Biomaterials最新文献_第9页

Structurally defined cartilaginous MEW-assembloids for critical-size long bone healing

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-19 DOI: 10.1016/j.biomaterials.2025.123202

Liuqi Peng , Amit Chandrakar , Gabriella Nilsson Hall , Konstantinos Ioannidis , Lorenzo Moroni , Paul Wieringa , Ioannis Papantoniou

Bone defects exceeding a critical size pose significant clinical challenges due to their inability to heal spontaneously. Traditional treatments including autografts and synthetic implants, are often suffer from limitations such as donor site morbidity, infection risk, and poor integration. This study explores a novel approach using MEW-assembloid which combine Melt electrowriting (MEW) scaffolds with cartilaginous microtissues to enhance bone healing. Here, we fabricated bucket-shaped MEW scaffolds (OMesh and CMesh) to optimize microtissue retention and integration, with the OMesh design showing effective shape retention after microtissue seeding. To adapt the scaffold dimensions for in vivo implantation, we introduced elongated MEW (EMesh) based on the OMesh design, forming EMesh-assembloid. These constructs were evaluated for their ability to undergo endochondral ossification and mineralization in subcutaneous implants. Additionally, tubular MEW scaffolds were also created as stabilizers around EMesh-assembloid for orthotopic implantation and showed substantial new bone formation and nearly full defect bridging in a critical-sized mouse tibia defect model after 8 weeks. Our results indicates that MEW-assembloid offer a robust strategy for tissue engineering, enhancing the structural and functional integration of implants, and providing an innovation solution for the repair and regeneration of critical bone defects, potentially advancing clinical treatments for bone regeneration.

{"title":"Structurally defined cartilaginous MEW-assembloids for critical-size long bone healing","authors":"Liuqi Peng , Amit Chandrakar , Gabriella Nilsson Hall , Konstantinos Ioannidis , Lorenzo Moroni , Paul Wieringa , Ioannis Papantoniou","doi":"10.1016/j.biomaterials.2025.123202","DOIUrl":"10.1016/j.biomaterials.2025.123202","url":null,"abstract":"<div><div>Bone defects exceeding a critical size pose significant clinical challenges due to their inability to heal spontaneously. Traditional treatments including autografts and synthetic implants, are often suffer from limitations such as donor site morbidity, infection risk, and poor integration. This study explores a novel approach using MEW-assembloid which combine Melt electrowriting (MEW) scaffolds with cartilaginous microtissues to enhance bone healing. Here, we fabricated bucket-shaped MEW scaffolds (OMesh and CMesh) to optimize microtissue retention and integration, with the OMesh design showing effective shape retention after microtissue seeding. To adapt the scaffold dimensions for <em>in vivo</em> implantation, we introduced elongated MEW (EMesh) based on the OMesh design, forming EMesh-assembloid. These constructs were evaluated for their ability to undergo endochondral ossification and mineralization in subcutaneous implants. Additionally, tubular MEW scaffolds were also created as stabilizers around EMesh-assembloid for orthotopic implantation and showed substantial new bone formation and nearly full defect bridging in a critical-sized mouse tibia defect model after 8 weeks. Our results indicates that MEW-assembloid offer a robust strategy for tissue engineering, enhancing the structural and functional integration of implants, and providing an innovation solution for the repair and regeneration of critical bone defects, potentially advancing clinical treatments for bone regeneration.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123202"},"PeriodicalIF":12.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463475","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 tumor heterogeneity-independent antigen-responsive nanocarrier enabled by bioorthogonal pre-targeting and click-activated self-immolative polymer

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-19 DOI: 10.1016/j.biomaterials.2025.123200

Ye Liu , Qingyu Zong , Yalan Tu , Xingzu Zhang , Qiaoling Tan , Ihsan Ullah , Youyong Yuan

Bioorthogonal pre-targeting alleviate the limitations of traditional nanomedicines in passive and active targeting delivery. However, the high selectivity of bioorthogonal pre-targeting depends on the high expression level of antigens in lesion sites, and there are very limited targets with sufficient overexpression. Herein, we propose a tumor heterogeneity-independent antigen-responsive nanocarrier utilizing bioorthogonal pre-targeting and click-activated self-immolative polymers for stimulus signal conversion and amplification. This approach comprises a tetrazine (Tz) conjugated with trastuzumab (T-Tz), and a bioorthogonally activatable nanocarrier CONP which self-assembled by isocyanide and polyethylene glycol-modified poly (thiocarbamate) (NC-PTC-PEG) and hydrogen sulfide (H₂S)-responsive self-immolative polymers. In practice, T-Tz is first injected to actively pretarget HER2-positive tumor cells and followed by the second injection of nanocarrier CONP. The NC-PTC-PEG in CONP undergoes a click reaction with Tz to generate H₂S, thereby achieving the transformation from antigen signal to H₂S signal. Finally, NO₂-PTC-PEG responds to H₂S stimulation and undergoes a head-to-tail depolymerization process similar to dominoes to produce a large amount of H₂S, further amplifying the stimulus signal. This bioorthogonal pre-targeting combine with click-activated self-immolative polymers is anticipated to enhance the effectiveness of existing pre-targeting strategies for tumor imaging and therapy, with the potential to overcome challenges posed by tumor heterogeneity.

