Biomaterials最新文献_第3页

PD-L1 antibody-modified plant-derived nanovesicles carrying a STING agonist for the combinational immunotherapy of melanoma 携带STING激动剂的PD-L1抗体修饰植物源性纳米囊泡用于黑色素瘤的联合免疫治疗

IF 12.8 1区医学

Biomaterials Pub Date : 2025-05-06 DOI: 10.1016/j.biomaterials.2025.123396

Zhanxue Xu , Xinrui Yang , Xingyu Lu , Dandan Su , Yidan Wang , Huixing Wu , Zhenhua Zhang , Changrui Long , Liqian Su , Yanyu Wang , Hongbo Chen , Shijian Xiang , Benjie Zhou

{"title":"PD-L1 antibody-modified plant-derived nanovesicles carrying a STING agonist for the combinational immunotherapy of melanoma","authors":"Zhanxue Xu , Xinrui Yang , Xingyu Lu , Dandan Su , Yidan Wang , Huixing Wu , Zhenhua Zhang , Changrui Long , Liqian Su , Yanyu Wang , Hongbo Chen , Shijian Xiang , Benjie Zhou","doi":"10.1016/j.biomaterials.2025.123396","DOIUrl":"10.1016/j.biomaterials.2025.123396","url":null,"abstract":"<div><div>Combination therapies for melanoma face challenges due to asynchronous drug delivery and associated toxicity, underscoring the need for advanced delivery systems. While immune checkpoint inhibitors (ICIs) enhance T cell activity, optimal cytotoxic responses require efficient antigen presentation by mature dendritic cells (DCs), which are often functionally impaired in the tumor microenvironment. Thus, effective treatment requires coordinated T cell activation, DC-mediated priming, and direct tumor suppression. Herein, wild Glycyrrhiza uralensis Fisch roots-derived nanovesicles (GC NV) are demonstrated to be effective inhibitors of melanoma proliferation. The vesicles exert this activity through the intracellular delivery of encapsulated miRNA (miR2916) and bioactive molecules (isoliquiritigenin), with this capacity for intracellular delivery extending to the STING agonist DMXAA. We also demonstrate how chemical modification can be used to install PD-L1 antibodies on the membrane surface of these GC NV, imbuing these vesicles with selectivity for tumor cells. Combining DMXAA encapsulation with surface-displayed PD-L1 antibodies creates vesicles (GP@DMX NV) that both promote DCs maturation and elicit CD8<sup>+</sup> T cell response. Our multifunctional GP@DMX NV reverse the immunosuppressive microenvironment of melanoma and significantly enhance the immunotherapeutic potential of immune checkpoints.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123396"},"PeriodicalIF":12.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941691","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}

引用次数: 0

Biomimicry-inspired zwitterionic polyurethane used for vascular implants showing water-induced stiffening and preventing intimal hyperplasia in stent 仿生启发两性离子聚氨酯用于血管植入物显示水诱导硬化和防止内膜增生的支架

IF 12.8 1区医学

Biomaterials Pub Date : 2025-05-06 DOI: 10.1016/j.biomaterials.2025.123394

Ruibo Yang , Chuwen Chen , Wenkai Liu , Ao Wang , Pengjun Jiang , Zhen Li , Feng Luo , Jiehua Li , Hong Tan

