Biomaterials最新文献

{"title":"Self-amplifying violet phosphorus-manganese nanocatalysts disrupt redox homeostasis and potentiate antitumor immunity via NIR-II phototherapy","authors":"Zhuo Mao ,&nbsp;Yitong Zhang ,&nbsp;Jingyue Xu ,&nbsp;Hanyue Li ,&nbsp;Tingxuan Li ,&nbsp;Rourou Miao ,&nbsp;Liu Yu ,&nbsp;Meitong Ou ,&nbsp;Ran Luo ,&nbsp;Fan Zhang ,&nbsp;Hanjie Zhang ,&nbsp;Lin Mei","doi":"10.1016/j.biomaterials.2025.123872","DOIUrl":"10.1016/j.biomaterials.2025.123872","url":null,"abstract":"<div><div>Nanocatalytic therapy holds great promise in tumor treatment. However, its antitumor efficacy is substantially hindered by limitations of the tumor microenvironment (TME), including substrate the type and concentration of substrates, pH value, antioxidant stress defense mechanisms, and immunosuppressive milieu. This study presents a nanoplatform composed of manganese-in-situ-mineralized violet phosphorus nanosheets (VPNSs), abbreviated as MVPs. This platform enables both the disruption of redox homeostasis and activation of antitumor immunity through regulation by the TME and near-infrared II region (NIR-II) light stimulation. Within MVPs, VPNSs not only function as electron donors to sustain the concentration of active Mn²⁺ in the TME and amplify the Mn²⁺-mediated self-enhanced chemodynamic therapy (CDT), but also serve as NIR-II photocatalysts. The photocatalytic properties synergistically elevate the level of reactive oxygen species (ROS) at the tumor site, thereby disrupting the redox homeostasis of tumor cells. Furthermore, the NIR-II photothermal characteristic of MVPs enhances the Mn²⁺-mediated activation of the stimulator of interferon genes (STING) pathway, endowing MVPs with antitumor immune activation capability. MVPs demonstrate excellent tumor therapeutic performance and biocompatibility in female tumor-bearing mice with a tumor inhibition rate of 85.24 %, achieving “catalysis-photothermal-immunity” synergistic antitumor activity.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123872"},"PeriodicalIF":12.9,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659819","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":"Molybdenum nanodots reprogram inflammatory-driven osteolysis via bone immune remodeling","authors":"Zi Fu ,&nbsp;Wanting Hao ,&nbsp;Xichun Qin ,&nbsp;Han Wang ,&nbsp;Dong Xie ,&nbsp;Meng Zhang ,&nbsp;Dalong Ni","doi":"10.1016/j.biomaterials.2025.123871","DOIUrl":"10.1016/j.biomaterials.2025.123871","url":null,"abstract":"<div><div>The translational potential of nanomedicines largely depends on compositional simplicity and scalable synthesis, with structurally intricate systems (e.g., hybrid composites) often struggling in manufacturing standardization. Single-element nanosystems bypass these limitations through inherent biosafety and bioactivity tunability. Herein, molybdenum nanodots (MoNDs), which synthesized via a facile and reproducible ultrasonic exfoliation method, were designed to address implant-associated osteolysis. These mono-component MoNDs displayed robust reactive oxygen species (ROS) scavenging and biocompatibility alongside recovering mitochondrial function to alleviate oxidative stress and curbing NF-κB-mediated M1 macrophage polarization. The MoNDs further regulated bone remodeling by suppressing osteoclastogenesis through NFATc1/CTSK downregulation and promoting osteogenic differentiation. <em>In vivo</em> evaluations using a titanium particle-induced osteolysis model revealed that the MoNDs effectively attenuated pathological bone loss, improved trabecular integrity, and rebalanced bone metabolic markers. Collectively, this work positions MoNDs as a clinically viable nanotherapeutic that harnesses elemental simplicity to resolve inflammation-driven osteolytic disorders, bridging material design with translational orthopedics.