Biomaterials最新文献_第3页

Seeds-and-soil inspired hydrogel microspheres: A dual-action antioxidant and cellular therapy for reversing intervertebral disc degeneration

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-04-09 DOI: 10.1016/j.biomaterials.2025.123326

Yilin Yang , Jiangbo Guo , Haifei Cao , Xin Tian , Hao Shen , Junjie Niu , Huilin Yang , Qin Shi , Yong Xu

Intervertebral disc degeneration (IVDD) is a globally prevalent disease, yet achieving dual repair of tissue and function presents significant challenges. Considering reactive oxygen species (ROS) is a primary cause of IVDD, and given the decrease of nucleus pulposus cells (NPCs) and extensive degradation of extracellular matrix (ECM) during IVDD development, the present study, inspired by the “seeds-and-soil” strategy, has developed NPCs-loaded TBA@Gel&Chs hydrogel microspheres. These microspheres serve as exogenous supplements of NPCs and ECM analogs, replenishing “seeds” and “soil” for nucleus pulposus repair, and incorporating polyphenol antioxidant components to interrupt the oxidative stress-IVDD cycle, thereby constructing a microsphere system where NPCs and ECM support each other. Experiments proved that TBA@Gel&Chs exhibited significant extracellular ROS-scavenging antioxidant capabilities while effectively upregulating intracellular antioxidant proteins expression (Sirt3 and Sod2). This dual-action antioxidant capability effectively protects the vitality and physiological functions of NPCs. The therapeutic effects of microspheres on IVDD were also confirmed in rat models, which was found significantly restore histological structure and mechanical properties of degenerated discs. Additionally, RNA-seq results have provided evidences of antioxidant mechanism by which TBA@Gel&Chs protected NPCs from oxidative stress. Therefore, the NPCs-loaded TBA@Gel&Chs microspheres developed in this study have achieved excellent therapeutic effects, offering a paradigm using antioxidant biomaterials combined with cellular therapy for IVDD treatment.

{"title":"Seeds-and-soil inspired hydrogel microspheres: A dual-action antioxidant and cellular therapy for reversing intervertebral disc degeneration","authors":"Yilin Yang , Jiangbo Guo , Haifei Cao , Xin Tian , Hao Shen , Junjie Niu , Huilin Yang , Qin Shi , Yong Xu","doi":"10.1016/j.biomaterials.2025.123326","DOIUrl":"10.1016/j.biomaterials.2025.123326","url":null,"abstract":"<div><div>Intervertebral disc degeneration (IVDD) is a globally prevalent disease, yet achieving dual repair of tissue and function presents significant challenges. Considering reactive oxygen species (ROS) is a primary cause of IVDD, and given the decrease of nucleus pulposus cells (NPCs) and extensive degradation of extracellular matrix (ECM) during IVDD development, the present study, inspired by the “seeds-and-soil” strategy, has developed NPCs-loaded TBA@Gel&Chs hydrogel microspheres. These microspheres serve as exogenous supplements of NPCs and ECM analogs, replenishing “seeds” and “soil” for nucleus pulposus repair, and incorporating polyphenol antioxidant components to interrupt the oxidative stress-IVDD cycle, thereby constructing a microsphere system where NPCs and ECM support each other. Experiments proved that TBA@Gel&Chs exhibited significant extracellular ROS-scavenging antioxidant capabilities while effectively upregulating intracellular antioxidant proteins expression (Sirt3 and Sod2). This dual-action antioxidant capability effectively protects the vitality and physiological functions of NPCs. The therapeutic effects of microspheres on IVDD were also confirmed in rat models, which was found significantly restore histological structure and mechanical properties of degenerated discs. Additionally, RNA-seq results have provided evidences of antioxidant mechanism by which TBA@Gel&Chs protected NPCs from oxidative stress. Therefore, the NPCs-loaded TBA@Gel&Chs microspheres developed in this study have achieved excellent therapeutic effects, offering a paradigm using antioxidant biomaterials combined with cellular therapy for IVDD treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123326"},"PeriodicalIF":12.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830352","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

Metal ion coordinated tea polyphenol nanocoating for enhanced probiotic therapy in inflammatory bowel disease

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-04-09 DOI: 10.1016/j.biomaterials.2025.123323

Lu Gao , Yunjian Liu , Ling Ye , Sizhi Liang , Jiancan Lin , Jiaying Zeng , Lei Lei , Qiang Huang , Yujun Wan , Bin Zhang