{"title":"Biomimicry-inspired zwitterionic polyurethane used for vascular implants showing water-induced stiffening and preventing intimal hyperplasia in stent","authors":"Ruibo Yang , Chuwen Chen , Wenkai Liu , Ao Wang , Pengjun Jiang , Zhen Li , Feng Luo , Jiehua Li , Hong Tan","doi":"10.1016/j.biomaterials.2025.123394","DOIUrl":"10.1016/j.biomaterials.2025.123394","url":null,"abstract":"<div><div>Polymeric vascular implants with ideal mechanical properties and biocompatibility are essential for dilating blood vessels and reducing the risk of secondary implant diseases. However, traditional polymer materials are still limited for vascular stents by diminished radial support post-expansion and inadequate surface modification techniques. Herein, we synthesized zwitterionic polyurethanes (ZPUs) featuring hydrophilic side chains derived from betaine sulfonate and full-hard main chains. These ZPUs demonstrate a remarkable increase in modulus during shape recovery in 37 °C warm water, ensuring that the stent remains soft during implantation for easy delivery, but becomes stiff once positioned at the lesion site to provide adequate radial support. The distinctive architecture promotes the migration of hydrophilic side chains to the surface upon hydration, establishing a \"core-shell structure\" with a hard interior and a highly hydrophilic surface that enhances antithrombotic properties, mitigates inflammation, and curbs intimal hyperplasia. Consequently, ZPUE20 stent showed significantly better blood flow patency than traditional PLA stent in carotid artery implantation for at least 3 months, ensuring the long-term biological safety of implantation. Compared to surface modification of bare stents, ZPU stents avoid the complex and unstable surface modifications. All in all, ZPUs represent a promising material for vascular implants, markedly improving both mechanical performance and biocompatibility.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123394"},"PeriodicalIF":12.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916422","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}

引用次数: 0

A multi-gradient organoid of articular cartilage with bionic matrix microenvironment 具有仿生基质微环境的关节软骨多梯度类器官

IF 12.8 1区医学

Biomaterials Pub Date : 2025-05-05 DOI: 10.1016/j.biomaterials.2025.123393

Yongjie Wu , Zenghui Jia , Kang Sun , Guangdong Zhou , Ke Tao

{"title":"A multi-gradient organoid of articular cartilage with bionic matrix microenvironment","authors":"Yongjie Wu , Zenghui Jia , Kang Sun , Guangdong Zhou , Ke Tao","doi":"10.1016/j.biomaterials.2025.123393","DOIUrl":"10.1016/j.biomaterials.2025.123393","url":null,"abstract":"<div><div>Reconstructing the zonal organization of articular cartilage, including the heterogeneity in matrix distribution and chondrocyte status, remains a significant challenge. In this study, we developed a compression technique to engineer artificial cartilage architecture. By controlling the orientation of fibers within a collagen hydrogel, we obtained a gradient from parallel alignment in the surface layer to random distribution in deeper layers. Simultaneously, we established a diverse concentration gradient of chondroitin sulfate to mimic cartilage composition. Encapsulating chondrocytes within this construct yielded a \"cartilage organoid.\" In vitro culture demonstrated that the plastic compression achieved an increased density, parallel alignment, and a flattened morphology of cells in the surface layer. Especially, type II collagen and superficial zone protein (SZP), which are crucial for the functional durability of articular cartilage, were specifically excreted by the regulated cells within the surface region. Subcutaneous implantation of the cartilage organoid confirmed the stable retention of these specific features of the organoid in vivo, accompanied by further tissue maturation. Following implantation into articular cartilage defects, successful regeneration of well-integrated cartilage tissue with region-specific characteristics was achieved. These findings suggest a biomimetic cartilage organoid fully mimicking the factors in the structure and composition of natural cartilages, which may be a promising candidate for cartilage reconstruction and functional regeneration.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123393"},"PeriodicalIF":12.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913217","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}

引用次数: 0

Radiation-triggerable bioreactors enable bioenergetic reprograming of cancer stem cell plasticity via targeted arginine metabolism disruption for augmented radio-immunotherapy 辐射触发生物反应器通过靶向精氨酸代谢破坏增强放射免疫治疗，实现癌症干细胞可塑性的生物能量重编程

IF 12.8 1区医学

Biomaterials Pub Date : 2025-05-05 DOI: 10.1016/j.biomaterials.2025.123391

Xuemei Yao , Huocheng Yang , Sizhe Guo, Ying Liu, Qiqi Zhang, Zao Zhou, Menghuan Li, Zhong Luo

