Biomaterials最新文献

{"title":"Profiling the T cell response to polypropylene mesh in a non-human primate sacrocolpopexy model","authors":"Srividya Kottapalli , Marrisa Therriault , Rui Liang , Malini Harinath , Gabby King , Pamela A. Moalli , Amanda Artsen","doi":"10.1016/j.biomaterials.2026.124008","DOIUrl":"10.1016/j.biomaterials.2026.124008","url":null,"abstract":"<div><div>Polypropylene mesh (PPM) improves anatomic outcomes in pelvic organ prolapse (POP) repair, yet complications—most commonly pain and mesh exposure—occur in ∼10 % of cases. Clinically, meshes that are implanted flat often demonstrate striking deformation at explanation, including pore collapse and wrinkling. Both computational models and <em>in vivo</em> studies confirm that mesh geometry changes substantially after tensioning during prolapse repair. Although T cells have been implicated in mesh-related complications, the specific impact of mesh deformation on adaptive immunity is not fully understood.</div><div>To address this gap, a lightweight PPM (Restorelle) was implanted in nonhuman primates either in its flat configuration (stable, R0) or engineered into two progressively deformed geometries: R45 (unstable: pore collapsed) and RD (predeformed: pore collapsed + wrinkled). Sham-operated animals served as controls. Twelve weeks post-implantation, mesh–tissue complexes were analyzed to quantify T-cell phenotypes, tissue remodeling, and downstream healing outcomes. Findings were integrated with a comparative proteomic analysis of flat versus deformed human mesh explants.</div><div>Mesh burden increased stepwise with deformation (R0 < R45 < RD). Deformation amplified T-cell infiltration within the vaginal adventitia, with helper T cells dominating and cytotoxic T cells contributing minimally. T<sub>regs</sub> were enriched in the moderately deformed R45 group—consistent with injury resolution—but were markedly reduced in RD, indicating a shift toward chronic, non-resolving inflammation. Whereas flat meshes maintained organized collagen and physiologic fibrotic encapsulation, deformed meshes—particularly RD—exhibited loss of organized ECM, increased fibroblast-driven remodeling, and elevated fibroblast growth factor-2 (FGF-2). Cytokine profiling revealed increased IL-1β and CXCL12 across all mesh groups, but RD uniquely showed suppression of Th2 cytokines (IL-4, IL-5), a signature of impaired immune resolution.</div><div>Human explants mirrored key primate findings: CD99, a marker of T-cell trafficking and persistent activation, was elevated in specimens from patients with complications, while CD84, which mediates T:B-cell interactions and memory formation, was reduced—suggesting repetitive T-cell activation without durable immune regulation.</div><div>Together, these results demonstrate that increasing mesh deformation drives a shift from a Th2/Treg-dominant, pro-resolution immune response toward chronic inflammation characterized by persistent T-cell activation and fibroblast-mediated ECM disruption. This work directly links mesh geometry–induced mechanical stress to adaptive immune dysregulation and disordered collagen remodeling and validates these signatures in human specimens. The findings highlight actionable opportunities for geometry-preserving mesh designs and targeted T-cell–directed immunomodulation to prevent complicati","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124008"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024841","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":"Shaping mesenchymal stem cell fate with a two-dimensional covalent triazine framework for calmodulin modulation","authors":"Lei Wang ,&nbsp;Boyu Zheng ,&nbsp;Maryam Salahvarzi ,&nbsp;Yi-An Yang ,&nbsp;Yan Nie ,&nbsp;Philip Nickl ,&nbsp;Mathias Dimde ,&nbsp;Kai Ludwig ,&nbsp;Xun Xu ,&nbsp;Yiduo Zhou ,&nbsp;Junyao Zhang ,&nbsp;Weiwei Wang ,&nbsp;Xiao Ling ,&nbsp;Xingjun Qin ,&nbsp;Lukas Prantl ,&nbsp;Oliver Felthaus ,&nbsp;Wenzhong Li ,&nbsp;Mohsen Adeli ,&nbsp;Nan Ma","doi":"10.1016/j.biomaterials.2026.123997","DOIUrl":"10.1016/j.biomaterials.2026.123997","url":null,"abstract":"<div><div>Calmodulin (CaM) is a central calcium sensor and signaling hub that critically governs stem cell fate. However, directly intracellular modulation of CaM remains challenging due to its activity is tightly coupled to finely balanced calcium homeostasis, and conventional chemicals or biomaterials have limited ability to access or target it. Here, we introduce a novel two-dimensional, porous, covalent triazine-based framework, CTF-Ca, synthesized under ambient conditions, that offers a new strategy