BMEMat最新文献

{"title":"Enhanced strategies for cuproptosis-like death in bacterial infection treatment","authors":"Wenqi Wang,&nbsp;Bolong Xu,&nbsp;Ruiyuan Zhu,&nbsp;Hengshuo Gui,&nbsp;Tian Xia,&nbsp;Shaokai Liu,&nbsp;Huiyu Liu,&nbsp;Xianwen Wang","doi":"10.1002/bmm2.70089","DOIUrl":"https://doi.org/10.1002/bmm2.70089","url":null,"abstract":"<p>Copper, a classical antibacterial metal, has long been of interest and widely used in medical and public health applications. Recent findings that copper can induce programmed cell death (cuproptosis) not only in eukaryotes but also in bacteria (cuproptosis-like death) provide a unique perspective for the development of novel antibacterial strategies. On the basis of these findings, current research is actively exploring various strategies to enhance the effects of cuproptosis-like death, thereby improving its antibacterial efficacy. In this review, we highlight current strategies to enhance cuproptosis-like death and potential strategies for its development, including aspects of copper transporter protein regulation, exogenous copper ion uptake, the application of nanotechnology, and combination therapy. In addition, we discuss the differences between cuproptosis-like death and cuproptosis in terms of key events, such as copper homeostasis regulation, lipoylated protein aggregation and iron‒sulfur cluster disruption. Finally, we introduce the limitations and challenges that enhanced bacterial cuproptosis-like death may face in future studies, which will help to deepen our understanding of the mechanisms of enhanced cuproptosis-like death.</p>","PeriodicalId":100191,"journal":{"name":"BMEMat","volume":"4 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmm2.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atomically precise metal cluster enzymes for pathological tissue regeneration","authors":"Ziqiang Xiong,&nbsp;Zhifeng Shi,&nbsp;Mengqing Li,&nbsp;Jien Han,&nbsp;Haoyan Chen,&nbsp;Maofei Ran,&nbsp;Shaojian Zhong,&nbsp;Limin Ma,&nbsp;Chengyun Ning,&nbsp;Youzhun Fan,&nbsp;Zhenghua Tang,&nbsp;Peng Yu","doi":"10.1002/bmm2.70073","DOIUrl":"https://doi.org/10.1002/bmm2.70073","url":null,"abstract":"<p>In pathological microenvironments of diabetes, neuroinflammation, arthritis and other chronic diseases marked by oxidative stress, chronic inflammation, and bacterial infection, severely disrupt cellular physiological functions leading to failure of tissue regeneration. Existing therapeutic strategies are difficult to achieve simultaneous pathological causative factor removal and tissue regeneration due to the cascading pathological reactions triggered by endogenous enzyme insufficiency. Biomimetic artificial enzymes have been used to remodel pathological microenvironments, but the lack of precise structural design and unclear structure-performance relationships limit their catalytic activities. As a new generation of enzyme-like materials, atomically precise metal cluster enzymes (MCEs) can mimic the spatial hierarchical structure of natural enzymes and significantly enhance the enzyme-like activity by regulating the configuration of the metal core and ligand, which is expected to enable pathological microenvironment repair. This review summarizes the design and controllable synthesis of atomically precise MCEs. The precise regulatory mechanisms of cluster enzymes are systematically analyzed for their mechanism of action in tissue repair microenvironments. In addition, the application of atomically precise MCEs for tissue regeneration in pathological microenvironments is discussed in detail. Finally, the future potential of atomically precise MCEs in pathological tissue regeneration is envisioned as perspectives.