{"title":"Radiation-triggerable bioreactors enable bioenergetic reprograming of cancer stem cell plasticity via targeted arginine metabolism disruption for augmented radio-immunotherapy","authors":"Xuemei Yao , Huocheng Yang , Sizhe Guo, Ying Liu, Qiqi Zhang, Zao Zhou, Menghuan Li, Zhong Luo","doi":"10.1016/j.biomaterials.2025.123391","DOIUrl":"10.1016/j.biomaterials.2025.123391","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) are a major cause for the insufficient tumor eradication in the clinic, which universally present enhanced mitochondrial oxidative phosphorylation (OXPHOS) to facilitate stemness maintenance and drive treatment resistance. Herein, we report a nanointegrative radiation-triggerable bioreactor (RTB) that selectively remodels CSC-intrinsic arginine metabolism to bioenergetically reprogram CSCs towards a therapeutically-vulnerable differentiated state, leading to durable radio-immunotherapeutic responses in vivo. The RTB nanosystem was developed through the supramolecular integration of radioresponsive iNOS-expressing genetic circuits (pDNA<sup>iNOS</sup>) and β-lapachone (LAP) into CSC-targeting cationic liposomes. Low-dose radiotherapy (LDR)-induced Nrf2 upregulation readily activates pDNA<sup>iNOS</sup> to express excessive iNOS, which then depletes CSC-intrinsic arginine while generating abundant nitric oxide (NO) for in-situ amplification of LDR-mediated cytotoxicity. Meanwhile, LDR also upregulates NQO1 expression to promote LAP-mediated ROS generation. These effects could act in a cooperative manner to potently damage CSC mitochondria, which not only blocks OXPHOS activity to drive the differentiation of CSCs for abolishing their self-renewal and resistance capability, but also enhances their propensity towards immunogenic necroptosis to elicit adaptive antitumor immunity, showing significant potential for treating therapy-persistent tumors.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123391"},"PeriodicalIF":12.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916420","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}

引用次数: 0

Hump-inspired ingestible magnetic capsules enable circular nutrition storage and supply for short bowel syndrome treatment 驼峰启发的可摄取磁胶囊使循环营养储存和供应短肠综合征的治疗

IF 12.8 1区医学

Biomaterials Pub Date : 2025-05-03 DOI: 10.1016/j.biomaterials.2025.123389

Jiahao Dai , Na Li , Bo Cai , Yueying Yang , Wenyu Liu , Lin Wang , Jianfeng Zang , Zheng Wang

{"title":"Hump-inspired ingestible magnetic capsules enable circular nutrition storage and supply for short bowel syndrome treatment","authors":"Jiahao Dai , Na Li , Bo Cai , Yueying Yang , Wenyu Liu , Lin Wang , Jianfeng Zang , Zheng Wang","doi":"10.1016/j.biomaterials.2025.123389","DOIUrl":"10.1016/j.biomaterials.2025.123389","url":null,"abstract":"<div><div>Parenteral nutrition and intestinal transplantation, essential clinical interventions for short bowel syndrome (SBS) patients, are limited by various complications such as impaired intestinal barrier, metabolic disorder, catheter-associated infection, and allogenic rejection, leading to inferior therapeutic outcomes. Here, inspired by the camel hump, an ingestible magnetic capsule (IMC) consisting of thermosensitive hydrogel microparticles (MPs) based on poly(N-isopropylacrylamide) and acrylamide and a magnetic shell made of NdFeB and polyvinyl alcohol is proposed to enable circular nutrition storage and supply to optimize enteral nutrition for SBS treatment. Thermosensitive hydrogel MPs absorb excessive fluid and subsequently release nutrients in response to the heat generated by the photothermal effect of the magnetic shell under near-infrared irradiation. IMC can be localized and retained in the small intestine by the attraction between the magnetic shell and the external ferromagnet. In a SBS rat model, consistent nutrition optimization significantly relieves the weight loss, improves the nutrition-related serological markers, and facilitates the adaptation of the remnant small intestinal epithelium. This study offers a proof of principle for the use of ingestible capsules for nutrient storage and supply, providing a potential strategy for SBS treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123389"},"PeriodicalIF":12.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913216","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}

引用次数: 0

A novel radio-immunotherapy strategy: Gut microbiota metabolite combined with radioactive hydrogel for the treatment of low rectal cancer 一种新的放射免疫治疗策略：肠道微生物代谢物联合放射性水凝胶治疗低位直肠癌