for intracellular CaM regulation. Unlike conventional approaches, CTF-Ca bypasses membrane calcium channels, enabling direct calcium influx into mesenchymal stem cells (MSCs) and triggering robust, sustained activation of the Ca²⁺/CaM signaling pathway. This activation markedly enhances osteogenic differentiation in MSCs. Remarkably, CTF-Ca also compensates for suppressed CaM function, restoring osteogenic potential in MSCs even under CaM-inhibited conditions. This compensatory effect was further demonstrated in C2C12 myogenic progenitor cells, a skeletal muscle model characterized with high endogenous CaM expression, where CTF-Ca rescued myotube formation in CaM deficient cells, underscoring its broad applicability. Together, these findings establish CTF-Ca as an effective 2D material for direct intracellular modulation of CaM, offers a promising new tool for regulating stem and progenitor cells fate.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 123997"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957853","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":"Cascade-enhanced Pt nanozyme platform anchored on microgels for effective lactate depletion and EndoMT attenuation post-myocardial infarction","authors":"Liang Song ,&nbsp;Yongyuan Kang ,&nbsp;Pai Peng ,&nbsp;Qiaoxuan Wang ,&nbsp;Liyin Shen ,&nbsp;Jinyue Zhang ,&nbsp;Yang Zhu ,&nbsp;Changyou Gao","doi":"10.1016/j.biomaterials.2026.124005","DOIUrl":"10.1016/j.biomaterials.2026.124005","url":null,"abstract":"<div><div>Myocardial infarction (MI) often leads to excessive lactate accumulation, which drives endothelial-to-mesenchymal transition (EndoMT) and subsequent myocardial fibrosis. Lactate oxidase (LOx) has been identified as a potential therapeutic enzyme capable of degrading excess lactate. However, the hypoxic environment characteristic of MI diminishes the catalytic efficiency of LOx. In this study, platinum (Pt) nanozymes with catalase-like (CAT-like) activity were introduced, which catalyzed the decomposition of hydrogen peroxide (H₂O₂) to generate oxygen (O₂), thereby enhancing LOx activity. A strategy involving microgel-anchored LOx-loaded Pt nanozymes (PPtL@MGs) was proposed by loading LOx-loaded Pt nanozymes to microgels, enabling targeted delivery and prolonged retention within the infarcted myocardium. The PPtL@MGs exhibited robust CAT-like activity and effectively enhanced LOx-mediated lactate clearance <em>in vitro</em>, thereby alleviating hypoxia/H₂O₂-induced EndoMT in HUVECs. Consequently, it promoted vascular endothelial cadherin (VE-cadherin) expression, suppressed fibroblast-specific protein 1 (FSP1), reduced myocardial fibrosis, and significantly improved cardiac function <em>in vivo</em>. These results demonstrate the potential of this microgel-anchored nanozyme system, which enables cascade-enhanced lactate modulation through O₂ generation and effective lactate clearance, thereby alleviating the MI-induced fibrosis and dysfunction.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124005"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024833","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":"Methionine-depleting engineered probiotics promote PD-L1 antibody immunotherapy by activating the STING pathway","authors":"Tiantian Sun ,&nbsp;Qiushuang Zhang ,&nbsp;Yicong Dai ,&nbsp;Yuhan Liu ,&nbsp;Xucong Teng ,&nbsp;Jinghong Li","doi":"10.1016/j.biomaterials.2026.124015","DOIUrl":"10.1016/j.biomaterials.2026.124015","url":null,"abstract":"<div><div>The metabolic differences between tumor cells and normal tissue cells offer potential targets for therapeutic intervention. For instance, compared to normal tissues, tumor cells exhibit a significantly higher dependency on methionine. However, current strategies for methionine restriction have limited clinical applicability due to systemic toxicity, poor patient compliance, and insufficient tumor targeting. In this study, we developed an engineered probiotic, Met-EcN, which is able to achieve targeted consumption of methionine within the tumor microenvironment. In the B16–F10 melanoma mouse model, the combination of Met-EcN and anti-PD-L1 antibody led to a 63 % increase in the tumor inhibition rate compared to anti-PD-L1 treatment alone, as well as a 50 % improvement in mouse survival rates. Additionally, this combination significantly enhanced T cell infiltration and activation. In the MC-38 colon cancer model, treatment with Met-EcN alongside anti-PD-L1 antibody inhibited tumor growth by 84.6 %, leading to complete regression of tumors in 80 % of the mice. The depletion of methionine levels by Met-EcN leads to a reduction in methylation levels within tumor cells, which facilitates the dissociation of cGAS protein from chromatin and activates the STING signaling pathway, thereby triggering an innate immune response. This study provides a novel therapeutic approach for overcoming tumor immune resistance.