Biomaterials最新文献_第5页

Advances in the application of smart materials in the treatment of ophthalmic diseases

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-04-01 DOI: 10.1016/j.biomaterials.2025.123316

Yida Liu , Hong Ren , Zhenkai Wu , Yukun Wu , Xuezhi Zhou , Dan Ji

Smart materials dynamically sense and respond to physiological signals like reactive oxygen species (ROS), pH, and light, surpassing traditional materials such as poly(lactic-co-glycolic acid), which have high drug loss rates and limited spatiotemporal control. These innovative materials offer new strategies for ophthalmic treatments, with core advantages including targeted delivery via ROS-sensitive nanocarriers, precise regulation through microvalves, and multifunctional integration, such as glucose-responsive contact lenses that create a "sensing-treatment" loop. However, challenges remain, like pathological microenvironment interference with material response specificity, and the need to address long-term biocompatibility and energy dependence issues. This article systematically examines three key treatment barriers: the blood-ocular barrier, immune rejection, and physiological fluctuations, while reviewing innovative smart material design strategies. Future research should focus on biomimetic interface engineering, for example, cornea mimicking nanostructures, AI-driven dynamic optimization like causal network-regulated drug release, and multidisciplinary approaches combining gene editing with smart materials. These efforts aim to shift from structural replacement to physiological function simulation, enabling precise treatment of ophthalmic diseases. Clinical translation must balance innovation with safety, prioritizing clinical value to ensure reliable, widespread application of smart materials in ophthalmology.

{"title":"Advances in the application of smart materials in the treatment of ophthalmic diseases","authors":"Yida Liu , Hong Ren , Zhenkai Wu , Yukun Wu , Xuezhi Zhou , Dan Ji","doi":"10.1016/j.biomaterials.2025.123316","DOIUrl":"10.1016/j.biomaterials.2025.123316","url":null,"abstract":"<div><div>Smart materials dynamically sense and respond to physiological signals like reactive oxygen species (ROS), pH, and light, surpassing traditional materials such as poly(lactic-co-glycolic acid), which have high drug loss rates and limited spatiotemporal control. These innovative materials offer new strategies for ophthalmic treatments, with core advantages including targeted delivery via ROS-sensitive nanocarriers, precise regulation through microvalves, and multifunctional integration, such as glucose-responsive contact lenses that create a \"sensing-treatment\" loop. However, challenges remain, like pathological microenvironment interference with material response specificity, and the need to address long-term biocompatibility and energy dependence issues. This article systematically examines three key treatment barriers: the blood-ocular barrier, immune rejection, and physiological fluctuations, while reviewing innovative smart material design strategies. Future research should focus on biomimetic interface engineering, for example, cornea mimicking nanostructures, AI-driven dynamic optimization like causal network-regulated drug release, and multidisciplinary approaches combining gene editing with smart materials. These efforts aim to shift from structural replacement to physiological function simulation, enabling precise treatment of ophthalmic diseases. Clinical translation must balance innovation with safety, prioritizing clinical value to ensure reliable, widespread application of smart materials in ophthalmology.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123316"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785599","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 transcatheter mitral valve clip with a central filler for mitral valve regurgitation

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-04-01 DOI: 10.1016/j.biomaterials.2025.123317

Tingchao Zhang , Weiwei Zhang , Xianzhang Zhen , Rifang Luo , Li Yang , Xingdong Zhang , Yunbing Wang

Despite the advantages of transcatheter edge-to-edge repair (TEER) devices for treating mitral regurgitation, challenges such as difficulties in leaflet grasping and clip dislodgement remain in clinical practice. In this study, we present the first detailed disclosure of a novel transcatheter mitral valve clip, the DragonFly, highlighting its material composition, design features, and associated benefits. The valve clip is constructed of nickel-titanium alloy, stainless steel, cobalt-chromium alloy, and polyethylene terephthalate, incorporating adjustable arms, grippers, and a unique central filler. The central filler, made of nitinol, offers remarkable compressibility and shape recovery. The whole valve clip can endure over 400 million fatigue cycles and ensure a robust grasp on valve leaflets at varying angles. The clip presents sufficient grasping force to prevent valve dislodgement, and the adjustable design accommodates various patient anatomies. Comprehensive biocompatibility assessments confirmed adherence to ISO 10993 standards through in vitro and in vivo experiments, including large-animal studies. The results demonstrated that the valve clip successfully creates a stable double-orifice structure without negatively impacting cardiac hemodynamics and has good biocompatibility. Overall, the DragonFly valve clip constitutes a technological advancement in the field of minimally invasive interventions for mitral valve disease, offering more treatment options for high-risk patients.

