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Optimization of culture conditions to generate vascularized multi-lineage liver organoids with structural complexity and functionality 优化培养条件,生成具有结构复杂性和功能性的血管化多系肝脏器官组织。
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-10-18 DOI: 10.1016/j.biomaterials.2024.122898
Kyun Yoo Chi , Gyeongmin Kim , Hyojin Kim , Hyemin Kim , Seongyea Jo , Jihun Lee , Youngseok Lee , Heeseok Yoon , Seunghyun Cho , Jeongjun Kim , Jin-Seok Lee , Gyu-Bum Yeon , Dae-Sung Kim , Han-Jin Park , Jong-Hoon Kim
{"title":"Optimization of culture conditions to generate vascularized multi-lineage liver organoids with structural complexity and functionality","authors":"Kyun Yoo Chi ,&nbsp;Gyeongmin Kim ,&nbsp;Hyojin Kim ,&nbsp;Hyemin Kim ,&nbsp;Seongyea Jo ,&nbsp;Jihun Lee ,&nbsp;Youngseok Lee ,&nbsp;Heeseok Yoon ,&nbsp;Seunghyun Cho ,&nbsp;Jeongjun Kim ,&nbsp;Jin-Seok Lee ,&nbsp;Gyu-Bum Yeon ,&nbsp;Dae-Sung Kim ,&nbsp;Han-Jin Park ,&nbsp;Jong-Hoon Kim","doi":"10.1016/j.biomaterials.2024.122898","DOIUrl":"10.1016/j.biomaterials.2024.122898","url":null,"abstract":"<div><div>Hepatic organoids (HOs), primarily composed of hepatobiliary cells, do not represent the pathogenesis of liver diseases due to the lack of non-parenchymal cells. Multi-lineage liver organoids (mLOs) containing various cell types found in the liver offer a promising <em>in vitro</em> disease model. However, their structural complexity remains challenging to achieve due to the difficulty in optimizing culture conditions that meet the growth need of all component cell types. Here, we demonstrate that cystic HOs generated from hPSCs can be expanded long-term and serve as a continuous source for generating complex mLOs. Assembling cystic HOs with hPSC-derived endothelial and hepatic stellate cell-like cells under conventional HO culture conditions failed to support the development of multiple cell types within mLOs, resulting in biased differentiation towards specific cell types. In contrast, modulating the cAMP/Wnt/Hippo signaling pathways with small molecules during assembly and differentiation phases efficiently generate mLOs containing both hepatic parenchymal and non-parenchymal cells. These mLOs exhibited structural complexity and functional maturity, including vascular network formation between parenchymal lobular structures, cell polarity for bile secretion, and the capacity to respond to fibrotic stimuli. Our study underscores the importance of modulating signaling pathways to enhance mLO structural complexity for applications in modeling liver pathologies.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122898"},"PeriodicalIF":12.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491864","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
Poly(β-amino ester) polymer library with monomer variation for mRNA delivery 用于递送 mRNA 的单体变化聚(β-氨基酯)聚合物库。
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-10-16 DOI: 10.1016/j.biomaterials.2024.122896
Hong Lyun Kim , Gurusamy Saravanakumar , Seowon Lee , Subin Jang , Seonwoo Kang , Mihyeon Park , Sivasangu Sobha , So-Hee Park , Soo-Min Kim , Jung-Ah Lee , Eunkyung Shin , You-jin Kim , Hye-Sook Jeong , Dokeun Kim , Won Jong Kim
{"title":"Poly(β-amino ester) polymer library with monomer variation for mRNA delivery","authors":"Hong Lyun Kim ,&nbsp;Gurusamy Saravanakumar ,&nbsp;Seowon Lee ,&nbsp;Subin Jang ,&nbsp;Seonwoo Kang ,&nbsp;Mihyeon Park ,&nbsp;Sivasangu Sobha ,&nbsp;So-Hee Park ,&nbsp;Soo-Min Kim ,&nbsp;Jung-Ah Lee ,&nbsp;Eunkyung Shin ,&nbsp;You-jin Kim ,&nbsp;Hye-Sook Jeong ,&nbsp;Dokeun Kim ,&nbsp;Won Jong Kim","doi":"10.1016/j.biomaterials.2024.122896","DOIUrl":"10.1016/j.biomaterials.2024.122896","url":null,"abstract":"<div><div>Non-viral vectors for mRNA delivery primarily include lipid nanoparticles (LNPs) and polymers. While LNPs are known for their high mRNA delivery efficiency, they can induce excessive immune responses and cause off-target effects, potentially