Biomaterials最新文献_第4页

ROS-triggered biomimetic hydrogel soft scaffold for ischemic stroke repair

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-25 DOI: 10.1016/j.biomaterials.2025.123217

Wen Zhang , Yang Liu , Yu Wu , Zhicun Wang , Xiyu Liu , Qinsheng Hu , Li Yang , Cheng Hu , Yunbing Wang

Millions of individuals worldwide suffer from ischemic stroke (IS). The focal hypo-perfused brain brings about hostile pathological environment, which further restricts endogenous neurogenesis post-stroke. In this work, we report an ROS-triggered hyaluronic acid (HA) and platelet lysates (pls) composite biomimetic hydrogel soft scaffold (pls gel) encapsulating matrix metalloproteinase (MMPs)-responsive triglycerol monostearate nanoparticles loaded with docosahexaenoic acid (TGMS@DHA, TD). Pls gel was chosen to be the hydrogel matrix to mimic brain extracellular matrix (ECM) to provide physical support for cell infiltration and accelerate angiogenesis as a growth factors (GFs) box. The borate ester bonded hydrogel could respond to reactive oxygen species and relieve oxidative stress. The loaded TD nanoparticles could be enzymatically cleaved by overexpressed MMPs in cerebral infarcted site, which could improve the adverse effects triggered by overexpressed MMPs. DHA with rich unsaturated bonds was proven that not only inhibit neuroinflammatory and oxidative stress, but also take part in promote neurogenesis. In brief, the ROS-triggered hydrogel scaffold pls gel@TD created an optimized microenvironment to manipulate the survival and differentiation of neural stem cells and promote endogenous regenerative repair processes. The in vitro results exhibited the biomimetic soft scaffold eliminated oxygen-glucose deprivation-derived free radical, saved mitochondrial dysfunction, reduced neuronal apoptosis, and promoted neovascularization. In the mice focal IS model, the biomimetic hydrogel scaffold regulated pathological environment in the ischemic site and induced migration and differentiation of endogenous neural stem cells, consequently relieved neuron ischemia injury. During the long-term observation, the hydrogel improved mice neurobehavioral functions. In conclusion, the hydrogel soft scaffold pls gel@TD was demonstrated to have promising therapeutic effects on remodeling pathological environment by transforming the hostile state into a pro-regenerative one in the infarct site, consequently promoting endogenous regenerative repair processes.

{"title":"ROS-triggered biomimetic hydrogel soft scaffold for ischemic stroke repair","authors":"Wen Zhang , Yang Liu , Yu Wu , Zhicun Wang , Xiyu Liu , Qinsheng Hu , Li Yang , Cheng Hu , Yunbing Wang","doi":"10.1016/j.biomaterials.2025.123217","DOIUrl":"10.1016/j.biomaterials.2025.123217","url":null,"abstract":"<div><div>Millions of individuals worldwide suffer from ischemic stroke (IS). The focal hypo-perfused brain brings about hostile pathological environment, which further restricts endogenous neurogenesis post-stroke. In this work, we report an ROS-triggered hyaluronic acid (HA) and platelet lysates (pls) composite biomimetic hydrogel soft scaffold (pls gel) encapsulating matrix metalloproteinase (MMPs)-responsive triglycerol monostearate nanoparticles loaded with docosahexaenoic acid (TGMS@DHA, TD). Pls gel was chosen to be the hydrogel matrix to mimic brain extracellular matrix (ECM) to provide physical support for cell infiltration and accelerate angiogenesis as a growth factors (GFs) box. The borate ester bonded hydrogel could respond to reactive oxygen species and relieve oxidative stress. The loaded TD nanoparticles could be enzymatically cleaved by overexpressed MMPs in cerebral infarcted site, which could improve the adverse effects triggered by overexpressed MMPs. DHA with rich unsaturated bonds was proven that not only inhibit neuroinflammatory and oxidative stress, but also take part in promote neurogenesis. In brief, the ROS-triggered hydrogel scaffold pls gel@TD created an optimized microenvironment to manipulate the survival and differentiation of neural stem cells and promote endogenous regenerative repair processes. The <em>in vitro</em> results exhibited the biomimetic soft scaffold eliminated oxygen-glucose deprivation-derived free radical, saved mitochondrial dysfunction, reduced neuronal apoptosis, and promoted neovascularization. In the mice focal IS model, the biomimetic hydrogel scaffold regulated pathological environment in the ischemic site and induced migration and differentiation of endogenous neural stem cells, consequently relieved neuron ischemia injury. During the long-term observation, the hydrogel improved mice neurobehavioral functions. In conclusion, the hydrogel soft scaffold pls gel@TD was demonstrated to have promising therapeutic effects on remodeling pathological environment by transforming the hostile state into a pro-regenerative one in the infarct site, consequently promoting endogenous regenerative repair processes.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123217"},"PeriodicalIF":12.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526632","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

