Pub Date : 2025-02-17DOI: 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}
Pub Date : 2025-02-15DOI: 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}
Pub Date : 2025-02-15DOI: 10.1016/j.biomaterials.2025.123195
Jiacheng Liu , Junyan Liu , Senrui Liu , Pengcheng Xiao , Chengcheng Du , Jingdi Zhan , Zhuolin Chen , Lu Chen , Ke Li , Wei Huang , Yiting Lei
Selenium (Se) deficiency is a critical factor contributing to the imbalance of redox homeostasis in chondrocytes and the progression of osteoarthritis (OA). However, traditional selenium supplements face challenges such as a narrow therapeutic window and lack of targeting. To address this, we designed hyaluronic acid (HA)-modified selenium nanoparticles (HA-SeNPs) and developed a cascade-targeted delivery system (HA-SeNPs@AHAMA-HMs) based on a nano-micron combined strategy. The system involves loading HA-SeNPs into aldehyde-functionalized hydrogel microspheres prepared via microfluidic technology. Through Schiff base reactions between the aldehyde groups of the microspheres and amino groups of the cartilage, the system selectively adheres to the surface of damaged cartilage, achieving micron-scale targeting while continuously releasing HA-SeNPs. Then, HA-SeNPs achieve nanoscale targeting by binding to CD44, which is highly expressed on OA chondrocyte membranes, via their HA surface. Once taken up by the cells, HA-SeNPs exert their effects by directly scavenging ROS and promoting selenoprotein synthesis through the generation of selenite, forming a multifaceted antioxidant defense system. This effectively alleviates oxidative stress and optimizes mitochondrial function. In vivo and in vitro results demonstrated that this system significantly improved the oxidative phosphorylation pathway associated with mitochondrial function, which markedly reduced joint space narrowing and cartilage matrix degradation, and delayed the progression of OA. In summary, this study suggests that the cascade-targeting hydrogel microspheres designed and constructed based on a nano-micron combined strategy represent a promising prospective approach for precise Se supplementation and OA treatment.
{"title":"Cascade targeting selenium nanoparticles-loaded hydrogel microspheres for multifaceted antioxidant defense in osteoarthritis","authors":"Jiacheng Liu , Junyan Liu , Senrui Liu , Pengcheng Xiao , Chengcheng Du , Jingdi Zhan , Zhuolin Chen , Lu Chen , Ke Li , Wei Huang , Yiting Lei","doi":"10.1016/j.biomaterials.2025.123195","DOIUrl":"10.1016/j.biomaterials.2025.123195","url":null,"abstract":"<div><div>Selenium (Se) deficiency is a critical factor contributing to the imbalance of redox homeostasis in chondrocytes and the progression of osteoarthritis (OA). However, traditional selenium supplements face challenges such as a narrow therapeutic window and lack of targeting. To address this, we designed hyaluronic acid (HA)-modified selenium nanoparticles (HA-SeNPs) and developed a cascade-targeted delivery system (HA-SeNPs@AHAMA-HMs) based on a nano-micron combined strategy. The system involves loading HA-SeNPs into aldehyde-functionalized hydrogel microspheres prepared via microfluidic technology. Through Schiff base reactions between the aldehyde groups of the microspheres and amino groups of the cartilage, the system selectively adheres to the surface of damaged cartilage, achieving micron-scale targeting while continuously releasing HA-SeNPs. Then, HA-SeNPs achieve nanoscale targeting by binding to CD44, which is highly expressed on OA chondrocyte membranes, via their HA surface. Once taken up by the cells, HA-SeNPs exert their effects by directly scavenging ROS and promoting selenoprotein synthesis through the generation of selenite, forming a multifaceted antioxidant defense system. This effectively alleviates oxidative stress and optimizes mitochondrial function. In vivo and in vitro results demonstrated that this system significantly improved the oxidative phosphorylation pathway associated with mitochondrial function, which markedly reduced joint space narrowing and cartilage matrix degradation, and delayed the progression of OA. In summary, this study suggests that the cascade-targeting hydrogel microspheres designed and constructed based on a nano-micron combined strategy represent a promising prospective approach for precise Se supplementation and OA treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123195"},"PeriodicalIF":12.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428791","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}
Pub Date : 2025-02-13DOI: 10.1016/j.biomaterials.2025.123192
Qifeng Guan , Sen Hou , Kai Wang , Linhao Li , Yating Cheng , Mingxia Zheng , Chen Liu , Xinbin Zhao , Jin Zhou , Ping Li , Xufeng Niu , Lizhen Wang , Yubo Fan