{"title":"A transcatheter mitral valve clip with a central filler for mitral valve regurgitation","authors":"Tingchao Zhang , Weiwei Zhang , Xianzhang Zhen , Rifang Luo , Li Yang , Xingdong Zhang , Yunbing Wang","doi":"10.1016/j.biomaterials.2025.123317","DOIUrl":"10.1016/j.biomaterials.2025.123317","url":null,"abstract":"<div><div>Despite the advantages of transcatheter edge-to-edge repair (TEER) devices for treating mitral regurgitation, challenges such as difficulties in leaflet grasping and clip dislodgement remain in clinical practice. In this study, we present the first detailed disclosure of a novel transcatheter mitral valve clip, the DragonFly, highlighting its material composition, design features, and associated benefits. The valve clip is constructed of nickel-titanium alloy, stainless steel, cobalt-chromium alloy, and polyethylene terephthalate, incorporating adjustable arms, grippers, and a unique central filler. The central filler, made of nitinol, offers remarkable compressibility and shape recovery. The whole valve clip can endure over 400 million fatigue cycles and ensure a robust grasp on valve leaflets at varying angles. The clip presents sufficient grasping force to prevent valve dislodgement, and the adjustable design accommodates various patient anatomies. Comprehensive biocompatibility assessments confirmed adherence to ISO 10993 standards through in vitro and in vivo experiments, including large-animal studies. The results demonstrated that the valve clip successfully creates a stable double-orifice structure without negatively impacting cardiac hemodynamics and has good biocompatibility. Overall, the DragonFly valve clip constitutes a technological advancement in the field of minimally invasive interventions for mitral valve disease, offering more treatment options for high-risk patients.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123317"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776352","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

Time-resolved T1 and T2 contrast for enhanced accuracy in MRI tumor detection

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-04-01 DOI: 10.1016/j.biomaterials.2025.123313

Zhongzhong Lu , Jincong Yan , Jianxian Zeng , Ruihao Zhang , Mingsheng Xu , Jihuan Liu , Lina Sun , Guangyue Zu , Xiaomin Chen , Ye Zhang , Renjun Pei , Yi Cao

Stimuli-responsive contrast agents (CAs) have shown great promise in enhancing magnetic resonance imaging (MRI) for more accurate tumor diagnosis. However, current CAs still face challenges in achieving high accuracy due to their low specificity and contrast signals being confounded by potential endogenous MRI artifacts. Herein, an extremely small iron oxide nanoparticle (ESIONP)-based smart responsive MRI contrast agent (LESPH) is proposed, which is meticulously designed with sequential dual biochemical stimuli-initiated, time-resolved T₁ and T₂ contrast presentation, ensuring high tumor specificity while minimizing interference from endogenous artifacts. LESPH is constructed using emulsion solvent evaporation by assembling poly(2-(hexamethyleneimino) ethyl methacrylate) terminally conjugated with a disulfide bond-linked catechol group (DSPH)-modified ESIONPs, with lauryl betaine serving as a surfactant. When LESPH undergoes sequential responses to the weak acidity and high-concentration glutathione (GSH) in the tumor microenvironment, it experiences an extremely rapid transition from sparse ESIONP assemblies to dispersed ESIONPs, followed by a slower transition to closely aggregated ones, concomitantly providing distinguishable brightening and darkening contrast enhancement at the tumor location on different time scales. By virtue of its sequential dual responsiveness and time-resolved distinguishable contrast enhancements, LESPH successfully detects tumors with extremely high accuracy, providing a novel paradigm for the precise medical diagnosis of cancer.

