Biomedical materials (Bristol, England)最新文献

{"title":"Alginate-methacrylate-RGD microspheres (Alg-MR-MS) for cell expansion and delivery in tissue engineering.","authors":"Alexandre Xavier Mendes, Serena Duchi, Carmine Onofrillo, Ying Zhou, Sanjeev Gambhir, Adriana Teixeira do Nascimento, Cathal O'Connell, Steven Posniak, Payal Mukherjee, Gordon G Wallace, Peter F Choong, Simon E Moulton","doi":"10.1088/1748-605X/aeb214","DOIUrl":"10.1088/1748-605X/aeb214","url":null,"abstract":"<p><p>Clinically relevant cell numbers are essential for many tissue engineering applications, requiring scalable expansion platforms. Microcarrier-based bioreactor systems address this demand; however, conventional non-dissolvable carriers require harsh enzymatic or mechanical detachment, reducing cell viability and integrity. Although dissolvable microcarriers improve recovery, most are designed only for harvesting and lack functionality for downstream tissue engineering. Here, we present a sequential dual-crosslinkable alginate-methacrylate-RGD microsphere system (Alg-MR-MS) that integrates scalable cell expansion with scaffold formation in a single platform. The workflow involves: (1) microsphere fabrication via calcium-mediated ionic crosslinking; (2) three-dimensional cell expansion in a microcarrier culture system; (3) controlled phase change through calcium chelation with sodium citrate, enabling efficient cell recovery while preserving viability and phenotype; and (4) photocrosslinking to form a stable, cell-laden hydrogel suitable for bioprinting and tissue engineering. This sequential dual-crosslinking strategy supports expansion, dissolution, and structural stabilisation within one system. Human adipose-derived stem cells cultured on Alg-MR-MS showed ∼5-fold increased metabolic activity over 7 d, comparable to 2D controls, with high viability and strong attachment. Compared with other dissolvable carriers, Alg-MR-MS offers efficient expansion, rapid phase transition, and simplified single-step fabrication, bridging biomanufacturing and functional tissue engineering.</p>","PeriodicalId":72389,"journal":{"name":"Biomedical materials (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silver sodium nitroprusside nano-aggregates for ultrasound-activated immunomodulatory therapy of MRSA pneumonia.","authors":"Minxian Ji, Guanxue Li, Lihua Xie, Guanhai Wang","doi":"10.1088/1748-605X/aeb215","DOIUrl":"10.1088/1748-605X/aeb215","url":null,"abstract":"<p><p>The clinical management of methicillin-resistant<i>S. aureus</i>(MRSA) pneumonia is hindered by biofilm infections and cytokine storms. A key challenge is the lack of real-time monitoring tools for the inflammatory microenvironment during treatment. In this study, we developed a theranostic platform (CS@EAgNP) using TPP-modified chitosan to load silver sodium nitroprusside nano-aggregates (AgNP) and epigallocatechin gallate (EGCG). This system combines ultrasound (US) imaging with US-activated therapy. The CS@EAgNP nano-aggregates can act as an excellent US contrast enhancer.<i>In vivo</i>US imaging indicated that AgNP generated significantly enhanced echo signals at the infection site, providing real-time and high-contrast visualization of the inflammatory foci that was unattainable with normal lung tissue. Moreover, these nano-aggregates release NO, silver and EGCG under US. The NO and silver penetrate biofilms to kill MRSA, while EGCG scavenges reactive oxygen species and modulates inflammation. This reduces pro-inflammatory cytokines like IL-6 and TNF-<i>α</i>, mitigating the cytokine storm.<i>In vivo</i>results further confirm that this image-guided strategy achieves significant bacterial clearance and promotes lung tissue regeneration without detectable toxicity to major organs. This integrated approach bridges diagnosis and treatment, offering a promising solution for managing MRSA pneumonia.</p>","PeriodicalId":72389,"journal":{"name":"Biomedical materials (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum: Scaffold-free bioprinted osteogenic and chondrogenic systems to model osteochondral physiology (2019 Biomed. Mater. 