Biomaterials最新文献

{"title":"Self-assembly prodrugs for controlled singlet oxygen release and resistance modulation in deep-tumor photodynamic therapy.","authors":"Zhiyao Li, Wei Yang, Jianwu Tian, Qianqian Liu, Guiyang Zhang, Yuqing Wu, Jundong Zhou, Chongzhi Wu, Yihui Ai, Yanni Wang, Ronglin Chen, Bowen Li","doi":"10.1016/j.biomaterials.2026.124712","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2026.124712","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) offers spatiotemporally controlled tumor ablation via photosensitizer-mediated singlet oxygen (¹O₂) generation, yet its application to deep-seated solid tumors remains fundamentally constrained by limited light penetration and tumor hypoxia. Endoperoxides (EPOs), which reversibly capture and release ¹O₂, offer a promising strategy to overcome these constraints. Nevertheless, existing EPO-based systems suffer from uncontrolled half-life-dependent ¹O₂ release and inefficient utilization. Moreover, PDT-induced oxidative stress upregulates inducible nitric oxide synthase (iNOS), leading to nitric oxide (NO) overproduction that quenches ¹O₂ and promote adaptive resistance. Herein, we report a self-assembly nano-prodrug enabling on-demand ¹O₂ release while suppressing NO-mediated resistance. An amphiphilic prodrug, L-NARG-SS-Py, comprising a ¹O₂-storing pyridone moiety and an iNOS inhibitor linked via a glutathione-responsive disulfide bond, co-assembles with protoporphyrin IX to form nano-prodrug (PPIX@L-NARG-SS-Py NPs). Upon irradiation, generated ¹O₂ is captured and stored as EPO intermediates, followed by glutathione-triggered release in tumor microenvironment. Simultaneously, released iNOS inhibitor suppresses NO production, thereby reducing ¹O₂ quenching and amplifying oxidative damage. In deep-seated pancreatic tumor models, the nano-prodrug achieves potent tumor suppression with minimal systemic toxicity. This work establishes a biologically amplified, light-independent PDT strategy for overcoming physical and adaptive resistance in deep-tissue phototherapy.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"338 Pt B","pages":"124712"},"PeriodicalIF":13.6,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222967","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":"Rare-earth-free magnesium-zinc alloy with controlled biodegradation and biocompatibility for novel biodegradable metallic stent.","authors":"Yubeen Park, Yerin Ha, Hyung Jin Roh, Hyun Lee, Seung Jin Eo, Do-Yoon Kang, Nayoung Lee, Hyun-Do Jung, Jun-Kyu Park, Kang-Sik Lee, Yu-Chan Kim, Hwa-Chul Jung, Joung Sik Suh, Jung-Hoon Park","doi":"10.1016/j.biomaterials.2026.124691","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2026.124691","url":null,"abstract":"<p><p>Biodegradable magnesium (Mg) alloy stents offer a transient alternative to permanent metallic implants; however, clinically used WE43 contains rare-earth (RE) elements, raising concerns regarding the long-term biosafety of RE-containing degradation products and their potential tissue accumulation. Here, we investigated two RE-free Mg-Zinc (Zn)-based alloys, MZ01 (Mg-1Zn-0.1Ca) and ZM115 (Mg-1Zn-1.5Mn-0.5Sr), and established a mechanistic cascade linking alloy composition and microstructure to electrochemical analyses revealed alloy-dependent differences in grain structure and interfacial corrosion resistance, with MZ01 exhibiting the highest charge-transfer resistance. In a mouse subcutaneous model, MZ01 showed more uniform degradation, smaller and more rapidly resolving hydrogen gas cavities, and a significantly lower microcrack area fraction at Day 56 than WE43 and ZM115, accompanied by attenuated inflammatory and fibrotic responses. In the rabbit iliac arteries, all stents maintained luminal patency without thrombosis through 56 days, while MZ01 exhibited lower neointimal thickness, lower perivascular apoptosis and late inflammation, and enhanced early endothelialization compared with WE43. Preliminary descriptive porcine coronary implantation further demonstrated the technical feasibility and sustained patency of MZ01 over 56 days. Collectively, these findings define a composition-microstructure-corrosion-cellular response-vascular healing axis and identify MZ01 as a RE-free Mg-Zn alloy with controlled biodegradation and favorable biocompatibility, supporting its further development as a biodegradable cardiovascular scaffold.