Biomaterials can play a crucial role in facilitating tissue regeneration, but their application is often limited by that they induce scarring rather than complete tissue restoration. Hydrogels with microporous architectures, engineered via 3D printing techniques or particle packing (granular hydrogels), have shown promise in providing a conducive microenvironment for cellular infiltration and favorable immune response. Nonetheless, there is a notably lacking in studies that demonstrate scarless regeneration solely through pore structure engineering. In this study, we demonstrate that optimizing micropore structure of injectable granular hydrogels via controlled liquid-liquid phase separation facilitates scarless wound healing. The building block particles are fabricated by precisely controlling the separation kinetics of two immiscible aqueous phases (gelling and porogenic) and timely arresting phase separation, to generate bicontinuous, hollow or closed porous structure. Employing a murine model, we reveal that the optimized pore structure significantly facilitates mature vascular network boosts pro-regenerative macrophage polarization (M2/M1) and CD4+/Foxp3+ regulatory T cells, culminating in scarless skin regeneration enriched with hair follicles. Moreover, our hydrogels outperform the clinical gold-standard collagen/proteoglycan scaffolds in a porcine model, showcasing superior cell infiltration, epidermal integration, and dermal regeneration. Micropore structure engineering of biomaterials presents a promising and biologics free pathway for tissue regeneration.
{"title":"Micropore structure engineering of injectable granular hydrogels via controlled liquid-liquid phase separation facilitates regenerative wound healing in mice and pigs","authors":"Qifeng Guan , Sen Hou , Kai Wang , Linhao Li , Yating Cheng , Mingxia Zheng , Chen Liu , Xinbin Zhao , Jin Zhou , Ping Li , Xufeng Niu , Lizhen Wang , Yubo Fan","doi":"10.1016/j.biomaterials.2025.123192","DOIUrl":"10.1016/j.biomaterials.2025.123192","url":null,"abstract":"<div><div>Biomaterials can play a crucial role in facilitating tissue regeneration, but their application is often limited by that they induce scarring rather than complete tissue restoration. Hydrogels with microporous architectures, engineered via 3D printing techniques or particle packing (granular hydrogels), have shown promise in providing a conducive microenvironment for cellular infiltration and favorable immune response. Nonetheless, there is a notably lacking in studies that demonstrate scarless regeneration solely through pore structure engineering. In this study, we demonstrate that optimizing micropore structure of injectable granular hydrogels via controlled liquid-liquid phase separation facilitates scarless wound healing. The building block particles are fabricated by precisely controlling the separation kinetics of two immiscible aqueous phases (gelling and porogenic) and timely arresting phase separation, to generate bicontinuous, hollow or closed porous structure. Employing a murine model, we reveal that the optimized pore structure significantly facilitates mature vascular network boosts pro-regenerative macrophage polarization (M2/M1) and CD4+/Foxp3+ regulatory T cells, culminating in scarless skin regeneration enriched with hair follicles. Moreover, our hydrogels outperform the clinical gold-standard collagen/proteoglycan scaffolds in a porcine model, showcasing superior cell infiltration, epidermal integration, and dermal regeneration. Micropore structure engineering of biomaterials presents a promising and biologics free pathway for tissue regeneration.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123192"},"PeriodicalIF":12.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419222","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}
Pub Date : 2025-02-13DOI: 10.1016/j.biomaterials.2025.123187
Min Liu , Yiwen Tang , Mijia Yan , Jiale Zhang , Hangrong Chen , Qiuhong Zhang
Cancer thermal immunotherapeutic strategy has garnered tremendous attention in nanomedicine frontier. Photothermal therapy (PTT) within the second near-infrared (NIR-II) window is popular hyperthermia technique, but the effect of NIR-II PTT on antitumor immunity remains extensive exploration. Here, we first reveal the inflammatory immunosuppressive tumor microenvironment (TME) characterized by high-influx of myeloid-derived suppressor cells (MDSCs) following NIR-II PTT. For this issue, we develop biomineralized copper sulfide nanoparticles (BCS NPs) as NIR-II photothermal agents (PTAs), and found for the first time that they are superior electron-donor antioxidants with pronounced anti-inflammatory activities. Impressively, the excessive inflammation triggered by BCS NPs-mediated NIR-II PTT can be self-alleviated to minimize the high-influx of MDSCs, and the immunosuppression-related reactive oxygen species produced by MDSCs can also be self-scavenged. Such reprogramming of TME facilitates the activation of systemic adaptive antitumor immunity and the strengthened tumour-infiltrating of cytotoxic T lymphocytes, thereby realizing self-reinforcing immunotherapy synergy with cancer NIR-II PTT. More importantly, a robust abscopal effect against distant tumors is also observed in bilateral tumor models. This work provides the first example to underscore the potential of PTAs with antioxidant and anti-inflammatory functions as innovative thermal immuno-nanomedicines.