14 065010.","authors":"Erick Breathwaite, Jessica Weaver, Angela Murchison, Michelle Treadwell, Justin Odanga, Jung Bok Lee","doi":"10.1088/1748-605X/aeb638","DOIUrl":"https://doi.org/10.1088/1748-605X/aeb638","url":null,"abstract":"<p><p>Three-dimensional bioprinted culture platforms mimic the native microenvironment of tissues more accurately than two-dimensional cell cultures or animal models. Scaffold-free bioprinting eliminates many complications associated with traditional scaffold-dependent printing as well as provides better cell-to-cell interactions and long-term functionality. In this study, constructs were produced from bone marrow derived mesenchymal stem cells (BM-MSCs) using a scaffold-free bioprinter. These constructs were cultured in either osteogenic, chondrogenic, a 50:50 mixture of osteogenic and chondrogenic ('osteo-chondro), or BM-MSC growth medium. Osteogenic and chondrogenic differentiation capacity was determined over an 8-week culture period using histological and immunohistochemical staining and RT-qPCR (Phase I). After 6 weeks in culture, individual osteogenic and chondrogenic differentiated constructs were adhered to create a bone-cartilage interaction model. Adhered differentiated constructs were cultured for an additional 8 weeks in either chondrogenic or osteo-chondro medium to evaluate sustainability of lineage specification and transdifferentiation potential (Phase II).&#xD;Constructs cultured in their respective osteogenic and/or chondrogenic medium differentiated directly into bone (model of intramembranous ossification) or cartilage. Positive histological and immunohistochemical staining for bone or cartilage identification was shown after 4 and 8 weeks in culture. Expression of osteogenesis and chondrogenesis associated genes increased between weeks 2 and 6. Adhered individual osteogenic and chondrogenic differentiated constructs sustained their differentiated phenotype when cultured in chondrogenic medium. However, adhered individual chondrogenic differentiated constructs cultured in osteo-chondro medium were converted to bone (model of metaplastic transformation).&#xD;These bioprinted models of bone-cartilage interaction, intramembranous ossification, and metaplastic transformation of cartilage into bone offer a useful and promising approach for bone and cartilage tissue engineering research. Specifically, these models can be potentially used as functional tissue systems for studying osteochondral defect repair, drug discovery and response, and many other potential applications.&#xD.</p>","PeriodicalId":72389,"journal":{"name":"Biomedical materials (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium oxamate-functionalized microspheres alleviate Intervertebral disc degeneration by inhibiting excessive glycolysis in nucleus pulposus cells.","authors":"Munan Guo, Zhuang Zhu, Hancheng Shi, Wei Yu, Yiwen Tang, Chen Wu, Kaichen Wan, Yuyang Sang, Heng Sun, Yixing Tian, Bin Li","doi":"10.1088/1748-605X/aeb5be","DOIUrl":"https://doi.org/10.1088/1748-605X/aeb5be","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IVDD) is a leading contributor to low back pain and is characterized by a proinflammatory microenvironment and disruption of extracellular matrix (ECM) metabolic homeostasis. Although aberrant glycolytic reprogramming has been implicated in IVDD pathogenesis, effective therapeutic strategies targeting this metabolic dysregulation remain limited. To address this gap, we developed the injectable gelatin methacrylate (GelMA) microspheres functionalized with sodium oxamate (SO) and co-loaded with transforming growth factor-β3 (TGF-β3) (S-T@GM) to enable the synergistic metabolic and regenerative therapy. Following confirmation of glycolytic abnormalities in human degenerated disc tissues and TNFα-stimulated nucleus pulposus cells (NPCs), we systematically characterized the biocompatibility of S-T@GM microspheres and evaluated their therapeutic efficacy both in vitro and in a rat puncture-induced IVDD model. SO effectively normalized glycolytic flux and attenuated inflammatory responses in NPCs; notably, the combined S-T@GM treatment-unlike either component alone-most efficiently restored ECM homeostasis by enhancing type Ⅱ collagen (COL Ⅱ) synthesis while suppressing the catabolic enzyme ADAMTS5. In vivo, S-T@GM treatment provided superior preservation of disc height, nucleus pulposus hydration, and overall tissue architecture, with immunohistochemical analyses confirming concurrent inflammation suppression and sustained COL Ⅱ retention. Collectively, these findings demonstrate that glycolytic reprogramming via SO synergizes potently with TGF-β3 to mitigate IVDD progression, and that the S-T@GM microsphere platform represents a promising integrative strategy that simultaneously targets metabolic dysfunction and impaired regeneration for effective intervertebral disc repair.