</p>","PeriodicalId":100191,"journal":{"name":"BMEMat","volume":"4 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmm2.70073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting neutrophil extracellular traps in metabolic and immune niche: Nanomaterials for diabetes tissue regeneration","authors":"Xinyi Jiang,&nbsp;Muxin Yue,&nbsp;Kai Mao,&nbsp;Boon Chin Heng,&nbsp;Noor Azlin Yahya,&nbsp;Yunsong Liu,&nbsp;Zheng Li","doi":"10.1002/bmm2.70070","DOIUrl":"https://doi.org/10.1002/bmm2.70070","url":null,"abstract":"<p>The effects of neutrophil extracellular traps (NETs) on diabetes tissue regeneration are very complex. Diabetes mellitus induces the metabolic and functional changes in neutrophils, including enhanced glucose utilization and increased NETosis. This tilts the balance of the immune microenvironment toward chronic inflammation, potentially ultimately delaying tissue regeneration. The therapeutic effect of using medications alone is limited. Here, we review NET-mediated metabolic reprogramming and antibacterial activity as well as chronic sterile inflammation. We focus on the newly developed nanomaterials targeting NETs in tissue defects. These nanomaterials are precisely regulated in space and time and can exert multiple functions as needed, including enhancing the antibacterial ability of NETs, inhibiting the generation of NETs, and removing the excessively accumulated NETs, thereby creating a metabolic and immune microenvironment that is conducive to tissue regeneration. Drug-loaded nanomaterials can exhibit more ideal therapeutic effects. It is hoped that this will aid a full comprehension of the connection between diabetes and NETs. Additionally, the review may inspire readers who seek clinically effective treatment modalities.</p>","PeriodicalId":100191,"journal":{"name":"BMEMat","volume":"4 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmm2.70070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasmall Fe-curcumin immunomodulators reinvigorate CAR-T cells to potentiate solid tumor immunotherapy by mitigating cell exhaustion and senescence","authors":"Jiazhi Duan,&nbsp;Yuchan Xue,&nbsp;Miao Zhang,&nbsp;Zihao Zhang,&nbsp;Shiyu Peng,&nbsp;Minghao Sui,&nbsp;Han Ding,&nbsp;Yingying Nie,&nbsp;Yuemin Feng,&nbsp;Le Wang,&nbsp;Tianru Zhang,&nbsp;Mingchuan Yu,&nbsp;He Xia,&nbsp;Hong Liu,&nbsp;Qiang Zhu,&nbsp;Songbo Zhao","doi":"10.1002/bmm2.70078","DOIUrl":"https://doi.org/10.1002/bmm2.70078","url":null,"abstract":"<p>CAR-T cell immunotherapy has achieved exciting success in hematologic malignancies, but the therapeutic efficacy is relatively limited in solid tumors due to negative cause induced suppressed cell expansion capability, limited infiltration ability as well as serious cell exhaustion and senescence. Herein, we creatively developed ultrasmall Fe–curcumin (Fe–Cur) immunomodulator energized CAR-T cells to potentiate solid tumor immunotherapy by mitigating CAR-T cell exhaustion and senescence. The ultrasmall Fe–Cur nanoparticles were synthesized by a facile coordination reaction between curcumin and Fe³⁺ with 5 nm uniform size and excellent T1 weight MRI property. In addition, the Fe–Cur nanoparticles possess large positive potential, endowing effective combination with the negative potential of the CAR-T cell membrane through electrostatic attraction. The Fe-Cur nanoparticles potently enhance tumor cell killing capacity by alleviating CAR-T cell senescence through p53 pathway suppression while mitigating T cell exhaustion. Moreover, in vivo studies demonstrate that Fe-Cur nanoparticle-enhanced CAR-T cell therapy synergistically improves solid tumor treatment outcomes, with real-time MRI guidance monitoring therapeutic responses. More significantly, Fe–Cur nanoparticles demonstrate potent tumor microenvironment-modulating capacity by alleviating hypoxia conditions, thereby enhancing both CAR-T cell and endogenous immune cell infiltration while reprogramming tumor-associated macrophages. The relived tumor microenvironment further activated the innate immunoactivity and stimulated CAR-T cell viability. The well-designed Fe–Cur nanoparticle- modified CAR-T cell- based immunotherapy strategy not only provides an effective solid tumor treatment strategy but also extends a novel biomaterial- conjugated immune cells-based therapeutic with firm supporting evidence and guidance.</p>","PeriodicalId":100191,"journal":{"name":"BMEMat","volume":"4 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmm2.