Materials Today Bio最新文献

{"title":"Lipid nanoparticle-mediated mRNA/siRNA dual-bioengineered dendritic cell vaccines combined of PD-1/PD-L1 blockade for boosting tumor immunotherapy","authors":"Dong Yang,&nbsp;Jing Zhan,&nbsp;Ling Miao,&nbsp;Chuan He,&nbsp;Hong Xu","doi":"10.1016/j.mtbio.2025.102357","DOIUrl":"10.1016/j.mtbio.2025.102357","url":null,"abstract":"<div><div>DC vaccines occupy a pivotal position in the realm of cancer treatment, leveraging the immune system to precisely target and effectively eliminate tumor cells. However, current challenges in tumor DC vaccine development include issues such as limited efficacy and potential upregulation of immunosuppressive molecules like PD-L1 on tumor cells. Herein, we employed microfluidic technology to fabricate lipid nanoparticles (LNPs) that simultaneously encapsulate OVA mRNA (mOVA), encoding the model antigen OVA, and siRNA targeting PD-L1. The LNP/mOVA/siPD-L1 nanoparticles were utilized to transfect bone marrow-derived dendritic cells (BMDCs) to construct dual-bioengineered DC vaccines. Subsequently, the efficacy of the dually bioengineered DC vaccines was verified in both prophylactic and therapeutic tumor vaccine models. The upregulation of PD-L1 protein expression on the surface of tumor cells was further blocked by combination of anti-PD-L1 antibody therapy. Notably, the combined therapy achieved complete tumor suppression and the rechallenge experiments demonstrated the tumor immune memory effect induced by the combined therapy, highlighting its potential to elicit long-lasting immunity against cancer. Overall, our findings suggest that this combined therapy holds significant promise for the treatment, metastasis prevention, and recurrence management of tumors, with potential clinical application value in the future.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102357"},"PeriodicalIF":10.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155466","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":"Vitamin C–functionalized copper nanozymes for treating drug-resistant intracellular infections and hyperinflammation","authors":"Yanwen Lu ,&nbsp;Ao He ,&nbsp;Jin Tao ,&nbsp;Xiaopeng Yang ,&nbsp;Simeng Wang ,&nbsp;Xiaoye Li ,&nbsp;Meng Dang ,&nbsp;Yu Zhang ,&nbsp;Zhuo Dai ,&nbsp;Qiang Li ,&nbsp;Heng Dong ,&nbsp;Xuepei Zhang","doi":"10.1016/j.mtbio.2025.102348","DOIUrl":"10.1016/j.mtbio.2025.102348","url":null,"abstract":"<div><div>Bacterial infections, particularly drug-resistant intracellular infections, remain a major clinical challenge due to antibiotic resistance and immune evasion. Here, we report a vitamin C–functionalized copper-based nanozymes (CVs) as multifunctional therapeutic agents capable of simultaneously eradicating intracellular bacteria and mitigating hyperinflammation. Benefiting from excellent biocompatibility and acid-responsive activity, CVs exhibit potent bactericidal, reactive oxygen species (ROS)-scavenging, and immunomodulatory functions. Mechanistically, CVs enter bacterial cytoplasm <em>via</em> copper transporters, induce intracellular copper overload, disrupt the tricarboxylic acid cycle, and promote lipid peroxides accumulation, thereby triggering a cuproptosis-like bacterial death pathway. Moreover, CVs mimic superoxide dismutase activity to efficiently eliminate excessive ROS, and regulate immune responses by suppressing macrophage polarization toward the pro-inflammatory M1 phenotype while reducing pro-inflammatory cytokine production. These combined effects attenuate inflammation and promote tissue repair within infection-associated microenvironments. In a methicillin-resistant <em>Staphylococcus aureus</em> (MRSA)-induced peritonitis mouse model, CVs achieved robust intracellular bacterial clearance and inflammation resolution, underscoring their potential as next-generation copper-based nanomaterials for treating refractory intracellular bacterial infections and hyperinflammation-related disorders.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102348"},"PeriodicalIF":10.