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"338 Pt B","pages":"124691"},"PeriodicalIF":13.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222860","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":"Spatial Lipidome and Transcriptome Profiling Reveals Stratified Lipid Architecture in Human Articular Cartilage","authors":"Yiyang Yan,&nbsp;Dingchao Ying,&nbsp;Ziwei Xue,&nbsp;Wei Sun,&nbsp;Jinghua Fang,&nbsp;Hang Su,&nbsp;Dian Yuan,&nbsp;Heling Xue,&nbsp;Yifei Yang,&nbsp;Zongyou Pan,&nbsp;Wei Zhang,&nbsp;Xiaozhao Wang,&nbsp;Wanlu Liu,&nbsp;David C. Hay,&nbsp;Yishan Chen,&nbsp;Hongwei Ouyang","doi":"10.1016/j.biomaterials.2026.124703","DOIUrl":"10.1016/j.biomaterials.2026.124703","url":null,"abstract":"<div><div>Lipids, as a class of endogenous biomaterials, are essential for regulating tissue properties and homeostasis. Articular cartilage is an anisotropic tissue that exhibits spatially organized tissue functions and lipid metabolism, and its microenvironment is sensitive to lipid-mediated regulation. However, the spatial lipid composition and its functional significance in cartilage pathophysiology remain elusive. In this study, we performed spatial lipidomic and transcriptomic analyses on healthy and diseased human articular cartilage. We demonstrate a layer-dependent lipid composition mainly in the extracellular matrix and chondrocyte region, and the stratified lipid architecture aligns with region-specific gene expression and cellular phenotypes. The tissue near the cartilage surfaces is enriched with phospholipids and genes relevant to matrix secretion and lipid transport, whereas the tissue adjacent to subchondral bone, is featured by lyso-phospholipids and genes related to biomineralization. Moreover, we highlight ceramide (CER) ’s role in mediating chondrocyte secretion and its potential protective function in early osteoarthritis (OA), suggesting that location-specific lipid diversity may contribute to the regulation of cartilage function. This study not only advances understanding of cartilage pathophysiology, but also provides a material-level blueprint for developing more biomimetic cartilage engineering strategies.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"338 ","pages":"Article 124703"},"PeriodicalIF":13.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149200457","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":"Microneedle-guided ultraviolet phototherapy with local calcipotriol delivery for enhanced psoriasis treatment.","authors":"Shiqi Wang, Wentao Zhang, Sheng Zhao, Hui Wang, Ruisi Cai, Shuangxu Jia, Xiaofeng Chen, Licheng Han, Anni Xie, Weiwei Chen, Jicheng Yu, Zhen Gu, Yuqi Zhang","doi":"10.1016/j.biomaterials.2026.124697","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2026.124697","url":null,"abstract":"<p><p>Narrow-band ultraviolet B (NB-UVB) phototherapy is clinically regarded as a first-line treatment for moderate-to-severe plaque psoriasis owing to its high tolerance, broad applicability and easy affordability. However, the therapeutic efficacy of short-wave UV light is limited by poor penetration through the thickened stratum corneum of psoriatic skin, whereas excessive NB-UVB irradiation may provoke cutaneous photodamage. Moreover, NB-UVB administration necessitates trained personnel and frequent hospital visits, resulting in poor patient compliance. Here, we developed microneedles with high UV transmittance (UVMNs) to enhance the transdermal delivery efficiency of NB-UVB, thereby reducing the required irradiation dosage and mitigating the risk of photodamage without compromising therapeutic effect. A vitamin D analog, calcipotriol, was further coated onto the UVMN patch to augment the overall efficacy of the phototherapeutic regimen. After insertion into the skin, the calcipotriol is released from the dissolvable coating within minutes to suppress keratinocyte proliferation, followed by UVMN-guided NB-UVB therapy for regulation of regulatory T/T helper 17 cell balance as well as inhibition of keratinocyte proliferation. The integration of phototherapy and topical therapy effectively ameliorated symptoms in a psoriatic mouse model.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"338 Pt B","pages":"124697"},"PeriodicalIF":13.