leading to side effects. In this study, we aimed to explore polymer-based mRNA delivery systems as a viable alternative to LNPs, focusing on their mRNA delivery efficiency and potential application in mRNA vaccines. We created a library of poly(β-amino ester) (PBAE) polymers by combining various amine monomers and acrylate monomers. Through screening this polymer library, we identified specific polymer nanoparticles (PNPs) that demonstrated high mRNA expression efficiency, with sustained mRNA expression for up to two weeks. Furthermore, the PNPs showed mRNA expression only at the injection site and did not exhibit liver toxicity. Additionally, when assessing immune activation, the PNPs significantly induced T-cell immune activation and were effective in the plaque reduction neutralization test. These results suggest that polymer-based mRNA delivery systems not only hold potential for use in mRNA vaccines but also show promise for therapeutic applications.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122896"},"PeriodicalIF":12.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454379","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
Anti-pyroptosis biomimetic nanoplatform loading puerarin for myocardial infarction repair: From drug discovery to drug delivery 用于心肌梗死修复的装载葛根素的抗血栓形成生物仿生纳米平台:从药物发现到药物输送。
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-10-16 DOI: 10.1016/j.biomaterials.2024.122890
Kun Wang , Yu Sun , Ke Zhu , Yiqiong Liu , Xiao Zheng , Zichen Yang , Fulong Man , Li Huang , Ziyang Zhu , Qi Huang , Yan Li , Haiqing Dong , Jun Zhao , Yongyong Li
{"title":"Anti-pyroptosis biomimetic nanoplatform loading puerarin for myocardial infarction repair: From drug discovery to drug delivery","authors":"Kun Wang ,&nbsp;Yu Sun ,&nbsp;Ke Zhu ,&nbsp;Yiqiong Liu ,&nbsp;Xiao Zheng ,&nbsp;Zichen Yang ,&nbsp;Fulong Man ,&nbsp;Li Huang ,&nbsp;Ziyang Zhu ,&nbsp;Qi Huang ,&nbsp;Yan Li ,&nbsp;Haiqing Dong ,&nbsp;Jun Zhao ,&nbsp;Yongyong Li","doi":"10.1016/j.biomaterials.2024.122890","DOIUrl":"10.1016/j.biomaterials.2024.122890","url":null,"abstract":"<div><div>Pyroptosis is a critical pathological mechanism implicated in myocardial damage following myocardial infarction (MI), and the crosstalk between macrophages and pyroptotic cardiomyocytes presents a formidable challenge for anti-pyroptosis therapies of MI. However, as single-target pyroptosis inhibitors frequently fail to address this crosstalk, the efficacy of anti-pyroptosis treatment post-MI remains inadequate. Therefore, the exploration of more potent anti-pyroptosis approaches is imperative for improving outcomes in MI treatment, particularly in addressing the crosstalk between macrophages and pyroptotic cardiomyocytes. Here, in response to this crosstalk, we engineered an anti-pyroptosis biomimetic nanoplatform (NM@PDA@PU), employing polydopamine (PDA) nanoparticles enveloped with neutrophil membrane (NM) for targeted delivery of puerarin (PU). Notably, network pharmacology is deployed to discern the most efficacious anti-pyroptosis drug (puerarin) among the 7 primary active monomers of TCM formulations widely applied in clinical practice and reveal the effect of puerarin on the crosstalk. Additionally, targeted delivery of puerarin could disrupt the malignant crosstalk between macrophages and pyroptotic cardiomyocytes, and enhance the effect of anti-pyroptosis by not only directly inhibiting cardiomyocytes pyroptosis through NLRP3-CASP1-IL-1β/IL-18 signal pathway, but reshaping the inflammatory microenvironment by reprogramming macrophages to anti-inflammatory M2 subtype. Overall, NM@PDA@PU could enhance anti-pyroptosis effect by disrupting the crosstalk between M1 macrophages and pyroptotic cardiomyocytes to protect cardiomyocytes, ameliorate cardiac function and improve ventricular remodeling, which providing new insights for the efficient treatment of MI.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122890"},"PeriodicalIF":12.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454375","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