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149028979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carrier-free self-assembled nanomedicine for combination-therapy of acute myeloid leukemia","authors":"Meihong Chai,&nbsp;Rui Zhang,&nbsp;Haiyin Yang,&nbsp;Jiyue Xing,&nbsp;Tianyuan Hu,&nbsp;Mengxi Zhu,&nbsp;Rui Li,&nbsp;Xiaoli Chen,&nbsp;Beibei Zhao,&nbsp;Yang Lan,&nbsp;Stefan Barth,&nbsp;Yuanyu Huang,&nbsp;Li Zhang,&nbsp;Mengjie Zhang,&nbsp;Huining He","doi":"10.1002/bmm2.70072","DOIUrl":"https://doi.org/10.1002/bmm2.70072","url":null,"abstract":"<p>As the main acute myeloid leukemia (AML) clinical treatment, the chemotherapy alone cannot meet the clinical therapeutic needs due to the high heterogeneity of AML. Although many chemo-immuno combination therapies based on immune checkpoint inhibitors have been approved for solid tumors, they have not yet shown significant clinical benefits in the treatment of leukemia. Herein, we proposed a chemoimmunotherapy strategy for AML by co-loading our newly developed immune checkpoint siRNA drug, the chemotherapeutic drug, and the cytotoxic peptide drug into a carrier-free nano-assembling drug delivery system. We developed the first siRNA drug that down-regulates the gene expression of leukocyte immunoglobulin-like receptor B4 (LILRB4), which was reported as a potential immune checkpoint target for leukemia, inhibiting T cell activity and mediating leukemia cell infiltration into the tissues. We further constructed tumor-targeting and pH-sensitive carrier-free nanoparticles (CPP44-p16-DNR@siLILRB4, CPDS) co-loaded with siLILRB4 to suppress the LILRB4-mediated immune escape pathway, along with the first-line chemotherapeutic drug daunorubicin (DNR) and the targeting and cytotoxic CPP44-p16 fusion peptide. This “all-in-one” therapeutic platform could effectively target leukemia cells, dissociate in the acidic lysosomal environment after endocytosis, reverse the immunosuppressive microenvironment, and exhibit a strong synergistic tumor growth inhibition effect in vivo. This system provides a promising therapeutic strategy for chemoimmunotherapy of AML.</p>","PeriodicalId":100191,"journal":{"name":"BMEMat","volume":"4 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmm2.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel biomimetic liposome drug delivery system mediated by macrophage targeting for precision treatment of encephalitis","authors":"Mengru Wu,&nbsp;Baoqin Song,&nbsp;Zhihao Chen,&nbsp;Wenzhong Li,&nbsp;Wanjun Liang,&nbsp;Xiu Wang","doi":"10.1002/bmm2.70077","DOIUrl":"https://doi.org/10.1002/bmm2.70077","url":null,"abstract":"<p>The highly selective and defensive properties of the blood-brain barrier (BBB) significantly hinder effective drug penetration and therapeutic efficacy, presenting significant challenges for treating central nervous system (CNS) disorders, particularly neuroinflammatory diseases. In this study, we innovatively developed a macrophage-mediated biomimetic liposomal drug delivery system (AC-LP@RAW) co-loaded with curcumin (Cur) and gold nanoclusters (AuNCs) for targeted therapy of acute encephalitis. By leveraging the unique immune homing properties of RAW 264.7 cells (RAW), AC-LP@RAW demonstrates enhanced BBB penetration and precise targeting to inflammatory sites, significantly improving Cur delivery to brain parenchyma. Near-infrared (NIR) irradiation-induced photothermal effects subsequently trigger the disintegration of the system and site-specific drug release at inflamed regions, exhibiting remarkable capabilities in recognizing acute inflammation and promoting tissue repair. Furthermore, AC-LP@RAW enables real-time imaging and monitoring of deep-brain inflammatory lesions in acute neuroinflammation models. This novel liposomal delivery system demonstrates tremendous potential for overcoming BBB limitations while achieving precise targeted therapy and visual tracking imaging for acute encephalitis.