{"title":"Time-resolved T1 and T2 contrast for enhanced accuracy in MRI tumor detection","authors":"Zhongzhong Lu , Jincong Yan , Jianxian Zeng , Ruihao Zhang , Mingsheng Xu , Jihuan Liu , Lina Sun , Guangyue Zu , Xiaomin Chen , Ye Zhang , Renjun Pei , Yi Cao","doi":"10.1016/j.biomaterials.2025.123313","DOIUrl":"10.1016/j.biomaterials.2025.123313","url":null,"abstract":"<div><div>Stimuli-responsive contrast agents (CAs) have shown great promise in enhancing magnetic resonance imaging (MRI) for more accurate tumor diagnosis. However, current CAs still face challenges in achieving high accuracy due to their low specificity and contrast signals being confounded by potential endogenous MRI artifacts. Herein, an extremely small iron oxide nanoparticle (ESIONP)-based smart responsive MRI contrast agent (LESPH) is proposed, which is meticulously designed with sequential dual biochemical stimuli-initiated, time-resolved T<sub>1</sub> and T<sub>2</sub> contrast presentation, ensuring high tumor specificity while minimizing interference from endogenous artifacts. LESPH is constructed using emulsion solvent evaporation by assembling poly(2-(hexamethyleneimino) ethyl methacrylate) terminally conjugated with a disulfide bond-linked catechol group (DSPH)-modified ESIONPs, with lauryl betaine serving as a surfactant. When LESPH undergoes sequential responses to the weak acidity and high-concentration glutathione (GSH) in the tumor microenvironment, it experiences an extremely rapid transition from sparse ESIONP assemblies to dispersed ESIONPs, followed by a slower transition to closely aggregated ones, concomitantly providing distinguishable brightening and darkening contrast enhancement at the tumor location on different time scales. By virtue of its sequential dual responsiveness and time-resolved distinguishable contrast enhancements, LESPH successfully detects tumors with extremely high accuracy, providing a novel paradigm for the precise medical diagnosis of cancer.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123313"},"PeriodicalIF":12.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768669","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

Clearance of senescent vascular smooth muscle cells retards aging-related restenosis following bioresorbable scaffolds implantation

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-31 DOI: 10.1016/j.biomaterials.2025.123312

Yang Wang , Hang Zou , Zhufeng Dong , Wen Shi , Junyang Huang , Miaolong Yang , Xiaoqing Xiang , Li Xiaotong , Liu Zhifeng , Guixue Wang , Yazhou Wang , Tieying Yin

In contrast to bioinert metal stents, the degradation of bioresorbable scaffolds (BRS) induces complex mechanical changes and accumulation of degradation products, potentially leading to adverse events following implantation into stenotic arteries. Atherosclerosis (AS) is a typical age-related disease, plaque formation and changes in vascular mechanical properties can significantly affect the process of restenosis and vascular repair after BRS implantation. The aging of vascular smooth muscle cells (VSMCs) is earlier than that of endothelial cells (ECs) and plays a decisive role in the mechanical properties of blood vessels. This study investigated the impact of senescent VSMCs (s-VSMCs) on the effectiveness of 3-D printed poly-l-lactide BRS implanted in the aged abdominal aortas of Sprague-Dawley rats over a 6-month period. Synthetic phenotype switch of s-VSMCs contribute to aging-related in-stent restenosis (ISR) and hinder neointima recovery, by reducing positive remodeling and impeding the neointima recovery of ECs. Further analysis indicated that the regulation of ECs was influenced by mechanoresponsive miRNAs and increased stiffness induced by s-VSMCs. To effectively eliminate s-VSMCs and accelerate vascular repair, two types of senolytic-coated BRS were developed and tested with ABT-263 and young plasma-derived exosomes. These results highlight the critical role of s-VSMCs in increasing aging-related ISR and delaying intima recovery following BRS implantation. The senolytic coatings, with their ability to clear senescent cells, promoted vascular repair. This study offers valuable insights for potential mechanisms responsible for the elevated ISR risks associated with BRS in aged aortas and the development of advanced BRS coatings.