Endothelium-targeted NF-κB siRNA nanogel for magnetic resonance imaging and visualized-anti-inflammation treatment of atherosclerosis 用于动脉粥样硬化的磁共振成像和可视化抗炎治疗的内皮靶向 NF-κB siRNA 纳米凝胶。
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-10-16 DOI: 10.1016/j.biomaterials.2024.122897
Yuanyuan Guo , Fujun Wang , Sunli Wan , Xinhua Liu , Yu Huang , Miao Xie , Xiaoer Wei , Wangshu Zhu , Tingting Yao , Yuehua Li , Chuan Zhang , Yueqi Zhu
{"title":"Endothelium-targeted NF-κB siRNA nanogel for magnetic resonance imaging and visualized-anti-inflammation treatment of atherosclerosis","authors":"Yuanyuan Guo ,&nbsp;Fujun Wang ,&nbsp;Sunli Wan ,&nbsp;Xinhua Liu ,&nbsp;Yu Huang ,&nbsp;Miao Xie ,&nbsp;Xiaoer Wei ,&nbsp;Wangshu Zhu ,&nbsp;Tingting Yao ,&nbsp;Yuehua Li ,&nbsp;Chuan Zhang ,&nbsp;Yueqi Zhu","doi":"10.1016/j.biomaterials.2024.122897","DOIUrl":"10.1016/j.biomaterials.2024.122897","url":null,"abstract":"<div><div>Atherosclerosis-induced lethal cardiovascular disease remains a severe healthcare threat due to the limited drug efficiency and untimely prediction of high-risk events caused by inadequate target specificity of medications, incapable recognition of insensitive patients, and variable morphology of vulnerable plaques. Therefore, it is necessary to develop efficient strategies to improve the diagnosis accuracy and achieve visualized treatment of atherosclerosis. Herein, we establish an inflamed endothelium-targeted three-in-one nucleic acid nanogel system that can reverse the inflammatory state of endothelial cells (ECs) in plaques and simultaneously achieve real-time monitoring of the therapy process for efficient atherosclerosis diagnosis and treatment. For this purpose, contrast agent (Gd-DOTA) and VCAM-1-targeted peptide (VP) are first covalently conjugated onto DNA strands by click reaction respectively, which could self-assemble into Y-shaped structures (Gd-Y1 and VP-Y2 motifs) with magnetic resonance (MR) imaging and endothelium targeting capacities. Thereafter, NF-κB subunit p65-targeting siRNA (siNF-κB) is crosslinked with Gd-Y1 and VP-Y2 motifs to construct the endothelium-targeting nanogel platform. With contrast agents inside, the nanogel enables MR-based diagnosis and visualized therapy of atherosclerosis, providing accurate prognostic analysis and indications for treatment results, which ensures timely disclosure of insensitive individuals and avoids acute lethal events. By delivering siNF-κB to inflammatory endothelium, the nanogel significantly regresses plaques in both the aorta and carotid artery with reduced inflammation cytokines, collagens, macrophages, and apoptotic cells, providing a potential anti-inflammation strategy to treat atherosclerosis and avoid acute cardiovascular disease.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122897"},"PeriodicalIF":12.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491860","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
Engineering probiotic biohydrogen micro-factories to initiate reductive stress for boosting tumor vulnerability 设计益生菌生物氢微型工厂,启动还原应激,提高肿瘤易感性。
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-10-15 DOI: 10.1016/j.biomaterials.2024.122892
Jie Jiang , Yuhao Lu , Xinyi Zheng , Maomao Xie , Aleksandra Jauković , Meng Gao , Huizhen Zheng