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123871"},"PeriodicalIF":12.9,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621101","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":"Well-defined electronic configuration cyano-bridged bimetallic nanozyme for cancer catalytic-immunotherapy","authors":"Qianqian Wu ,&nbsp;Xiaohui Chen ,&nbsp;Sitong Wang ,&nbsp;Xing Wang ,&nbsp;Zhixin Cha ,&nbsp;Hengyi Chen ,&nbsp;Yangguang Ren ,&nbsp;Yao Luo ,&nbsp;Xin Cui ,&nbsp;Yan Zhao ,&nbsp;Yufang Zhang ,&nbsp;Yican Li ,&nbsp;Zhongyao Ge ,&nbsp;Sergio Benardini ,&nbsp;Zhizeng Wang ,&nbsp;Jichun Yang ,&nbsp;Yang Luo","doi":"10.1016/j.biomaterials.2025.123868","DOIUrl":"10.1016/j.biomaterials.2025.123868","url":null,"abstract":"<div><div>Heterobimetallic nanozymes hold great promising in cancer catalytic therapy by leveraging dual-active sites that are electronically coupled. However, their therapeutic potential is limited by high inherent complexity and lack of clarity regarding their electron conformation. In this study, we developed a ligand coordination field engineering strategy to construct a cyano-bridged bimetallic nanozyme Cu₂[Fe(CN)₆] (SANE) with a well-defined electronic configuration for cancer catalytic-immunotherapy. Density functional theory (DFT) calculations revealed that cyano groups, acting as strong-field bridging ligands, could form an electron delocalization network. This network, driven by electronegativity gradient of the Cu (d⁹) and Fe (d⁶) bimetallic active centers, induces synergistic distortion of d-band energy levels, which in turn enhances electron transfer and significantly improves catalytic efficiency. Furthermore, the cyano-bridging, stabilizes the structure through a strong coordination field inhibiting metal aggregation, and allowing Cu to exhibit a single-atom distribution. This further strengthens SANE catalytic therapy ability. Biomimetic modification of SANE with immunogenic tumor exosomes (iEV) enhances biocompatibility, and provides efficient Peroxidase (POD)-like and Glutathione oxidase (GSHox)-like enzymatic activities within the tumor microenvironment achieving a catalytic-immune synergistic effect. This study provides a comprehensive framework to design heterobimetallic nanozyme with ideal catalytic structure from bimetallic active sites to bridged-ligand, opening a new avenue for precisely regulating of electronic configuration in catalytic-immunotherapeutic nanoplatform.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123868"},"PeriodicalIF":12.9,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621100","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":"Masking macrophage injury sensing via poly I sustained release system reduces inflammation and fibrosis","authors":"Keyi Chen ,&nbsp;Xingjian You ,&nbsp;Wei Yu ,&nbsp;Zeng Xu ,&nbsp;Bicheng Wang ,&nbsp;Jinquan Ma ,&nbsp;Xudong Zhao ,&nbsp;Wenyu Zhang ,&nbsp;Shatong He ,&nbsp;Chenfei Gao ,&nbsp;Tenghui Zhang ,&nbsp;Wei-en Yuan ,&nbsp;Bo Hu ,&nbsp;Huajiang Chen","doi":"10.1016/j.biomaterials.2025.123865","DOIUrl":"10.1016/j.biomaterials.2025.123865","url":null,"abstract":"<div><div>Tissue fibrosis following injury often leads to severe complications in humans. Recent research highlights that macrophage hypermigration and activation play a critical role in fibrosis development. Emerging evidence suggests that macrophage sensing of tissue injury via damage-associated molecular patterns (DAMPs) is crucial for their migration and activation. Excessive injury sensing is linked to macrophage hyperactivity, aberrant inflammation, and fibrosis. Recent studies have shown that polyinosinic acid (Poly I) can reduce macrophage activation by inhibiting signaling pathway associated with macrophage scavenger receptors (MSR). Based on this, we developed an electrospun polycaprolactone (PCL) fibrous membrane incorporating Poly I (PCL-Poly I) to ensure its early sustained release and function as an effective physical barrier. <em>In vitro</em> and <em>in vivo</em> results showed that Poly I could mask macrophage early injury sensing by downregulating MSR1/PI3K/AKT/SPP1 pathway. The local implantation of PCL-Poly I could reduce the early aggregation and activation of macrophages in the epidural fibrosis (EF) zone, thus suppressing the fibroblast activation and EF progress, with its therapeutic efficacy lasting up to 8 weeks after laminectomy. In conclusion, this study demonstrates the potential of biomaterial-based strategies to modulate immune responses, offering a novel upstream solution for treating fibrosis-related conditions.