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221385","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":"Isoliquiritigenin micellar microneedle for pH monitoring and diabetic wound healing","authors":"Huaqian Xue ,&nbsp;Chen Zhang ,&nbsp;Dini Lin ,&nbsp;Qiancheng Gu ,&nbsp;Chuchu Sun ,&nbsp;Xiufei Lin ,&nbsp;Chi Zhang ,&nbsp;Lanjie Lei ,&nbsp;Liangle Liu","doi":"10.1016/j.mtbio.2025.102356","DOIUrl":"10.1016/j.mtbio.2025.102356","url":null,"abstract":"<div><div>Chronic inflammation, oxidative stress, and insufficient angiogenesis hinder wound healing in patients with diabetes, necessitating long-term management strategies. In this study, we developed pH-responsive hydrogel microneedles (LSI-GCA) based on <em>Lycium barbarum</em> polysaccharide stearate micelles that could achieve real-time pH monitoring and intelligent drug release for effective wound management. LSI-GCA was prepared through hydrophobic modification and isoliquiritigenin (ISO) loading, followed by its combination with a chitosan/anthocyanin backing layer. LSI-GCA exhibited excellent biocompatibility and antibacterial and antioxidant properties by activating the NRF2 pathway and inhibiting pro-inflammatory factors. Animal experiments confirmed that LSI-GCA significantly accelerated wound healing in a diabetic model and promoted angiogenesis, collagen deposition, and M2 macrophage polarization. Genomic and network pharmacological analyses revealed a multi-target synergistic mechanism involving the modulation of EGFR/VEGF signaling to promote proliferation, inhibition of inflammatory pathway (NF-κB), and repair of DNA damage through upregulation of BRCA1/2. This study provides an integrated \"monitoring-treatment\" strategy for diabetic wounds, offering great potential for clinical transformation and personalized treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102356"},"PeriodicalIF":10.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155489","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 membrane biomimetic nanoplatforms: a new strategy for immune escape and precision targeted therapy","authors":"Jian Feng ,&nbsp;Dixin He ,&nbsp;Jingxia Chen ,&nbsp;Mucong Li ,&nbsp;Jiaxin Luo ,&nbsp;Yuzhu Han ,&nbsp;Xuyan Wei ,&nbsp;Sicong Ren ,&nbsp;Zhibo Wang ,&nbsp;Yunxiao Wu ,&nbsp;Hanchi Wang ,&nbsp;Yidi Zhang ,&nbsp;Yanmin Zhou","doi":"10.1016/j.mtbio.2025.102343","DOIUrl":"10.1016/j.mtbio.2025.102343","url":null,"abstract":"<div><div>Cell membrane biomimetic nanoplatforms represent an innovative approach to addressing key challenges in nanodrug delivery systems by encapsulating natural cell membranes onto nanomaterials. This strategy confers unique biological properties that overcome immune clearance, extend in vivo circulation time, and enhance targeting specificity. This review systematically examines the construction strategies of these nanoplatforms and provides an in-depth analysis of immune escape mechanisms across different membrane sources—including erythrocyte, leukocyte, platelet, and tumor cell membranes—and their applications in precision-targeted therapies. We comprehensively explore cell membrane extraction and purification methods, nanocarrier selection, functionalization strategies, and membrane-nanocarrier integration techniques. The therapeutic applications of these platforms are examined across tumor treatment, inflammatory conditions, neurological disorders, and infectious diseases. Despite their significant clinical potential, challenges remain in large-scale production, standardized preparation protocols, and long-term safety assessment. This review also discusses future directions, including smart-responsive nanoplatform development, novel membrane source exploration, and multifunctionalization strategies, providing a theoretical foundation and technical reference for clinical translation of cell membrane biomimetic nanoplatforms.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102343"},"PeriodicalIF":10.