Pub Date : 2025-01-22DOI: 10.1016/j.bioactmat.2025.01.015
Yaqian Li , Weijie Tian , Jianbin Guo , Yang Ye , Qianqian Gao , Yiwei Zhang , Xiaoyue Zhao , Jianwu Dai , Lan Zhu
Congenital deficiency or extensive cervical injury leads to female genital tract obstruction and cervical laxity, resulting in infertility or miscarriage. Current clinical approaches could be conducted to restore the continuity of cervix. However, full-thickness and large-scale cervical regeneration with complete structural and functional restoration have not been reported. In this study, we fabricated a double-layered collagen membrane (CM) scaffold based on decellularized extracellular matrix. Each layer was adapted to support the growth of epithelial cells and stromal cells, respectively. Further, the thickness and folded “sandwich” structure were tailored to match the cervical structure. When transplanted into rabbit full-thickness and total ectocervix excision models, only CM scaffold groups enabled the regeneration of neo-ectocervix tissue, including epithelium, stroma and muscular layers after 3 and 6 months. The neo-ectocervix regenerated by CM scaffolds exhibited significantly higher expression of secretory glands and estrogen receptors, more secretion of neutral and acidic mucins, showing functional maturity of regenerated epithelium. Notably, CM scaffolds supported the regeneration of stroma and muscular layers. The mechanical strength of neo ectocervix was comparable to that of normal ectocervix. CM scaffolds demonstrate good biocompatibility, support different cell growth, and enhance superior regeneration of epithelium, stromal and muscular tissue, confirming its construction capacity as new strategies for addressing cervical deficiency and damage.
{"title":"Full-thickness cervix reconstruction via collagen scaffolds in rabbits","authors":"Yaqian Li , Weijie Tian , Jianbin Guo , Yang Ye , Qianqian Gao , Yiwei Zhang , Xiaoyue Zhao , Jianwu Dai , Lan Zhu","doi":"10.1016/j.bioactmat.2025.01.015","DOIUrl":"10.1016/j.bioactmat.2025.01.015","url":null,"abstract":"<div><div>Congenital deficiency or extensive cervical injury leads to female genital tract obstruction and cervical laxity, resulting in infertility or miscarriage. Current clinical approaches could be conducted to restore the continuity of cervix. However, full-thickness and large-scale cervical regeneration with complete structural and functional restoration have not been reported. In this study, we fabricated a double-layered collagen membrane (CM) scaffold based on decellularized extracellular matrix. Each layer was adapted to support the growth of epithelial cells and stromal cells, respectively. Further, the thickness and folded “sandwich” structure were tailored to match the cervical structure. When transplanted into rabbit full-thickness and total ectocervix excision models, only CM scaffold groups enabled the regeneration of neo-ectocervix tissue, including epithelium, stroma and muscular layers after 3 and 6 months. The neo-ectocervix regenerated by CM scaffolds exhibited significantly higher expression of secretory glands and estrogen receptors, more secretion of neutral and acidic mucins, showing functional maturity of regenerated epithelium. Notably, CM scaffolds supported the regeneration of stroma and muscular layers. The mechanical strength of neo ectocervix was comparable to that of normal ectocervix. CM scaffolds demonstrate good biocompatibility, support different cell growth, and enhance superior regeneration of epithelium, stromal and muscular tissue, confirming its construction capacity as new strategies for addressing cervical deficiency and damage.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 170-180"},"PeriodicalIF":18.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135334","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}
Pub Date : 2025-01-22DOI: 10.1016/j.bioactmat.2025.01.010
Yu Zhang , Haiyan Liu , Weiqi Zhang , Yinghao Ding , Shengyi Zhang , Xiaowan Huang , Jiali Chen , Zhimou Yang , Feng Lin
Iodine is widely acknowledged for its potent antimicrobial properties. However, its clinical utility is often hampered by its unsatisfactory stability, uncontrolled release of active iodine and toxicity in moist environments. In this study, we report a novel iodine-containing hydrogel (I2@Nap-FFGP) designed for sustained iodine delivery under humid physiological and pathological conditions. I2@Nap-FFGP was fabricated using a self-assembling peptide-based hydrogel containing a proline motif to form a stable iodine complex. The resulting hydrogel exhibited excellent biocompatibility and robust antibacterial effect, it significantly inhibited bacteria-associated endometrial infections in mice and effectively alleviated inflammation. Moreover, the hydrogel successfully restored endometrial architecture and function. Notably, I2@Nap-FFGP remarkably improved pregnancy rates in mice with endometritis owing to its therapeutic effects. Our findings highlight the potential of this innovative hydrogel system for stable iodine application under humid and aqueous physiological conditions, offering a promising platform for future antibacterial therapies in clinical settings.