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124015"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075194","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":"Iron oxide nanoparticles-driven mitochondrial renewal rejuvenates the aged bone marrow niche","authors":"Xiaoqing Sun ,&nbsp;Xingyou Wang ,&nbsp;Meihua Zhang ,&nbsp;Shuyao Liu ,&nbsp;Yue Zhu ,&nbsp;Jing He ,&nbsp;Yao Wu","doi":"10.1016/j.biomaterials.2026.123989","DOIUrl":"10.1016/j.biomaterials.2026.123989","url":null,"abstract":"<div><div>With the aging population, treating age-related osteoporosis remains challenging due to the dysfunctional bone marrow microenvironment characterized by chronic inflammation, metabolic dysregulation, and impaired mitochondrial function in senescent cells. While mitochondrial transfer from macrophages to bone marrow mesenchymal stem cells (BMSCs) offers a promising therapeutic avenue, its efficacy is limited in aged niches where donor mitochondria exhibit functional deficits and poor recipient compatibility. We engineered KGM-PEG-SPIONs, functionalized Fe₃O₄ nanoparticles that enhance donor mitochondrial quality via autophagy activation and Fe–S cluster biogenesis, promote M2 macrophage polarization, and improve compatibility with the oxidative and inflammatory environment of senescent BMSCs. These M2-like mitochondria are transferred through connexin 43 gap junctions, restoring membrane potential, ATP production, calcium homeostasis, and osteogenic differentiation in recipient cells. In aged osteoporotic models, KGM-PEG-SPION-functionalized scaffolds remodel immune niches and promote bone formation. By integrating organelle quality control with environment-adapted mitochondrial transfer, this strategy surpasses approaches focusing solely on transfer quantity or polarization, establishing a programmable nanoplatform for organelle-based regeneration.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 123989"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957408","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":"Recapitulating tumor extracellular matrix alignment to decipher its role in eliciting malignant cell phenotypes using a peptide liquid crystal hydrogel","authors":"Si-Yong Qin ,&nbsp;Wei-Wei Cheng ,&nbsp;Meng-Yun Peng ,&nbsp;Chuang Cai ,&nbsp;Qi Lei ,&nbsp;Rong Huang ,&nbsp;Yin-Jia Cheng ,&nbsp;Wen-Long Liu ,&nbsp;Yi-Han Ma ,&nbsp;Ai-Qing Zhang ,&nbsp;Lei Wang","doi":"10.1016/j.biomaterials.2026.124017","DOIUrl":"10.1016/j.biomaterials.2026.124017","url":null,"abstract":"<div><div>The aligned microarchitecture of extracellular matrix (ECM) has been recognized as a significant and novel hallmark of certain tumors, which is gradually uncovered to relate to their malignant progression. However, most artificial scaffolds are isotropic and fail to mimic such aligned organization of tumor-associated ECMs. To address this limitation, we developed a self-assembling peptide-based liquid crystal (LC) hydrogel model to recapitulate the aligned topology of tumor ECM, thereby establishing a platform to investigate the relationship between ECM alignment and malignant cell phenotype. The screened peptide self-assembled into aligned nanofibers via a thermal pathway, forming an LC hydrogel with engineered biological properties. When cultured within the peptide LC hydrogel, tumor cells displayed enhanced proliferation, migration, invasion, and drug-resistance, underscoring the critical role of ECM alignment in promoting aggressive phenotypes. Leveraging the LC hydrogel model, we provided initial insights into the mechanisms underlying malignant progression via Western blot, reverse transcription-quantitative PCR and RNA sequencing analyses. Moreover, by implanting LC hydrogel precultured cancer cells into C57BL/6 mice, we established a tumor model exhibiting accelerated growth. Our findings demonstrate that the self-assembled peptide LC hydrogel can recapitulate tumor ECM alignment and enable the development of rapidly progressing tumor models for cancer research and drug screening.