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Metal-free antioxidant nanozyme incorporating bioactive hydrogel as an antioxidant scaffold for accelerating bone reconstruction 含生物活性水凝胶的无金属抗氧化纳米酶作为加速骨重建的抗氧化支架
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-21 DOI: 10.1016/j.biomaterials.2025.123285
Yang Yang , Qianrui Zeng , Chaoyue Zhao , Jie Shi , Wanmeng Wang , Yunkai Liang , Changyi Li , Qingxin Guan , Bo Chen , Wei Li
{"title":"Metal-free antioxidant nanozyme incorporating bioactive hydrogel as an antioxidant scaffold for accelerating bone reconstruction","authors":"Yang Yang ,&nbsp;Qianrui Zeng ,&nbsp;Chaoyue Zhao ,&nbsp;Jie Shi ,&nbsp;Wanmeng Wang ,&nbsp;Yunkai Liang ,&nbsp;Changyi Li ,&nbsp;Qingxin Guan ,&nbsp;Bo Chen ,&nbsp;Wei Li","doi":"10.1016/j.biomaterials.2025.123285","DOIUrl":"10.1016/j.biomaterials.2025.123285","url":null,"abstract":"<div><div>Oxidative stress at bone defect sites mediates inflammation and even osteoblast apoptosis, severely hindering the repair process. While current antioxidant bone tissue engineering (BTE) scaffolds lack broad-spectrum reactive oxygen species (ROS) scavenging capability and structure-activity elucidation. Herein, we report a three-dimensional nitrogen-doped carbon antioxidant nanozyme (ZIFC) derived from metal-organic frameworks, which exhibits cascading superoxide dismutase- and catalase-like activities, along with the ability to scavenge other harmful free radicals. Through the experimental studies and theoretical calculations, we reveal that the catalase-like activity arises from the synergistic catalytic interaction between graphitized pyridinic nitrogen and its adjacent carbon atom. Moreover, hybrid double network hydrogel integrated with ZIFC is utilized to construct composite scaffold (Gel/ZIFC) by 3D printing. <em>In vivo</em> transcriptome analysis confirms that Gel/ZIFC can rapidly activate antioxidant defense system and suppress local inflammation under oxidative stress microenvironment, thereby protecting cells from oxidative damage. Subsequently, owing to the unique osteoinductive property of carbon nanomaterials and the osteoconductive property of 3D-printed scaffold, Gel/ZIFC composite scaffold exhibits desirable bone repair efficacy. The elucidation of structure-activity relationship and therapeutic mechanism provides new insights and guidance for devising antioxidant BTE scaffolds, and demonstrates their feasibility for clinical application.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123285"},"PeriodicalIF":12.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682951","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
Gel@CAT-L hydrogel mediates mitochondrial unfolded protein response to regulate reactive oxygen species and mitochondrial homeostasis in osteoarthritis Gel@CAT-L水凝胶介导线粒体未折叠蛋白反应,调节骨关节炎中的活性氧和线粒体稳态
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-21 DOI: 10.1016/j.biomaterials.2025.123283
Jiajia Lu , Jiao Cai , Zhibin Zhou , Jun Ma , Tianyu Han , Nan Lu , Lei Zhu
{"title":"Gel@CAT-L hydrogel mediates mitochondrial unfolded protein response to regulate reactive oxygen species and mitochondrial homeostasis in osteoarthritis","authors":"Jiajia Lu ,&nbsp;Jiao Cai ,&nbsp;Zhibin Zhou ,&nbsp;Jun Ma ,&nbsp;Tianyu Han ,&nbsp;Nan Lu ,&nbsp;Lei Zhu","doi":"10.1016/j.biomaterials.2025.123283","DOIUrl":"10.1016/j.biomaterials.2025.123283","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;This study investigates the role of Gelatin-Catalase (Gel@CAT)-L hydrogel in mediating reactive oxygen species (ROS) production and maintaining mitochondrial homeostasis through SIRT3-mediated unfolded protein response (UPR&lt;sup&gt;mt&lt;/sup&gt;), while exploring its involvement in the molecular mechanism of osteoarthritis (OA).