</p>","PeriodicalId":100191,"journal":{"name":"BMEMat","volume":"4 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmm2.70077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming intranasal delivery barriers with ultrastable polyzwitterionic siRNA nanocages for enhanced glioblastoma therapy","authors":"Jingwen Xie,&nbsp;Jingxing Si,&nbsp;Xiaobei Deng,&nbsp;Jing Tan,&nbsp;Ruijie Zhu,&nbsp;Jizhou Qi,&nbsp;Gaoxia Ma,&nbsp;Bin Wang,&nbsp;Yi Wang,&nbsp;Yunzhou Guo,&nbsp;Yuping Chen,&nbsp;Shiqun Shao,&nbsp;Youqing Shen","doi":"10.1002/bmm2.70068","DOIUrl":"https://doi.org/10.1002/bmm2.70068","url":null,"abstract":"<p>Intranasal administration presents a direct, non-invasive pathway for delivering small interfering RNA (siRNA) to glioblastoma (GBM), but its efficiency is hampered by intranasal and intratumoral barriers. To overcome these barriers, here, we develop a multipotent nanocage system featuring a crosslinked yet reactive oxygen species (ROS)-cleavable, zwitterionic poly (tertiary amine oxide) (PTAO) shell for efficient intranasal siRNA delivery. This design ensures ultrastable siRNA encapsulation under physiological conditions while enabling traceless siRNA release selectively in tumor cells with elevated ROS levels. Notably, the gene silencing efficacy of the nanocages remains unaffected after 1 month of room-temperature storage in solution. By leveraging the zwitterionic property of PTAO, the nanocages exhibit prolonged intranasal residence and enhanced mucus penetration. Furthermore, they induce lipid raft-dependent macropinocytosis and subsequent transcytosis that promotes brain accumulation via the trigeminal nerve pathway and enables deep tumor penetration. This endocytosis mechanism directs nanocages into the non-degradative endoplasmic reticulum-Golgi pathway for intracellular trafficking, bypassing lysosomal trapping. In an orthotopic GBM mouse model, intranasal administration of nanocages loading PLK1 siRNA significantly suppressed glioma growth and extended survival without obvious safety issues. Our study demonstrates the potential of the nanocage platform as an intranasal delivery vehicle, promising broad therapeutic applications in GBM and other neurological disorders.</p>","PeriodicalId":100191,"journal":{"name":"BMEMat","volume":"4 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmm2.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward clone-on-a-chip: Ethical and legal considerations for organ-on-a-chip evolution","authors":"Muhammed Erkan Karabekmez,&nbsp;Aliakbar Ebrahimi,&nbsp;Hamed Ghorbanpoor,&nbsp;Nicole Bassous,&nbsp;Su Ryon Shin,&nbsp;Yu Shrike Zhang,&nbsp;Huseyin Avci","doi":"10.1002/bmm2.70096","DOIUrl":"https://doi.org/10.1002/bmm2.70096","url":null,"abstract":"<p>Organ-on-a-chip (OoC) is a promising technology that can be used to investigate tissue formation, organ function, and disease etiology as well as an in vitro test platform for evaluating drug and radiation efficacies along with their side effects. The OoC technology provides substantial advantages like the ability to precisely control cellular processes in microenvironments for extended periods and the ease of applying a diffusion gradient to improve pharmacokinetics and pharmacodynamics. As a precursor to personalized medicine, the OoC systems are expected to serve as a milestone technology, especially after the United States Food and Drug Administration Modernization Act 2.0, and more recently, 3.0. Of importance, the OoC platforms could be engineered to produce genetically identical or near-identical tissue and organ models derived from an individuals' cells, enabling detailed studies of specific genetic and epigenetic phenotypes and better capturing interpersonal differences. To describe this conceptual extension, we introduce the term “clone-on-a-chip (CoC)” as a conceptual warning and not to suggest technological feasibility; also referring not to whole-organism cloning but to the replication of patient-specific biological profiles in vitro for personalized therapeutics development and testing. This approach holds unique potential for tailoring therapeutic strategies; however, future projections may present new ethical dilemmas. A CoC ethical discussion extends beyond issues arising from the requirements for informed consent, property rights, commercialization efforts, and cell sourcing to include potentially controversial applications and societal concerns.