Biomimetic peroxisome targets myocardial injury and promotes heart repair and regeneration

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-25 DOI: 10.1016/j.biomaterials.2025.123214

Ning Zhang , Menghan Gao , Xiaolong Hu , Peng Wang , Yuan Cheng , Hui Wei , Guosheng Fu , Junbo Ge , Hongjun Li , Wenbin Zhang , Binquan Zhou

Heart ischemic injury predominately causes mitochondrial dysfunction, leading to the accumulation of ROS and lactate. The ROS-associated DNA damage response (DDR) contributes to myocardial cell cycle arrest and the inhibition of proliferation, while lactate accumulation is often accompanied by a high risk of acute death. In this study, to restore myocardial metabolism and regenerate the heart, we established a biomimetic peroxisome by loading the Mn₃O₄ nanozyme into mesenchymal stem cell-derived extracellular vesicles (MSC-EV (Mn@EV)). This setup mimics the peroxidases of peroxisome to catalyze ROS, and inhibit DDR. Next, the Mn@EV was immobilized with lactate oxidase (LOX) after encompassed platelet membrane to obtain biomimetic peroxisome (Mn@LPEV). This mimics the substrate-oxidizing function to detoxify lactate and prevent death. Supported by its biomimetic and lactate-response delivery system, our biomimetic peroxisome effectively targeted deep tissues in the hearts of I/R mice, achieving a 4-fold increase in targeting compared with control vesicles. It maintained myocardial redox homeostasis by scavenging ROS and lactate, inhibiting DDR pathway, promoting myocardial regeneration, reducing acute mortality and fibrosis remodeling, accelerating immunomodulation and angiogenesis, and significantly protecting heart function.

{"title":"Biomimetic peroxisome targets myocardial injury and promotes heart repair and regeneration","authors":"Ning Zhang , Menghan Gao , Xiaolong Hu , Peng Wang , Yuan Cheng , Hui Wei , Guosheng Fu , Junbo Ge , Hongjun Li , Wenbin Zhang , Binquan Zhou","doi":"10.1016/j.biomaterials.2025.123214","DOIUrl":"10.1016/j.biomaterials.2025.123214","url":null,"abstract":"<div><div>Heart ischemic injury predominately causes mitochondrial dysfunction, leading to the accumulation of ROS and lactate. The ROS-associated DNA damage response (DDR) contributes to myocardial cell cycle arrest and the inhibition of proliferation, while lactate accumulation is often accompanied by a high risk of acute death. In this study, to restore myocardial metabolism and regenerate the heart, we established a biomimetic peroxisome by loading the Mn<sub>3</sub>O<sub>4</sub> nanozyme into mesenchymal stem cell-derived extracellular vesicles (MSC-EV (Mn@EV)). This setup mimics the peroxidases of peroxisome to catalyze ROS, and inhibit DDR. Next, the Mn@EV was immobilized with lactate oxidase (LOX) after encompassed platelet membrane to obtain biomimetic peroxisome (Mn@LPEV). This mimics the substrate-oxidizing function to detoxify lactate and prevent death. Supported by its biomimetic and lactate-response delivery system, our biomimetic peroxisome effectively targeted deep tissues in the hearts of I/R mice, achieving a 4-fold increase in targeting compared with control vesicles. It maintained myocardial redox homeostasis by scavenging ROS and lactate, inhibiting DDR pathway, promoting myocardial regeneration, reducing acute mortality and fibrosis remodeling, accelerating immunomodulation and angiogenesis, and significantly protecting heart function.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123214"},"PeriodicalIF":12.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535124","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