Probiotics encapsulated with metal-phenolic networks (MPNs) present a promising approach for treating inflammatory bowel diseases (IBD). However, current MPN systems predominantly use tannic acid (TA) as the phenolic source, with limited exploration of other polyphenols, and face challenges in long-term stability and biocompatibility. Herein, three alternative tea polyphenols, gallic acid (GA), epigallocatechin (EGC) and epigallocatechin gallate (EGCG), were coordinated with ferric ions, to fabricate MPN-coated Lactobacillus rhamnosus LGG (MPN@L). These were compared with TA-based MPN@L to evaluate their effectiveness in alleviating IBD. All MPN@L complexes demonstrated superior adhesion and retention compared to uncoated probiotics in both ex vivo and in vivo models. Specifically, EGC@L exhibited the highest survival rate throughout gastrointestinal digestion, with a 2.7 log CFU/mL improvement over uncoated probiotics, and showed optimal retention in murine intestine with a fluorescence intensity of 24.3 × 10⁶ p/s/cm²/sr by day four. All MPN@L formation effectively alleviated ulcerative colitis by reducing myeloperoxidase levels, modulating cytokines profiles, and enhancing gut microbiota. EGC@L particularly increased beneficial bacterial genera, including Lactobacillus, Adlercreutzia, and Oscillospira, while decreasing the pro-inflammatory genera. This study highlights the potential of MPN-based probiotic microencapsulation to enhanced treatment for gastrointestinal disorders, expending the application of probiotic microencapsulation in IBD therapy.

{"title":"Metal ion coordinated tea polyphenol nanocoating for enhanced probiotic therapy in inflammatory bowel disease","authors":"Lu Gao , Yunjian Liu , Ling Ye , Sizhi Liang , Jiancan Lin , Jiaying Zeng , Lei Lei , Qiang Huang , Yujun Wan , Bin Zhang","doi":"10.1016/j.biomaterials.2025.123323","DOIUrl":"10.1016/j.biomaterials.2025.123323","url":null,"abstract":"<div><div>Probiotics encapsulated with metal-phenolic networks (MPNs) present a promising approach for treating inflammatory bowel diseases (IBD). However, current MPN systems predominantly use tannic acid (TA) as the phenolic source, with limited exploration of other polyphenols, and face challenges in long-term stability and biocompatibility. Herein, three alternative tea polyphenols, gallic acid (GA), epigallocatechin (EGC) and epigallocatechin gallate (EGCG), were coordinated with ferric ions, to fabricate MPN-coated <em>Lactobacillus rhamnosus</em> LGG (MPN@L). These were compared with TA-based MPN@L to evaluate their effectiveness in alleviating IBD. All MPN@L complexes demonstrated superior adhesion and retention compared to uncoated probiotics in both <em>ex vivo</em> and <em>in vivo</em> models. Specifically, EGC@L exhibited the highest survival rate throughout gastrointestinal digestion, with a 2.7 log CFU/mL improvement over uncoated probiotics, and showed optimal retention in murine intestine with a fluorescence intensity of 24.3 × 10<sup>6</sup> p/s/cm<sup>2</sup>/sr by day four. All MPN@L formation effectively alleviated ulcerative colitis by reducing myeloperoxidase levels, modulating cytokines profiles, and enhancing gut microbiota. EGC@L particularly increased beneficial bacterial genera, including <em>Lactobacillus</em>, <em>Adlercreutzia</em>, and <em>Oscillospira</em>, while decreasing the pro-inflammatory genera. This study highlights the potential of MPN-based probiotic microencapsulation to enhanced treatment for gastrointestinal disorders, expending the application of probiotic microencapsulation in IBD therapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123323"},"PeriodicalIF":12.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817734","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

Gelatin sponge patch grafting of microcryogel-based three-dimensional mesenchymal stem cells to alleviate acute liver failure

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-04-09 DOI: 10.1016/j.biomaterials.2025.123324

Haimeng Song , Xinyue Du , Yuanyuan Zhang , Wei Liu , Yi Luo , Yuxin Liu , Yongjia Xue , Mingyang Xu , Jizhen Lu , Wenwen Jia , Yanan Du , Lining Cao , Jianfeng Lu , Wencheng Zhang , Zhiying He