{"title":"Self-regulating immunosuppressive tumor microenvironment by NIR-II photothermal agent with anti-inflammatory activity for self-reinforcing immunotherapy synergy with cancer photothermal ablation","authors":"Min Liu , Yiwen Tang , Mijia Yan , Jiale Zhang , Hangrong Chen , Qiuhong Zhang","doi":"10.1016/j.biomaterials.2025.123187","DOIUrl":"10.1016/j.biomaterials.2025.123187","url":null,"abstract":"<div><div>Cancer thermal immunotherapeutic strategy has garnered tremendous attention in nanomedicine frontier. Photothermal therapy (PTT) within the second near-infrared (NIR-II) window is popular hyperthermia technique, but the effect of NIR-II PTT on antitumor immunity remains extensive exploration. Here, we first reveal the inflammatory immunosuppressive tumor microenvironment (TME) characterized by high-influx of myeloid-derived suppressor cells (MDSCs) following NIR-II PTT. For this issue, we develop biomineralized copper sulfide nanoparticles (BCS NPs) as NIR-II photothermal agents (PTAs), and found for the first time that they are superior electron-donor antioxidants with pronounced anti-inflammatory activities. Impressively, the excessive inflammation triggered by BCS NPs-mediated NIR-II PTT can be self-alleviated to minimize the high-influx of MDSCs, and the immunosuppression-related reactive oxygen species produced by MDSCs can also be self-scavenged. Such reprogramming of TME facilitates the activation of systemic adaptive antitumor immunity and the strengthened tumour-infiltrating of cytotoxic T lymphocytes, thereby realizing self-reinforcing immunotherapy synergy with cancer NIR-II PTT. More importantly, a robust abscopal effect against distant tumors is also observed in bilateral tumor models. This work provides the first example to underscore the potential of PTAs with antioxidant and anti-inflammatory functions as innovative thermal immuno-nanomedicines.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123187"},"PeriodicalIF":12.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419272","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}
Pub Date : 2025-02-13DOI: 10.1016/j.biomaterials.2025.123186
Shirun Chu , Linlong Li , Jiahao Zhang , Jing You , Xiaolan Li , Yuanyuan Zhou , Xiao Huang , Qiaoli Wu , Fang Chen , Xue Bai , Huan Tan , Jie Weng
Novel interconnected porous scaffolds featuring suitable micro-interface structures hold significance in bone regeneration. Therefore, a hierarchical interconnected porous scaffold with nanotopography interface of pores, mimicking natural bone structure and extracellular matrix microenvironment, are designed to enhance bone regeneration by improving cell adhesion, proliferation, alleviate inflammation, and tissue integration capabilities. The scaffold is fabricated through Pickering emulsion templating method, with aminated gelatin and copper-hydroxyapatite nanoparticles serving as co-stabilizers. This process results in a dual nanoparticles-decorated interface, which could provide ample anchoring points for cells. Adjusting the ratio of the two nanoparticles leads to scaffold with different interfacial roughness. The resultant scaffold increases the number of cellular focal adhesions, enhancing cell adhesion, while its high porosity supports cell recruitment, proliferation and immunomodulation. Copper-hydroxyapatite adsorption at the pore interface reduces copper ion usage and exposes nanoparticles for direct cell contact, endowing the scaffold with enhanced antibacterial and angiogenic properties. An initial burst release phase of copper ions exerts inhibitory effects on mRNA expression, followed by a sustained and optimal release phase that promotes osteogenesis. The molecular mechanism underlying the scaffold of osteogenic potential has been elucidated through RNA sequencing analysis, along with the regulation of inflammatory cytokine expression. In vitro and in vivo studies alike verify its neovascularization-promoting capacity. The efficacy shown in a rat model with critical cranial defects underscores its clinical promise for bone regeneration, as Cu-doped scaffolds retain osteoinductive qualities after 10 weeks in vivo. This study innovates a manufacturing method for a novel scaffold in bone tissue engineering.