Mechanical confinement triggers spreading and migration of immobile cells by deforming nucleus

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-25 DOI: 10.1016/j.biomaterials.2025.123209

Ran Rao , Haoxiang Yang , Kailong Qiu , Min Xu , Hao Liu , Jinghao Shen , Weihao Wang , Runjie Nie , Huan Chen , Hongyuan Jiang

Cells in vivo are often subject to the challenge of spatial confinement from neighboring cells and extracellular matrix (ECM) that are usually adhesive and deformable. Here, we showed that confinement makes initially quiescent round cells on soft adhesive substrates spread and migrate, exhibiting a phenotype similar to that of cells on unconfined stiff substrates. Interestingly, the confinement-induced cell spreading and migration exist widely in many cell types, and depend on formins, cell contractility and endonuclear YAP-TEAD interaction. Finally, we demonstrated the nucleus is a mechanosensor independent of ECM rigidity, and its flattening alone is sufficient to trigger YAP nuclear translocation, assembly of focal adhesions and stress fibers, cell spreading and migration. Thus, our findings revealed a new inside-out mechanism through which the nucleus directly detects and responds to external mechanical confinement, and could have important implications for cell migration in crowded micro-environments during cancer metastasis, wound healing and embryonic development.

{"title":"Mechanical confinement triggers spreading and migration of immobile cells by deforming nucleus","authors":"Ran Rao , Haoxiang Yang , Kailong Qiu , Min Xu , Hao Liu , Jinghao Shen , Weihao Wang , Runjie Nie , Huan Chen , Hongyuan Jiang","doi":"10.1016/j.biomaterials.2025.123209","DOIUrl":"10.1016/j.biomaterials.2025.123209","url":null,"abstract":"<div><div>Cells <em>in vivo</em> are often subject to the challenge of spatial confinement from neighboring cells and extracellular matrix (ECM) that are usually adhesive and deformable. Here, we showed that confinement makes initially quiescent round cells on soft adhesive substrates spread and migrate, exhibiting a phenotype similar to that of cells on unconfined stiff substrates. Interestingly, the confinement-induced cell spreading and migration exist widely in many cell types, and depend on formins, cell contractility and endonuclear YAP-TEAD interaction. Finally, we demonstrated the nucleus is a mechanosensor independent of ECM rigidity, and its flattening alone is sufficient to trigger YAP nuclear translocation, assembly of focal adhesions and stress fibers, cell spreading and migration. Thus, our findings revealed a new inside-out mechanism through which the nucleus directly detects and responds to external mechanical confinement, and could have important implications for cell migration in crowded micro-environments during cancer metastasis, wound healing and embryonic development.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123209"},"PeriodicalIF":12.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550614","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

Zn2+-driven metformin conjugated with siRNA attenuates osteoarthritis progression by inhibiting NF-κB signaling and activating autophagy

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-24 DOI: 10.1016/j.biomaterials.2025.123210

Haoqiang He , Chanting Huang , Hongjun Huang , Nihan Lan , Siyi Liu , Yan Luo , Li Zheng , Gang Liu , Zainen Qin , Jinmin Zhao