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123865"},"PeriodicalIF":12.9,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577060","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":"Nano-in-microalgae integrated modular hydrogel system for spatiotemporally targeted oral gene therapy of ulcerative colitis","authors":"Weili Zhao ,&nbsp;Yixin Sun ,&nbsp;Jiaqi Yang ,&nbsp;Xiaoxue He ,&nbsp;Linsheng Wu ,&nbsp;Lili Yan ,&nbsp;Yanfei Chen ,&nbsp;Yanhua Liu ,&nbsp;Yongbing Sun ,&nbsp;Zhonggui He ,&nbsp;Jin Sun ,&nbsp;Qikun Jiang","doi":"10.1016/j.biomaterials.2025.123862","DOIUrl":"10.1016/j.biomaterials.2025.123862","url":null,"abstract":"<div><div>Small interfering RNAs (siRNAs) have brought revolutionary advances as promising therapeutic candidates for ulcerative colitis, owing to the durable anti-inflammatory efficacy and favorable biocompatibility. Nevertheless, the clinical translation of oral siRNA therapeutics remains hindered by the harsh conditions of the gastrointestinal tract. Thus, a colon-specific modular hydrogel platform (IG@SP@FK LNPs@siTNFα) was engineered through integration of microalgal biotechnology and nanomedicines. The system comprised three functionally components: (i) a cathepsin B/glutathione (GSH) dual-responsive gemini-like cationic MA-FK-SS lipid nanoparticles core encapsulating tumor necrosis factor-α siRNA (FK LNPs@siTNFα); (ii) a negatively charged Spirulina (SP) intermediate layer (SP@FK LNPs@siTNFα); and (iii) an outer inulin-derived hydrogel (IG) coating. The IG layer provided robust protection against harsh gastrointestinal conditions and regulated the gut microbiota homeostasis. Subsequent colonic degradation of IG triggered site-specific release of SP@FK LNPs@siTNFα, which exhibited enhanced mucosal adhesion through the intrinsic helical architecture of SP. Notably, FK LNPs@siTNFα demonstrated efficient cellular internalization, proton-sponge effect-driven endosomal escape and dual-responsive siRNA release, ultimately silencing the expression of TNF-α. IG@SP@FK LNPs@siTNFα significantly attenuated the progression of ulcerative colitis via suppression of pro-inflammatory cytokine cascades (IL-6, IL-1β, TNF-α), restoration of intestinal barrier integrity, and normalization of gut microbiota homeostasis. This nano-biohybrid system established a paradigm for oral nucleic acid delivery, combining spatiotemporal control and multi-mechanistic intervention for precise gene therapy of ulcerative colitis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123862"},"PeriodicalIF":12.9,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621102","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":"Functional targeting of Glypican-4 by a conformation-specific single-domain antibody","authors":"Remi Bonjean ,&nbsp;Rossana Cuciniello ,&nbsp;Brigitte Kerfelec ,&nbsp;Patrick Chames ,&nbsp;Rosanna Dono","doi":"10.1016/j.biomaterials.2025.123864","DOIUrl":"10.1016/j.biomaterials.2025.123864","url":null,"abstract":"<div><div>The heparan sulphate proteoglycan, Glypican-4 (GPC-4), is an integral component of cell surfaces that fulfils key functions as a modulator of cell communication. Over time, human GPC-4 (hGPC4) has gained recognition as a valuable target for enhancing the therapeutic potential of human pluripotent stem cells (hPSCs). hGPC-4 is also a promising diagnostic and therapeutic target for a range of developmental and neurological disorders, as well as cancer. Its involvement in multiple biological processes and its impact on cellular signaling pathways make it a compelling candidate for future research and clinical applications. Here, we report RB1 and RB3 as the first hGPC-4-specific nanobodies. Both RB3 and RB1, bind recombinant hGPC4 with affinities in the tens of nanomolar range, whereas only RB1 recognizes native, cell-expressed hGPC4, highlighting its potential for functional studies. Notably, the bivalent nanobody Fc-fusion form of RB1, termed RB1-Fc, demonstrates a significant ∼14-fold increase in apparent binding affinity on cells when compared to the monovalent RB1. Furthermore, binding of RB1-Fc to hGPC-4 is dependent on the native conformation of hGPC-4, demonstrating that RB1-Fc is a conformational nanobody. Notably, RB1-Fc neutralizes the activity of GPC-4, as shown by our functional studies in hPSCs. These studies demonstrate the potent efficacy of the lead hGPC4 nanobodies, RB1-Fc and RB3. They also provide a solid rationale for using these nanobodies in the detection and characterization of physiologically and clinically relevant hGPC-4. Additionally, their potential as agents for therapeutic targeting of hGPC-4 opens new avenues for treating disorders associated with dysregulated hGPC-4 activity.