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124017"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045926","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":"Tumor disaggregation sensitizes radio-therapy for low rectal tumor","authors":"Hanyong Dong ,&nbsp;Yuedong Guo ,&nbsp;Jianlin Shi ,&nbsp;Ping Hu","doi":"10.1016/j.biomaterials.2026.124029","DOIUrl":"10.1016/j.biomaterials.2026.124029","url":null,"abstract":"<div><div>Hypoxia within solid tumors has been identified as one of the main obstacles in radiotherapy due to the severely reduced radiosensitivity. Current strategies to alleviate tumor hypoxia mainly rely on oxygen supplementation using oxygen carriers (e.g., hemoglobin- or perfluorocarbon-based systems), hypoxia-activated prodrugs, or tumor oxygen consumption modulators, leading to limited efficacies due to poor tumor-specific targeting, insufficient oxygen delivery in the complex tumor microenvironment, and potential systemic toxicity. Here we propose an alternative but novel strategy for radiosensitization in colorectal cancer radiotherapy by uncompacting the tumor tissue via tumor disaggregation, thus alleviating tumor hypoxia and enhancing radiosensitivity. This strategy has been realized by developing a nanomedicine composed of ethylene diamine tetraacetic acid-loaded layered double hydroxide (LDH/EDTA) featuring intratumoral acidity-responsive EDTA release. The released EDTA deprives Ca²⁺ ions from the intercellular cadherins that connect tumor cells through EDTA- Ca²⁺ chelation, thus disrupting the inter-cellular junctions in tumor tissue by cadherin damages. As a result, compactness and rigidity of tumor tissues are greatly reduced, and the ambient oxygen is allowed to diffuse deep into the tumor interior, thereby alleviating the hypoxia of solid tumors and effectively enhancing their sensitivity to radiotherapy. This work proposes a novel yet facile strategy to enhance radiosensitivity simply by overcoming the physical barriers of tumors and alleviating hypoxia.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124029"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074806","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":"3D culture reveals dual role of ICAM-1 in mediating tissue-specific human MSC spheroid formation & enhanced immunomodulation","authors":"Li-Tzu Wang ,&nbsp;Hsiu-Huan Wang ,&nbsp;Duong Thi Thuy Doan ,&nbsp;Yun-Fei Lin ,&nbsp;Chien-Yu Liao ,&nbsp;Pei-Ju Hsu ,&nbsp;Chia-Chih Chang ,&nbsp;Men-Luh Yen ,&nbsp;Ko-Jiunn Liu ,&nbsp;Huey-Kang Sytwu ,&nbsp;B. Linju Yen","doi":"10.1016/j.biomaterials.2026.123998","DOIUrl":"10.1016/j.biomaterials.2026.123998","url":null,"abstract":"<div><div>Three-dimensional (3D) <em>in vitro</em> culture systems may better mimic <em>in vivo</em> physiological conditions, and are easily accessible methods to improve therapeutic effectiveness of human mesenchymal stem cells (MSCs), which with its many sources appear to harbor clinically relevant functional differences. We therefore investigated the impact and elucidated the mechanism(s) of 3D culture on the immunomodulatory capacity of two commonly used MSC sources, bone marrow (BM) and placental (P). In 3D conditions, PMSCs (PMSC 3D) form larger spheroids than BMMSCs (BMMSC 3D), with whole transcriptome profiling revealing significant enrichment of cell adhesion and immunomodulatory pathways. qPCR and functional validation demonstrated the highest expression of numerous key immunomodulatory factors and strongest capacity to inhibit T cell proliferation with PMSC 3D. Bioinformatics analyses predicted Intercellular Adhesion Molecule 1 (ICAM-1) as crucial for both PMSC 3D spheroid formation and enhanced immunomodulatory capacity, which was validated with flow cytometric analyses and further delineated with single-cell RNA sequencing data. To assess mechanistic involvement, we performed knockdown of ICAM-1 which significantly reduced PMSC 3D spheroid size as well as both <em>in vitro</em> and <em>in vivo</em> immunomodulatory capacity. These findings demonstrate that 3D culture significantly enhances the immunomodulatory potential of PMSCs, and reveal ICAM-1 as having a dual role in spheroid formation as well as modulation of immune responses. Our study also highlights the importance of understanding source-specific differences as well as the profound influence of 3D <em>in vitro</em> systems on MSC functions.