{"title":"A tumor heterogeneity-independent antigen-responsive nanocarrier enabled by bioorthogonal pre-targeting and click-activated self-immolative polymer","authors":"Ye Liu , Qingyu Zong , Yalan Tu , Xingzu Zhang , Qiaoling Tan , Ihsan Ullah , Youyong Yuan","doi":"10.1016/j.biomaterials.2025.123200","DOIUrl":"10.1016/j.biomaterials.2025.123200","url":null,"abstract":"<div><div>Bioorthogonal pre-targeting alleviate the limitations of traditional nanomedicines in passive and active targeting delivery. However, the high selectivity of bioorthogonal pre-targeting depends on the high expression level of antigens in lesion sites, and there are very limited targets with sufficient overexpression. Herein, we propose a tumor heterogeneity-independent antigen-responsive nanocarrier utilizing bioorthogonal pre-targeting and click-activated self-immolative polymers for stimulus signal conversion and amplification. This approach comprises a tetrazine (Tz) conjugated with trastuzumab (T-Tz), and a bioorthogonally activatable nanocarrier CONP which self-assembled by isocyanide and polyethylene glycol-modified poly (thiocarbamate) (NC-PTC-PEG) and hydrogen sulfide (H<sub>2</sub>S)-responsive self-immolative polymers. In practice, T-Tz is first injected to actively pretarget HER2-positive tumor cells and followed by the second injection of nanocarrier CONP. The NC-PTC-PEG in CONP undergoes a click reaction with Tz to generate H<sub>2</sub>S, thereby achieving the transformation from antigen signal to H<sub>2</sub>S signal. Finally, NO<sub>2</sub>-PTC-PEG responds to H<sub>2</sub>S stimulation and undergoes a head-to-tail depolymerization process similar to dominoes to produce a large amount of H<sub>2</sub>S, further amplifying the stimulus signal. This bioorthogonal pre-targeting combine with click-activated self-immolative polymers is anticipated to enhance the effectiveness of existing pre-targeting strategies for tumor imaging and therapy, with the potential to overcome challenges posed by tumor heterogeneity.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123200"},"PeriodicalIF":12.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471675","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

Multi-dimensional donor engineering of NIR-II AIEgens for multimodal phototheranostics of orthotopic breast cancer

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-19 DOI: 10.1016/j.biomaterials.2025.123193

Tao Yuan , Jie Cui , Jun Zhu , Ju Mei , Dong Wang , Jianli Hua

“One-for-all” multimodal phototheranostic agents, which integrate multiple photodiagnostic and phototherapeutic functionalities into a single component, have emerged as promising platforms for advancing cancer treatment. Among these, agents featuring second near-infrared (NIR-II) emission are particularly appealing due to their superior tissue penetration depth and high signal-to-background ratio (SBR). However, most reported NIR-II fluorophores suffer from severely imbalanced radiative and non-radiative excited-state energy dissipation in biological environments, resulting in extremely low fluorescence quantum yields (QYs) and limited diagnostic efficacy. This highlights the urgent need for innovative molecular design strategies to develop high-performance NIR-II “one-for-all” multimodal phototheranostic agents. Herein, we present, for the first time, a multi-dimensional donor engineering protocol that optimizes donor design at the molecular, aggregated, and solvent-interaction levels. By introducing 2,4,4-trimethylpentan-2-yl groups into the diphenylamine indeno[1,2-b]thiophene donor unit, we developed a donor-acceptor-donor (D-A-D) type NIR-II aggregation-induced emission-active luminogen (AIEgen), i.e. OPITBT. When formulated into nanoparticles (NPs), OPITBT NPs exhibited a 16-fold enhancement in fluorescence QY compared to OPITBT in tetrahydrofuran, along with excellent photothermal conversion efficiency (PCE) and acceptable type-I reactive oxygen species (ROS) generation. When further fabricated into tumor-targeting NPs, the resulted OPITBT-R NPs effectively eliminated orthotopic breast cancer through fluorescence-photoacoustic-photothermal multimodal imaging-guided photodynamic-photothermal synergistic therapy under single 808 nm laser irradiation. Notably, the exceptional NIR-II fluorescence brightness of OPITBT-R NPs enables high-resolution NIR-IIb whole-body vascular imaging in living mice. This work provides a versatile strategy to enhance radiative dissipation of NIR-II fluorophores for balanced phototheranostic performance and advances the development of “one-for-all” phototheranostic systems.