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219795","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":"Genetically engineering mast cells as effectors for targeted cancer cell cytotoxicity.","authors":"Xiao Han, Di Wen, Ruxing Fu, Jennifer Soto, Yang Song, Yifan Wu, Zejun Wang, Xiao Lin, Jicheng Yu, Tao Sheng, Song Li, Zhen Gu, Kaixin He","doi":"10.1016/j.biomaterials.2026.124699","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2026.124699","url":null,"abstract":"<p><p>Type-I hypersensitivity is a mast cell-mediated degranulation process induced by IgE-antigen recognition. Inspired by this highly specific mechanism, we developed a new cell therapy platform by genetically engineering mouse mast cell line MC/9 to overexpress the cytotoxic proteins perforin and granzyme B (PG-MCs) via lentiviral transduction. In the melanoma model utilizing B16 cells expressing membrane-bound OVA, a polarized degranulation of mast cells towards cancer cells was validated upon the recognition of antigens by anti-OVA IgE. PG-MCs could selectively kill cancer cells via IgE-antigen recognition. The IgE-sensitized PG-MCs administered through an intertumoral route delivered perforin 1 (Prf1) and granzyme B (Gmzb) toward target cells to potentiate anti-tumor efficacy. Moreover, we demonstrated the reprogramming effect of tumor microenvironment by PG-MC-induced hypersensitivity, driving an immune remodeling of the tumor milieu, characterized by the increased lymphocyte infiltration. In addition, this mast cell therapy, in combination with 5- fluorouracil (5-Fu), induced a significant inhibition of tumor growth in a B16-OVA mouse model, which is associated with the depletion of myeloid-derived suppressor cells (MDSCs).</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"338 Pt B","pages":"124699"},"PeriodicalIF":13.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222923","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":"Molecularly nanoengineered dendritic cells for tumor-specific antigen capture and sono-activatable cytokine-mediated immunotherapy.","authors":"Ningyue Yu, Shengze Lu, Bing Xiao, Zhong Guo, Jingchao Li","doi":"10.1016/j.biomaterials.2026.124693","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2026.124693","url":null,"abstract":"<p><p>Engineering artificial dendritic cells (DCs) holds great promise for cancer immunotherapy, but achieving spatiotemporally controlled multifunctionality within the immunosuppressive tumor microenvironment remains a challenge. Here, we report a chemically engineered, ultrasound (US)-activatable artificial DCs nanosystem (nDC-M) that mimics the DC-mediated T-cell immunity through a rationally designed molecular assembly. The nDC-M integrates three key functional modules including a semiconducting polymer nanoparticle and interleukin-2 (IL-2) crosslinked by hypoxia-cleavable fragment for on-demand cytokine release upon US trigger, a matured DC membrane cloak for tumor cell recognition and a surface-anchored maleimide (MAL) group for covalent antigen capture and presentation. Under US treatment, sonodynamic effect of semiconducting polymer ablates tumors and consumes oxygen to allow breakage of hypoxia-cleavable fragments, leading to IL-2 leakage. This nDC-M exhibits a comprehensive and conferred mimicking functions including tumor cell recognition, antigen presentation and sono-activatable cytokine secretion. In bilateral breast cancer and lung metastasis models, US-driven nDC-M therapy significantly suppresses tumor progression and metastasis. Moreover, combining nDC-M with checkpoint blockade achieves complete eradication of local and distant tumors and establishes long-term immunological memory against recurrence. This work presents a modular and stimuli-responsive artificial DC platform that integrates chemical synthesis, molecular nanoengineering, and function modulation, offering a versatile strategy for cancer immunotherapy.