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引用次数: 0

A remotely controlled nanotherapeutic with immunomodulatory property for MRSA-induced bone infection

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-29 DOI: 10.1016/j.biomaterials.2025.123298

Zhe Zhao , Yufei Zhang , Jie Li , Siyuan Huang , Guosheng Xing , Kai Zhang , Xinlong Ma , Xinge Zhang , Yingze Zhang

Osteomyelitis is a deep bone tissue infection caused by pathogenic microorganisms, with the primary pathogen being methicillin-resistant Staphylococcus aureus (MRSA). Due to the tendency of the infection site to form biofilms that shield drugs and immune cells to kill bacteria, combined with the severe local inflammatory response causing bone tissue destruction, the treatment of osteomyelitis poses a significant challenge. Herein, we developed a remotely controlled nanotherapeutic (TLBA) with immunomodulatory to treat MRSA-induced osteomyelitis. TLBA, combined with baicalin and gold nanorods, is positively charged to actively target and penetrate biofilms. Near-infrared light (808 nm) triggers spatiotemporal, controllable drug release, while bacteria are eliminated through synergistic interaction of non-antibiotic drugs and photothermal therapy, enhancing bactericidal efficiency and minimizing drug resistance. TLBA eliminated nearly 100 % of planktonic bacteria and dispersed 90 % of biofilms under NIR light stimulation. In MRSA-induced osteomyelitis rat models, laser irradiation raised the infection site temperature to 50 °C, effectively eradicating bacteria, promoting M2 macrophage transformation, inhibiting bone inflammation, curbing bone destruction, and fostering bone tissue repair. In summary, TLBA proposes a more comprehensive treatment strategy for the two characteristic pathological changes of bacterial infection and bone tissue damage in osteomyelitis.

{"title":"A remotely controlled nanotherapeutic with immunomodulatory property for MRSA-induced bone infection","authors":"Zhe Zhao , Yufei Zhang , Jie Li , Siyuan Huang , Guosheng Xing , Kai Zhang , Xinlong Ma , Xinge Zhang , Yingze Zhang","doi":"10.1016/j.biomaterials.2025.123298","DOIUrl":"10.1016/j.biomaterials.2025.123298","url":null,"abstract":"<div><div>Osteomyelitis is a deep bone tissue infection caused by pathogenic microorganisms, with the primary pathogen being methicillin-resistant <em>Staphylococcus aureus</em> (MRSA). Due to the tendency of the infection site to form biofilms that shield drugs and immune cells to kill bacteria, combined with the severe local inflammatory response causing bone tissue destruction, the treatment of osteomyelitis poses a significant challenge. Herein, we developed a remotely controlled nanotherapeutic (TLBA) with immunomodulatory to treat MRSA-induced osteomyelitis. TLBA, combined with baicalin and gold nanorods, is positively charged to actively target and penetrate biofilms. Near-infrared light (808 nm) triggers spatiotemporal, controllable drug release, while bacteria are eliminated through synergistic interaction of non-antibiotic drugs and photothermal therapy, enhancing bactericidal efficiency and minimizing drug resistance. TLBA eliminated nearly 100 % of planktonic bacteria and dispersed 90 % of biofilms under NIR light stimulation. In MRSA-induced osteomyelitis rat models, laser irradiation raised the infection site temperature to 50 °C, effectively eradicating bacteria, promoting M2 macrophage transformation, inhibiting bone inflammation, curbing bone destruction, and fostering bone tissue repair. In summary, TLBA proposes a more comprehensive treatment strategy for the two characteristic pathological changes of bacterial infection and bone tissue damage in osteomyelitis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123298"},"PeriodicalIF":12.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738402","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 functional cardiac patch with “gas and ion” dual-effect intervention for reconstructing blood microcirculation in myocardial infarction repair

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-29 DOI: 10.1016/j.biomaterials.2025.123300

Chaoran Zhao , Junjie Liu , Ye Tian , Zhentao Li , Jiang Zhao , Xianglong Xing , Xiaozhong Qiu , Leyu Wang