{"title":"Engineering probiotic biohydrogen micro-factories to initiate reductive stress for boosting tumor vulnerability","authors":"Jie Jiang ,&nbsp;Yuhao Lu ,&nbsp;Xinyi Zheng ,&nbsp;Maomao Xie ,&nbsp;Aleksandra Jauković ,&nbsp;Meng Gao ,&nbsp;Huizhen Zheng","doi":"10.1016/j.biomaterials.2024.122892","DOIUrl":"10.1016/j.biomaterials.2024.122892","url":null,"abstract":"<div><div>Disruption of redox homeostasis profoundly affects cellular metabolism and activities. While oxidative stress is extensively studied in cancer therapies, research on reductive stress remains in its infancy. Molecular hydrogen (H<sub>2</sub>), a well-known antioxidant, holds significant potential to induce reductive stress due to its strong antioxidative properties, making it a promising candidate for cancer therapy. However, it remains a major challenge to develop a sustainable H<sub>2</sub> delivery system <em>in vivo</em>. Herein, we designed a micro-factory by engineering a gel-based microcapsule that encapsulates <em>Enterobacter aerogenes</em>, <em>a.k.a</em>. probiotic biohydrogen microcapsules (PBMCs), enabling the sustained H<sub>2</sub> generation within tumor microenvironment. Notably, PBMCs effectively suppressed the proliferation of eight tumor cell lines as well as drug-resistant cancer cells. The prolonged H<sub>2</sub> release from PBMCs induced reductive stress, as evidenced by a significant increase in the GSH/GSSG ratio in 4T1 cells. Moreover, PBMCs displayed significant antitumor effects in breast, melanoma and liver cancer models. The inhibition of PI3K-AKT pathway and the activation of MAPK pathway were identified as key mechanisms responsible for inducing tumor cell cycle arrest and apoptosis. The PBMCs also exhibited synergistic effects in combination with chemotherapeutics, resulting in robust inhibitions of preinvasive carcinoma growth and commonly associated pulmonary metastasis. Overall, our study introduces an innovative strategy to manipulate reductive stress in the tumor microenvironment through <em>in situ</em> H<sub>2</sub> generation, thereby enhancing tumor vulnerability.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122892"},"PeriodicalIF":12.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454378","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
Exosomes from hypoxic urine-derived stem cells facilitate healing of diabetic wound by targeting SERPINE1 through miR-486-5p 缺氧尿源干细胞的外泌体通过 miR-486-5p 靶向 SERPINE1 促进糖尿病伤口愈合
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-10-15 DOI: 10.1016/j.biomaterials.2024.122893
Ming-Hui Fan , Xiu-Zhen Zhang , Yan-Lin Jiang , Jin-Kui Pi , Ji-Ye Zhang , Yue-Qi Zhang , Fei Xing , Hui-Qi Xie
{"title":"Exosomes from hypoxic urine-derived stem cells facilitate healing of diabetic wound by targeting SERPINE1 through miR-486-5p","authors":"Ming-Hui Fan ,&nbsp;Xiu-Zhen Zhang ,&nbsp;Yan-Lin Jiang ,&nbsp;Jin-Kui Pi ,&nbsp;Ji-Ye Zhang ,&nbsp;Yue-Qi Zhang ,&nbsp;Fei Xing ,&nbsp;Hui-Qi Xie","doi":"10.1016/j.biomaterials.2024.122893","DOIUrl":"10.1016/j.biomaterials.2024.122893","url":null,"abstract":"<div><div>Vascular pathologies and injuries are important factors for the delayed wound healing in diabetes. Previous studies have demonstrated that hypoxic environments could induce formation of new blood vessels by regulating intercellular communication and cellular behaviors. In this study, we have enhanced the angiogenic potential of exosomes by subjecting urine-derived stem cells (USCs) to hypoxic preconditioning. To prolong the retention of exosomes at the wound site, we have also engineered a novel dECM hydrogel termed SISMA, which was modified from porcine small intestinal submucosa (SIS). For its rapid and controllable gelation kinetics, excellent biocompatibility, and exosome release capability, the SISMA hydrogel has proven to be a reliable delivery vehicle for exosomes. The hypoxia-induced exosomes-loaded hydrogel has promoted endothelial cell proliferation, migration, and tube formation. More importantly, as evidenced by significant <em>in vivo</em> vascular regeneration in the early stages post-injury, it has facilitated tissue repair. This may because miR-486–5p in H-exo inhibit <em>SERPINE1</em> activity in endothelial cell. Additionally, miRNA sequencing analysis suggested that the underlying mechanism for enhanced angiogenesis may be associated with the activation of classical HIF-1α signaling pathway. In summary, our study has presented a novel non-invasive, cell-free therapeutic approach for accelerating diabetes wound healing and development of a practical and efficient exosomes delivery platform.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122893"},"PeriodicalIF":12.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446106","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