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Self-assembled Gel@CAT-L hydrogels were fabricated and characterized using transmission electron microscopy, mechanical testing, external release property evaluation, and oxygen production measurement. Biocompatibility was assessed via live/dead cell staining and CCK8 assays. An OA mouse model was established using destabilization of the medial meniscus (DMM) surgery. X-ray and micro-CT imaging were employed to evaluate the structural integrity of the mouse knee joints, while histological staining was used to assess cartilage degeneration. Immunohistochemistry was performed to analyze the expression of proteins including Col2a1, Aggrecan, MMP13, ADAMTS5, SIRT3, PINK1, and Parkin. Multi-omics analyses—encompassing high-throughput sequencing, proteomics, and metabolomics—were conducted to identify key genes and metabolic pathways targeted by Gel@CAT-L hydrogel intervention in OA. Immunofluorescence techniques were utilized to measure ROS levels, mitochondrial membrane potential, and the expression of SIRT3, PINK1, Parkin, LYSO, LC3B, Col2a1, and MMP13 in primary mouse chondrocytes and mouse knee joints. Flow cytometry was applied to quantify ROS-positive cells. RT-qPCR analysis was conducted to determine mRNA levels of Aggrecan, Col2a1, ADAMTS5, MMP13, SIRT3, mtDNA, HSP60, LONP1, CLPP, and Atf5 in primary mouse chondrocytes, mouse knee joints, and human knee joints. Western blotting was performed to measure protein expression levels of SIRT3, HSP60, LONP1, CLPP, and Atf5 in both primary mouse chondrocytes and mouse knee joints. Additionally, 20 samples each from the control (CON) and OA groups were collected for analysis. Hematoxylin and eosin staining was used to evaluate cartilage degeneration in human knee joints. The Mankin histological scoring system quantified the degree of cartilage degradation, while immunofluorescence analyzed SIRT3 protein expression in human knee joints.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;&lt;em&gt;In vitro&lt;/em&gt; experiments demonstrated that self-assembled Gel@CAT-L hydrogels exhibited excellent biodegradability and oxygen-releasing capabilities, providing a stable three-dimensional environment conducive to cell viability and proliferation while reducing ROS levels. Multi-omics analysis identified SIRT3 as a key regulatory gene in mitigating OA and revealed its central role in the UPR&lt;sup&gt;mt&lt;/sup&gt; pathway. Furthermore, Gel@CAT-L was confirmed to regulate mitochondrial homeostasis. Both &lt;em&gt;in vitro&lt;/em&gt; experiments and &lt;em&gt;in vivo&lt;/em&gt; mouse model studies confirmed that Gel@CAT-L significantly reduced ROS levels and regulated mitochondrial autop","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123283"},"PeriodicalIF":12.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823849","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
Molybdoenzymes-emulating bio-heterojunction hydrogel with rapid disinfection and macrophage reprogramming for wound regeneration 具有快速消毒和巨噬细胞重编程的模拟钼酶生物异质结水凝胶用于伤口再生
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-21 DOI: 10.1016/j.biomaterials.2025.123284
Xiong Zhou , Peiqi Wang , Lu Xie , Yau Kei Chan , Zheng Jiao , Rui Shu , Ding Bai , Shuangquan Lai , Yi Deng
{"title":"Molybdoenzymes-emulating bio-heterojunction hydrogel with rapid disinfection and macrophage reprogramming for wound regeneration","authors":"Xiong Zhou ,&nbsp;Peiqi Wang ,&nbsp;Lu Xie ,&nbsp;Yau Kei Chan ,&nbsp;Zheng Jiao ,&nbsp;Rui Shu ,&nbsp;Ding Bai ,&nbsp;Shuangquan Lai ,&nbsp;Yi Deng","doi":"10.1016/j.biomaterials.2025.123284","DOIUrl":"10.1016/j.biomaterials.2025.123284","url":null,"abstract":"<div><div>Developing hydrogel dressings with the capabilities to accommodate irregular wounds and provide a cascade disinfective-regenerative microenvironment for wound repair is of great importance to combating pathogenic bacteria-infected wounds but remains an ongoing challenge. To address the conundrum, we devise a molybdoenzymes-emulating bio-heterojunction (M-bioHJ) doped double network (DN) hydrogel dressing for bacterial-infected wound healing. The near-infrared (NIR) photothermal effect of the M-bioHJ facilitates the exchange of multiple dynamic crosslinking sites in the hydrogel, endowing the hydrogel with photo-remote reprocessing capabilities to completely accommodate the encountered irregular wounds and ultimately accomplish the admirable therapeutic effect. Meanwhile, the introduced M-bioHJ shows NIR light-enhanced photodynamic activity to induce a massive engendering