{"title":"Injectable iodine-containing peptide hydrogel for treatment of MRSA infection","authors":"Yu Zhang , Haiyan Liu , Weiqi Zhang , Yinghao Ding , Shengyi Zhang , Xiaowan Huang , Jiali Chen , Zhimou Yang , Feng Lin","doi":"10.1016/j.bioactmat.2025.01.010","DOIUrl":"10.1016/j.bioactmat.2025.01.010","url":null,"abstract":"<div><div>Iodine is widely acknowledged for its potent antimicrobial properties. However, its clinical utility is often hampered by its unsatisfactory stability, uncontrolled release of active iodine and toxicity in moist environments. In this study, we report a novel iodine-containing hydrogel (I<sub>2</sub>@Nap-FFGP) designed for sustained iodine delivery under humid physiological and pathological conditions. I<sub>2</sub>@Nap-FFGP was fabricated using a self-assembling peptide-based hydrogel containing a proline motif to form a stable iodine complex. The resulting hydrogel exhibited excellent biocompatibility and robust antibacterial effect, it significantly inhibited bacteria-associated endometrial infections in mice and effectively alleviated inflammation. Moreover, the hydrogel successfully restored endometrial architecture and function. Notably, I<sub>2</sub>@Nap-FFGP remarkably improved pregnancy rates in mice with endometritis owing to its therapeutic effects. Our findings highlight the potential of this innovative hydrogel system for stable iodine application under humid and aqueous physiological conditions, offering a promising platform for future antibacterial therapies in clinical settings.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 198-208"},"PeriodicalIF":18.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135379","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}
Pub Date : 2025-01-22DOI: 10.1016/j.bioactmat.2025.01.016
Danmei Li , Shuai Li , Shukun He , Hongpu He , Guangxun Yuan , Binbin Ma , Yijun Zhang , Chengjie Yuan , Zhiqin Liu , Zhenhan Deng , Jian Xu
Tendinopathy is a common musculoskeletal disorder in which a significant number of patients do not attain effective therapeutic outcomes. The extent of the inflammatory response and the dynamics of collagen synthesis metabolism are critical factors that influence the intrinsic self-repair capacity of tendons. However, the poor microenvironment within the tendon significantly impedes the self-repair process in tendinopathy. In this study, an injectable tendon-derived decellularized extracellular matrix (tdECM) hydrogel was utilized to treat tendinopathy. This hydrogel provides a more cytocompatible microenvironment while retaining certain bioactive factors of native tendon extracellular matrix (ECM), compared to collagen hydrogel. Notably, it was discovered for the first time that the tdECM hydrogel promotes M2 macrophage polarization, thereby exerting an anti-inflammatory effect in vivo. Furthermore, utilizing tdECM as a carrier for the sustained release of tendon-derived stem cells exosomes (TDSCs-Exos), our findings from both in vitro and in vivo studies indicate that the tdECM hydrogel, in conjunction with exosomes, demonstrated a pronounced synergistic enhancement in modulating inflammation, promoting M2 macrophage polarization, and facilitating tendon regeneration and repair efficacy. These results suggest its potential as a promising therapeutic strategy for tendon disorders.