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123864"},"PeriodicalIF":12.9,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621098","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":"Macrophage-to-myofibroblast transition (MMT) – An adverse response to polypropylene mesh implanted for pelvic organ prolapse repair surgery in a non-human primate model","authors":"Marrisa A. Therriault ,&nbsp;Katrina Knight ,&nbsp;Srividya Kottapalli ,&nbsp;Temitope Obisesan ,&nbsp;Malini Harinath ,&nbsp;Bryan N. Brown ,&nbsp;Pamela A. Moalli","doi":"10.1016/j.biomaterials.2025.123861","DOIUrl":"10.1016/j.biomaterials.2025.123861","url":null,"abstract":"<div><div>Surgical repair of pelvic organ prolapse (POP) is often augmented by polypropylene mesh to provide mechanical support to the vagina and improve anatomical outcomes as compared to native tissue repair. However, POP repair surgeries utilizing PPM have complications (most often pain or mesh exposure into the vagina) in over 10% of cases. Previous work has demonstrated that tensioning of meshes with certain geometries (diamond and hexagon pores), results in both planar (pore collapse) and nonplanar (wrinkles) deformations, significantly altering textile properties and impacting the host response. To further investigate the impact of mesh deformation on the host response, we implanted mesh in a validated non-human primate model via sacrocolpopexy with stable flat (square pores, N = 20) versus deformed geometries (mesh loaded on the diamond prior to implantation resulting in collapsed pores and wrinkles, N = 20). To investigate the impact of tension independent of deformation, we implanted on and off tension (10 N, N = 10 in each group). We hypothesized that more stable geometries trigger a healing response that achieves homeostasis while deformed mesh, by increasing the amount of material in contact with the host, triggers a maladaptive remodeling response with the formation of myofibroblasts. After twelve weeks, we found that mesh deformations and the absence of tension increase the amount of mesh per area on the vagina (mesh burden) and reproduced clinical complications (mesh exposure and vaginal thinning). Interestingly, MMT cells, or myofibroblasts co-expressing a macrophage marker (CD68), were seen to significantly increase in response to mesh burden, as well as respond hyper-locally to the mesh fiber interface. We observed decreased collagen density and more immature matrix deposited in conditions with higher MMT cell presence, showing more disorganization in deposited matrix with increased mesh burden, and the loss of tension. TGF-β1, in both active and latent forms, increased with increasing mesh burden, and highest expression was observed in conditions precipitating the highest percentage of MMT cells, a possible mechanism of transdifferentiation. This study showed the importance of PPM mesh properties on mesh burden following tensioning, impact on MMT transdifferentiation, and the downstream effect of these changes on the host response and healing outcomes.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123861"},"PeriodicalIF":12.9,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577084","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":"Target anesthesia and surgery induced senescent cell via composite microsphere hydrogels as nose-to-brain amplifiers of platelet factor 4 delivery for neurocognitive dysfunction repair","authors":"Zheng Xie ,&nbsp;Zehao Chen ,&nbsp;Weifeng Wu ,&nbsp;Miaomiao Fei ,&nbsp;Wenting Li ,&nbsp;Silu Cao ,&nbsp;Nan Wang ,&nbsp;Xiaoyue Xu ,&nbsp;Xiaoxiao Sun ,&nbsp;Qiang Liu ,&nbsp;Xiao-fei Gao ,&nbsp;Cheng Li","doi":"10.1016/j.biomaterials.2025.123863","DOIUrl":"10.1016/j.biomaterials.2025.123863","url":null,"abstract":"<div><div>Perioperative neurocognitive disorder (PND) is a common complication in older surgical patients, leading to increased neurodegenerative and death risk, augment socioeconomic burdens. Despite its prevalence, the reasons of why this complication occurs highly in older, underlying pathogenesis mechanisms, and effective treatments remain unclear. Senescence associated secretory phenotype (SASP), resulting from cellular