{"title":"Hierarchical interconnected porous scaffolds with regulated interfacial nanotopography exhibit antimicrobial, alleviate inflammation, neovascularization, and tissue integration for bone regeneration","authors":"Shirun Chu , Linlong Li , Jiahao Zhang , Jing You , Xiaolan Li , Yuanyuan Zhou , Xiao Huang , Qiaoli Wu , Fang Chen , Xue Bai , Huan Tan , Jie Weng","doi":"10.1016/j.biomaterials.2025.123186","DOIUrl":"10.1016/j.biomaterials.2025.123186","url":null,"abstract":"<div><div>Novel interconnected porous scaffolds featuring suitable micro-interface structures hold significance in bone regeneration. Therefore, a hierarchical interconnected porous scaffold with nanotopography interface of pores, mimicking natural bone structure and extracellular matrix microenvironment, are designed to enhance bone regeneration by improving cell adhesion, proliferation, alleviate inflammation, and tissue integration capabilities. The scaffold is fabricated through Pickering emulsion templating method, with aminated gelatin and copper-hydroxyapatite nanoparticles serving as co-stabilizers. This process results in a dual nanoparticles-decorated interface, which could provide ample anchoring points for cells. Adjusting the ratio of the two nanoparticles leads to scaffold with different interfacial roughness. The resultant scaffold increases the number of cellular focal adhesions, enhancing cell adhesion, while its high porosity supports cell recruitment, proliferation and immunomodulation. Copper-hydroxyapatite adsorption at the pore interface reduces copper ion usage and exposes nanoparticles for direct cell contact, endowing the scaffold with enhanced antibacterial and angiogenic properties. An initial burst release phase of copper ions exerts inhibitory effects on mRNA expression, followed by a sustained and optimal release phase that promotes osteogenesis. The molecular mechanism underlying the scaffold of osteogenic potential has been elucidated through RNA sequencing analysis, along with the regulation of inflammatory cytokine expression. <em>In vitro</em> and <em>in vivo</em> studies alike verify its neovascularization-promoting capacity. The efficacy shown in a rat model with critical cranial defects underscores its clinical promise for bone regeneration, as Cu-doped scaffolds retain osteoinductive qualities after 10 weeks <em>in vivo</em>. This study innovates a manufacturing method for a novel scaffold in bone tissue engineering.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123186"},"PeriodicalIF":12.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429014","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}
Pub Date : 2025-02-12DOI: 10.1016/j.biomaterials.2025.123188
Lei Sun , Kailin Feng , Dean Bai, Yiyan Yu, Wei-Ting Shen, Jiayuan Alex Zhang, Ronnie H. Fang, Weiwei Gao, Liangfang Zhang
Drug overdose is a pressing global public health challenge, with current detoxification treatments often lacking the broad-spectrum efficacy needed for emergency applications. Inspired by the unique advantages of cell membrane-derived nanodiscs (CNDs), including their compact size, rapid distribution, and preservation of native cell membrane functions, we developed endoplasmic reticulum (ER)-derived nanodiscs (ER-NDs) from the ER membranes of mouse hepatic cells for broad-spectrum drug detoxification. ER-NDs retain natural cytochrome P450 (CYP) enzymes, enabling effective detoxification of three model drugs: bupropion, haloperidol, and propranolol. Cell-based assays demonstrated ER-NDs' ability to mitigate drug-induced cytotoxicity, reduce oxidative stress, and restore antioxidant defenses. In mouse models of drug intoxication, ER-ND treatment significantly improved survival rates and alleviated drug-induced oxidative damage. Importantly, ER-NDs showed no evidence of acute toxicity in vivo. These findings underscore the potential of ER-NDs as a versatile platform for broad-spectrum drug detoxification and as a promising tool for managing drug intoxication in emergency and clinical settings.