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156040","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":"Multifunctional hydrogels for synergistic therapy of cutaneous melanoma-associated tumor recurrence and wound regeneration","authors":"Muyang Li ,&nbsp;Yishuai Sun ,&nbsp;Chengjun Hu ,&nbsp;Hang Luo ,&nbsp;Min Li ,&nbsp;Ying Yang","doi":"10.1016/j.mtbio.2025.102331","DOIUrl":"10.1016/j.mtbio.2025.102331","url":null,"abstract":"<div><div>Cutaneous melanoma is a highly aggressive malignant tumor originated from melanocytes, and its postoperative recurrence and metastatic risk seriously threaten patient survival. Traditional treatments like surgical resection and chemoradiotherapy can merely control the disease in the short term, which faces severe limitations such as immunosuppression of tumor microenvironments (TME), drug resistance and systemic toxicity. Local recurrence, wound infection, and slow healing are common challenges in melanoma post-operation. In recent years, synergistic therapeutic strategies based on multifunctional hydrogels have been at the forefront of research due to their exceptional biomaterial properties, such as high biocompatibility, programmable drug release and tissue regeneration support. Different types of complexes are utilized to synthesize multifunctional hydrogels in different oncology therapeutic application scenarios, and various novel preparation processes and powerful functional components are introduced. Hydrogels have the ability to achieve responsive-triggered precision drug delivery, forming a synergistic system in immunotherapy, radiotherapy and phototherapy, reverse the inhibitory TME, and exert powerful anti-tumor effects through multiple signaling pathways. In addition, its improved hydrophilicity and biomimetic microcellular structure could accelerate postoperative wound regeneration, and the combination of antimicrobial components can effectively prevent postoperative wound infections resulting from disturbed local immune microenvironment. In this paper, we systematically reviewed and summarized the cutting-edge advances of hydrogels used for treating cutaneous melanoma, focusing on their functionalized design, anti-tumor molecular mechanisms, immune microenvironment regulation, antibacterial efficacy and synergistic strategies of wound regeneration, with a view to providing theoretical basis and technical references for future clinical translation of tissue engineering materials for tumor-associated wounds.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102331"},"PeriodicalIF":10.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156044","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 ROS-responsive nanocarrier co-delivering cerium nanozymes and thalidomide for synergistic ulcerative colitis therapy","authors":"Jintao Shen ,&nbsp;Wencheng Jiao ,&nbsp;Yizhi Zhang ,&nbsp;Bo Zhuang ,&nbsp;Shuxiu Zhang ,&nbsp;Guiyu Huang ,&nbsp;Lei Ma ,&nbsp;Junzhe Yang ,&nbsp;Yanping Wu ,&nbsp;Lina Du ,&nbsp;Yiguang Jin","doi":"10.1016/j.mtbio.2025.102346","DOIUrl":"10.1016/j.mtbio.2025.102346","url":null,"abstract":"<div><div>Ulcerative colitis (UC) is a chronic and recurrent inflammatory disorder of the gastrointestinal tract, posing major clinical challenges due to its increasing incidence and complex pathogenesis involving immune dysregulation and oxidative stress. Current therapies are often limited by poor efficacy and severe side effects, leaving an urgent need for improved treatments. Here, we present a novel ROS-responsive nanocarrier (TPN) for the synergistic therapy of colitis via ROS scavenging and immune modulation. TPN were fabricated by encapsulating cerium oxide nanozymes (Ceria NPs) and thalidomide (Tha) within a specially designed amphiphilic ROS-responsive polymer (PP). TPN exhibited strong ROS-scavenging activity and ROS-triggered Tha release. <em>In vitro</em>, TPN effectively attenuated ROS-induced oxidative stress and apoptosis. In a DSS-induced mouse colitis model, TPN passively accumulated in the colon and significantly alleviated body weight loss, colon shortening, disease activity index, and histological damage. Mechanistically, TPN modulated the immune response, reduced oxidative stress, and reshaped the gut microbiota toward a healthier composition. Moreover, biosafety assessments confirmed the absence of systemic toxicity. Collectively, these findings demonstrate that TPN represents a potent and safe therapeutic strategy for UC by integrating targeted delivery with synergistic antioxidant and immunomodulatory functions.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102346"},"PeriodicalIF":10.