senescence, drives inflammaging and cognitive decline. However, the association between cellular senescent and poor cognitive outcome is seldomly defined in PND. Herein, we showed that anesthesia and surgery in aged mice further increase hippocampal neuron senescent burden, manifest as increased senescence-like markers (CDKN2A/p16, CDKN1A/p21, SASP, SA-β-Gal), along with lipofuscin and lipid droplet accumulation and synaptic dysfunction. We identified elevated PF4, a platelet-derived factor, as a defensive response in older PND mice. Intraperitoneal PF4 administration mitigated neuronal senescence burden and improved cognitive dysfunction. Considering the older, frail patients and shorter perioperative period, we developed microfluidic hydrogel microspheres and cationic thermosensitive hydrogel complexes for nasal PF4 delivery enabling satisfy minimally invasive, less frequent dosing and sustained treatment. These findings reveal a critical role for cellular senescence in PND and propose PF4-based therapies as a promising translational strategy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123863"},"PeriodicalIF":12.9,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601603","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 “Lactate metabolism regulating nanosystem synergizes cuproptosis and ferroptosis to enhance cancer immunotherapy” [Biomaterials 325 (2026) 123538]","authors":"Hui Zhi ,&nbsp;Weimin Yin ,&nbsp;Shiyu Chen ,&nbsp;Xiaoyou Zhang ,&nbsp;Zichen Yang ,&nbsp;Fulong Man ,&nbsp;Rongjie Li ,&nbsp;Yanni Cai ,&nbsp;Yang Li ,&nbsp;Caoyi You ,&nbsp;Yan Li ,&nbsp;Yongyong Li ,&nbsp;Haiqing Dong","doi":"10.1016/j.biomaterials.2025.123859","DOIUrl":"10.1016/j.biomaterials.2025.123859","url":null,"abstract":"","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"327 ","pages":"Article 123859"},"PeriodicalIF":12.9,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145547491","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":"Flexoelectricity-boosted core-shell nanoparticles with self-amplified Fenton-like activity for tumor piezocatalytic immunotherapy","authors":"Peiran Chen ,&nbsp;Chao Qi ,&nbsp;Ke Zhang ,&nbsp;Shupeng Wang ,&nbsp;Xiaotong Lu ,&nbsp;Kun Qian ,&nbsp;Mingyue Zhang ,&nbsp;Shiyao Guo ,&nbsp;Yuhong Zhuo ,&nbsp;Chenguo Yao ,&nbsp;Kaiyong Cai","doi":"10.1016/j.biomaterials.2025.123856","DOIUrl":"10.1016/j.biomaterials.2025.123856","url":null,"abstract":"<div><div>Piezocatalytic therapy, which utilizes ultrasonic activation of piezoelectric materials to generate reactive oxygen species (ROS), holds significant potential. However, its efficacy is constrained by the limited ROS generation capacity of piezoelectric materials. In this study, a gradient ion replacement strategy was employed to construct Cu_xBa_1-xTiO₃-shell structured BaTiO₃ (Cu-BTO) piezoelectric materials with flexoelectric properties. This process induces the BTO surface to transition from a crystalline state to an amorphous state and subsequently recrystallize. The phase transformation introduces flexoelectric properties in Cu-BTO surface, while the disparity in ionic radii between Cu²⁺ and Ba²⁺ enhances lattice asymmetry. Consequently, Cu-BTO exhibits significantly enhanced piezoelectric and piezocatalytic properties, with the <em>d</em>_<em>33</em> value reaching 129.91 pm/V, representing an increase of 345.93 %. Under ultrasonic stimulation, Cu-BTO can not only directly generate ^•OH and H₂O₂ through piezocatalysis, but also achieve self-amplified Fenton-like catalysis and GSH depletion by promoting charge transfer via the built-in electric field. The strong oxidative stress induces severe immunogenic cell death (ICD) of tumor cells, and triggers a series of antitumor immune responses such as dendritic cell (DC) maturation and T cell activation. Ultimately, an 83.7 % tumor inhibition rate is achieved, and lung metastasis of the tumor is effectively prevented. This work not only demonstrates a method to describes a method for inducing the flexoelectric effect in piezoelectric nanomaterials but also provides novel insights into the design and optimization of piezoelectric nanomaterials.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123856"},"PeriodicalIF":12.9,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145555908","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}