{"title":"Hepatic endoplasmic reticulum-derived nanodiscs for broad-spectrum drug detoxification","authors":"Lei Sun , Kailin Feng , Dean Bai, Yiyan Yu, Wei-Ting Shen, Jiayuan Alex Zhang, Ronnie H. Fang, Weiwei Gao, Liangfang Zhang","doi":"10.1016/j.biomaterials.2025.123188","DOIUrl":"10.1016/j.biomaterials.2025.123188","url":null,"abstract":"<div><div>Drug overdose is a pressing global public health challenge, with current detoxification treatments often lacking the broad-spectrum efficacy needed for emergency applications. Inspired by the unique advantages of cell membrane-derived nanodiscs (CNDs), including their compact size, rapid distribution, and preservation of native cell membrane functions, we developed endoplasmic reticulum (ER)-derived nanodiscs (ER-NDs) from the ER membranes of mouse hepatic cells for broad-spectrum drug detoxification. ER-NDs retain natural cytochrome P450 (CYP) enzymes, enabling effective detoxification of three model drugs: bupropion, haloperidol, and propranolol. Cell-based assays demonstrated ER-NDs' ability to mitigate drug-induced cytotoxicity, reduce oxidative stress, and restore antioxidant defenses. In mouse models of drug intoxication, ER-ND treatment significantly improved survival rates and alleviated drug-induced oxidative damage. Importantly, ER-NDs showed no evidence of acute toxicity <em>in vivo</em>. These findings underscore the potential of ER-NDs as a versatile platform for broad-spectrum drug detoxification and as a promising tool for managing drug intoxication in emergency and clinical settings.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123188"},"PeriodicalIF":12.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419224","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}
In diabetic-infected wounds, the local hyperglycemic state leads to unique pathological characteristics of diabetic ulcers, such as secondary chronic infections, abnormal angiogenesis, oxidative stress, and diabetic peripheral neuropathy. Glucose oxidase (GOx) is an enzyme that catalyzes the breakdown of glucose into hydrogen peroxide and gluconic acid, making it a candidate enzyme for regulating the hyperglycemic microenvironment in diabetic wounds. However, multifunctional hydrogel therapeutic systems built around the glucose-lowering capability of GOx have rarely been reported. Here, we loaded stachydrine and Au–FePS3 nanosheets onto a quaternized chitosan (QC) - oxidized dextran (OD) hydrogel to construct a synergistic QC-OD@AF/S hydrogel therapeutic system. In vitro experiments showed that Au–FePS3 possesses GOx-POD cascade catalytic activity, capable of reducing glucose concentration and decomposing generated hydrogen peroxide into reactive oxygen species (ROS). Concurrently, Au–FePS3 exhibits excellent photothermal performance under 808 nm infrared light, synergistically exerting antibacterial capabilities with ROS and quaternary ammonium groups. Stachydrine has been demonstrated to mediate the metabolic reprogramming of macrophages and alleviate high-glucose-induced oxidative stress and impairment of angiogenesis in HUVECs through the LARP7-SIRT1 pathway. In summary, the QC-OD@AF/S hydrogel demonstrates superior capabilities in antibacterial activity, immune modulation, promotion of angiogenesis, and reduction of local glucose concentration, making it a potential clinical therapy.
{"title":"Glucose-regulating hydrogel for immune modulation and angiogenesis through metabolic reprogramming and LARP7-SIRT1 pathway in infected diabetic wounds","authors":"Yuheng Liao , Zhenhe Zhang , Weixian Hu , Shengming Zhang , Yanzhi Zhao, Lizhi Ouyang, Chenyan Yu, Mengfei Liu, Bobin Mi, Guohui Liu","doi":"10.1016/j.biomaterials.2025.123182","DOIUrl":"10.1016/j.biomaterials.2025.123182","url":null,"abstract":"<div><div>In diabetic-infected wounds, the local hyperglycemic state leads to unique pathological characteristics of diabetic ulcers, such as secondary chronic infections, abnormal angiogenesis, oxidative stress, and diabetic peripheral neuropathy. Glucose oxidase (GOx) is an enzyme that catalyzes the breakdown of glucose into hydrogen peroxide and gluconic acid, making it a candidate enzyme for regulating the hyperglycemic microenvironment in diabetic wounds. However, multifunctional hydrogel therapeutic systems built around the glucose-lowering capability of GOx have rarely been reported. Here, we loaded stachydrine and Au–FePS<sub>3</sub> nanosheets onto a quaternized chitosan (QC) - oxidized dextran (OD) hydrogel to construct a synergistic QC-OD@AF/S hydrogel therapeutic system. In vitro experiments showed that Au–FePS<sub>3</sub> possesses GOx-POD cascade catalytic activity, capable of reducing glucose concentration and decomposing generated hydrogen peroxide into reactive oxygen species (ROS). Concurrently, Au–FePS<sub>3</sub> exhibits excellent photothermal performance under 808 nm infrared light, synergistically exerting antibacterial capabilities with ROS and quaternary ammonium groups. Stachydrine has been demonstrated to mediate the metabolic reprogramming of macrophages and alleviate high-glucose-induced oxidative stress and impairment of angiogenesis in <em>HUVECs</em> through the LARP7-SIRT1 pathway. In summary, the QC-OD@AF/S hydrogel demonstrates superior capabilities in antibacterial activity, immune modulation, promotion of angiogenesis, and reduction of local glucose concentration, making it a potential clinical therapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123182"},"PeriodicalIF":12.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403240","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}