{"title":"Multi-dimensional donor engineering of NIR-II AIEgens for multimodal phototheranostics of orthotopic breast cancer","authors":"Tao Yuan , Jie Cui , Jun Zhu , Ju Mei , Dong Wang , Jianli Hua","doi":"10.1016/j.biomaterials.2025.123193","DOIUrl":"10.1016/j.biomaterials.2025.123193","url":null,"abstract":"<div><div>“One-for-all” multimodal phototheranostic agents, which integrate multiple photodiagnostic and phototherapeutic functionalities into a single component, have emerged as promising platforms for advancing cancer treatment. Among these, agents featuring second near-infrared (NIR-II) emission are particularly appealing due to their superior tissue penetration depth and high signal-to-background ratio (SBR). However, most reported NIR-II fluorophores suffer from severely imbalanced radiative and non-radiative excited-state energy dissipation in biological environments, resulting in extremely low fluorescence quantum yields (QYs) and limited diagnostic efficacy. This highlights the urgent need for innovative molecular design strategies to develop high-performance NIR-II “one-for-all” multimodal phototheranostic agents. Herein, we present, for the first time, a multi-dimensional donor engineering protocol that optimizes donor design at the molecular, aggregated, and solvent-interaction levels. By introducing 2,4,4-trimethylpentan-2-yl groups into the diphenylamine indeno[1,2-<em>b</em>]thiophene donor unit, we developed a donor-acceptor-donor (D-A-D) type NIR-II aggregation-induced emission-active luminogen (AIEgen), i.e. OPITBT. When formulated into nanoparticles (NPs), OPITBT NPs exhibited a 16-fold enhancement in fluorescence QY compared to OPITBT in tetrahydrofuran, along with excellent photothermal conversion efficiency (PCE) and acceptable type-I reactive oxygen species (ROS) generation. When further fabricated into tumor-targeting NPs, the resulted OPITBT-R NPs effectively eliminated orthotopic breast cancer through fluorescence-photoacoustic-photothermal multimodal imaging-guided photodynamic-photothermal synergistic therapy under single 808 nm laser irradiation. Notably, the exceptional NIR-II fluorescence brightness of OPITBT-R NPs enables high-resolution NIR-IIb whole-body vascular imaging in living mice. This work provides a versatile strategy to enhance radiative dissipation of NIR-II fluorophores for balanced phototheranostic performance and advances the development of “one-for-all” phototheranostic systems.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123193"},"PeriodicalIF":12.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474081","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

Immunogenic cuproptosis in cancer immunotherapy via an in situ cuproptosis-inducing system

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-19 DOI: 10.1016/j.biomaterials.2025.123201

Jiehan Li , Ge Zhang , Zhao Sun , Meimei Jiang , Guiyun Jia , Hao Liu , Nannan Liu , Liyang Shi , Lingling Zhang , Liming Nie , Yingjie Zhang , Yang Fu

Cell death-based therapies combined with immunotherapy have great potential in cancer therapy. To further explore and apply the combined therapies, the immunogenicity of different cell death modes in colorectal cancer (CRC) was evaluated by a cause-and-effect framework encompassing 12 cell death modes. Results show robust correlations among cuproptosis, immunogenic cell death (ICD) and immunity in CRC, as observed in our in-house and other independent cohorts, which are substantiated by in vitro and in vivo experiments. Subsequent investigations demonstrate that cuproptosis induces endoplasmic reticulum stress, leading to the release of damage-associated molecular patterns from CRC cells and triggering the maturation of antigen-presenting cells. Moreover, for in vivo therapeutic approaches, an in situ cuproptosis-inducing system was devised, which can further strengthen the effects of immune cells. Through the combined analysis including single-cell RNA sequencing, cuproptosis is shown to mobilize cytotoxic T lymphocytes and M1 macrophages within the tumor microenvironment (TME). Additionally, co-treatment with Imiquimod, the TLR7 agonist, augments the anti-tumor immune responses induced by cuproptosis. Overall, we provide compelling evidence that cuproptosis induces ICD thus fostering an inflammatory TME, and the cuproptosis-based delivery system further promotes this inflammatory environment, demonstrating considerable potential for enhancing tumor therapy efficacy.