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"338 Pt B","pages":"124693"},"PeriodicalIF":13.6,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222938","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 HIF-2α stabilization with an intelligent switchable nanoplatform for tumor immunity reprogramming and enhanced therapy","authors":"Zelun Li ,&nbsp;Guanhua Qiu ,&nbsp;Wenwen Guo ,&nbsp;Yuanquan Zhao ,&nbsp;Yangchun Du ,&nbsp;Huimin Li ,&nbsp;Fumao Yang ,&nbsp;Guozhen Huang ,&nbsp;Ruibiao Fu ,&nbsp;Yan Zou ,&nbsp;Tingting Tan ,&nbsp;Jie Chen ,&nbsp;Xiaofeng Dong","doi":"10.1016/j.biomaterials.2026.124022","DOIUrl":"10.1016/j.biomaterials.2026.124022","url":null,"abstract":"<div><div>Chronic hypoxia is a critical barrier to the effective treatment of solid tumors, including hepatocellular carcinoma (HCC), as it not only restricts the oxygen supply required for sonodynamic therapy (SDT) but also upregulates hypoxia-inducible factor-2α (HIF-2α), thereby accelerating tumor progression, inducing abnormal angiogenesis, suppressing antitumor immune responses, and diminishing the efficacy of targeted therapies. Here, we developed an intelligent switchable organic–inorganic hybrid nanoplatform (VitK3/P–Ce6@H–MnO₂) that integrates oxygen self-supply, reactive oxygen species (ROS) storm induction, and immune microenvironment reprogramming. The acidic tumor microenvironment serves as an “endogenous switch,” triggering the decomposition of H–MnO₂ to release oxygen and Vitamin K3, thereby alleviating chronic hypoxia, facilitating HIF-2α degradation, and providing oxygen support for Ce6-mediated SDT. Upon ultrasound exposure as an “exogenous switch,” activated Ce6, together with Vitamin K3 and Mn²⁺, induces a robust ROS storm, resulting in mitochondrial dysfunction and immunogenic cell death (ICD), while effectively reprogramming the chronic hypoxia–HIF-2α-driven immunosuppressive tumor microenvironment. Furthermore, in vivo studies demonstrated that Lenvatinib therapy, when combined with the nanoplatform, further suppressed chronic hypoxia–HIF-2α–driven abnormal angiogenesis, enhanced CD8⁺ T-cell infiltration, and boosted antitumor immune responses, ultimately achieving a potent synergistic therapeutic effect and promoting the conversion of “cold tumors” into “hot tumors.” This study provides strong experimental evidence that nanoplatform-mediated immune microenvironment reprogramming represents a precisely controllable and highly effective therapeutic strategy for solid tumors, with promising translational potential in hepatocellular carcinoma.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124022"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075196","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 4D-printed shape-memory scaffold with a triple-acting liposomal strategy for the treatment of infectious bone defects","authors":"Xulin Hu ,&nbsp;Shuhao Yang ,&nbsp;Qianshui Hu ,&nbsp;Zhengguang Pu ,&nbsp;Yingkun Hu ,&nbsp;Wang Gong ,&nbsp;Haoming Wu ,&nbsp;Zhixiang Gao ,&nbsp;Jun Wang ,&nbsp;Jianye Yang ,&nbsp;Yao Zhang ,&nbsp;Xin Yong ,&nbsp;Leilei Qin ,&nbsp;Ning Hu","doi":"10.1016/j.biomaterials.2026.124020","DOIUrl":"10.1016/j.biomaterials.2026.124020","url":null,"abstract":"<div><div>Infectious bone defects (IBD) are complex bone tissue injuries caused by pathogenic bacterial invasion, characterized by delayed bone healing due to bacterial infection and chronic inflammation. In this study, we developed an adaptive filling shape memory scaffold (PTC@PS-EGCG) with temporal and spatial sequence regulation capabilities, integrating multiple functions including antibacterial, immune modulation, and osteogenic induction. The shape memory scaffold (PT) was fabricated using low-temperature 4D printing technology, and a pH-responsive chitosan hydrogel (CS) was used to load phosphatidylserine-modified epigallocatechin gallate liposomes (PS-EGCG) on the scaffold surface to form a coating. The PTC@PS-EGCG scaffold can achieve adaptive filling and integration of irregular defect interfaces at body temperature (37 °C) while providing mechanical support. In the early stages of infection, PS-EGCG is released in response to the infection, clearing bacteria and being phagocytosed by macrophages. Subsequently, PS-EGCG promotes metabolic reprogramming by regulating macrophage oxidative phosphorylation, achieving a “triple effect.” In the middle and late stages, the internal scaffold continues to sustain bone formation. In a rat model of IBD, the PTC@PS-EGCG significantly reduced the expression of inflammatory cytokines and bacterial load, promoted bone regeneration, and improved gait function. This integrated scaffold provides a promising and reliable solution for the clinical treatment of IBD.