The clinical application of human umbilical cord mesenchymal stem cells (hUCMSCs) in the treatment of liver failure faces challenges due to cell quality, short engraftment time, and limited efficacy. Here, gelatin microcryogel (GM) microcarriers with pore sizes ranging from 15 to 36 μm were tuned from mixed gelatin and glutaraldehyde to develop a 3D culture system of hUCMSCs with improved therapeutic effects. Bulk RNA sequencing and in vitro assays showed that 3D-hUCMSCs exhibited significant improvement in signaling pathways related to paracrine secretion and anti-inflammation. These 3D-hUCMSCs superior compared to 2D-hUCMSCs not only in terms of paracrine secretion, protection from oxidation, and resistance to mechanical force damage, but also had better liver function improvement effect than 2D-hUCMSCs when they were transplanted as single cells into liver injury mice. Furthermore, a gelatin sponge patch grafting (GSPG) strategy was developed to enable the direct engraftment of 3D-hUCMSCs within the GM microcarriers. The results showed that overall engraftment in the host liver was significantly improved, and the life span of transplanted hosts was extended. Our study provided a practical strategy to achieve high engraftment and long retraining time of 3D-hUCMSCs in rescuing acute liver failure with gelatin matrixes.

{"title":"Gelatin sponge patch grafting of microcryogel-based three-dimensional mesenchymal stem cells to alleviate acute liver failure","authors":"Haimeng Song , Xinyue Du , Yuanyuan Zhang , Wei Liu , Yi Luo , Yuxin Liu , Yongjia Xue , Mingyang Xu , Jizhen Lu , Wenwen Jia , Yanan Du , Lining Cao , Jianfeng Lu , Wencheng Zhang , Zhiying He","doi":"10.1016/j.biomaterials.2025.123324","DOIUrl":"10.1016/j.biomaterials.2025.123324","url":null,"abstract":"<div><div>The clinical application of human umbilical cord mesenchymal stem cells (hUCMSCs) in the treatment of liver failure faces challenges due to cell quality, short engraftment time, and limited efficacy. Here, gelatin microcryogel (GM) microcarriers with pore sizes ranging from 15 to 36 μm were tuned from mixed gelatin and glutaraldehyde to develop a 3D culture system of hUCMSCs with improved therapeutic effects. Bulk RNA sequencing and <em>in vitro</em> assays showed that 3D-hUCMSCs exhibited significant improvement in signaling pathways related to paracrine secretion and anti-inflammation. These 3D-hUCMSCs superior compared to 2D-hUCMSCs not only in terms of paracrine secretion, protection from oxidation, and resistance to mechanical force damage, but also had better liver function improvement effect than 2D-hUCMSCs when they were transplanted as single cells into liver injury mice. Furthermore, a gelatin sponge patch grafting (GSPG) strategy was developed to enable the direct engraftment of 3D-hUCMSCs within the GM microcarriers. The results showed that overall engraftment in the host liver was significantly improved, and the life span of transplanted hosts was extended. Our study provided a practical strategy to achieve high engraftment and long retraining time of 3D-hUCMSCs in rescuing acute liver failure with gelatin matrixes.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123324"},"PeriodicalIF":12.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848503","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

Glucose-triggered NO-evolving coating bestows orthopedic implants with enhanced anti-bacteria and angiectasis for safeguarding diabetic osseointegration

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-04-09 DOI: 10.1016/j.biomaterials.2025.123334

Hongxing Shi , Hao Yang , Chao Wu , Song Wang , Shuai He , Lin Chen , Yau Kei Chan , Shuangquan Lai , Kunneng Liang , Yi Deng

As a common chronic metabolic disease, diabetes mellitus (DM) features a hyperglycemic micromilieu around implants, resulting in the critical implantation failure and high complications such as peri-implantitis and angiectasis disorder. To address the plaguing issue, we devise and develop a glucose-unlocked NO-evolving orthopedic implant consisted of polyetheretherketone (PEEK), glucose oxidase (GOx) and l-arginine (Arg) with enhanced angiogenesis for boosting diabetic osseointegration. Upon hyperglycemic niche, GOx on implants catalytically exhaust glucose to H₂O₂, which immediately reacts with Arg to in situ liberate nitric oxide (NO), resulting in enhanced angiogenesis and angiectasis around PEEK implant. Besides, the engineered implant exhibits great anti-bacterial properties against both Gram-positive and Gram-negative bacteria, as well as fortifies osteogenicity of osteoblasts in terms of cell proliferation, alkaline phosphatase activity and calcium matrix mineralization. Intriguingly, in vivo evaluations utilizing diabetic infectious bone defect models of rat further authenticate that the engineered implants substantially augment bone remodeling and osseointegration at weeks 4 and 8 through dampening pathogens, anti-inflammatory as well as promoting angiectasis. Altogether, this work proposed a new tactic to remedy stalled diabetic osseointegration with hyperglycemic micromilieu-responsive therapeutic gas-evolving orthopedic implants.