of reactive oxygen species (ROS), allowing rapid sterilization without reliance on exogenous hydrogen peroxide. Furthermore, the Mo ions released from the M-bioHJ-encapsulated hydrogel can play a crucial role in reprogramming the macrophage phenotype and determining tissue regeneration. Both <em>in vitro</em> and <em>in vivo</em> evidences authenticate the accelerated healing potential of infected wounds through the synergistic effects of photo-reprocessing, disinfection, and macrophage-reprogramming facilitated by the hydrogel. These findings highlight the promising application prospects of such neoteric M-bioHJ-encapsulated hydrogel dressings for wound disinfection and tissue regeneration.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123284"},"PeriodicalIF":12.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682950","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
Development of an innovative extracellular vesicle mimetic delivery platform for efficient miRNA delivery to tumours 开发一种创新的细胞外囊泡模拟递送平台,用于有效地向肿瘤递送miRNA
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-20 DOI: 10.1016/j.biomaterials.2025.123282
Rui Chen , Chintan Bhavsar , Rohan Lourie , Shuying Li , Sherry Y. Wu
{"title":"Development of an innovative extracellular vesicle mimetic delivery platform for efficient miRNA delivery to tumours","authors":"Rui Chen ,&nbsp;Chintan Bhavsar ,&nbsp;Rohan Lourie ,&nbsp;Shuying Li ,&nbsp;Sherry Y. Wu","doi":"10.1016/j.biomaterials.2025.123282","DOIUrl":"10.1016/j.biomaterials.2025.123282","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) display high degree of tissue tropism and therefore represent promising carriers for tissue-specific delivery of genes or drugs for the treatment of human diseases. However, current approaches for the loading of therapeutics into EVs have low entrapment efficiency and also do not adequately deplete endogenous EV content; thus, more effective approaches are needed. Here, we report an innovative EXtraCElluar vesicle surface Ligand-NanoParticles (EXCEL NPs), generated by transferring moieties of EVs onto the surface of synthetic nanoparticles. EXCEL NPs facilitate the efficient entrapment of therapeutics (89 % efficiency) and are completely devoid of pre-existing unwanted EV internal content. Importantly, we show that EXCEL NPs formulated using EVs derived from endothelial cells, astrocytes and macrophages retain the delivery characteristics of the original EVs. Using miRNA-146a as a model anti-cancer therapeutic, we further demonstrated successful delivery of miRNA-146a to IG10 orthotopic ovarian tumours in immune competent mice using EXCEL NPs formulated with macrophage-derived EVs. Our findings establish a new clinically translatable approach to leverage characteristics of endogenous EVs for therapeutic delivery. The versatility of the platform enables future application to different target cell types and therapeutic modalities.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123282"},"PeriodicalIF":12.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Magnesium hexacyanoferrate mitigates sepsis-associated encephalopathy through inhibiting microglial activation and neuronal cuproptosis 六氰合铁酸镁通过抑制小胶质细胞活化和神经元杯突变化缓解败血症相关脑病
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-20 DOI: 10.1016/j.biomaterials.2025.123279
Yabing Zhang , Juan Xin , Di Zhao , Gezi Chen , Penghao Ji , Panmiao Liu , Hua Wei , Hongwei Wang , Yuzhong Xia , Yong Wang , Zhongyu Wang , Xiangyi Ren , Minfeng Huo , Hai Yu , Jianjun Yang
{"title":"Magnesium hexacyanoferrate mitigates sepsis-associated encephalopathy through inhibiting microglial activation and neuronal cuproptosis","authors":"Yabing Zhang ,&nbsp;Juan Xin ,&nbsp;Di Zhao ,&nbsp;Gezi Chen ,&nbsp;Penghao Ji ,&nbsp;Panmiao Liu ,&nbsp;Hua Wei ,&nbsp;Hongwei Wang ,&nbsp;Yuzhong Xia ,&nbsp;Yong Wang ,&nbsp;Zhongyu Wang ,&nbsp;Xiangyi Ren ,&nbsp;Minfeng Huo ,&nbsp;Hai Yu ,&nbsp;Jianjun Yang","doi":"10.1016/j.biomaterials.2025.123279","DOIUrl":"10.1016/j.biomaterials.2025.123279","url":null,"abstract":"<div><div>Sepsis-associated encephalopathy (SAE) is a severe neurological complication stemming from sepsis, characterized