Postinfarction revascularization is critical for repairing the infarcted myocardium and for stopping disease progression. Considering the limitations of surgical intervention, engineered cardiac patches (ECPs) are more effective in establishing rich blood supply networks. For efficacy, ECPs should promote the formation of more mature blood vessels to improve microcirculatory dysfunction and mitigate hypoxia-induced apoptosis. Developing collateral circulation between infarcted myocardium and ECPs for restoring blood perfusion remains a challenge. Here, an ion-conductive composite ECPs (GMA@OSM) with powerful angiogenesis-promoting ability was constructed. Based on dual-effect intervention of oxygen and strontium, the developed ECPs can promote the formation of high-density circulating microvascular network at the infarcted myocardium. In addition, the GMA@OSM possesses effective reactive oxygen species-scavenging capacity and can facilitate electrophysiological repair of myocardium with ionic conductivity. In vitro and in vivo studies indicate that the multifunctional GMA@OSM ECPs form well-developed collateral circulation with infarcted myocardium to protect cardiomyocytes and improve cardiac function. Overall, this study highlights the potential of a multifunctional platform for developing collateral circulation, which can lead to an effective therapeutic strategy for repairing myocardial infarction.

{"title":"A functional cardiac patch with “gas and ion” dual-effect intervention for reconstructing blood microcirculation in myocardial infarction repair","authors":"Chaoran Zhao , Junjie Liu , Ye Tian , Zhentao Li , Jiang Zhao , Xianglong Xing , Xiaozhong Qiu , Leyu Wang","doi":"10.1016/j.biomaterials.2025.123300","DOIUrl":"10.1016/j.biomaterials.2025.123300","url":null,"abstract":"<div><div>Postinfarction revascularization is critical for repairing the infarcted myocardium and for stopping disease progression. Considering the limitations of surgical intervention, engineered cardiac patches (ECPs) are more effective in establishing rich blood supply networks. For efficacy, ECPs should promote the formation of more mature blood vessels to improve microcirculatory dysfunction and mitigate hypoxia-induced apoptosis. Developing collateral circulation between infarcted myocardium and ECPs for restoring blood perfusion remains a challenge. Here, an ion-conductive composite ECPs (GMA@OSM) with powerful angiogenesis-promoting ability was constructed. Based on dual-effect intervention of oxygen and strontium, the developed ECPs can promote the formation of high-density circulating microvascular network at the infarcted myocardium. In addition, the GMA@OSM possesses effective reactive oxygen species-scavenging capacity and can facilitate electrophysiological repair of myocardium with ionic conductivity. <em>In vitro</em> and <em>in vivo</em> studies indicate that the multifunctional GMA@OSM ECPs form well-developed collateral circulation with infarcted myocardium to protect cardiomyocytes and improve cardiac function. Overall, this study highlights the potential of a multifunctional platform for developing collateral circulation, which can lead to an effective therapeutic strategy for repairing myocardial infarction.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123300"},"PeriodicalIF":12.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738404","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

Modification of MSCs with aHSCs-targeting peptide pPB for enhanced therapeutic efficacy in liver fibrosis

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-28 DOI: 10.1016/j.biomaterials.2025.123295

Mengqin Yuan , Zhengrong Yin , Zheng Wang , Zhiyu Xiong , Ping Chen , Lichao Yao , Pingji Liu , Muhua Sun , Kan Shu , Lanjuan Li , Yingan Jiang