</p>","PeriodicalId":100191,"journal":{"name":"BMEMat","volume":"4 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmm2.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real time in vivo efficacy monitoring of desialylation and perforation enhanced immunotherapy of cancer","authors":"Yuanjiao Yang,&nbsp;Yuru Wang,&nbsp;Xuemei Li,&nbsp;Chaoyi Yang,&nbsp;Yuhui Yang,&nbsp;Yanyun Fang,&nbsp;Lin Ding,&nbsp;Yunlong Chen,&nbsp;Huangxian Ju","doi":"10.1002/bmm2.70079","DOIUrl":"https://doi.org/10.1002/bmm2.70079","url":null,"abstract":"<p>Efficient enhanced NK cell therapy is of critical importance in the immune treatment of cancer. Real time monitoring provides the necessary means for precise treatment and improving its efficacy. This work designed a powerful nanomedicine (MFMAF-7) to engineer NK cells for perforation and desialylation by encapsulating streptolysin O conjugated neuraminidase, adenosinetriphosphate (ATP)-responsive DNA and granzyme B (GrB)-responsive peptide (SLO-NEU, SLO-AD, SLO-GP) in cholesterol and aptamer-modified zeolitic metal azolate framework-7. After targeted delivery of the engineered NK cells to tumor region, the nanomedicine is degraded to release SLO-NEU, SLO-AD and SLO-GP, which then perforate tumor cells to promote the delivery of cytokines. The anchored SLO-NEU can cleave sialic acids for inhibiting the immune evasion of tumor cells and activating the NK cells to release cytokines, while the SLO-AD and SLO-GP can in situ visualize the levels of both ATP and GrB for assessing the efficacy in real time. The in vivo experiments with tumor-bearing mice demonstrate the enhanced efficacy of immunotherapy and the feasibility of real time monitoring with the proposed nanomedicine.</p>","PeriodicalId":100191,"journal":{"name":"BMEMat","volume":"4 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmm2.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149028977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bifunctional injectable selenium-containing polyurethane hydrogels for periodontal regeneration through endoplasmic reticulum stress modulation","authors":"Mingchu Zhao,&nbsp;Mo Zhai,&nbsp;Zhuoxin Ge,&nbsp;Xiaodong Guo,&nbsp;Zhuqing Wan,&nbsp;Xiaoqiang Bai,&nbsp;Huaping Xu,&nbsp;Yongsheng Zhou,&nbsp;Longwei Lv","doi":"10.1002/bmm2.70105","DOIUrl":"https://doi.org/10.1002/bmm2.70105","url":null,"abstract":"<p>Periodontitis causes progressive destruction of both periodontal soft and hard tissues, leading to tooth loss and functional impairment. Conventional treatments, such as mechanical debridement and antibiotic therapy, are often insufficient for effective regeneration due to persistent local inflammation and the complex architecture of gingival and alveolar bone defects. In this study, we developed a thermo-responsive, injectable hydrogel composed of hydroxybutyl chitosan (HBC) and selenium-containing polyurethane (SePU), which undergoes rapid sol-gel transition at physiological temperature. SePU/HBC not only facilitated the adhesion and migration of human gingival fibroblasts but also effectively inhibited osteoclast formation and resorptive activity. Mechanistically, it efficiently scavenged intracellular reactive oxygen species and activated an ATF6-mediated protective unfolded protein response, thereby re-establishing endoplasmic reticulum function and preventing apoptosis. By integrating targeted stress modulation with bifunctional cellular regulation, SePU/HBC offers an innovative strategy for coordinated periodontal tissue regeneration, offering potential benefits in both early inflammation control and late-stage defect repair.</p>","PeriodicalId":100191,"journal":{"name":"BMEMat","volume":"4 3","pages":""},"PeriodicalIF":15.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmm2.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149028988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}