mediated immune dysregulation and bacterial biofilm formation. We developed a bilayer microneedle system (DAg/HTMS-MNs) combining dextran-modified silver nanoparticles for deep-tissue antibacterial action with heparin-coated taurine-loaded microspheres for immunomodulation. The upper microneedle segment enables biofilm penetration through lectin targeting and gas propulsion, while the lower segment implements a “global decompression-local enhancement” strategy: heparin sequesters MCP-1 to reduce inflammatory cell recruitment, and sustained taurine release promotes macrophage reprogramming to M2 phenotypes. Systematic evaluation demonstrated simultaneous biofilm eradication, inflammation resolution (2-fold enhanced M2 polarization), and accelerated wound healing. This “missile-guided” approach represents a paradigm shift in diabetic wound therapy by concurrently addressing infection control, oxidative stress, and immune dysregulation in a spatially and temporally controlled manner.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"55 ","pages":"Pages 426-445"},"PeriodicalIF":18.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217802","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}