Mesenchymal stem cells (MSCs) hold significant therapeutic potential for liver fibrosis but face translational challenges due to suboptimal homing efficiency and poor retention at injury sites. Activated hepatic stellate cells (aHSCs), the primary drivers of fibrogenesis, overexpress platelet-derived growth factor receptor-beta (PDGFRB), a validated therapeutic target in liver fibrosis. Here, we engineered pPB peptide-functionalized MSCs (pPB-MSCs) via hydrophobic insertion of DMPE-PEG-pPB (DPP) into the MSC membrane, creating a targeted “MSC-pPB-aHSC” delivery system. Our findings demonstrated that pPB modification preserved MSC viability, differentiation potential, and paracrine functions. pPB-MSCs exhibited higher binding affinity to TGF-β1-activated HSCs in vitro and greater hepatic accumulation in TAA-induced fibrotic mice, as quantified by in vivo imaging. Moreover, pPB-MSCs attenuated collagen deposition, suppressed α-SMA⁺ HSCs, and restored serum ALT/AST levels to near-normal ranges. Mechanistically, pPB-MSCs promoted hepatocyte regeneration via HGF upregulation, inhibited epithelial-mesenchymal transition through TGF-β/Smad pathway suppression, and polarized macrophages toward an M2 phenotype, reducing pro-inflammatory IL-6/TNF-α while elevating anti-inflammatory IL-10. Overall, our study raised a non-genetic MSC surface engineering strategy that synergizes PDGFRB-targeted homing with multifactorial tissue repair, addressing critical barriers in cell therapy for liver fibrosis. By achieving enhanced spatial delivery without compromising MSC functionality, our approach provides a clinically translatable platform for enhancing regenerative medicine outcomes.

间充质干细胞（MSCs）具有治疗肝纤维化的巨大潜力，但由于在损伤部位的归巢效率不理想和滞留能力差，在转化方面面临挑战。活化的肝星状细胞（aHSCs）是肝纤维化的主要驱动因素，它过度表达血小板衍生生长因子受体-beta（PDGFRB），而PDGFRB是肝纤维化的有效治疗靶点。在这里，我们通过将 DMPE-PEG-pPB (DPP) 疏水插入间充质干细胞膜，设计出了 pPB 肽功能化的间充质干细胞（pPB-MSCs），从而创建了一种靶向的 "间充质干细胞-pPB-造血干细胞 "递送系统。我们的研究结果表明，pPB修饰能保持间充质干细胞的活力、分化潜能和旁分泌功能。pPB-间充质干细胞在体外与TGF-β1激活的造血干细胞有更高的结合亲和力，在TAA诱导的肝纤维化小鼠体内有更高的肝脏蓄积量，并通过体内成像进行量化。此外，pPB-间充质干细胞还能减轻胶原沉积，抑制α-SMA+造血干细胞，并使血清ALT/AST水平恢复到接近正常范围。从机制上讲，pPB-间充质干细胞通过上调 HGF 促进肝细胞再生，通过抑制 TGF-β/Smad 通路抑制上皮-间充质转化，并将巨噬细胞极化为 M2 表型，降低促炎性 IL-6/TNF-α，同时升高抗炎性 IL-10。总之，我们的研究提出了一种非遗传性间充质干细胞表面工程策略，它能协同 PDGFRB 靶向归巢和多因素组织修复，解决了细胞疗法治疗肝纤维化的关键障碍。通过在不损害间充质干细胞功能的情况下实现增强的空间输送，我们的方法为提高再生医学成果提供了一个可临床转化的平台。

{"title":"Modification of MSCs with aHSCs-targeting peptide pPB for enhanced therapeutic efficacy in liver fibrosis","authors":"Mengqin Yuan , Zhengrong Yin , Zheng Wang , Zhiyu Xiong , Ping Chen , Lichao Yao , Pingji Liu , Muhua Sun , Kan Shu , Lanjuan Li , Yingan Jiang","doi":"10.1016/j.biomaterials.2025.123295","DOIUrl":"10.1016/j.biomaterials.2025.123295","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) hold significant therapeutic potential for liver fibrosis but face translational challenges due to suboptimal homing efficiency and poor retention at injury sites. Activated hepatic stellate cells (aHSCs), the primary drivers of fibrogenesis, overexpress platelet-derived growth factor receptor-beta (PDGFRB), a validated therapeutic target in liver fibrosis. Here, we engineered pPB peptide-functionalized MSCs (pPB-MSCs) via hydrophobic insertion of DMPE-PEG-pPB (DPP) into the MSC membrane, creating a targeted “MSC-pPB-aHSC” delivery system. Our findings demonstrated that pPB modification preserved MSC viability, differentiation potential, and paracrine functions. pPB-MSCs exhibited higher binding affinity to TGF-β1-activated HSCs <em>in vitro</em> and greater hepatic accumulation in TAA-induced fibrotic mice, as quantified by <em>in vivo</em> imaging. Moreover, pPB-MSCs attenuated collagen deposition, suppressed α-SMA<sup>+</sup> HSCs, and restored serum ALT/AST levels to near-normal ranges. Mechanistically, pPB-MSCs promoted hepatocyte regeneration via HGF upregulation, inhibited epithelial-mesenchymal transition through TGF-β/Smad pathway suppression, and polarized macrophages toward an M2 phenotype, reducing pro-inflammatory IL-6/TNF-α while elevating anti-inflammatory IL-10. Overall, our study raised a non-genetic MSC surface engineering strategy that synergizes PDGFRB-targeted homing with multifactorial tissue repair, addressing critical barriers in cell therapy for liver fibrosis. By achieving enhanced spatial delivery without compromising MSC functionality, our approach provides a clinically translatable platform for enhancing regenerative medicine outcomes.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123295"},"PeriodicalIF":12.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783939","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