IF 12.8 1区医学

Biomaterials Pub Date : 2025-05-03 DOI: 10.1016/j.biomaterials.2025.123386

Chonghai Zhang , Wenhao Shen , Zhifang Leng , Shu Liu , Pei Pei , Teng Liu , Lin Hu , Kai Yang

{"title":"A novel radio-immunotherapy strategy: Gut microbiota metabolite combined with radioactive hydrogel for the treatment of low rectal cancer","authors":"Chonghai Zhang , Wenhao Shen , Zhifang Leng , Shu Liu , Pei Pei , Teng Liu , Lin Hu , Kai Yang","doi":"10.1016/j.biomaterials.2025.123386","DOIUrl":"10.1016/j.biomaterials.2025.123386","url":null,"abstract":"<div><div>Colorectal cancer (CRC), especially low rectal cancer, often requires surgical resection of the anus, which severely affects the quality of life of patients. This study aims to develop a novel treatment method that can effectively control tumor growth while preserving anal function. We design a radioactive hydrogel (<sup>177</sup>Lu-RH) based on the cross-linking of metal ions and sodium alginate, which can be directly injected into the tumor to achieve local radiotherapy. In mouse experiments, we observe significant differences in the therapeutic efficacy of <sup>177</sup>Lu-RH among treated mice. Through 16S rDNA microbial diversity and targeted metabolomics studies, it has been revealed that the intestinal microbiota, particularly the <em>Rikenella</em> bacteria, and their metabolite propionate, are positively correlated with a favorable treatment response. We subsequently select the genus <em>Rikenella</em>, which exhibit a significantly higher abundance in the near-complete response (nCR) compared to the partial response (PR) group, for further mechanistic investigation. We discover that propionate, a metabolite produced by <em>Rikenella</em>, plays a crucial role in promoting tumor cell apoptosis and may augment the efficacy of tumor immunotherapy. Therefore, we improve the radioactive hydrogel by adding sodium propionate (SP) to form <sup>177</sup>Lu-RH@SP. In vivo experiments show that <sup>177</sup>Lu-RH@SP combined with anti-programmed death ligand 1 (αPD-L1) not only inhibits tumor growth but also promotes DC maturation and reverses T cell exhaustion, thereby enhancing the efficacy of tumor immunotherapy. Our work provides a new approach for the treatment of low rectal tumors, with the potential to improve the prognosis and quality of life for patients.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123386"},"PeriodicalIF":12.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908054","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}

引用次数: 0

Bioelectric and physicochemical foundations of bioelectronics in tissue regeneration 生物电子学在组织再生中的生物电和物理化学基础

IF 12.8 1区医学

Biomaterials Pub Date : 2025-05-02 DOI: 10.1016/j.biomaterials.2025.123385

Yuze Zheng , Guangqing Yang , Pengju Li , Bozhi Tian

{"title":"Bioelectric and physicochemical foundations of bioelectronics in tissue regeneration","authors":"Yuze Zheng , Guangqing Yang , Pengju Li , Bozhi Tian","doi":"10.1016/j.biomaterials.2025.123385","DOIUrl":"10.1016/j.biomaterials.2025.123385","url":null,"abstract":"<div><div>Understanding and exploiting bioelectric signaling pathways and physicochemical properties of materials that interface with living tissues is central to advancing tissue regeneration. In particular, the emerging field of bioelectronics leverages these principles to develop personalized, minimally invasive therapeutic strategies tailored to the dynamic demands of individual patients. By integrating sensing and actuation modules into flexible, biocompatible devices, clinicians can continuously monitor and modulate local electrical microenvironments, thereby guiding regenerative processes without extensive surgical interventions. This review provides a critical examination of how fundamental bioelectric cues and physicochemical considerations drive the design and engineering of next-generation bioelectronic platforms. These platforms not only promote the formation and maturation of new tissues across neural, cardiac, musculoskeletal, skin, and gastrointestinal systems but also precisely align therapies with the unique structural, functional, and electrophysiological characteristics of each tissue type. Collectively, these insights and innovations represent a convergence of biology, electronics, and materials science that holds tremendous promise for enhancing the efficacy, specificity, and long-term stability of regenerative treatments, ushering in a new era of advanced tissue engineering and patient-centered regenerative medicine.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123385"},"PeriodicalIF":12.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935009","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}