</p>","PeriodicalId":72389,"journal":{"name":"Biomedical materials (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-targeted tertiary amine N-Oxide nanoparticles with photosensitizer conjugation for photopyroptotic cancer therapy.","authors":"Yixuan Zhu, Yue Wang, Yuxin Huang, Zhuofan Diao, Shaoqi Shen, Licheng Yang, Haibao Peng, Wuli Yang","doi":"10.1088/1748-605X/aeb5bf","DOIUrl":"https://doi.org/10.1088/1748-605X/aeb5bf","url":null,"abstract":"<p><p>Although photodynamic therapy has emerged as a promising strategy for cancer treatment, its efficacy is often restricted by the extremely short diffusion radius of reactive oxygen species (ROS). Concentrating ROS generation within vulnerable organelles, such as mitochondria, represents an effective avenue to overcome the limited immunogenicity often associated with conventional apoptosis and amplify photodynamic damage. To address this challenge, this study introduces a zwitterionic polymer, poly(2-(N-oxide-dimethylamino)ethyl methacrylate) (OPDMA), featuring a tertiary amine N-oxide (TANO) structure. To evaluate its therapeutic potential, the model photosensitizer pyropheophorbide-a (Ppa) was chemically conjugated to the OPDMA matrix, enabling its self-assembly into OPDMA-Ppa nanoparticles. This design endows the nanoparticles with favorable hydration and colloidal stability, thereby contributing directly to an extended blood circulation. Notably, without relying on traditional, potentially cytotoxic cationic ligands, this material achieves subcellular localization to mitochondria, thereby facilitating the mitochondrial targeting of the conjugated photosensitizer. Under 660 nm laser irradiation, the nanoparticles successfully trigger a localized oxidative burst and the collapse of mitochondrial membrane potential. This organelle dysfunction subsequently activates the classical caspase-1/gasdermin D-mediated pyroptotic pathway, accompanied by characteristic cellular swelling and the release of cellular contents. In an EMT6 tumor-bearing mouse model, the OPDMA-Ppa nanoparticles achieved a final tumor inhibition rate of 80.0%. Overall, this work provides a promising approach for designing organelle-specific nanoparticles to enhance photopyroptosis-mediated cancer therapy.</p>","PeriodicalId":72389,"journal":{"name":"Biomedical materials (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A regenerative tissue adhesive based on PEG-NHS crosslinked porcine urinary bladder matrix hydrogel for rapid sealing and enhanced defect repair.","authors":"Yiwen Xu, Weidong Zhong, Wenyue Cheng, Xiaoyu Zhou, Junya Xu, Jing Dai, Guoyi Shao, Jian Zhang","doi":"10.1088/1748-605X/aeae96","DOIUrl":"10.1088/1748-605X/aeae96","url":null,"abstract":"<p><p>Tissue adhesives have attracted significant interest owing to their convenience and excellent sealing properties. However, commercial adhesives are often limited by cytotoxicity, excessive swelling, and a lack of pro-regenerative bioactivity. Porcine urinary bladder matrix (UBM), an excellent extracellular matrix (ECM) material, has demonstrated substantial potential in tissue repair and regeneration. Here, we developed an injectable ECM hydrogel adhesive by crosslinking between poly(ethylene glycol)-N-hydroxysuccinimide (PEG-NHS) and enzymatically digested UBM (DUBM), enabling<i>in situ</i>gelation for immediate sealing. Concurrently, the NHS groups reacted with amino groups on the tissue surface, endowing the adhesive with robust interfacial bonding for both tissue adhesion and implant fixation. The DUBM adhesive exhibited high adhesive strength, low swelling, favorable burst pressure, and significantly improved cellular affinity compared to conventional PEG hydrogels.<i>In vivo</i>, it effectively sealed vascular defects and rapidly secured implants. In abdominal wall defect models, the DUBM adhesive provided high mechanical strength and low swelling, enabling stable structural support while promoting collagen deposition, cell proliferation, and neovascularization, thereby accelerating tissue healing. These findings highlight the promising clinical translation potential of the DUBM hydrogel as a regenerative tissue adhesive.