Osteoarthritis (OA) is a type of joint disease that influences millions of individuals. Regrettably, effective treatment for OA is currently unavailable. The challenge lies in the deep location of chondrocytes within the dense cartilage matrix that hinders the delivery and efficiency of clinical OA drugs. To overcome this obstacle, the present study proposed a hybrid nanodrug by Zinc(II) metal-drug coordination-driven self-assembly as highly efficient delivery system. This nano-assembly formulations possessed the ability to deliver two types of drugs, namely metformin (Met) and therapeutic genes (p65 siRNA). Results showed that this nano-assembly not only exhibited positive charge-driven anchoring to the cartilage matrix and effective drug delivery capacity, but also synergistically inhibited NF-κB activity and activates autophagy of OA chondrocytes, thus safeguarding the cartilage. The successful achievement of this project not only contribute to the advancement of research on bio-nanomaterials for treating OA, but also establish a robust theoretical foundation for realizing promising and functional integration of nanomedicine targeting OA.

{"title":"Zn2+-driven metformin conjugated with siRNA attenuates osteoarthritis progression by inhibiting NF-κB signaling and activating autophagy","authors":"Haoqiang He , Chanting Huang , Hongjun Huang , Nihan Lan , Siyi Liu , Yan Luo , Li Zheng , Gang Liu , Zainen Qin , Jinmin Zhao","doi":"10.1016/j.biomaterials.2025.123210","DOIUrl":"10.1016/j.biomaterials.2025.123210","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a type of joint disease that influences millions of individuals. Regrettably, effective treatment for OA is currently unavailable. The challenge lies in the deep location of chondrocytes within the dense cartilage matrix that hinders the delivery and efficiency of clinical OA drugs. To overcome this obstacle, the present study proposed a hybrid nanodrug by Zinc(II) metal-drug coordination-driven self-assembly as highly efficient delivery system. This nano-assembly formulations possessed the ability to deliver two types of drugs, namely metformin (Met) and therapeutic genes (p65 siRNA). Results showed that this nano-assembly not only exhibited positive charge-driven anchoring to the cartilage matrix and effective drug delivery capacity, but also synergistically inhibited NF-κB activity and activates autophagy of OA chondrocytes, thus safeguarding the cartilage. The successful achievement of this project not only contribute to the advancement of research on bio-nanomaterials for treating OA, but also establish a robust theoretical foundation for realizing promising and functional integration of nanomedicine targeting OA.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123210"},"PeriodicalIF":12.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529641","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

Platelet-derived extracellular vesicle drug delivery system loaded with kaempferol for treating corneal neovascularization 含有山奈酚的血小板衍生细胞外囊泡给药系统用于治疗角膜新生血管病变

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-24 DOI: 10.1016/j.biomaterials.2025.123205

Guei-Sheung Liu , Huai-An Chen , Che-Yi Chang , Yin-Ju Chen , Yu-Yi Wu , Ariel Widhibrata , Ya-Han Yang , Erh-Hsuan Hsieh , Liling Delila , I-Chan Lin , Thierry Burnouf , Ching-Li Tseng

Platelet-derived extracellular vesicles (PEVs) have drawn attention due to their multifunctionality, ease of procurement, and abundant supply from clinical-grade platelet concentrates. PEVs can be readily endocytosed due to their lipid bilayer membrane and nanoscale structure, enhancing the bioavailability and efficacy of their therapeutic effects. PEVs also contain various trophic factors that enhance their effectiveness as therapeutic agents. Given that nanomedicine provides benefits over traditional treatments for eye diseases by surpassing physical ocular barriers, PEVs combined with the anti-angiogenic agent, kaempferol (KM), were assessed for their capacity to inhibit abnormal blood vessel formation in the cornea. Characterization of the nanoparticles suggested the successful preparation of KM-loaded PEVs (PEV-KM) with a mean diameter of approximately 160 nm and an encapsulation efficiency of around 61 %. PEV-KM was effectively internalized into human vascular endothelial cells, resulting in inhibited function, as evidenced by lower wound closure rates, decreased tube formation capacity, and downregulation of angiogenesis-related gene expression. Moreover, prolonged ocular retention was observed following the topical application of PEV and PEV-KM in mouse eyes. In an alkali-burned corneal neovascularization (CoNV) mouse model, PEV (1 %) was found to decrease vessel formation in the injured cornea. However, the combination of PEV and KM (1 % PEV with KM 6 μg/mL) showed an even stronger effect in inhibiting CoNV and decreasing the expression of proangiogenic and inflammatory cytokines. Overall, our data suggests that the topical administration of PEVs, either alone or alongside KM (PEV-KM), is a promising therapy for the management of CoNV.