{"title":"Glucose-triggered NO-evolving coating bestows orthopedic implants with enhanced anti-bacteria and angiectasis for safeguarding diabetic osseointegration","authors":"Hongxing Shi , Hao Yang , Chao Wu , Song Wang , Shuai He , Lin Chen , Yau Kei Chan , Shuangquan Lai , Kunneng Liang , Yi Deng","doi":"10.1016/j.biomaterials.2025.123334","DOIUrl":"10.1016/j.biomaterials.2025.123334","url":null,"abstract":"<div><div>As a common chronic metabolic disease, diabetes mellitus (DM) features a hyperglycemic micromilieu around implants, resulting in the critical implantation failure and high complications such as peri-implantitis and angiectasis disorder. To address the plaguing issue, we devise and develop a glucose-unlocked NO-evolving orthopedic implant consisted of polyetheretherketone (PEEK), glucose oxidase (GOx) and <span>l</span>-arginine (Arg) with enhanced angiogenesis for boosting diabetic osseointegration. Upon hyperglycemic niche, GOx on implants catalytically exhaust glucose to H<sub>2</sub>O<sub>2</sub>, which immediately reacts with Arg to <em>in situ</em> liberate nitric oxide (NO), resulting in enhanced angiogenesis and angiectasis around PEEK implant. Besides, the engineered implant exhibits great anti-bacterial properties against both Gram-positive and Gram-negative bacteria, as well as fortifies osteogenicity of osteoblasts in terms of cell proliferation, alkaline phosphatase activity and calcium matrix mineralization. Intriguingly, <em>in vivo</em> evaluations utilizing diabetic infectious bone defect models of rat further authenticate that the engineered implants substantially augment bone remodeling and osseointegration at weeks 4 and 8 through dampening pathogens, anti-inflammatory as well as promoting angiectasis. Altogether, this work proposed a new tactic to remedy stalled diabetic osseointegration with hyperglycemic micromilieu-responsive therapeutic gas-evolving orthopedic implants.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123334"},"PeriodicalIF":12.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830353","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

Non-invasive ultrasonic debridement of implant biofilms via hydrogen-sulfide releasing peptide nanoemulsions

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-04-09 DOI: 10.1016/j.biomaterials.2025.123337

Harminder Singh , Diptomit Biswas , Ji Ho Park , Mary E. Landmesser , Dino J. Ravnic , Scott H. Medina

Implant contamination by bacterial biofilms remains a significant healthcare burden, often necessitating revision surgeries due to biofilm-enabled antibiotic resistance. Physical debridement, in combination with chemical antiseptics, is a simple and effective therapeutic strategy, but requires highly invasive surgical procedures and risks secondary infection events. Herein, we report a non-invasive, nanoparticle-enabled ultrasonic debridement strategy that exerts synergistic physical and chemical antiseptic effects to rapidly and efficiently clear implant-associated biofilms in situ. This approach is realized through the development of hydrogen sulfide releasing peptide nanoemulsions that preferentially target bacterial biofilms and can be vaporized via diagnostic ultrasound to spatiotemporally clear methicillin-resistant Staphylococcus aureus (MRSA) infections. Biophysical studies elucidate the mechanistic basis for the platform's anti-biofilm activity, and in vitro, ex vivo and in vivo experiments confirm efficacy in the context of MRSA-infected titanium implants. By exploiting the portable, low cost and safe nature of low intensity diagnostic ultrasound, this non-invasive approach avoids the collateral tissue damage associated with current surgical and high intensity acoustic ablative modalities.