</p>","PeriodicalId":72389,"journal":{"name":"Biomedical materials (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ropivacaine-and ascorbic acid-loaded thermosensitive hydrogels for pain management.","authors":"In Kyu Park, Hyun Ho Shin, Da Han Hyun, Hyun Kang, Jun Seok Park, Ji Hyun Ryu","doi":"10.1088/1748-605X/aeb3e1","DOIUrl":"https://doi.org/10.1088/1748-605X/aeb3e1","url":null,"abstract":"<p><p>Postoperative pain management is one of the significant components of patient care, with the reduction of the risks of complications. However, there is a perceived unmet need for pain management due to both the adverse effects of systemic analgesics and the shortcomings of local anaesthetics. In this study, ropivacaine- and ascorbic acid-loaded hyaluronic acid/Pluronic F127 (HA/F127) composite thermosensitive hydrogels were prepared for sustained analgesia and antioxidant activity. The HA/F127 hydrogels showed thermosensitive sol-gel behavior and injectable properties at room temperature. The hydrogels showed sustained release of ropivacaine and ascorbic acid over 72 h with significant radical scavenging activity. In vivo studies indicated that the HA/F127 hydrogels resulted in increased mechanical withdrawal thresholds compared to free ropivacaine, without causing motor impairment, and serum levels of IL-1β and IL-6 were reduced. In addition, hematological, biochemical, and histological analyses showed acceptable ranges of biocompatibility without evidence of systemic toxicity or adverse local tissue reactions. Thus, the thermosensitive HA/F127 composite hydrogels provided sustained drug release, prolonged analgesic effects, reduced inflammatory responses, and acceptable biocompatibility. These findings indicate that these thermosensitive composite hydrogels may be a promising strategy for local drug delivery in managing postoperative pain and inflammation.</p>","PeriodicalId":72389,"journal":{"name":"Biomedical materials (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, characterization and in vitro evaluation of biomimetic hierarchical scaffolds with TPMS‑gyroid structure for bone regeneration.","authors":"Jiaqi Ma, Yunqian Li, Sijing Wang, Yumeng Li, Yue Wang, Feng Wang, Pengfei Zhu, Zhuoqun Jia, Jue Wang, Yanlei Kong, Yujing Mi, Bing Meng, Fan Yawei","doi":"10.1088/1748-605X/aeb340","DOIUrl":"https://doi.org/10.1088/1748-605X/aeb340","url":null,"abstract":"<p><p>Human physical and mental health are significantly impacted by maxillofacial alveolar bone defects. The emergence of additive manufacturing metamaterial scaffolds provides a new treatment strategy for this. Due to the complexity of the jawbone and the difficulty in preparing bionic hierarchical gradient scaffolds, most current research focuses on human long bones. This study first proposes a metamaterial scaffold that simulates the jawbone. The stratified scaffolds (G300-600, G300-750,G300-900) adopt the Gyroid structure of the triply periodic minimum surfaces (TPMS), with the upper and lower layers respectively simulating the cortical bone and cancellous bone of the jawbone. And a large-aperture uniform scaffold (G750) was designed as a control. And it is prepared through digital light processing (DLP) 3D printing technology. The results show that sintering the scaffold to 1170℃ and holding it for 48 hours can improve the mechanical properties and biocompatibility of the scaffold, making it match. G300-600 not only improves in vitro neovascularization and new bone formation, but also features a high level of compressive strength (9.86MPa) and outstanding degradability. This gradient metamaterial scaffold has a structure, mechanical properties and biological activity that conform to the jawbone, providing a new strategy for bone defects in the maxillofacial region.