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 123998"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957407","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 cascade “four-in-one” Nanozyme for remodeling the redox tumor microenvironment and disrupting energy homeostasis to enhance ferroptosis against triple-negative breast cancer","authors":"Lei Li ,&nbsp;Annan Liu ,&nbsp;Ze Wang ,&nbsp;Hao Liang ,&nbsp;Andrew K. Whittake ,&nbsp;Hui Guo ,&nbsp;Quan Lin","doi":"10.1016/j.biomaterials.2026.124001","DOIUrl":"10.1016/j.biomaterials.2026.124001","url":null,"abstract":"<div><div>Ferroptosis, a promising therapeutic strategy for triple-negative breast cancer (TNBC), faces significant challenges due to intrinsic tumor defense mechanisms. To enhance ferroptosis against TNBC, a biomimetic “four-in-one' cascade nanozyme AuPd/Cu₂O@Cancer cell membrane (APCM) was engineered to remodel tumoral redox microenvironment and disrupt cancer cell energy metabolism. APCM nanozyme integrates four enzyme-mimicking activities into a single nanoplatform, including peroxidase-like, glucose oxidase-like, catalase-like, and glutathione peroxidase-like. This synergistic cascade converts endogenous H₂O₂ to cytotoxic ·OH, depletes glucose to block energy supply while self-supplying H₂O₂, alleviates hypoxia, and depletes glutathione to suppress antioxidant defense, collectively triggering lethal reactive oxygen species (ROS) accumulation for ferroptosis. APCM further enables photothermal therapy (PTT), inducing direct thermal ablation and providing localized heat to augment nanocatalytic efficacy. Coating with tumor-derived membrane facilitates homologous targeting and immune evasion. Transcriptomic analysis confirmed profound APCM-mediated modulation of ferroptosis, metabolic, and redox-associated gene signatures. Notably, the APCM nanozyme enables dual-mode imaging, offering visualization of the location of TNBC and precise guidance for treatment. Collectively, this “four-in-one' biomimetic nanozyme, which integrates multiple enzyme-mimicking activities and tumor-cell-membrane camouflage, effectively disrupts redox and metabolic homeostasis to potentiate ferroptosis, establishing a promising therapeutic paradigm for TNBC.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124001"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975837","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":"Prolonging the anti-tumor effects of cold atmospheric plasma via exosome-mediated signaling","authors":"Wen Li ,&nbsp;Li Cao ,&nbsp;Jiaqi Zhu ,&nbsp;Hui Wang ,&nbsp;Yijie Liu ,&nbsp;Lingyu Zhang ,&nbsp;Chen Guo ,&nbsp;Jing Yan ,&nbsp;Wenjing Wang ,&nbsp;Bo Zhou ,&nbsp;Jiangfang Lian ,&nbsp;Bo Guo ,&nbsp;Chen Huang","doi":"10.1016/j.biomaterials.2026.124011","DOIUrl":"10.1016/j.biomaterials.2026.124011","url":null,"abstract":"<div><div>Cold atmospheric plasma (CAP) has emerged as a promising non-thermal modality in cancer research due to its ability to induce selective cytotoxicity through reactive oxygen and nitrogen species. However, the limited penetration depth and instability of plasma-derived reactive species in complex biological environments remain major obstacles to its therapeutic application. In this study, we investigated whether exosomes derived from CAP-treated cancer cells (CAP-Exo) could serve as functional mediators to extend and amplify the anti-tumor effects of CAP. Using chronic myeloid leukemia K562 cells as a primary model, we demonstrate that CAP treatment induces pronounced oxidative stress, apoptosis, and sustained proliferative suppression. Importantly, exosomes isolated from CAP-treated cells exhibited enhanced anti-proliferative and pro-apoptotic activity in recipient cells compared to exosomes from untreated controls. To assess the broader applicability of this strategy, we further evaluated the effects of CAP and CAP-Exo in multiple solid tumor models, including breast, renal, and hepatocellular carcinoma cells, both <em>in vitro</em> and <em>in vivo</em>. CAP exposure consistently reduced cell viability across solid tumor cell lines, while CAP-Exo retained potent cytotoxic activity against breast cancer cells and significantly suppressed tumor growth in corresponding xenograft models without inducing systemic toxicity. Mechanistically, CAP-induced stress reprogrammed exosomal cargo, enabling the transfer of death-associated molecular signals to recipient tumor cells and thereby promoting apoptosis. Collectively, our findings indicate that CAP-modified exosomes represent a biologically active, cell-free approach that extends the anti-tumor effects of CAP treatment across both hematological malignancies and solid tumors. Rather than replacing existing therapeutic modalities, CAP-Exo may serve as a complementary strategy to enhance CAP-based cancer interventions and overcome current limitations associated with direct CAP application.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124011"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045957","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}