{"title":"Immunogenic cuproptosis in cancer immunotherapy via an in situ cuproptosis-inducing system","authors":"Jiehan Li , Ge Zhang , Zhao Sun , Meimei Jiang , Guiyun Jia , Hao Liu , Nannan Liu , Liyang Shi , Lingling Zhang , Liming Nie , Yingjie Zhang , Yang Fu","doi":"10.1016/j.biomaterials.2025.123201","DOIUrl":"10.1016/j.biomaterials.2025.123201","url":null,"abstract":"<div><div>Cell death-based therapies combined with immunotherapy have great potential in cancer therapy. To further explore and apply the combined therapies, the immunogenicity of different cell death modes in colorectal cancer (CRC) was evaluated by a cause-and-effect framework encompassing 12 cell death modes. Results show robust correlations among cuproptosis, immunogenic cell death (ICD) and immunity in CRC, as observed in our in-house and other independent cohorts, which are substantiated by <em>in vitro</em> and <em>in vivo</em> experiments. Subsequent investigations demonstrate that cuproptosis induces endoplasmic reticulum stress, leading to the release of damage-associated molecular patterns from CRC cells and triggering the maturation of antigen-presenting cells. Moreover, for <em>in vivo</em> therapeutic approaches, an in situ cuproptosis-inducing system was devised, which can further strengthen the effects of immune cells. Through the combined analysis including single-cell RNA sequencing, cuproptosis is shown to mobilize cytotoxic T lymphocytes and M1 macrophages within the tumor microenvironment (TME). Additionally, co-treatment with Imiquimod, the TLR7 agonist, augments the anti-tumor immune responses induced by cuproptosis. Overall, we provide compelling evidence that cuproptosis induces ICD thus fostering an inflammatory TME, and the cuproptosis-based delivery system further promotes this inflammatory environment, demonstrating considerable potential for enhancing tumor therapy efficacy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123201"},"PeriodicalIF":12.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510882","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

Novel “hot spring”-mimetic scaffolds for sequential neurovascular network reconstruction and osteoporosis reversion

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-18 DOI: 10.1016/j.biomaterials.2025.123191

Yanan Zhao , Jiawei Liu , Liangcong Hu , Xiaokang Yao , Rong Tu , Takashi Goto , Lianmeng Zhang , Xiaopei Wu , Guohui Liu , Honglian Dai

Neurovascular network damage and excessive hydrogen peroxide (H₂O₂) accumulation are the main obstacles for osteoporotic bone defect repair. It is extremely essential to endow the implants with sequential neuroangiogenesis promotion and osteoporosis pathological microenvironment improvement. Hot springs exhibits excellent facilitation on angiogenesis and bone regeneration due to abundant minerals, trace elements and modest thermal stimulation. Inspired by the hot spring effect, we propose a novel porous photothermal calcium magnesium phosphate bone cement (MCPC) compounded with manganese-substituted Fe₃O₄ (Mn_xFe_3-xO₄), which is perfused by temperature-responsive PLGA hydrogel loaded with vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). At the initial stage of implantation, Mn_xFe_3-xO₄ scavenges excessive H₂O₂ under the heat stimulation triggered by near-infrared (NIR) light, and the factors are released from the hydrogel that stimulate the impaired neurovascular network reconstruction; at the later stage, the continuous hot spring effect maintains mild thermal stimulation and sustained release of bioactive ions (Ca²⁺, Mn²⁺, Mg²⁺ and PO₄³⁻), which inhibits osteoclast function and activity, and promotes osteogenic differentiation and mineralization. The osteoporotic bone defect model in ovariectomized (OVX) rats further verifies that a synergy effect of photothermal therapy and bioactive factors/ions significantly promotes neurovascular bone regeneration. It demonstrates that the hot spring mimetic effect possesses huge potential for the sequential treatment of osteoporosis bone defect.

{"title":"Novel “hot spring”-mimetic scaffolds for sequential neurovascular network reconstruction and osteoporosis reversion","authors":"Yanan Zhao , Jiawei Liu , Liangcong Hu , Xiaokang Yao , Rong Tu , Takashi Goto , Lianmeng Zhang , Xiaopei Wu , Guohui Liu , Honglian Dai","doi":"10.1016/j.biomaterials.2025.123191","DOIUrl":"10.1016/j.biomaterials.2025.123191","url":null,"abstract":"<div><div>Neurovascular network damage and excessive hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) accumulation are the main obstacles for osteoporotic bone defect repair. It is extremely essential to endow the implants with sequential neuroangiogenesis promotion and osteoporosis pathological microenvironment improvement. Hot springs exhibits excellent facilitation on angiogenesis and bone regeneration due to abundant minerals, trace elements and modest thermal stimulation. Inspired by the hot spring effect, we propose a novel porous photothermal calcium magnesium phosphate bone cement (MCPC) compounded with manganese-substituted Fe<sub>3</sub>O<sub>4</sub> (Mn<sub>x</sub>Fe<sub>3-x</sub>O<sub>4</sub>), which is perfused by temperature-responsive PLGA hydrogel loaded with vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). At the initial stage of implantation, Mn<sub>x</sub>Fe<sub>3-x</sub>O<sub>4</sub> scavenges excessive H<sub>2</sub>O<sub>2</sub> under the heat stimulation triggered by near-infrared (NIR) light, and the factors are released from the hydrogel that stimulate the impaired neurovascular network reconstruction; at the later stage, the continuous hot spring effect maintains mild thermal stimulation and sustained release of bioactive ions (Ca<sup>2+</sup>, Mn<sup>2+</sup>, Mg<sup>2+</sup> and PO<sub>4</sub><sup>3−</sup>), which inhibits osteoclast function and activity, and promotes osteogenic differentiation and mineralization. The osteoporotic bone defect model in ovariectomized (OVX) rats further verifies that a synergy effect of photothermal therapy and bioactive factors/ions significantly promotes neurovascular bone regeneration. It demonstrates that the hot spring mimetic effect possesses huge potential for the sequential treatment of osteoporosis bone defect.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123191"},"PeriodicalIF":12.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562903","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