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124020"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075207","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":"Biosponge-armored polydopamine-modified conducting polypyrrole restores redox-iron homeostasis for enhanced neuroprotection​ in retinal ischemia-reperfusion injury","authors":"Zhiqing Lin ,&nbsp;Haoyue Deng ,&nbsp;Guang Yang ,&nbsp;Keke Huang","doi":"10.1016/j.biomaterials.2026.124007","DOIUrl":"10.1016/j.biomaterials.2026.124007","url":null,"abstract":"<div><div>Retinal ischemia-reperfusion injury (RIRI) is a central pathological mechanism in vision-impairing disorders such as glaucoma and retinal vascular occlusion. Current treatment modalities are significantly constrained by their inability to simultaneously address the multifaceted injury cascades driven by lethal oxidative stress, ferroptosis, and neuroinflammation, which considerably limits their clinical efficacy. To overcome these challenges, we designed a nanocomposite, termed P-PPy, by integrating polydopamine with conducting polypyrrole. Within this construct, surface-modified polydopamine (PDA) acts as a biosponge that effectively chelates excess iron ions. A single intravitreal injection of P-PPy elicited broad therapeutic responses, including efficient reactive oxygen species (ROS) scavenging, inhibition of ferroptosis in retinal ganglion cells accompanied by restoration of mitochondrial functionality, and induction of M2 microglial polarization leading to attenuated neuroinflammation. Together, these mechanisms synergistically restored the electrophysiological microenvironment of the retina, markedly preserving both its structural integrity and functional performance. The P-PPy nanocomposite also demonstrated an excellent biosafety profile, exhibiting no detectable toxicity in both cellular assays and following intravitreal administration in animal models. In summary, this readily synthesizable, multifunctional conductive nanoplatform provides strong neuroprotective effects in vivo, offering a promising therapeutic avenue based on conductive nanomaterials for the treatment of neurodegenerative retinal diseases.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124007"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024836","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":"Spatiotemporally programmed VEGF/IL-4 delivery via HMSNs enhances endothelialization and immune-mediated matrix remodeling in acellular vascular grafts","authors":"Zeguo Chen ,&nbsp;Zhongshi Wu ,&nbsp;Can Huang ,&nbsp;Qiying Wu ,&nbsp;Chao Xie ,&nbsp;Sicheng Chen ,&nbsp;Liang Yi ,&nbsp;Haoyong Yuan ,&nbsp;Sixi Liu ,&nbsp;Abdulraheem Mustapha ,&nbsp;Siyao Chen ,&nbsp;Wansong Chen ,&nbsp;Ting Lu ,&nbsp;Zhenjie Tang ,&nbsp;Yuhong Liu","doi":"10.1016/j.biomaterials.2026.124016","DOIUrl":"10.1016/j.biomaterials.2026.124016","url":null,"abstract":"<div><div>Delayed endothelialization and inadequate matrix remodeling remain major obstacles in the development of small-diameter vascular grafts (SDVGs; &lt;6 mm). To address these challenges, we developed an immunomodulatory tissue-engineered vascular graft (iTEVG) by integrating hollow mesoporous silica nanoparticles (HMSNs) with tailored mesopore sizes as delivery carriers for immunoregulatory factors. VEGF was selectively immobilized on the intimal surface, while the adventitia incorporated a sequential release system for VEGF and IL-4. VEGF exhibited rapid release (64.04 ± 4.44 % in 7 days), promoting monocyte recruitment and adventitial neovascularization, while IL-4 showed sustained release (65.94 ± 2.06 % over 28 days), driving long-term M2 macrophage polarization. In rats, iTEVGs achieved 88 % endothelial coverage and smooth muscle cell infiltration within 1 month, full-thickness cellularization with a complete trilaminar structure by 3 months, and maintained mechanical integrity without aneurysm formation up to 6 months. This spatially partitioned platform, built on an acellular vascular scaffold, enables precise spatiotemporal regulation of the immune microenvironment and offers a design paradigm that synergistically promotes endothelialization and vascular matrix remodeling. The “intima-targeted regeneration and adventitia-sequential-release” strategy provides a promising template for SDVG design that may be extended to other complex organ constructs.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124016"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074807","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}