Novel laser-textured grooves extended to the sidewall edges of CoCr surfaces for rapid and selective endothelialization following coronary artery stenting

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-27 DOI: 10.1016/j.biomaterials.2025.123299

Mohamed S. Ibrahim , Hassan Beheshti Seresht , Chang Hun Kum , Jae Hwa Cho , Gyuhyun Jin , Sang Hyun An , Sangho Ye , Seungil Kim , William R. Wagner , Youngjae Chun

The long-term performance of coronary stents is often compromised by delayed endothelialization and late thrombosis, particularly in drug-eluting stents (DES) that impair vascular healing. To address these challenges, we report a novel micro-hierarchical surface modification that integrates sidewall edge structuring into grid patterns on cobalt-chromium (CoCr) stents, enhancing endothelial cell (EC) interactions without compromising mechanical integrity. Laser fabrication was used to create microgrooves (5–30 μm) with extended sidewall edges, designed to promote rapid EC adhesion and proliferation. Comprehensive in vitro evaluations, including EC viability, adhesion, and platelet aggregation assays, demonstrated that stents with grid pattern and sidewall edge structuring on an already fabricated stent enhanced EC viability approximately six-fold compared to the non-patterned controls, reaching 2276 ± 220 cells/ml by day three of culture. The sidewall edges provided possible promising stable anchoring sites and gateway channels, improving EC attachment and selective alignment, while also substantially reducing platelet deposition in grooved regions. To ensure these surface modifications did not affect mechanical performance, comprehensive three-point bending and radial compression tests were conducted. No significant differences were observed compared to coronary stents, confirming that the micro-hierarchical texture with sidewall edges maintains essential mechanical properties. Together, these findings highlight the potential of sidewall edge-integrated grid patterns to accelerate endothelialization and reduce thrombogenic risks, offering a promising strategy for improving the design and long-term performance of next-generation coronary stents.

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引用次数: 0

An “all-in-one” therapeutic platform for programmed antibiosis, immunoregulation and neuroangiogenesis to accelerate diabetic wound healing

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-26 DOI: 10.1016/j.biomaterials.2025.123293

Yang Xue , Lan Zhang , Jun Chen , Dayan Ma , Yingang Zhang , Yong Han

Pathological microenvironment of diabetes induces a high risk of bacterial invasion, aggressive inflammatory response, and hindered neuroangiogenesis, leading to retarded ulcer healing. To address this, an “all-in-one” therapeutic platform, named MZZ, was constructed by loading maltodextrin onto a MOF-on-MOF structure (with ZIF-67 as the core and ZIF-8 as the shell) through a hybrid process of solvent treatment and electrostatic adsorption. Maltodextrin acts as a target to bind surrounding bacteria, and ZIF-8 as well as ZIF-67 responsively release Zn and Co ions, which not only kill most bacteria, but also improve the phagocytosis and xenophagy of M1 macrophages by up-regulating the expression levels of ATG5, Bcl1 and FLT4, helping the residual bacterial clearance. In inflammatory stage, MZZ scavenges extracellular and intracellular ROS by valence transition between Co²⁺ and Co³⁺, and promote M1 macrophages to transform into M2 phenotype. In tissue reconstruction stage, the synergistic effect of Zn and Co ions as well as cytokines secreted by macrophages up-regulates cell vitality and biofunctions of endotheliocytes, neurocytes and fibroblasts. The programmed effects of MZZ on antibiosis, anti-inflammatory and neuroangiogenesis to accelerate wound repair are further confirmed in an infected diabetic model, and this “all-in-one” platform shows great clinical application potential.