{"title":"Platelet-derived extracellular vesicle drug delivery system loaded with kaempferol for treating corneal neovascularization","authors":"Guei-Sheung Liu , Huai-An Chen , Che-Yi Chang , Yin-Ju Chen , Yu-Yi Wu , Ariel Widhibrata , Ya-Han Yang , Erh-Hsuan Hsieh , Liling Delila , I-Chan Lin , Thierry Burnouf , Ching-Li Tseng","doi":"10.1016/j.biomaterials.2025.123205","DOIUrl":"10.1016/j.biomaterials.2025.123205","url":null,"abstract":"<div><div>Platelet-derived extracellular vesicles (PEVs) have drawn attention due to their multifunctionality, ease of procurement, and abundant supply from clinical-grade platelet concentrates. PEVs can be readily endocytosed due to their lipid bilayer membrane and nanoscale structure, enhancing the bioavailability and efficacy of their therapeutic effects. PEVs also contain various trophic factors that enhance their effectiveness as therapeutic agents. Given that nanomedicine provides benefits over traditional treatments for eye diseases by surpassing physical ocular barriers, PEVs combined with the anti-angiogenic agent, kaempferol (KM), were assessed for their capacity to inhibit abnormal blood vessel formation in the cornea. Characterization of the nanoparticles suggested the successful preparation of KM-loaded PEVs (PEV-KM) with a mean diameter of approximately 160 nm and an encapsulation efficiency of around 61 %. PEV-KM was effectively internalized into human vascular endothelial cells, resulting in inhibited function, as evidenced by lower wound closure rates, decreased tube formation capacity, and downregulation of angiogenesis-related gene expression. Moreover, prolonged ocular retention was observed following the topical application of PEV and PEV-KM in mouse eyes. In an alkali-burned corneal neovascularization (CoNV) mouse model, PEV (1 %) was found to decrease vessel formation in the injured cornea. However, the combination of PEV and KM (1 % PEV with KM 6 μg/mL) showed an even stronger effect in inhibiting CoNV and decreasing the expression of proangiogenic and inflammatory cytokines. Overall, our data suggests that the topical administration of PEVs, either alone or alongside KM (PEV-KM), is a promising therapy for the management of CoNV.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123205"},"PeriodicalIF":12.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526631","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

Synergistic microglial modulation by laminarin-based platinum nanozymes for potential intracerebral hemorrhage therapy 基于层粘连素的铂纳米酶对小胶质细胞的协同调节可用于潜在的脑出血治疗

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-24 DOI: 10.1016/j.biomaterials.2025.123212

Xiumei Guo , Qionghua Zheng , Wen Gao , Yinfeng Xiao , Liyong Shi , Fenglin Lin , Yu Xiong , Yin Zhang , Qiuxia Xu , Lingxing Wang , Shaobin He , Feng Zheng

Abnormal microglial activation increases inflammation, causing significant brain damage after intracerebral hemorrhage (ICH). To aid recovery, treatments should regulate oxidative stress and inhibit the M1-like phenotype (pro-inflammation) of microglia. Recently, antioxidant nanozymes have emerged as tools for modulating microglial states, but detailed studies on their role in ICH treatment are limited. To address this, we developed an ultra-small (3–4 nm) laminarin-modified platinum nanozyme (Pt@LA) for the synergistic regulation of microglial polarization, offering a novel therapeutic strategy for ICH. Pt@LA effectively scavenges reactive oxygen species (ROS) through superoxide dismutase (SOD) and catalase (CAT)-like activities. Laminarin may inhibit the Dectin-1 receptor on microglia and its inflammatory pathway, Syk/NF-κB, reducing neuroinflammation. In vitro, Pt@LA decreased pro-inflammatory microglia and cytokine expression by inhibiting the Dectin-1/Syk/NF-κB and ROS-mediated NF-κB pathways. Furthermore, Pt@LA protected neurons, inhibited glial scar formation, and improved neurological function in ICH rats. Overall, this study presents Pt nanozymes based on naturally extracted laminarin and explores their application in alleviating oxidative stress and neuroinflammation after ICH, bridging nanozyme research and neuroscience.