by cognitive impairment. The underlying mechanisms involve oxidative stress, neuroinflammation, and disruptions in copper/iron homeostasis. This study introduces magnesium hexacyanoferrate (MgHCF) as a novel compound and explores its therapeutic potential in SAE. Our investigation reveals that MgHCF features intriguing properties in effectively scavenging reactive oxygen species (ROS), and chelating excess copper and iron. Treatment with MgHCF significantly attenuates microglia activation, and protects neuronal cells from oxidative damage and cytotoxicity induced by activated microglia in vitro and in vivo. Furthermore, the cognitive impairment in SAE mice is effectively alleviated by MgHCF treatment, mechanically through a reduction in the copper/iron-responsive histone methylation, and neuronal cuproptosis. These findings suggest MgHCF as a promising therapeutic agent for SAE, targeting the copper/iron signaling pathway to alleviate neuroinflammation, and neuronal cuproptosis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123279"},"PeriodicalIF":12.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734545","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
Stromal fibrin shapes immune infiltration landscape of pancreatic ductal adenocarcinoma 间质纤维蛋白影响胰腺导管腺癌的免疫浸润景观
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-20 DOI: 10.1016/j.biomaterials.2025.123280
Mazharul Karim , Md Mahedi Hasan , Seung Hyun Kim , Zulfikar Azam , Riajul Wahab , Tamanna Islam , Farzana Alam , Yun-Jae Kim , Dong-Jun Bae , Sourav Roy , Paul Grippo , Faraz Bishehsari , Jeong Uk Choi , Taslim A. Al-Hilal
{"title":"Stromal fibrin shapes immune infiltration landscape of pancreatic ductal adenocarcinoma","authors":"Mazharul Karim ,&nbsp;Md Mahedi Hasan ,&nbsp;Seung Hyun Kim ,&nbsp;Zulfikar Azam ,&nbsp;Riajul Wahab ,&nbsp;Tamanna Islam ,&nbsp;Farzana Alam ,&nbsp;Yun-Jae Kim ,&nbsp;Dong-Jun Bae ,&nbsp;Sourav Roy ,&nbsp;Paul Grippo ,&nbsp;Faraz Bishehsari ,&nbsp;Jeong Uk Choi ,&nbsp;Taslim A. Al-Hilal","doi":"10.1016/j.biomaterials.2025.123280","DOIUrl":"10.1016/j.biomaterials.2025.123280","url":null,"abstract":"<div><div>In pancreatic ductal adenocarcinoma (PDAC), in-situ coagulation creates a thrombotic, crosslinked fibrin (x-fibrin)-rich tumor stroma (FibTS), whose impact on immune cell behavior remains unclear. We aimed to elucidate how FibTS in PDAC regulates immune cell infiltration, polarization, and crosstalk that favors immunosuppressive microenvironment and tumor growth. We assessed the spatial distribution of immune cells by multiplex immunostaining of human PDAC tissues, along with novel bioengineering and mouse tumor models. We investigated how FibTS influences the infiltration of tumor-associated macrophage (TAM) and T-cell subtypes and identified two distinct variants of PDAC, fibrin-high (Fib<sup>hi</sup>) and fibrin-low (Fib<sup>low</sup>). Our findings reveal that PDAC cells secrete fibrinogen and thrombin to form FibTS, which acts as a physical barrier and biochemical niche that restricts CD8<sup>+</sup> T-cell and TAM penetration into the tumor. The FibTS impeded immune cell penetration from the tumor stroma into the tumor parenchyma. Selective inhibition of FibTS formation by genetic and pharmacological tools altered the infiltration patterns of CD8<sup>+</sup> T-cells and TAMs, decelerating PDAC growth. This study demonstrates that the barrier function of FibTS is crucial for immune evasion, particularly against macrophage and T-cell activity, presenting a potential therapeutic strategy to reshape the immune landscape within PDAC and slow tumor progression.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123280"},"PeriodicalIF":12.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715335","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
In situ forming AIEgen-alginate hydrogel for remodeling tumor microenvironment to boost FLASH immunoradiotherapy 原位形成aiegen -海藻酸盐水凝胶重塑肿瘤微环境,促进FLASH免疫放疗
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-20 DOI: 10.1016/j.biomaterials.2025.123281
Meng Lyu , Tianfu Zhang , Zhirong Bao , Pei Li , Mingzhu Chen , Hong Quan , Cunchuan Wang , Ligang Xia , Yang Li , Benzhong Tang