{"title":"Non-invasive ultrasonic debridement of implant biofilms via hydrogen-sulfide releasing peptide nanoemulsions","authors":"Harminder Singh , Diptomit Biswas , Ji Ho Park , Mary E. Landmesser , Dino J. Ravnic , Scott H. Medina","doi":"10.1016/j.biomaterials.2025.123337","DOIUrl":"10.1016/j.biomaterials.2025.123337","url":null,"abstract":"<div><div>Implant contamination by bacterial biofilms remains a significant healthcare burden, often necessitating revision surgeries due to biofilm-enabled antibiotic resistance. Physical debridement, in combination with chemical antiseptics, is a simple and effective therapeutic strategy, but requires highly invasive surgical procedures and risks secondary infection events. Herein, we report a non-invasive, nanoparticle-enabled ultrasonic debridement strategy that exerts synergistic physical and chemical antiseptic effects to rapidly and efficiently clear implant-associated biofilms <em>in situ</em>. This approach is realized through the development of hydrogen sulfide releasing peptide nanoemulsions that preferentially target bacterial biofilms and can be vaporized via diagnostic ultrasound to spatiotemporally clear methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) infections. Biophysical studies elucidate the mechanistic basis for the platform's anti-biofilm activity, and <em>in vitro</em>, <em>ex vivo</em> and <em>in vivo</em> experiments confirm efficacy in the context of MRSA-infected titanium implants. By exploiting the portable, low cost and safe nature of low intensity diagnostic ultrasound, this non-invasive approach avoids the collateral tissue damage associated with current surgical and high intensity acoustic ablative modalities.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123337"},"PeriodicalIF":12.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825554","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

Tailoring the therapeutic potential of stem cell spheroid-derived decellularized ECM through post-decellularization BDNF incorporation to enhance brain repair

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-04-08 DOI: 10.1016/j.biomaterials.2025.123332

Ying-Chi Kao , Pei-Ching Yang , Yu-Ping Lin , Grace H. Chen , Shao-Wen Liu , Chia-Hsin Ho , Shih-Chen Huang , Peng-Ying Lee , Linyi Chen , Chieh-Cheng Huang

Decellularized extracellular matrix (dECM) from tissues has significant therapeutic potential but is limited by its rigid molecular composition and reliance on post-decellularization modifications to tailor its functionality. Harsh decellularization processes often result in substantial glycosaminoglycan (GAG) loss, impairing natural growth factor incorporation and necessitating chemical modifications that complicate processing and limit clinical translation. To address these challenges, we developed mesenchymal stem cell (MSC) spheroid-derived three-dimensional (3D) dECM using gentle decellularization techniques. This study demonstrated a crucial advancement—the retention of endogenous GAGs—enabling direct growth factor incorporation without chemical agents. As a proof-of-concept, brain-derived neurotrophic factor (BDNF) was incorporated into the 3D dECM to enhance its therapeutic potential for brain repair. In vitro, BDNF-loaded 3D dECM enabled sustained growth factor release, significantly enhancing the proneuritogenic, neuroprotective, and proangiogenic effects. In a mouse model of traumatic brain injury, the implantation of BDNF-loaded 3D dECM significantly enhanced motor function and facilitated brain repair. These findings highlight the adaptability of MSC spheroid-derived 3D dECM for tissue-specific customization through straightforward and translatable growth factor incorporation, demonstrating its potential as a pro-regenerative biomaterial for advancing regenerative medicine applications.

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引用次数: 0

Dual-miRNA Guided in-vivo Imaging and Multimodal Nanomedicine Approaches for Precise Hepatocellular Carcinoma Differentiation and Synergistic Cancer Theranostics using DNA Hairpins and Dual-Ligand functionalized Zirconium-MOF Nanohybrids

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-04-08 DOI: 10.1016/j.biomaterials.2025.123330

Kun Wang , Siyu Jiang , Wanli Wang , Wansong Chen , Tianhan Kai

As one of the most common and heterogeneous liver malignancies, hepatocellular carcinoma (HCC) remains a significant clinical challenge due to the lack of biomarkers for early diagnosis, challenges in accurate subtyping, and limitations of current therapeutic strategies with poor efficacy. Herein, based on DNA hairpin probes and dual-ligand zirconium (Zr)-based metal-organic frameworks (DMOFs), the multifunctional nanohybrids (DMOF@MnCO@CuS@Hairpin probe, DMCH) were developed to overcome these diagnostic and therapeutic obstacles. Two improved DNA molecular beacons and APE1 enzyme within HCC cells were utilized for sensitive miRNAs imaging in vivo with high accuracy to differentiate HCC subtypes precisely. Furthermore, this “all-in-one” theranostic platform not only facilitates the generation of active oxygen species and conversion of near-infrared light into heat, but also releases carbon monoxide to inhibit the expression of HSP70 protein to improve photothermal (PTT) therapy efficiency during laser radiation, which enables PTT, photodynamic (PDT), chemodynamic (CDT), and gas therapy (GAT) for HCC treatment simultaneously. The developed nano-theranostics platform provides a novel way for efficient early screening, diagnosis, and intervention of HCC, and paves the path for future “bench-to-bedside” design of theranostics.