Mitigation of arteriosclerosis through transcriptional regulation of ferroptosis and lipid metabolism by magnesium

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-18 DOI: 10.1016/j.biomaterials.2025.123135

Han Yu , Changyi Zhou , Shi Yang , Jinlong Yu , Xiyue Zhang , Zhaojia Liang , Shuang Tan , Yang Song , Wenhui Wang , Yu Sun , Rui Zan , Hua Qiu , Li Shen , Xiaonong Zhang

Metallic cardiovascular stents are crucial for preventing atherosclerosis-induced infarction by offering mechanical support. However, the effects of metal ions released from these stents on atherosclerosis remain ambiguous. This study evaluates the potential impact posed by the degradation products of magnesium-based stents, with a focus on ferroptosis, a key mechanism driving atherosclerosis. Remarkably, our results demonstrate that Mg effectively inhibits ferroptosis in human umbilical vein endothelial cells and in murine, rat and rabbit models. Our studies reveal that magnesium ions impede the dephosphorylation of ERK proteins, thereby enhancing the expression of SLC7A11 and GCL proteins via activation of the MAPK pathway mechanistically. Additionally, magnesium ions downregulate ACSL4 protein expression, leading to decreased levels of acyl-CoA and ether-phospholipids. Eventually, multiple animal experiments indicate that biodegradable Mg stents can inhibit ferroptosis and decelerate the progression of arteriosclerosis, highlighting the therapeutic potential of Mg stents in treating arteriosclerosis.

{"title":"Mitigation of arteriosclerosis through transcriptional regulation of ferroptosis and lipid metabolism by magnesium","authors":"Han Yu , Changyi Zhou , Shi Yang , Jinlong Yu , Xiyue Zhang , Zhaojia Liang , Shuang Tan , Yang Song , Wenhui Wang , Yu Sun , Rui Zan , Hua Qiu , Li Shen , Xiaonong Zhang","doi":"10.1016/j.biomaterials.2025.123135","DOIUrl":"10.1016/j.biomaterials.2025.123135","url":null,"abstract":"<div><div>Metallic cardiovascular stents are crucial for preventing atherosclerosis-induced infarction by offering mechanical support. However, the effects of metal ions released from these stents on atherosclerosis remain ambiguous. This study evaluates the potential impact posed by the degradation products of magnesium-based stents, with a focus on ferroptosis, a key mechanism driving atherosclerosis. Remarkably, our results demonstrate that Mg effectively inhibits ferroptosis in human umbilical vein endothelial cells and in murine, rat and rabbit models. Our studies reveal that magnesium ions impede the dephosphorylation of ERK proteins, thereby enhancing the expression of SLC7A11 and GCL proteins via activation of the MAPK pathway mechanistically. Additionally, magnesium ions downregulate ACSL4 protein expression, leading to decreased levels of acyl-CoA and ether-phospholipids. Eventually, multiple animal experiments indicate that biodegradable Mg stents can inhibit ferroptosis and decelerate the progression of arteriosclerosis, highlighting the therapeutic potential of Mg stents in treating arteriosclerosis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123135"},"PeriodicalIF":12.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452952","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

BBPs-functionalized tetrahedral framework nucleic acid hydrogel scaffold captures endogenous BMP-2 to promote bone regeneration

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-17 DOI: 10.1016/j.biomaterials.2025.123194

Wumeng Yin , Xingyu Chen , Long Bai , Yong Li , Wen Chen , Yueying Jiang , Yutian He , Yichen Yang , Yunfeng Lin , Taoran Tian , Xiaoxiao Cai