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引用次数: 0

STING-activating layered double hydroxide nano-adjuvants for enhanced cancer immunotherapy 用于增强癌症免疫疗法的 STING 激活层状双氢氧化物纳米佐剂

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-26 DOI: 10.1016/j.biomaterials.2025.123294

Lirui Jia , Yang Qin , Xin Li , Hongzhuo Liu , Zhonggui He , Yongjun Wang

Cancer vaccines represent a promising therapeutic strategy in oncology, yet their effectiveness is often hampered by suboptimal antigen targeting, insufficient induction of cellular immunity, and the immunosuppressive tumor microenvironment. Advanced delivery systems and potent adjuvants are needed to address these challenges, though a restricted range of adjuvants for human vaccines that are approved, and even fewer are capable of stimulating robust cellular immune response. In this work, we engineered a unique self-adjuvanted platform (MLDHs) by integrating STING agonists manganese into a layered double hydroxide nano-scaffold, encapsulating the model antigen ovalbumin (OVA). The MLDHs platform encompasses Mn-doped MgAl-LDH (MLMA) and Mn-doped MgFe-LDH (MLMF). Upon subcutaneous injection, OVA/MLDHs specifically accumulated within lymph nodes (LNs), where they were internalized by resident antigen-presenting cells. The endosomal degradation of MLDHs facilitated the cytoplasmic release of antigen and Mn²⁺, promoting cross-presentation and triggering the STING pathway, which in turn induced a potent cellular immune response against tumors. Notably, OVA/MLMF induced stronger M1 macrophage polarization and a more potent T-cell response within tumor-infiltrating lymphocytes compared to OVA/MLMA, leading to significant tumor regression in B16F10-OVA bearing mice with minimal adverse effects. Additionally, combining MLMF with the vascular disrupting agent Vadimezan disrupted the tumor's central region, typically resistant to immune cell infiltration, further extending survival in tumor-bearing mice. This innovative strategy may show great potential for improving cancer immunotherapy and offers hope for more effective treatments in the future.

癌症疫苗是一种前景广阔的肿瘤治疗策略，但其有效性往往受到抗原靶向性不理想、细胞免疫诱导不足以及免疫抑制性肿瘤微环境的影响。要应对这些挑战，需要先进的递送系统和强效佐剂，但目前获批的人用疫苗佐剂种类有限，能激发强大细胞免疫反应的佐剂更是少之又少。在这项工作中，我们将 STING 激动剂锰整合到层状双氢氧化物纳米支架中，并包裹模型抗原卵清蛋白（OVA），从而设计出一种独特的自佐剂平台（MLDHs）。MLDHs 平台包括掺锰 MgAl-LDH（MLMA）和掺锰 MgFe-LDH（MLMF）。皮下注射后，OVA/MLDHs 会在淋巴结（LNs）内聚集，并被驻留的抗原递呈细胞内化。MLDHs 的内质体降解促进了抗原和 Mn2+ 的胞浆释放，促进了交叉呈递并触发了 STING 通路，进而诱导了针对肿瘤的强效细胞免疫反应。值得注意的是，与 OVA/MLMA 相比，OVA/MLMF 能诱导更强的 M1 巨噬细胞极化和肿瘤浸润淋巴细胞内更强的 T 细胞反应，从而使携带 B16F10-OVA 的小鼠的肿瘤显著消退，且不良反应极小。此外，将 MLMF 与血管破坏剂 Vadimezan 结合使用，还能破坏肿瘤的中心区域（该区域通常对免疫细胞浸润具有抵抗力），从而进一步延长肿瘤小鼠的生存期。这种创新策略可能会显示出改进癌症免疫疗法的巨大潜力，并为未来更有效的治疗方法带来希望。

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引用次数: 0