Neutrophils exhibit flexible migration strategies and trail formation mechanisms on varying adhesive substrates 中性粒细胞在不同的粘附基质上表现出灵活的迁移策略和痕迹形成机制。
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-10-13 DOI: 10.1016/j.biomaterials.2024.122881
Wenbo Gao , Xiaoning Zhang , Wenhui Hu , Jie Han , Xiaoheng Liu , Yan Zhang , Mian Long
{"title":"Neutrophils exhibit flexible migration strategies and trail formation mechanisms on varying adhesive substrates","authors":"Wenbo Gao ,&nbsp;Xiaoning Zhang ,&nbsp;Wenhui Hu ,&nbsp;Jie Han ,&nbsp;Xiaoheng Liu ,&nbsp;Yan Zhang ,&nbsp;Mian Long","doi":"10.1016/j.biomaterials.2024.122881","DOIUrl":"10.1016/j.biomaterials.2024.122881","url":null,"abstract":"<div><div>Substrate anchorage is essential for cell migration, and actin polymerization at cell front and myosin contractility at cell rear are known to govern cell forward movement. Yet their differential driving strategies for neutrophil migration on distinct adhesiveness substrates and their contributions to the migration-induced trail formation remain unclear. Here we explore the morphological changes, migration dynamics, and trail formation of neutrophils on ICAM-1 and PLL substrates, with a focus on the relationships among adhesive forces, traction forces, and out-of-plane forces. Results indicate that, on ICAM-1, neutrophil migration and trail formation rely on the coordinated interactions of Arp2/3 and myosin, along with biochemical regulation (<em>via</em> Syk and calpain) of adhesion and de-adhesion. This pattern leads to traction forces being concentrated at relatively fewer adhesive sites, facilitating cell forward migration. On PLL, however, neutrophils primarily depend on Arp2/3-mediated actin polymerization, resulting in a broader distribution of traction forces and weaker adhesions, which allows for higher leading-edge migrating velocities. Elevated membrane tension and out-of-plane forces generated by bleb protrusions on PLL reduce the reliance on myosin-driven contraction at the trailing edge, enabling easier tail detachment through elastic recoil. This work highlights the differential impact of substrate adhesiveness on neutrophil migration and trail formation and dynamics, providing new insights into cell migration mechanisms and potential therapeutic targets for inflammatory and immune-related disorders.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122881"},"PeriodicalIF":12.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491863","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
Engineered endothelium model enables recapitulation of vascular function and early atherosclerosis development 工程内皮模型可重现血管功能和早期动脉粥样硬化的发展过程
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-10-12 DOI: 10.1016/j.biomaterials.2024.122889
Avelino Dos Santos Da Costa , Kopych Vadym , Kwideok Park
{"title":"Engineered endothelium model enables recapitulation of vascular function and early atherosclerosis development","authors":"Avelino Dos Santos Da Costa ,&nbsp;Kopych Vadym ,&nbsp;Kwideok Park","doi":"10.1016/j.biomaterials.2024.122889","DOIUrl":"10.1016/j.biomaterials.2024.122889","url":null,"abstract":"<div><div>Human health relies heavily on the vascular endothelium. Here, we propose a novel engineered endothelium model (EEM), which recapitulated both normal vascular function and pathology. An artificial basement membrane (aBM), where porous polyvinyl alcohol hydrogel was securely integrated with human fibroblast-derived, decellularized extracellular matrix on both sides was fabricated first and followed by endothelial cells (ECs) and pericytes (PCs) adhesion, respectively. Our EEM formed robust adherens junction (VE-cad) and built an