Bone Morphogenetic Protein-2 (BMP-2) is a key growth factor for inducing osteogenic differentiation and promoting bone remodeling. However, the exogenous application of delivery systems for BMP-2 has been hampered by various postoperative complications, poor stability and high price. Hence, in situ enrichment of endogenous BMP-2 is promising. The discovery of a small molecule BMP-2 binding peptide (BBP) that binds specifically to BMP-2 with high affinity lays the foundation for the construction of bioactive materials that capture endogenous BMP-2. In contrast, conventional enrichment strategies have low binding efficiency due to steric hindrance caused by the disordered arrangement of BBPs. Tetrahedral framework nucleic acid (tFNA) exhibits good editability and unique three-dimensional spatial structure that enables topological control of multivalent ligands in spatial distribution. The BBPs are further designed to be stably modified on tFNA (BBPs-tFNA) via click chemistry of the azide-alkyne addition to achieve the orderly arrangement of BBPs in spatial organization, to improve the binding efficiency of BMP-2. Therefore, in this study, BBPs-tFNA is modified on biocompatible hyaluronic acid methacryloyl (HAMA) to construct the functionalized bioactive composite hydrogel scaffolds, with the aim of achieving precise and efficient capture of endogenous BMP-2, stimulating osteogenic differentiation and promoting in situ osteogenesis for bone defect repair.

{"title":"BBPs-functionalized tetrahedral framework nucleic acid hydrogel scaffold captures endogenous BMP-2 to promote bone regeneration","authors":"Wumeng Yin , Xingyu Chen , Long Bai , Yong Li , Wen Chen , Yueying Jiang , Yutian He , Yichen Yang , Yunfeng Lin , Taoran Tian , Xiaoxiao Cai","doi":"10.1016/j.biomaterials.2025.123194","DOIUrl":"10.1016/j.biomaterials.2025.123194","url":null,"abstract":"<div><div>Bone Morphogenetic Protein-2 (BMP-2) is a key growth factor for inducing osteogenic differentiation and promoting bone remodeling. However, the exogenous application of delivery systems for BMP-2 has been hampered by various postoperative complications, poor stability and high price. Hence, in situ enrichment of endogenous BMP-2 is promising. The discovery of a small molecule BMP-2 binding peptide (BBP) that binds specifically to BMP-2 with high affinity lays the foundation for the construction of bioactive materials that capture endogenous BMP-2. In contrast, conventional enrichment strategies have low binding efficiency due to steric hindrance caused by the disordered arrangement of BBPs. Tetrahedral framework nucleic acid (tFNA) exhibits good editability and unique three-dimensional spatial structure that enables topological control of multivalent ligands in spatial distribution. The BBPs are further designed to be stably modified on tFNA (BBPs-tFNA) via click chemistry of the azide-alkyne addition to achieve the orderly arrangement of BBPs in spatial organization, to improve the binding efficiency of BMP-2. Therefore, in this study, BBPs-tFNA is modified on biocompatible hyaluronic acid methacryloyl (HAMA) to construct the functionalized bioactive composite hydrogel scaffolds, with the aim of achieving precise and efficient capture of endogenous BMP-2, stimulating osteogenic differentiation and promoting in situ osteogenesis for bone defect repair.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123194"},"PeriodicalIF":12.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437804","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

Reprogramming peritoneal macrophages with outer membrane vesicle-coated PLGA nanoparticles for endometriosis prevention

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-17 DOI: 10.1016/j.biomaterials.2025.123198

Ning Wu , Ziwei Han , Wenxing Lv , Yanjuan Huang , Jingwen Zhu , Jinqi Deng , Qing Xue

Endometriosis is a chronic inflammatory disease that primarily affects women of reproductive age. The current hormonal treatments are unsuitable for women who wish to conceive, highlighting the need for non-hormonal therapeutic alternatives. In this study, we engineered outer membrane vesicle (OMV)-coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (OMV-NPs) as a potential therapy for endometriosis. These OMV-NPs were internalized by macrophages more efficiently than bacterial OMVs and preserved the immunostimulatory properties of OMVs. In vivo administration of OMV-NPs in mice achieved prolonged retention in the peritoneal cavity, with effective uptake by nearly 80 % of the peritoneal macrophages. Notably, treatment with OMV-NPs reprogrammed macrophages toward the M1 phenotype, resulting in a significant decrease in the M2 to M1 ratio within the peritoneal cavity and in endometriotic lesions. This shift from M2 to M1 was associated with reduced TGF-β1 production and suppressed myofibroblast activation, which led to substantial inhibition of endometriosis progression. Furthermore, immunohistochemical imaging of paired eutopic and ectopic endometrial tissues from endometriosis patients revealed a positive correlation between M2-polarized macrophages and fibrosis. This finding suggests that reprogramming macrophages with OMV-NPs could be a promising therapeutic approach for endometriosis.