{"title":"Synergistic microglial modulation by laminarin-based platinum nanozymes for potential intracerebral hemorrhage therapy","authors":"Xiumei Guo , Qionghua Zheng , Wen Gao , Yinfeng Xiao , Liyong Shi , Fenglin Lin , Yu Xiong , Yin Zhang , Qiuxia Xu , Lingxing Wang , Shaobin He , Feng Zheng","doi":"10.1016/j.biomaterials.2025.123212","DOIUrl":"10.1016/j.biomaterials.2025.123212","url":null,"abstract":"<div><div>Abnormal microglial activation increases inflammation, causing significant brain damage after intracerebral hemorrhage (ICH). To aid recovery, treatments should regulate oxidative stress and inhibit the M1-like phenotype (pro-inflammation) of microglia. Recently, antioxidant nanozymes have emerged as tools for modulating microglial states, but detailed studies on their role in ICH treatment are limited. To address this, we developed an ultra-small (3–4 nm) laminarin-modified platinum nanozyme (Pt@LA) for the synergistic regulation of microglial polarization, offering a novel therapeutic strategy for ICH. Pt@LA effectively scavenges reactive oxygen species (ROS) through superoxide dismutase (SOD) and catalase (CAT)-like activities. Laminarin may inhibit the Dectin-1 receptor on microglia and its inflammatory pathway, Syk/NF-κB, reducing neuroinflammation. In vitro, Pt@LA decreased pro-inflammatory microglia and cytokine expression by inhibiting the Dectin-1/Syk/NF-κB and ROS-mediated NF-κB pathways. Furthermore, Pt@LA protected neurons, inhibited glial scar formation, and improved neurological function in ICH rats. Overall, this study presents Pt nanozymes based on naturally extracted laminarin and explores their application in alleviating oxidative stress and neuroinflammation after ICH, bridging nanozyme research and neuroscience.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123212"},"PeriodicalIF":12.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526644","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

Bio-orthogonal-labeled exosomes reveals specific distribution in vivo and provides potential application in ARDS therapy 生物正交标记外泌体揭示了其在体内的特异性分布，并为 ARDS 治疗提供了潜在的应用前景

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-24 DOI: 10.1016/j.biomaterials.2025.123208

Song Yang , Haomiao Zhu , Hongzhen Jin , Kun Wang , Junna Song , Na Sun , Yonghui Liu , Xiaona Yin , Rui Wang , Xiao Wu , Huadong Liu , Chunling Zhang , Wei Zhao , Fan Yu

Exosomes derived from specific cells may be useful for targeted drug delivery, but tracking them in vivo is essential for their clinical application. However, their small size and complex structure challenge the development of exosome-tracking techniques, and traditional labeling methods are limited by weak affinity and potential toxicity. To address these issues, here we developed a novel bio-orthogonal labeling strategy based on phosphatidylinositol derivatives to fluorescently label exosomes from various human and mouse cell types. The different cell-derived exosomes revealed organ-specific distribution patterns and a favorable safety profile. Notably, 4T1 cell-derived exosomes specifically targeted the lungs. When used as drug carriers loaded with anti-inflammatory resveratrol, these exosomes showed significant therapeutic efficacy in mice with acute respiratory distress syndrome (ARDS), effectively reducing inflammatory responses, mitigating pulmonary fibrosis, and restoring lung tissue morphology and function. Our findings provide a novel exosome labeling strategy and an invaluable tool for their in vivo tracking and targeting screening, while exosomes that specifically target the lungs offer a potential therapeutic strategy for organ-specific diseases such as ARDS.