impermeable barrier with time, along with the nitric oxide (NO) secretion. In our EEM, ECs and PCs interacted each other via aBM and led to hemoglobin alpha 1 (Hb-α1) development, which was involved in NO control and was strongly interconnected with VE-cad as well. A resilient property of EEM under inflammatory milieu was also confirmed by VE-cad and barrier recovery with time. In particular interest, foam cells formation, a hallmark of atherosclerotic initiation was successfully recapitulated in our EEM, where a series of sequential events were confirmed: human monocytes adhesion, transendothelial migration, and oxidized low-density lipoprotein uptake by macrophages. Collectively, our EEM is excellent in recapitulating not only normal endothelium but early pathologic one, thereby enabling EEM to be a physiologically relevant model for vascular study and disease modeling.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122889"},"PeriodicalIF":12.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446105","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
In situ photocrosslinkable hydrogel treats radiation-induced skin injury by ROS elimination and inflammation regulation 原位光交联水凝胶通过消除 ROS 和调节炎症治疗辐射引起的皮肤损伤
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-10-12 DOI: 10.1016/j.biomaterials.2024.122891
Jintao Shen , Wencheng Jiao , Junzhe Yang , Bo Zhuang , Shumin Du , Yanping Wu , Guiyu Huang , Yizhi Zhang , Yaxin Wang , Caixia Xu , Lina Du , Yiguang Jin
{"title":"In situ photocrosslinkable hydrogel treats radiation-induced skin injury by ROS elimination and inflammation regulation","authors":"Jintao Shen ,&nbsp;Wencheng Jiao ,&nbsp;Junzhe Yang ,&nbsp;Bo Zhuang ,&nbsp;Shumin Du ,&nbsp;Yanping Wu ,&nbsp;Guiyu Huang ,&nbsp;Yizhi Zhang ,&nbsp;Yaxin Wang ,&nbsp;Caixia Xu ,&nbsp;Lina Du ,&nbsp;Yiguang Jin","doi":"10.1016/j.biomaterials.2024.122891","DOIUrl":"10.1016/j.biomaterials.2024.122891","url":null,"abstract":"<div><div>The clinical management of radiation-induced skin injury (RSI) poses a significant challenge, primarily due to the acute damage caused by an overabundance of reactive oxygen species (ROS) and the ongoing inflammatory microenvironment. Here, we designed a dual-network hydrogel composed of 5 % (w/v) Pluronic F127 diacrylate and 2 % (w/v) hyaluronic acid methacryloyl, termed the FH hydrogel. To confer antioxidant and anti-inflammation properties to the hydrogel, we incorporated PVP-modified Prussian blue nanoparticles (PPBs) and resveratrol (Res) to form PHF@Res hydrogels. PHF@Res hydrogels not only exhibited multiple free radical scavenging activities (DPPH, ABTS), but also displayed multiple enzyme-like activities (POD-, catalase). Meanwhile, PHF@Res-2 hydrogels significantly suppressed intracellular ROS and promoted the migration of fibroblasts in a high-oxidative stress environment. Moreover, in the RSI mouse model, the PHF@Res-2 hydrogel regulated inflammatory factors and collagen deposition, significantly reduced epithelial hyperplasia, promoted limb regeneration and neovascularization, and accelerated wound healing, outperforming the commercial antiradiation formulation, Kangfuxin. The PHF@Res-2 hydrogel dressing shows great potential in accelerating wound healing in RSI, offering tremendous promise for clinical wound management and regeneration.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122891"},"PeriodicalIF":12.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441915","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
Cell calcification reverses the chemoresistance of cancer cells via the conversion of glycolipid metabolism 细胞钙化可通过糖脂代谢转换逆转癌细胞的化疗抗性。
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-10-10 DOI: 10.1016/j.biomaterials.2024.122886
Lihong Zhang , Yandi Sun , Yindan Lin , Hanhui Li , Yuqiao Huang , Ning Tang , Xueyun Zhang , Yin Lu , Vassili A. Kovalev , Eduard V. Snezhko , Yan Luo , Ben Wang
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