{"title":"Reprogramming peritoneal macrophages with outer membrane vesicle-coated PLGA nanoparticles for endometriosis prevention","authors":"Ning Wu , Ziwei Han , Wenxing Lv , Yanjuan Huang , Jingwen Zhu , Jinqi Deng , Qing Xue","doi":"10.1016/j.biomaterials.2025.123198","DOIUrl":"10.1016/j.biomaterials.2025.123198","url":null,"abstract":"<div><div>Endometriosis is a chronic inflammatory disease that primarily affects women of reproductive age. The current hormonal treatments are unsuitable for women who wish to conceive, highlighting the need for non-hormonal therapeutic alternatives. In this study, we engineered outer membrane vesicle (OMV)-coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (OMV-NPs) as a potential therapy for endometriosis. These OMV-NPs were internalized by macrophages more efficiently than bacterial OMVs and preserved the immunostimulatory properties of OMVs. In vivo administration of OMV-NPs in mice achieved prolonged retention in the peritoneal cavity, with effective uptake by nearly 80 % of the peritoneal macrophages. Notably, treatment with OMV-NPs reprogrammed macrophages toward the M1 phenotype, resulting in a significant decrease in the M2 to M1 ratio within the peritoneal cavity and in endometriotic lesions. This shift from M2 to M1 was associated with reduced TGF-β1 production and suppressed myofibroblast activation, which led to substantial inhibition of endometriosis progression. Furthermore, immunohistochemical imaging of paired eutopic and ectopic endometrial tissues from endometriosis patients revealed a positive correlation between M2-polarized macrophages and fibrosis. This finding suggests that reprogramming macrophages with OMV-NPs could be a promising therapeutic approach for endometriosis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123198"},"PeriodicalIF":12.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508310","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

A Di-aptamer-functionalized scaffold promotes bone regeneration by facilitating the selective retention of MSCs and EPCs and then promoting crosstalk between osteogenesis and angiogenesis

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-17 DOI: 10.1016/j.biomaterials.2025.123197

Qiandong Yang , Jiangling Zhou , Ming Yang , Jiayi Wei , Yingtao Gui , Fan Yang , Sihao He , Juan Cai , Bo Yu , Qijie Dai , Zhenzhen Tang , Tianyong Hou

The crosstalk between osteogenesis and angiogenesis plays an important role in promoting the formation of a microenvironment that supports bone regeneration. This suggests that the retention of endogenous osteogenic and angiogenic cells in the bone defect area can promote tissue-engineered bone (TEB) osteogenesis and cell–cell interactions. In this study, a Di-Aptamer-functionalized HA/β-TCP (Di-Aptamer-H/T) scaffold was prepared by sequential modification of APTES and sulfo-SMCC and connected with aptamer HM69 and EPC1. We confirmed that aptamers HM69 and EPC1 can specifically identify mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), respectively. This process triggers the expression of adhesion-related genes in these cells and allows these cells to selectively stay coupled to Di-Aptamer-H/T. The osteogenic differentiation ability of MSCs treated with Di-Aptamer-H/T in vitro was significantly increased. Similarly, the ability of Di-Aptamer-H/T-treated EPCs to form blood vessels was also enhanced. Notably, the osteogenic and angiogenic abilities of cocultured MSCs and EPCs treated with the Di-Aptamer-H/T scaffold were significantly better than those of cells cultured individually. In vivo, the results of micro-CT angiography, H&E staining, Masson's staining and histochemical staining further confirmed that Di-Aptamer-H/T formed new bones and vessels more readily than those treated with a single aptamer linked to HA/β-TCP or with HA/β-TCP alone. In brief, our study demonstrated that crosstalk between osteogenesis and angiogenesis is promoted by the Di-Aptamer-H/T scaffold, which serves as a potential treatment strategy for bone defects and can improve outcomes.