肝细胞癌（HCC）是最常见的异质性肝脏恶性肿瘤之一，由于缺乏早期诊断的生物标志物、准确的亚型鉴定面临挑战，以及目前治疗策略的局限性和疗效不佳，它仍然是一项重大的临床挑战。本文基于DNA发夹探针和双配体锆（Zr）基金属有机框架（DMOF），开发了多功能纳米混合物（DMOF@MnCO@CuS@发夹探针，DMCH），以克服这些诊断和治疗障碍。利用两种改良的DNA分子信标和HCC细胞内的APE1酶，在体内进行敏感的miRNAs成像，准确区分HCC亚型。此外，该 "一体化 "治疗平台不仅能产生活性氧，将近红外光转化为热能，还能在激光照射过程中释放一氧化碳抑制HSP70蛋白的表达，提高光热（PTT）治疗效率，从而实现PTT、光动力（PDT）、化学动力（CDT）和气体疗法（GAT）同时治疗HCC。所开发的纳米治疗仪平台为高效地早期筛查、诊断和干预 HCC 提供了一种新方法，并为未来治疗仪的 "从台架到床边 "设计铺平了道路。

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引用次数: 0

Tensile acoustic rheometry for rapid and contactless characterization of soft viscoelastic biomaterials

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-04-08 DOI: 10.1016/j.biomaterials.2025.123325

Weiping Li , Eric C. Hobson , Kiera Downey , Timothy L. Hall , Jan P. Stegemann , Cheri X. Deng

Accurately measuring the viscoelastic properties of biomaterials is critical for understanding their functions in biological systems and optimizing their development for specific applications. Conventional methods often require direct physical contact, which hinders longitudinal studies of sterile samples and impose strict requirements in sample preparation. Here, we introduce tensile acoustic rheometry (TAR), a technique for rapid, contactless characterization of soft viscoelastic biomaterials. TAR uses a dual-mode ultrasound approach to apply an upward force impulse, generating oscillatory tensile and compressive motion in a small, free-standing sample (∼30 mm³) with its bottom immobilized on a pre-wetted flat surface by capillary stiction. High frequency ultrasound pulse echo detection is employed to track this motion via the movement of the top surface of the sample in real time. In this study, we developed a theoretical framework of the tensile-compression motion of the sample from which Young's modulus and viscosity of the sample are determined based on the TAR measurements. TAR was validated across a variety of samples, including engineered hydrogels and commercially available natural food products. Results from TAR measurements aligned closely with theoretical predictions, reported values, and shear wave elastography measurements. These findings underscore the versatility and flexibility of TAR as a robust, versatile rheological method for biomaterial characterization with minimal sample preparation requirements.

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引用次数: 0

Dynamic hydration driven adhesiveness self-reinforcement of powdery protein for rapid artery hemostasis 用于快速动脉止血的动态水合驱动的粉末状蛋白质粘附性自我强化技术

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-04-08 DOI: 10.1016/j.biomaterials.2025.123328

Junlian Nie , Yingchuan Sun , Shengjie Zhang , Guang Wen , Tong Li , Jianwu Zhao , Wen Li

Surgical adhesives with rapid and tough adhesion under wet or aqueous conditions are highly desirable for artery hemostasis yet still extremely challenging. We here explored a kind of protein powder featured with hydration-driven adhesiveness self-reinforcement in water. The protein powder, consisting of corn-derived protein (zein), sodium dodecyl sulfate (SDS), and poly-lysine (PLL), was conveniently produced via sandcastle worm-inspired multivalent ionic crosslinking between zein/SDS colloid and PLL, which showed rapidly water-contacting gelation and tough adhesion on wet surfaces. We revealed that the interfacial water removal and bulk heterogeneity of the hydrated zein/SDS-PLL powder synergistically improved both the interfacial adhesion and the bulk cohesion, resulting in tough wet adhesion within 2 min. The rapid interfacial adhesion of the zein/SDS-PLL powder is attributed to the highly hydrated propensity of the ionic complex and self-gelation via interfacial water removal, while the bulk heterogeneity resulted from the incompletely hydrated ionic domains, which functioned as rigid fillers to improve the cross-density and bulk cohesion of the hydrated adhesive matrix. This bulk heterogeneity mechanism fulfills the existing knowledge gap of adhesiveness enhancement of the hydrated powdery adhesives. The hydrated zein/SDS-PLL powdery adhesive with excellent biocompatibility and biodegradation can resist high bursting pressure (118.2–129.4 mmHg), which can achieve rapid and reliable artery hemostasis on rat, rabbit and pig models.