{"title":"In situ forming AIEgen-alginate hydrogel for remodeling tumor microenvironment to boost FLASH immunoradiotherapy","authors":"Meng Lyu ,&nbsp;Tianfu Zhang ,&nbsp;Zhirong Bao ,&nbsp;Pei Li ,&nbsp;Mingzhu Chen ,&nbsp;Hong Quan ,&nbsp;Cunchuan Wang ,&nbsp;Ligang Xia ,&nbsp;Yang Li ,&nbsp;Benzhong Tang","doi":"10.1016/j.biomaterials.2025.123281","DOIUrl":"10.1016/j.biomaterials.2025.123281","url":null,"abstract":"<div><div>FLASH radiotherapy, which involves the delivery of an ultra-high radiation dose rate exceeding 40 Gy/s, has emerged as a promising tumor ablation strategy. While this approach generally spares normal tissues, the incomplete killing of tumors may sometimes lead to recurrence due to the immunosuppressive tumor microenvironment (TME). Herein, an aggregation-induced-emission luminogen (AIEgen)-alginate hydrogel was used to sensitize colon cancer via photodynamic therapy (PDT). Flower-like calcium carbonate nanoparticles, doped with an AIEgen termed CQu, were designed and applied as a cocktail with sodium alginate. When exposed to the acidic TME, Ca<sup>2+</sup> is released from this structure, resulting in sodium alginate termed FA forming a hydrogel in situ within the TME. This hydrogel also captures high concentrations of CQu in the local TME. Under laser irradiation, the CQu can generate sustained reactive oxygen species (ROS) production, thereby facilitating Ca<sup>2+</sup> influx and causing mitochondrial damage. Through a single injection of established FA hydrogel, followed by PDT and FLASH radiotherapy, immunogenic tumor cell death was induced which promoted antitumor immunity, thereby protecting against tumor recurrence while realizing abscopal effect. The results highlight the potential to improve the sensitivity of tumor cells to FLASH radiotherapy through sustained ROS production and Ca<sup>2+</sup> overload, thereby yielding optimal immunotherapy outcomes.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123281"},"PeriodicalIF":12.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697421","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
Development of an electroconductive Heart-on-a-chip model to investigate cellular and molecular response of human cardiac tissue to gold nanomaterials 开发一种导电心脏芯片模型,以研究人类心脏组织对金纳米材料的细胞和分子反应
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-19 DOI: 10.1016/j.biomaterials.2025.123275
Hamid Esmaeili , Yining Zhang , Kalpana Ravi , Keagan Neff , Wuqiang Zhu , Raymond Q. Migrino , Jin G. Park , Mehdi Nikkhah
{"title":"Development of an electroconductive Heart-on-a-chip model to investigate cellular and molecular response of human cardiac tissue to gold nanomaterials","authors":"Hamid Esmaeili ,&nbsp;Yining Zhang ,&nbsp;Kalpana Ravi ,&nbsp;Keagan Neff ,&nbsp;Wuqiang Zhu ,&nbsp;Raymond Q. Migrino ,&nbsp;Jin G. Park ,&nbsp;Mehdi Nikkhah","doi":"10.1016/j.biomaterials.2025.123275","DOIUrl":"10.1016/j.biomaterials.2025.123275","url":null,"abstract":"<div><div>To date, various strategies have been developed to construct biomimetic and functional <em>in vitro</em> cardiac tissue models utilizing human induced pluripotent stem cells (hiPSCs). Among these approaches, microfluidic-based Heart-on-a-chip (HOC) models are promising, as they enable the engineering of miniaturized, physiologically relevant <em>in vitro</em> cardiac tissues with precise control over cellular constituents and tissue architecture. Despite significant advancements, previously reported HOC models often lack the electroconductivity features of the native human myocardium. In this study, we developed a 3D electroconductive HOC (referred to as eHOC) model through the co-culture of isogenic hiPSC-derived cardiomyocytes (hiCMs) and cardiac fibroblasts (hiCFs), embedded within an electroconductive hydrogel scaffold in a microfluidic-based chip system. Functional and gene expression analyses demonstrated that, compared to non-conductive HOC, the eHOC model exhibited enhanced contractile functionality, improved calcium transients, and increased expression of structural and calcium handling genes. The eHOC model was further leveraged to investigate the underlying electroconduction-induced