{"title":"A Di-aptamer-functionalized scaffold promotes bone regeneration by facilitating the selective retention of MSCs and EPCs and then promoting crosstalk between osteogenesis and angiogenesis","authors":"Qiandong Yang , Jiangling Zhou , Ming Yang , Jiayi Wei , Yingtao Gui , Fan Yang , Sihao He , Juan Cai , Bo Yu , Qijie Dai , Zhenzhen Tang , Tianyong Hou","doi":"10.1016/j.biomaterials.2025.123197","DOIUrl":"10.1016/j.biomaterials.2025.123197","url":null,"abstract":"<div><div>The crosstalk between osteogenesis and angiogenesis plays an important role in promoting the formation of a microenvironment that supports bone regeneration. This suggests that the retention of endogenous osteogenic and angiogenic cells in the bone defect area can promote tissue-engineered bone (TEB) osteogenesis and cell–cell interactions. In this study, a Di-Aptamer-functionalized HA/β-TCP (Di-Aptamer-H/T) scaffold was prepared by sequential modification of APTES and sulfo-SMCC and connected with aptamer HM69 and EPC1. We confirmed that aptamers HM69 and EPC1 can specifically identify mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), respectively. This process triggers the expression of adhesion-related genes in these cells and allows these cells to selectively stay coupled to Di-Aptamer-H/T. The osteogenic differentiation ability of MSCs treated with Di-Aptamer-H/T in vitro was significantly increased. Similarly, the ability of Di-Aptamer-H/T-treated EPCs to form blood vessels was also enhanced. Notably, the osteogenic and angiogenic abilities of cocultured MSCs and EPCs treated with the Di-Aptamer-H/T scaffold were significantly better than those of cells cultured individually. In vivo, the results of micro-CT angiography, H&E staining, Masson's staining and histochemical staining further confirmed that Di-Aptamer-H/T formed new bones and vessels more readily than those treated with a single aptamer linked to HA/β-TCP or with HA/β-TCP alone. In brief, our study demonstrated that crosstalk between osteogenesis and angiogenesis is promoted by the Di-Aptamer-H/T scaffold, which serves as a potential treatment strategy for bone defects and can improve outcomes.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123197"},"PeriodicalIF":12.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453691","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

3D-printed multifunctional bilayer scaffold with sustained release of apoptotic extracellular vesicles and antibacterial coacervates for enhanced wound healing

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-15 DOI: 10.1016/j.biomaterials.2025.123196

Linli Jiang , Jia Dong , Minwen Jiang , Weiwei Tan , Yiwei Zeng , Xuanqi Liu , Pu Wang , Hejin Jiang , Jiajing Zhou , Xiaojing Liu , Hui Li , Lei Liu

Full-thickness skin defects pose significant challenges to physical and psychological health while traditional skin grafting techniques are associated with limitations. Herein, we present a 3D-printed multifunctional bilayer scaffold that incorporates apoptotic extracellular vesicles (ApoEVs) and antibacterial coacervates to prevent wound infection and promote wound healing. The ApoEVs were continuously released from the lower layer of the scaffold with large pores to promote angiogenesis and collagen deposition. Meanwhile, the pH-responsive curcumin-containing coacervates were released from the upper layer of the scaffold with dense pores to exert antibacterial and reactive oxygen species scavenging ability. In vivo experiments showed that the scaffold accelerated wound healing and improved healing quality by promoting a more organized collagen arrangement and reducing hyperplastic scar tissue. Furthermore, it effectively reduced hyperplastic scar tissue, resulting in a decrease in the average scar area from 73.3 % to 19.9 %. RNA sequencing analysis revealed that the scaffold upregulated genes associated with cell proliferation and downregulated genes related to inflammation, indicating its potential therapeutic applications for wound healing. This multifunctional bilayer scaffold represents a promising candidate for the treatment of full-thickness skin defects, offering rationales for designing skin scaffolds for regenerative medicine applications.

{"title":"3D-printed multifunctional bilayer scaffold with sustained release of apoptotic extracellular vesicles and antibacterial coacervates for enhanced wound healing","authors":"Linli Jiang , Jia Dong , Minwen Jiang , Weiwei Tan , Yiwei Zeng , Xuanqi Liu , Pu Wang , Hejin Jiang , Jiajing Zhou , Xiaojing Liu , Hui Li , Lei Liu","doi":"10.1016/j.biomaterials.2025.123196","DOIUrl":"10.1016/j.biomaterials.2025.123196","url":null,"abstract":"<div><div>Full-thickness skin defects pose significant challenges to physical and psychological health while traditional skin grafting techniques are associated with limitations. Herein, we present a 3D-printed multifunctional bilayer scaffold that incorporates apoptotic extracellular vesicles (ApoEVs) and antibacterial coacervates to prevent wound infection and promote wound healing. The ApoEVs were continuously released from the lower layer of the scaffold with large pores to promote angiogenesis and collagen deposition. Meanwhile, the pH-responsive curcumin-containing coacervates were released from the upper layer of the scaffold with dense pores to exert antibacterial and reactive oxygen species scavenging ability. In vivo experiments showed that the scaffold accelerated wound healing and improved healing quality by promoting a more organized collagen arrangement and reducing hyperplastic scar tissue. Furthermore, it effectively reduced hyperplastic scar tissue, resulting in a decrease in the average scar area from 73.3 % to 19.9 %. RNA sequencing analysis revealed that the scaffold upregulated genes associated with cell proliferation and downregulated genes related to inflammation, indicating its potential therapeutic applications for wound healing. This multifunctional bilayer scaffold represents a promising candidate for the treatment of full-thickness skin defects, offering rationales for designing skin scaffolds for regenerative medicine applications.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123196"},"PeriodicalIF":12.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428792","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