引用次数: 0

Multi-modal microcarriers reprogram mitochondrial metabolism and activate efferocytosis in macrophages for osteoporotic bone repair 多模态微载体重编程线粒体代谢，激活巨噬细胞的efferocytosis，用于骨质疏松性骨修复

IF 12.8 1区医学

Biomaterials Pub Date : 2025-05-02 DOI: 10.1016/j.biomaterials.2025.123384

Xin Wang , Chenjun Liu , Mingyue Wang , Bohao Yin , Yuwei Ge , Linyuan Shu , Hui Sun , Wei Zhang

{"title":"Multi-modal microcarriers reprogram mitochondrial metabolism and activate efferocytosis in macrophages for osteoporotic bone repair","authors":"Xin Wang , Chenjun Liu , Mingyue Wang , Bohao Yin , Yuwei Ge , Linyuan Shu , Hui Sun , Wei Zhang","doi":"10.1016/j.biomaterials.2025.123384","DOIUrl":"10.1016/j.biomaterials.2025.123384","url":null,"abstract":"<div><div>Osteoporotic bone repair remains challenging due to the ineffectiveness of traditional bone repair materials in adapting to the complex immune microenvironment of aging bone tissue. Exploiting the key role of macrophages in regulating this immune environment through the rational design of osteoimmunomodulatory biomaterials has emerged as a promising approach. However, current designs inadequately address the complexity of macrophage functions in aging environments, resulting in suboptimal regulatory effects. Hence, we explored multi-modal microcarriers for enhancing macrophage functionality. In this work, we developed a VGX-1027-loaded mesoporous silica nanosphere composite PLLA microcarrier. The dual-carrier system, featuring a micro-nano hybrid design by spatially separating the mesoporous silica nanoparticles and PLLA microspheres, enables sustained intracellular release of VGX-1027, addressing the chronic nature of osteoporotic fractures. Our studies demonstrate this VGX-1027 microcarrier (PMVGX) promotes M2 macrophage polarization by reprogramming mitochondrial metabolism. Simultaneously, it enhances efferocytosis, facilitating the clearance of dead or senescent cells and reducing inflammatory responses, thus reshaping the aging osteoimmunomodulatory. Furthermore, PMVGX induces macrophages to release osteogenic exosomes containing miR-5106 through paracrine signaling, significantly enhancing osteogenic function. In a postmenopausal osteoporosis animal model, PMVGX exhibited remarkable efficacy in repairing osteoporotic bone defects. This proof-of-concept study demonstrates that our multi-modal microcarrier effectively regulates macrophage functions via mitochondrial homeostasis, efferocytosis, and exosome content, offering great potential for osteoporotic bone repair.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123384"},"PeriodicalIF":12.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899041","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}

引用次数: 0

A dual-cascade-activatable molecular probe with microenvironment-adapted performance for accurate differentiation of hepatopathy 一种具有微环境适应性的双级联激活分子探针，用于肝病的准确鉴别