{"title":"Bio-orthogonal-labeled exosomes reveals specific distribution in vivo and provides potential application in ARDS therapy","authors":"Song Yang , Haomiao Zhu , Hongzhen Jin , Kun Wang , Junna Song , Na Sun , Yonghui Liu , Xiaona Yin , Rui Wang , Xiao Wu , Huadong Liu , Chunling Zhang , Wei Zhao , Fan Yu","doi":"10.1016/j.biomaterials.2025.123208","DOIUrl":"10.1016/j.biomaterials.2025.123208","url":null,"abstract":"<div><div>Exosomes derived from specific cells may be useful for targeted drug delivery, but tracking them <em>in vivo</em> is essential for their clinical application. However, their small size and complex structure challenge the development of exosome-tracking techniques, and traditional labeling methods are limited by weak affinity and potential toxicity. To address these issues, here we developed a novel bio-orthogonal labeling strategy based on phosphatidylinositol derivatives to fluorescently label exosomes from various human and mouse cell types. The different cell-derived exosomes revealed organ-specific distribution patterns and a favorable safety profile. Notably, 4T1 cell-derived exosomes specifically targeted the lungs. When used as drug carriers loaded with anti-inflammatory resveratrol, these exosomes showed significant therapeutic efficacy in mice with acute respiratory distress syndrome (ARDS), effectively reducing inflammatory responses, mitigating pulmonary fibrosis, and restoring lung tissue morphology and function. Our findings provide a novel exosome labeling strategy and an invaluable tool for their <em>in vivo</em> tracking and targeting screening, while exosomes that specifically target the lungs offer a potential therapeutic strategy for organ-specific diseases such as ARDS.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123208"},"PeriodicalIF":12.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519329","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

Precision delivery of pretreated macrophage-membrane-coated Pt nanoclusters for improving Alzheimer's disease-like cognitive dysfunction induced by Porphyromonas gingivalis

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-24 DOI: 10.1016/j.biomaterials.2025.123211

Kang Liu , Xuejing Ma , Yifei Zhang , Liang Zhao , Yijie Shi

Oral infection with Porphyromonas gingivalis (P. gingivalis), a kind of pathogenic bacteria causing periodontitis, can increase the risk of Alzheimer's disease (AD) and cause cognitive decline. Therefore, precise intracerebral antimicrobial therapy to reduce the load of P. gingivalis in brain may serve as a potential therapeutic approach to improve AD-like cognitive impairment. A kind of nano-delivery system precisely targets bacteria in the brain through coating P. gingivalis stimulated macrophage membrane onto the surface of platinum nanoclusters (Pg-M-PtNCs). Approximate 50 nm spherical Pg-M-PtNCs demonstrate good biocompatibility and the pretreated macrophage membranes can inhibit macrophages phagocytosis and increase the adherence to bacteria. Pg-M-PtNCs can significantly inhibit the growth of P.gingivalis in vitro, and are effectively delivered and remain at the infection site in the mice brain to reduce the bacterial load and neuronal damage, and then improve the AD-like cognitive dysfunction in the chronic periodontitis mice. Platinum nanoclusters coated with P. gingivalis pretreated macrophage membrane play an important role in targeting bacteria in the brain, and effectively improve AD-like cognitive function disorder caused by P. gingivalis infection in the brain.