Pub Date : 2025-02-11DOI: 10.1016/j.biomaterials.2025.123185
Qianqian Niu , Junjie Shen , Wenhao Liang , Suna Fan , Xiang Yao , Haifeng Wei , Yaopeng Zhang
Applying electrical stimulation (ES) on nerve or muscle denervation can significantly restore the nerve function and prevent muscle atrophy. The triboelectric nanogenerator (TENG) can couple the mechanical energy and electrical energy for ES. However, the triboelectric performance of fully biodegradable TENGs and the effect of ES need to be optimized and verified. Here, the triboelectric performance of silk fibroin (SF) is regulated by ions to fabricate SF-TENGs with full biodegradability, good biocompatibility, and excellent output. This SF-TENG shows a good electrostimulation recovery effect and is used for function restoration of the injured sciatic nerve and innervated muscle. Li+ effectively improves the dielectric constant and increases the positively charged ability of SF. The highest output power density of SF-TENG is 128 mW/m2, which is superior to most reported fully biodegradable TENGs. The morphology, protein expression levels, neural/muscular function are assessed to evaluate the recovery of damaged nerves and innervated muscle. The function restoration of the injured nerve and innervated muscle under ES of SF-TENG is significantly close to the normal nerve and muscle. This TENG has great potential to achieve in vivo energy generation, ES, and biodegradability as an implantable electrical stimulator for the therapy of nerve, muscle, and tissue injury.
{"title":"Fully biodegradable ion-induced silk fibroin-based triboelectric nanogenerators with enhanced performance prevent muscle atrophy","authors":"Qianqian Niu , Junjie Shen , Wenhao Liang , Suna Fan , Xiang Yao , Haifeng Wei , Yaopeng Zhang","doi":"10.1016/j.biomaterials.2025.123185","DOIUrl":"10.1016/j.biomaterials.2025.123185","url":null,"abstract":"<div><div>Applying electrical stimulation (ES) on nerve or muscle denervation can significantly restore the nerve function and prevent muscle atrophy. The triboelectric nanogenerator (TENG) can couple the mechanical energy and electrical energy for ES. However, the triboelectric performance of fully biodegradable TENGs and the effect of ES need to be optimized and verified. Here, the triboelectric performance of silk fibroin (SF) is regulated by ions to fabricate SF-TENGs with full biodegradability, good biocompatibility, and excellent output. This SF-TENG shows a good electrostimulation recovery effect and is used for function restoration of the injured sciatic nerve and innervated muscle. Li<sup>+</sup> effectively improves the dielectric constant and increases the positively charged ability of SF. The highest output power density of SF-TENG is 128 mW/m<sup>2</sup>, which is superior to most reported fully biodegradable TENGs. The morphology, protein expression levels, neural/muscular function are assessed to evaluate the recovery of damaged nerves and innervated muscle. The function restoration of the injured nerve and innervated muscle under ES of SF-TENG is significantly close to the normal nerve and muscle. This TENG has great potential to achieve <em>in vivo</em> energy generation, ES, and biodegradability as an implantable electrical stimulator for the therapy of nerve, muscle, and tissue injury.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123185"},"PeriodicalIF":12.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419223","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}
Pub Date : 2025-02-11DOI: 10.1016/j.biomaterials.2025.123177
Marrisa A. Therriault , Srividya Kottapalli , Amanda Artsen , Katrina Knight , Gabrielle King , Leslie Meyn , Bryan N. Brown , Pamela A. Moalli