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221356","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":"Ultrafast in situ formed robust and adhesive photo-crosslinked hydrogel encapsulating curcumin for ulcerative colitis alleviation via regulating inflammation and gut microbiota","authors":"Yaya Bai ,&nbsp;Ting Chen ,&nbsp;Yao Zhang ,&nbsp;Jingwei Zhao ,&nbsp;Chunling Ren ,&nbsp;Yizhou Zhao ,&nbsp;Chao Sun ,&nbsp;Yixun Jin ,&nbsp;Ziyun Yang ,&nbsp;Bingkun Bao ,&nbsp;Qiuning Lin ,&nbsp;Linyong Zhu ,&nbsp;Yunlong Yang ,&nbsp;Weiyan Yao ,&nbsp;Duowu Zou","doi":"10.1016/j.mtbio.2025.102312","DOIUrl":"10.1016/j.mtbio.2025.102312","url":null,"abstract":"<div><div>Ulcerative colitis (UC) is a chronic, relapsing-remitting inflammatory condition that primarily affects the colonic mucosa. Its treatment is significantly constrained by the systemic side effects of non-specific drugs like glucocorticoids. Curcumin (Cur) is known as a safe and potent compound for mitigating UC, but its application is hindered by low colonic bioavailability. Hydrogel presents a promising colonic delivery system for drugs to reduce side effects and enhance colonic bioavailability. However, achieving hydrogel adhesion and stability in the harsh colonic environment is quite challenging. Here, to overcome these challenges, we have developed an adhesive and robust photo-crosslinked hydrogel encapsulated with Cur loaded poly (lactic-co-glycolic acid) (PLGA) microspheres (Cur@PLGA-Gel) for effective UC alleviation. The pre-gel solution can be delivered into the colon to form a tough hydrogel with strong tissue adhesion via the photo-triggered transient radical and persistent radical coupling (PTPC) reaction, enabling colonic retention of Cur for over 72 h. Moreover, PLGA enhances the stability, solubility and dispersibility of Cur. Through the integration of <em>in vivo</em> and <em>in vitro</em> approaches, we have confirmed that Cur@PLGA-Gel can promote cell proliferation, eliminate reactive oxygen species (ROS), and regulate immune responses and gut microbiota balance, thereby effectively alleviating UC symptoms. Collectively, this study provides an effective and safe strategy for UC treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102312"},"PeriodicalIF":10.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221342","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 self-adaptive multifunctional hydrogels elicit immunomodulation mediated wound healing","authors":"Jintao Fang ,&nbsp;Yicheng Wang ,&nbsp;Ping Ling ,&nbsp;Dian Yu ,&nbsp;Junwen Hu ,&nbsp;Jinwei Wang ,&nbsp;Qin Xia ,&nbsp;Weihan Zhu ,&nbsp;Wenjun Xu ,&nbsp;Jintao Shi ,&nbsp;Xijin Wu ,&nbsp;YuJia Li ,&nbsp;Xiaxin Zhu ,&nbsp;Huiyin Fu ,&nbsp;Qiyang Shou ,&nbsp;Wei Zhang ,&nbsp;Shengyu Li","doi":"10.1016/j.mtbio.2025.102340","DOIUrl":"10.1016/j.mtbio.2025.102340","url":null,"abstract":"<div><div>Herein, we report a microenvironment self-adaptive multifunctional hydrogel (GBOD-PF) dressing with intrinsic hemostasis, antimicrobial and anti-inflammatory properties that promotes collagen deposition, activates the immune response, and angiogenesis, accelerates large-scale chronic wound healing. To address these needs, aldehyde-functionalized dextran (ODT) was first synthesized through oxidation, and an injectable hydrogel was prepared by mixing Gel and ODT solutions in the presence of borax and paeoniflorin (PF) through the formation of dynamic Schiff base bonds (GBOD-PF). This multifunctional hydrogel exhibits remodeling and self-healing properties, enhanced adhesion strength and biocompatibility. Moreover, it possesses broad-spectrum antibacterial activity and superior hemostasis, providing early-stage protection for complex wounds. Notably, GBOD-PF targets the TLR4/NF-κB signaling pathway, a core mediator of inflammation, thereby dampening the inflammatory cascade. The results demonstrate the application of the GBOD-PF hydrogel in an infection wound and diabetic model wound healing model, which enhanced immune response, induced M1-to-M2 macrophage repolarization to establish anti-inflammatory microenvironment, regulated MMP-9, promoted angiogenesis, thereby inducing a pro-regenerative response. Therefore, this work provides an effective strategy for the treatment of chronic wound repair and tissue regeneration.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102340"},"PeriodicalIF":10.