IF 12.8 1区医学

Biomaterials Pub Date : 2025-05-01 DOI: 10.1016/j.biomaterials.2025.123382

Ying Wen , Zefeng Hu , Wenhao Tian , Huming Yan , Fangjun Huo , Caixia Yin

{"title":"A dual-cascade-activatable molecular probe with microenvironment-adapted performance for accurate differentiation of hepatopathy","authors":"Ying Wen , Zefeng Hu , Wenhao Tian , Huming Yan , Fangjun Huo , Caixia Yin","doi":"10.1016/j.biomaterials.2025.123382","DOIUrl":"10.1016/j.biomaterials.2025.123382","url":null,"abstract":"<div><div>Fluorescence imaging utilizing biomarker-activatable fluorescent probes has emerged as a powerful tool for the precise and early diagnosis of hepatopathy. However, the development of effective molecular probes remains challenging due to limitations, such as single-stimulus responsiveness and incompatible with microenvironment characteristic of hepatopathy. These limitations often result in a lower signal-to-noise ratio, false positives and ultimately reduced diagnostic accuracy. In this study, we developed a novel dual-lock-controlled fluorescent probe (<strong>H<sub>dual</sub></strong>) based on basic blue 3 dye. This probe was designed to be sequentially activated by two potential hepatopathy biomarkers, leucine aminopeptidase (LAP) and monoamine oxidase (MAO), through a cascade mechanism. Moreover, after addition LAP and MAO, <strong>H<sub>dual</sub></strong> exhibited a linear fluorescence change within a pH range of 6.2–6.8, ensuring high compatibility with the weakly acidic microenvironment characteristic of hepatopathy. The dual-cascade-activatable design, combined with the probe's microenvironment-adapted property, enabled <strong>H<sub>dual</sub></strong> to achieve a significantly higher target-to-noise ratio (T/N) of 2.40 in <em>in vivo</em> imaging for drug-induced liver injury, compared to “single-locked” probe (T/N < 0.79). Notably, <strong>H<sub>dual</sub></strong> demonstrated the ability to differentiate between cirrhotic and hepatitis B samples by analyzing patient blood samples through both fluorescent imaging and a distinct colorimetric change, observable either visually or <em>via</em> smartphone-based color analysis. These findings highlight <strong>H<sub>dual</sub></strong>'s high specificity and accuracy in fluorescence imaging-based detection, underscoring its potential to improve the early diagnosis of hepatopathy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123382"},"PeriodicalIF":12.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901884","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}

引用次数: 0

Osteoclasts drive bone formation in ectopic and orthotopic environments 破骨细胞在异位和正位环境中驱动骨形成

IF 12.8 1区医学

Biomaterials Pub Date : 2025-04-30 DOI: 10.1016/j.biomaterials.2025.123377

Yang Zhang , Taozhao Yu , Qianfeng Xiang , Femke van den Tillaart , Jinling Ma , Zhumei Zhuang , Talita Stessuk , Huanan Wang , Jeroen J.J.P. van den Beucken

{"title":"Osteoclasts drive bone formation in ectopic and orthotopic environments","authors":"Yang Zhang , Taozhao Yu , Qianfeng Xiang , Femke van den Tillaart , Jinling Ma , Zhumei Zhuang , Talita Stessuk , Huanan Wang , Jeroen J.J.P. van den Beucken","doi":"10.1016/j.biomaterials.2025.123377","DOIUrl":"10.1016/j.biomaterials.2025.123377","url":null,"abstract":"<div><div>To date, cell-based approaches to stimulate bone formation have primarily focused on mesenchymal stromal cells (MSCs) for their supposed osteogenic potential, but despite some pre-clinical successes, clinical outcomes have remained unsatisfactory. Emerging data suggest that osteoclasts play crucial roles in stimulating bone formation beyond their catabolic function in bone resorption. Interestingly, osteoclastic activity precedes osteoblastic bone formation in the physiological bone remodeling cycle. To explore the role of osteoclasts in bone formation further, we prepared osteoclast-based constructs and implanted them (i) ectopically to evaluate their potential to induce bone formation, and (ii) orthotopically to evaluate effects on bone regeneration. Remarkably, constructs containing primary mouse osteoclasts showed consistent and robust <em>de novo</em> bone formation, which presented comparable osteogenic efficacy to BMP-2 treatment. Additionally, we observed <em>de novo</em> bone marrow formation upon ectopic implantation of osteoclast-based constructs (incidence 73 %) and BMP-2 loaded controls (incidence 91 %). Importantly, constructs containing macrophages (MФs) or scaffold only (negative control) showed neither bone nor bone marrow formation. Further, a mouse cranial defect model confirmed the stimulatory bone regeneration capabilities of Osteoclast-based constructs, evidenced by 2.5-fold increased bone formation compared to scaffold only. These findings demonstrate the osteoinduction and osteogenesis capacity of osteoclasts, reshaping our understanding of their role in bone formation and opening new avenues for the design and development of cell-based constructs for bone repair.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123377"},"PeriodicalIF":12.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901883","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}

引用次数: 0