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引用次数: 0

Wireless discharge of piezoelectric nanogenerator opens voltage-gated ion channels for calcium overload-mediated tumor treatment

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-04-04 DOI: 10.1016/j.biomaterials.2025.123311

Yuchu He , Xiaoyu Yang , Meng Yuan , Xuwu Zhang , Wenkang Tu , Weili Xue , Dong Wang , Dawei Gao

Calcium overload-mediated tumor treatment conventionally necessitates calcium-containing drugs. However, these drugs are susceptible to calcium ion leakage during in vivo delivery, potentially causing adverse effects such as hypercalcemia and hypertension. Furthermore, voltage-gated ion channels (VGICs) on the tumor cell membrane stringently regulate calcium ion influx to preserve intracellular calcium homeostasis. To address these issues, a calcium-free piezoelectric nanogenerator, (K, Na) NbO₃ (KNN), capable of local and wireless discharge (at a voltage of up to 0.4 mV) into tumors under ultrasound (US) excitation, is designed to open VGICs. Given the significantly higher extracellular calcium ion concentration compared to intracellular levels (approximately 15,000-fold), a substantial influx of calcium ions ensures, leading to intracellular calcium overload. Concurrently, US stimulates KNN to undergo piezoelectric catalysis, converting water into reactive oxygen species (ROS). The synergistic effect of calcium overload and high ROS oxidation induces mitochondrial damage, culminating in tumor elimination. Additionally, the calcium ion influx induces polarization of tumor-associated macrophages from an immunosuppressive M2 phenotype to an immunity-promoting M1 phenotype, thereby enhancing systemic anti-tumor immune responses. This study demonstrates that local electric field within tumors can open VGICs for efficient and safe calcium overload-mediated tumor treatment, showing great potential for clinical translation.

{"title":"Wireless discharge of piezoelectric nanogenerator opens voltage-gated ion channels for calcium overload-mediated tumor treatment","authors":"Yuchu He , Xiaoyu Yang , Meng Yuan , Xuwu Zhang , Wenkang Tu , Weili Xue , Dong Wang , Dawei Gao","doi":"10.1016/j.biomaterials.2025.123311","DOIUrl":"10.1016/j.biomaterials.2025.123311","url":null,"abstract":"<div><div>Calcium overload-mediated tumor treatment conventionally necessitates calcium-containing drugs. However, these drugs are susceptible to calcium ion leakage during <em>in vivo</em> delivery, potentially causing adverse effects such as hypercalcemia and hypertension. Furthermore, voltage-gated ion channels (VGICs) on the tumor cell membrane stringently regulate calcium ion influx to preserve intracellular calcium homeostasis. To address these issues, a calcium-free piezoelectric nanogenerator, (K, Na) NbO<sub>3</sub> (KNN), capable of local and wireless discharge (at a voltage of up to 0.4 mV) into tumors under ultrasound (US) excitation, is designed to open VGICs. Given the significantly higher extracellular calcium ion concentration compared to intracellular levels (approximately 15,000-fold), a substantial influx of calcium ions ensures, leading to intracellular calcium overload. Concurrently, US stimulates KNN to undergo piezoelectric catalysis, converting water into reactive oxygen species (ROS). The synergistic effect of calcium overload and high ROS oxidation induces mitochondrial damage, culminating in tumor elimination. Additionally, the calcium ion influx induces polarization of tumor-associated macrophages from an immunosuppressive M2 phenotype to an immunity-promoting M1 phenotype, thereby enhancing systemic anti-tumor immune responses. This study demonstrates that local electric field within tumors can open VGICs for efficient and safe calcium overload-mediated tumor treatment, showing great potential for clinical translation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123311"},"PeriodicalIF":12.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792544","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