{"title":"Restoring tendon microenvironment in tendinopathy: Macrophage modulation and tendon regeneration with injectable tendon hydrogel and tendon-derived stem cells exosomes","authors":"Danmei Li , Shuai Li , Shukun He , Hongpu He , Guangxun Yuan , Binbin Ma , Yijun Zhang , Chengjie Yuan , Zhiqin Liu , Zhenhan Deng , Jian Xu","doi":"10.1016/j.bioactmat.2025.01.016","DOIUrl":"10.1016/j.bioactmat.2025.01.016","url":null,"abstract":"<div><div>Tendinopathy is a common musculoskeletal disorder in which a significant number of patients do not attain effective therapeutic outcomes. The extent of the inflammatory response and the dynamics of collagen synthesis metabolism are critical factors that influence the intrinsic self-repair capacity of tendons. However, the poor microenvironment within the tendon significantly impedes the self-repair process in tendinopathy. In this study, an injectable tendon-derived decellularized extracellular matrix (tdECM) hydrogel was utilized to treat tendinopathy. This hydrogel provides a more cytocompatible microenvironment while retaining certain bioactive factors of native tendon extracellular matrix (ECM), compared to collagen hydrogel. Notably, it was discovered for the first time that the tdECM hydrogel promotes M2 macrophage polarization, thereby exerting an anti-inflammatory effect in vivo. Furthermore, utilizing tdECM as a carrier for the sustained release of tendon-derived stem cells exosomes (TDSCs-Exos), our findings from both in vitro and in vivo studies indicate that the tdECM hydrogel, in conjunction with exosomes, demonstrated a pronounced synergistic enhancement in modulating inflammation, promoting M2 macrophage polarization, and facilitating tendon regeneration and repair efficacy. These results suggest its potential as a promising therapeutic strategy for tendon disorders.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 152-169"},"PeriodicalIF":18.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135378","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}
Pub Date : 2025-01-22DOI: 10.1016/j.bioactmat.2025.01.017
Kaichao Hu , Junrui Ye , Pinglong Fan , Ruifang Zheng , Shasha Wang , Ye Peng , Yuan Ruan , Xu Yan , Zhao Zhang , Shifeng Chu , Naihong Chen
Stroke remains one of the leading causes of adult disability worldwide, with neovascularization is crucial for brain repair after stroke. However, neutrophil infiltration hinders effective neovascularization, necessitating timely clearance by microglia through phagocytosis. Unfortunately, microglial phagocytic function is often impaired by metabolic defects, hindering post-stroke recovery. Ginsenoside Rg1, derived from Panax ginseng, exhibits neuroprotective properties and regulates cellular metabolism in vitro but its therapeutic application is limited by poor brain penetration. Here, we present a targeted delivery system utilizing neutrophil-like cell membrane vesicles (NCM), prepared via nitrogen cavitation, to enhance Rg1 delivery to the brain. These biomimetic vesicles exploit the inherent targeting ability of neutrophil membranes to reach brain injury sites and are subsequently taken up by microglia. Our findings demonstrate that Rg1-loaded vesicles enhance microglial clearance of neutrophils, reduce neutrophil extracellular traps release, and mitigate tissue damage. These effects improve the post-stroke microenvironment, promote vascular remodeling, and ultimately contribute to functional recovery. This strategy highlights the potential of targeted reprogramming microglial cells to enhance their endogenous repair capabilities, offering a promising therapeutic avenue for ischemic stroke management.