</p>","PeriodicalId":72389,"journal":{"name":"Biomedical materials (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A preliminary investigation of nanomechanical and vascular compatibility of phase-engineered CuCoZrNbAl high-entropy alloys for stent-graft applications.","authors":"Chin-En Yen, Cheng-Hsien Tu, Guan-Lin Wu, Yuan-De Lin, Jun-Neng Roan, Chuan-Feng Shih, Ming-Long Yeh","doi":"10.1088/1748-605X/aea5c4","DOIUrl":"10.1088/1748-605X/aea5c4","url":null,"abstract":"<p><p>High-entropy alloys (HEAs) have emerged as promising candidates for cardiovascular implants due to their adjustable phase structure and excellent mechanical reliability. However, it remains challenging to achieve both mechanical resilience and biological endothelialization simultaneously. This study engineered CuCoZrNbAl HEAs by adjusting the Al content and thermal processing to explore the relationship between composition, microstructure, nanomechanical, and biological properties for stent-graft applications. Increasing the Al content alongside prolonged heat treatment facilitated the formation of a refined dual-phase microstructure comprising a face-centered cubic matrix and body-centered cubic ZrAl intermetallic domains. Among all tested alloys, the optimized CCZN(Al_1.0)-H60 alloy exhibited favorable nanomechanical properties, achieving a contact hardness of 11.2 GPa, a Young's modulus of 186.20 GPa, and a remarkably high H/E ratio of 0.060, alongside a reduced indentation depth of 6.51 nm and reduced hysteretic dissipated energy of 455.52 × 10^-18J. Furthermore, this alloy displayed enhanced electrochemical stability with a low corrosion current density of 1.53 μA/cm². Surface homogenization and Al-rich phase stabilization significantly enhanced endothelial cell attachments, supporting cell viability exceeding 100% and preserved migration capacity. The hemocompatibility test indicated a hemolysis rate below 2%, suggesting non-hemolytic behavior. These findings demonstrate that Al-driven phase engineering effectively strengthens local deformation resistance and corrosion stability while supporting endothelial cell growth, highlighting CuCoZrNbAl HEAs as potential candidates for further development of stent-grafts.</p>","PeriodicalId":72389,"journal":{"name":"Biomedical materials (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiopep-2-functionalized Cu-Mn oxide nanoplatform for blood-brain barrier penetration and radiotherapy-enhanced cuproptosis in glioma therapy.","authors":"Kaiwei Wang, Guangyu Ju, Hongcang Gu, Qi Ding, Xiao Liu, Anran Ma, Zimeng Wang, Rao Liu, Jian You, Shuanghu Yuan, Junchao Qian","doi":"10.1088/1748-605X/aea8b0","DOIUrl":"10.1088/1748-605X/aea8b0","url":null,"abstract":"<p><p>Glioblastoma (GBM) suffers from a poor prognosis due to its highly invasive nature, limited drug delivery across the blood-brain barrier (BBB), and intrinsic radioresistance. Although radiotherapy (RT) can perturb copper homeostasis and induce cuproptosis, the extent of copper accumulation is typically insufficient for effective tumor suppression. Herein, we develop a multifunctional composite nanoplatform, Mn₃O₄@PDA/Cu₂O-Angiopep-2 (MPCA), that integrates BBB penetration, radiosensitization, and copper-mediated cytotoxicity. Angiopep-2 facilitates LRP1-mediated BBB transcytosis and glioma targeting, x-ray diffraction and x-ray photoelectron spectroscopy confirmed the coexistence of crystalline Mn₃O₄and Cu₂O phases and the predominantly Cu(I) state of copper in the composite nanoplatform. Following cellular internalization, MPCA functions as both a copper reservoir and a reactive oxygen species (ROS) amplifier. The Cu₂O component enables sustained copper release, whereas Mn₃O₄enhances irradiation-induced oxidative stress. Under mildly acidic conditions, MPCA exhibits increased copper release, while x-ray irradiation amplifies ROS generation, with the strongest oxidative response observed under combined acidic and irradiation conditions. Mechanistically, MPCA combined with RT increases intracellular copper accumulation, disrupts copper homeostasis, and exacerbates mitochondrial oxidative stress, thereby inducing cuproptosis-associated mitochondrial dysfunction. These effects markedly enhance the radiosensitivity of GBM and inhibit orthotopic tumor growth. Overall, this study presents an Angiopep-2-functionalized Cu-Mn oxide composite nanoplatform that combines BBB targeting with copper-mediated radiosensitization, providing a promising strategy for GBM RT.</p>","PeriodicalId":72389,"journal":{"name":"Biomedical materials (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}