pathway(s) associated with cardiac tissue development through single-cell RNA sequencing (scRNA-seq). Notably, scRNA-seq analyses revealed a significant downregulation of a set of cardiac genes, associated with the fetal stage of heart development, as well as upregulation of sarcomere- and conduction-related genes within the eHOC model. Additionally, upregulation of the cardiac muscle contraction and motor protein pathways were observed in the eHOC model, consistent with enhanced contractile functionality of the engineered cardiac tissues. Comparison of scRNA-seq data from the 3D eHOC model with published datasets of adult human hearts demonstrated a similar expression pattern of fetal- and adult-like cardiac genes. Overall, this study provides a unique eHOC model with improved biomimcry and organotypic features, which could be potentially used for drug testing and discovery, as well as disease modeling applications.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123275"},"PeriodicalIF":12.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697423","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
Photo-responsive self-expanding catheter with photosensitizer-integrated silicone-covered membrane for minimally invasive local therapy in malignant esophageal cancer 光敏剂集成硅膜光响应自膨胀导管在恶性食管癌微创局部治疗中的应用
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-19 DOI: 10.1016/j.biomaterials.2025.123265
Dae Sung Ryu , Hyeonseung Lee , Seung Jin Eo , Ji Won Kim , Yuri Kim , Seokin Kang , Jin Hee Noh , Sanghee Lee , Jung-Hoon Park , Kun Na , Do Hoon Kim
{"title":"Photo-responsive self-expanding catheter with photosensitizer-integrated silicone-covered membrane for minimally invasive local therapy in malignant esophageal cancer","authors":"Dae Sung Ryu ,&nbsp;Hyeonseung Lee ,&nbsp;Seung Jin Eo ,&nbsp;Ji Won Kim ,&nbsp;Yuri Kim ,&nbsp;Seokin Kang ,&nbsp;Jin Hee Noh ,&nbsp;Sanghee Lee ,&nbsp;Jung-Hoon Park ,&nbsp;Kun Na ,&nbsp;Do Hoon Kim","doi":"10.1016/j.biomaterials.2025.123265","DOIUrl":"10.1016/j.biomaterials.2025.123265","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) using photosensitizer (PS)-integrated covered self-expandable metallic stents (SEMS) is proposed a new therapeutic approach for the treatment of palliative malignancies; however, the currently hydrophobic PS reduces the photoreactive effect, which leads to aggregation with low water solubility. In here, an aluminum (III)-phthalocyanine chloride tetrasulfonic acid (Al-PcS4)-integrated silicone-covered self-expanding catheter was successfully fabricated to perform localized PDT. The ratio of MeOH and Al-PcS4 concentrations was optimized to achieve PS coating uniformity. The photodynamic activity of the Al-PcS4-integrated silicone membrane was evaluated through laser exposure on membrane-layered tumor cell lines, tumor xenograft-bearing mice. PDT with the Al-PcS4-integrated membrane successfully generated sufficient cytotoxic singlet oxygen, inducing cell death in the esophageal cancer cell lines. PDT-treated tumor xenograft-bearing mice undergo apoptotic cell death and showed significant tumor regression. Localized PDT using an Al-PcS4-integrated silicone-covered self-expanding catheter was technically successful in the rabbit esophagus without severe complications. Based on the endoscopy, esophagography, histology, and immunohistochemistry, our study verified that localized PDT using the Al-PcS4-integrated silicone-covered self-expanding catheter was effective and safe to evenly induce tissue damage. Al-PcS4-integrated silicone-covered self-expanding catheter has substantial potential for the minimally invasive local therapy in malignant esophageal cancer.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123265"},"PeriodicalIF":12.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nanomaterial technologies for precision diagnosis and treatment of brain hemorrhage 纳米材料技术用于脑出血的精确诊断和治疗
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-19 DOI: 10.1016/j.biomaterials.2025.123269
Peisen Zhang , Yi'an Ran , Lei Han , Yao Li , Wanru Tian , Xiao Sun , Mingxia Jiao , Lihong Jing , Xiliang Luo
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