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221345","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":"T7 peptide-modified erythrocyte membrane-camouflaged amphiphilic self-delivery biomimetic nanodrug for targeting therapy oral squamous cell carcinoma","authors":"Yun Deng ,&nbsp;Wangxiang Yan ,&nbsp;Dalong Shu ,&nbsp;Li Zhu ,&nbsp;Songling Chen ,&nbsp;Yu Chen","doi":"10.1016/j.mtbio.2025.102345","DOIUrl":"10.1016/j.mtbio.2025.102345","url":null,"abstract":"<div><div>Oral squamous cell carcinoma (OSCC) is a common oral malignancy. However, conventional chemotherapeutic strategies present many limitations. To overcome these challenges, a cell membrane-camouflaged amphiphilic self-delivery nano-prodrug was developed for the targeted treatment of OSCC. In this system, the hydrophobic anticancer drug methotrexate (MTX) and the hydrophilic drug gemcitabine (GEM) were conjugated <em>via</em> amide bonds to form an amphiphilic drug-drug conjugate (ADDC), which self-assembled into nanoparticles (MG NPs). Phospholipids were modified with T7 peptide, capable of targeting the highly expressed transferrin receptor (TFR) on tumor cell surfaces, and subsequently loaded onto red blood cell membranes (RBCM) to prepare T7 peptide-modified RBCM (T7-RBCM). The MG NPs were then encapsulated with T7-RBCM by co-extrusion to form T7-RBCM@MG NPs. <em>In vitro</em> studies demonstrated that T7-RBCM@MG NPs were more efficiently internalized by tumor cells due to specific recognition between the T7 peptide and TFR, exhibited stronger inhibitory activity against SCC-7 cells, and significantly induced apoptosis. <em>In vivo</em> experiments confirmed that T7-RBCM@MG NPs exhibited favourable biosafety, prolonged circulation, and enhanced tumor-targeting delivery, resulting in significant tumor growth inhibition without notable toxicity to major organs.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102345"},"PeriodicalIF":10.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155468","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":"Integration of lymphatic vasculature to a human lymph node-on-chip enhances physiological immune properties","authors":"Andrew I. Morrison ,&nbsp;Jonas Jäger ,&nbsp;Charlotte M. de Winde ,&nbsp;Tanja Konijn ,&nbsp;Henk P. Roest ,&nbsp;Luc J.W. van der Laan ,&nbsp;Susan Gibbs ,&nbsp;Jasper J. Koning ,&nbsp;Reina E. Mebius","doi":"10.1016/j.mtbio.2025.102326","DOIUrl":"10.1016/j.mtbio.2025.102326","url":null,"abstract":"<div><div>To study systemic human innate and adaptive immune responses in detail, competent <em>in vitro</em> lymph node (LN) models with LN stromal cells (LNSCs) are required to recapitulate the physiological microenvironment. The multicellular organisation of LNs possesses a challenge for designing such microphysiological systems (MPS), particularly with the structural complexity of LNs and the lymphatic vasculature. Here, we established an organotypic LN model with integrated lymphatics in an organ-on-chip (OoC) platform containing a printed sacrificial structure, and studied the influence of a perfused lymphatic endothelial cell (LEC)-lined channel on the LN-on-chip microenvironment. Upon one-week of culture under lymphatic flow, LECs lined the tubular structure forming a lymphatic vessel through the LN model, and stable metabolic conditions within the LN-on-chip were confirmed. Interestingly, LECs in the LN-on-chip displayed the phenotype found in human LNs with upregulation of LEC-specific LN markers, such as atypical chemokine receptor 4 (ACKR4). The presence of the LEC-lined perfused vessel in the LN-on-chip resulted in the increase of native immune cells, most notably B cells, and the secretion of survival and migratory signals, namely interleukin-7 (IL-7) and CC motif chemokine ligand 21 (CCL21). Likewise, LECs promoted the abundance of immune cell clusters closer to the vessel. As such, these features represent an enhanced physiological microenvironment to allow for immune cell migration and interactions for efficient LN functioning. This approach paves the way for LN integration into multi-OoC (MOC) platforms to investigate immunological crosstalk between tissue-derived factors, immune cell trafficking and organ-specific adaptive immune responses.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"35 ","pages":"Article 102326"},"PeriodicalIF":10.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155488","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}