Pelvic organ prolapse (POP) surgical repair with polypropylene mesh (PPM) offers improved anatomical outcomes compared to reconstruction using native tissue. However, PPM repair is hampered by complications, most commonly pain or mesh exposure, occurring in over 10 % of cases. This maladaptive response is, in part, attributed to the host response to a foreign material. Previous studies have demonstrated that mesh properties, such as weight, pore size, and porosity, influence downstream outcomes. In addition, computational models and in vivo mechanistic studies demonstrate that mesh deforms after tensioning in prolapse surgery resulting in collapsed pores and wrinkles. To further investigate the role of pore collapse in mesh complications, PPM was implanted flat, or in configurations that would deform upon tensioning in a POP repair surgery using a non-human primate model. After twelve weeks, we analyzed mesh-tissue complexes to characterize the overall host response, profile the macrophage response, and observe the influence of macrophages in downstream healing outcomes that may lead to complications. The results confirm that mesh deformations reproduce mesh exposure and thinning of vagina. In the PPM configurations with the greatest deformation, mesh burden was the highest, which resulted in an overall decrease in the number of cells within the implantation site. Among the cells that were present, we observed a predominance of M1 pro-inflammatory macrophages. While flat mesh was associated with an organized cellular response, deformed mesh led to an increasingly disorganized response as mesh burden increased. Nearly half of the responding macrophages expressed markers associated both with M1 and M2 phenotypes concurrently, suggesting the possibility of newly recruited macrophages responding even 12 weeks after implantation and/or a repetitive microinjury in which macrophages are continuously recruited and polarized without resolution of the host response. Biochemically, we observed a predominantly M1 pro-inflammatory signaling environment and decreased collagen content as a response to implanted mesh. This study evidences the importance of PPM mesh properties, which may alter mesh burden upon tensioning and impact downstream healing outcomes and emphasizes the need for devices that maintain their geometry following implantation in POP surgical repair.
{"title":"Profiling of the macrophage response to polypropylene mesh burden in vivo","authors":"Marrisa A. Therriault , Srividya Kottapalli , Amanda Artsen , Katrina Knight , Gabrielle King , Leslie Meyn , Bryan N. Brown , Pamela A. Moalli","doi":"10.1016/j.biomaterials.2025.123177","DOIUrl":"10.1016/j.biomaterials.2025.123177","url":null,"abstract":"<div><div>Pelvic organ prolapse (POP) surgical repair with polypropylene mesh (PPM) offers improved anatomical outcomes compared to reconstruction using native tissue. However, PPM repair is hampered by complications, most commonly pain or mesh exposure, occurring in over 10 % of cases. This maladaptive response is, in part, attributed to the host response to a foreign material. Previous studies have demonstrated that mesh properties, such as weight, pore size, and porosity, influence downstream outcomes. In addition, computational models and <em>in vivo</em> mechanistic studies demonstrate that mesh deforms after tensioning in prolapse surgery resulting in collapsed pores and wrinkles. To further investigate the role of pore collapse in mesh complications, PPM was implanted flat, or in configurations that would deform upon tensioning in a POP repair surgery using a non-human primate model. After twelve weeks, we analyzed mesh-tissue complexes to characterize the overall host response, profile the macrophage response, and observe the influence of macrophages in downstream healing outcomes that may lead to complications. The results confirm that mesh deformations reproduce mesh exposure and thinning of vagina. In the PPM configurations with the greatest deformation, mesh burden was the highest, which resulted in an overall decrease in the number of cells within the implantation site. Among the cells that were present, we observed a predominance of M1 pro-inflammatory macrophages. While flat mesh was associated with an organized cellular response, deformed mesh led to an increasingly disorganized response as mesh burden increased. Nearly half of the responding macrophages expressed markers associated both with M1 and M2 phenotypes concurrently, suggesting the possibility of newly recruited macrophages responding even 12 weeks after implantation and/or a repetitive microinjury in which macrophages are continuously recruited and polarized without resolution of the host response. Biochemically, we observed a predominantly M1 pro-inflammatory signaling environment and decreased collagen content as a response to implanted mesh. This study evidences the importance of PPM mesh properties, which may alter mesh burden upon tensioning and impact downstream healing outcomes and emphasizes the need for devices that maintain their geometry following implantation in POP surgical repair.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123177"},"PeriodicalIF":12.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419220","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}
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