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引用次数: 0

Synthetic vascular graft that heals and regenerates

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-24 DOI: 10.1016/j.biomaterials.2025.123206

Le Zhen , Elina Quiroga , Sharon A. Creason , Ningjing Chen , Tanmay R. Sapre , Jessica M. Snyder , Sarah L. Lindhartsen , Brendy S. Fountaine , Michael C. Barbour , Syed Faisal , Alberto Aliseda , Brian W. Johnson , Jonathan Himmelfarb , Buddy D. Ratner

Millions of synthetic vascular grafts (sVG) are needed annually to address vascular diseases (a leading cause of death in humans) and kidney failure (as vascular access). However, in 70+ years since the first sVG in humans, we still do not have sVGs that fully endothelialize (the “holy grail” for truly successful grafts). The lack of healthy endothelium is believed to be a main cause for thrombosis, stenosis, and infection (the major reasons for graft failure). The immune-mediated foreign body response to traditional sVG materials encapsulates the materials in fibrotic scar suppressing vascularized healing. Here, we describe the first sVG optimized for vessel wall vascularization via uniform, spherical 40 μm pores. This sVG induced unprecedented rapid healing of luminal endothelium in a demanding and clinically relevant sheep model, probably by attracting and modulating macrophages and foreign body giant cells towards diverse, pro-healing phenotypes. Both this sVG and the control (PTFE grafts) remained 100 % patent during the implantation period. This advancement has broad implications beyond sVGs in tissue engineering and biocompatibility.

每年需要数百万例合成血管移植物（sVG）来治疗血管疾病（人类的主要死因）和肾衰竭（作为血管通路）。然而，自人类首次使用合成血管移植物以来，70 多年过去了，我们仍然没有完全内皮化的合成血管移植物（真正成功移植物的 "圣杯"）。缺乏健康的内皮被认为是血栓形成、血管狭窄和感染（移植物失败的主要原因）的主要原因。免疫介导的异物反应会将传统的 sVG 材料包裹在纤维化瘢痕中，抑制血管愈合。在这里，我们描述了第一种通过 40 μm 的均匀球形孔隙优化血管壁血管化的 sVG。这种 sVG 可能通过吸引和调节巨噬细胞和异物巨细胞，使其趋向于多样化的促进愈合表型，从而在要求苛刻且与临床相关的绵羊模型中诱导了管腔内皮前所未有的快速愈合。这种 sVG 和对照组（聚四氟乙烯移植物）在植入期间都保持了 100% 的通透性。这一进展不仅在组织工程和生物相容性方面具有广泛的意义，而且还超出了 sVG 的范围。

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引用次数: 0

Chiral nanoassembly remodels tumor microenvironment through non-oxygen-dependent depletion lactate for eﬀective photodynamic immunotherapy

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-21 DOI: 10.1016/j.biomaterials.2025.123203

Xuan Zhang , Jinwei Bai , Shihao Sun , Yu Li , Xinxin Li , Genping Meng , Wenyuan Cheng , Yuhui Yin , Zhiyi Wang , Baodui Wang

Targeting lactate metabolism in tumor microenvironment (TME) has emerged as a promising strategy for enhancing immunotherapy. However, the commonly used strategy of lactate oxidation by lactate oxidase consumes oxygen, exacerbating tumor hypoxia and hindering immunotherapy. Here, we present a novel tumor-targeting, near infrared light-activated and TME-responsive chiral nanoassembly (Zn-UCMB) for enhancing photodynamic triggered immunogenic cell death (ICD) through a nonoxygen-dependent depletion of lactate. In the moderately acidic TME, the chiral Zn complex liberated from the Zn-UCMB selectively coordinates with l-lactate, leading to the depletion of lactate. Additionally, the Zn-UCMB facilitates the decomposition of H₂O₂ into O₂, which significantly enhances the efficacy of photodynamic therapy (PDT) and triggers a robust ICD effect. Moreover, the nonoxygen-dependent depletion of lactate can reprogram the TME by reducing the expression of HIF-1α, decreasing VEGF expression, and mitigating immunosuppressive conditions. This prompts the phenotypic transformation of tumor-associated macrophages from M2 to M1. Consequently, Zn-UCMB not only enhances the efficacy of PDT but also elicits a potent ICD during 980 nm laser irradiation, thereby effectively suppressing tumor growth and metastasis. The findings offer a novel approach to overcome the limitations of existing lactate metabolism-targeting strategies and provide a promising therapeutic option for enhancing the efficacy of immunotherapy.

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引用次数: 0