{"title":"Targeting and reprogramming microglial phagocytosis of neutrophils by ginsenoside Rg1 nanovesicles promotes stroke recovery","authors":"Kaichao Hu , Junrui Ye , Pinglong Fan , Ruifang Zheng , Shasha Wang , Ye Peng , Yuan Ruan , Xu Yan , Zhao Zhang , Shifeng Chu , Naihong Chen","doi":"10.1016/j.bioactmat.2025.01.017","DOIUrl":"10.1016/j.bioactmat.2025.01.017","url":null,"abstract":"<div><div>Stroke remains one of the leading causes of adult disability worldwide, with neovascularization is crucial for brain repair after stroke. However, neutrophil infiltration hinders effective neovascularization, necessitating timely clearance by microglia through phagocytosis. Unfortunately, microglial phagocytic function is often impaired by metabolic defects, hindering post-stroke recovery. Ginsenoside Rg1, derived from Panax ginseng, exhibits neuroprotective properties and regulates cellular metabolism <em>in vitro</em> but its therapeutic application is limited by poor brain penetration. Here, we present a targeted delivery system utilizing neutrophil-like cell membrane vesicles (NCM), prepared via nitrogen cavitation, to enhance Rg1 delivery to the brain. These biomimetic vesicles exploit the inherent targeting ability of neutrophil membranes to reach brain injury sites and are subsequently taken up by microglia. Our findings demonstrate that Rg1-loaded vesicles enhance microglial clearance of neutrophils, reduce neutrophil extracellular traps release, and mitigate tissue damage. These effects improve the post-stroke microenvironment, promote vascular remodeling, and ultimately contribute to functional recovery. This strategy highlights the potential of targeted reprogramming microglial cells to enhance their endogenous repair capabilities, offering a promising therapeutic avenue for ischemic stroke management.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 181-197"},"PeriodicalIF":18.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135333","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}
Pub Date : 2025-01-20DOI: 10.1016/j.bioactmat.2025.01.007
Yaqiang Li , Xiaowei Xun , Liang Duan , Erji Gao , Jiaxin Li , Lei Lin , Xinping Li , Aijuan He , Haiyong Ao , Yong Xu , Huitang Xia
Tissue engineering strategies hold promise for constructing biomimetic tracheal substitutes to repair circumferential tracheal defects. However, current strategies for constructing off-the-shelf cartilage analogs for artificial trachea grafts face challenges of chondrocyte scarcity and inadequate culture strategies, which require extensive cell expansion and prolonged in vitro culture to generate robust neo-cartilage. To address these issues, we developed a nanofiber-hydrogel composite with superior mechanical performance by incorporating fragment oxidized bacterial cellulose (BC) nanofibers into a gelatin methacryloyl (GelMA) hydrogel network. Additionally, a biomaterial system was developed based on this composite, featuring dual-release functionality of fibroblast growth factor (FGF) and transforming growth factor beta (TGF-β) to facilitate step-wise maturation of neo-cartilage tissue. This process includes early-stage proliferation followed by second-stage extracellular matrix (ECM) deposition, driving the transition from proliferation to chondrogenesis. By encapsulating chondrocytes within the biomaterial system, mature neo-cartilage tissues with typical cartilage lacunae structures and abundant homogeneous cartilage-specific ECM deposition were successfully regenerated in vitro and in vivo. Furthermore, with a tailor-made growth factor-releasing strategy, the biomaterial system with low cell seeding density achieved biochemically and biomechanically functional neo-cartilage tissue regeneration, comparable to that achieved with high cell seeding density in the nanofiber-hydrogel composite. Based on the current biomaterial system, mature and functional cartilage-ring analogs were successfully constructed and applied to repair tracheal defects. Overall, the biomaterial system developed in this study provides a promising strategy for engineering transplantable, high-quality cartilage substitutes, with translational potential for artificial trachea construction.
{"title":"Cartilage structure-inspired nanofiber-hydrogel composite with robust proliferation and stable chondral lineage-specific differentiation function to orchestrate cartilage regeneration for artificial tracheal construction","authors":"Yaqiang Li , Xiaowei Xun , Liang Duan , Erji Gao , Jiaxin Li , Lei Lin , Xinping Li , Aijuan He , Haiyong Ao , Yong Xu , Huitang Xia","doi":"10.1016/j.bioactmat.2025.01.007","DOIUrl":"10.1016/j.bioactmat.2025.01.007","url":null,"abstract":"<div><div>Tissue engineering strategies hold promise for constructing biomimetic tracheal substitutes to repair circumferential tracheal defects. However, current strategies for constructing off-the-shelf cartilage analogs for artificial trachea grafts face challenges of chondrocyte scarcity and inadequate culture strategies, which require extensive cell expansion and prolonged <em>in vitro</em> culture to generate robust neo-cartilage. To address these issues, we developed a nanofiber-hydrogel composite with superior mechanical performance by incorporating fragment oxidized bacterial cellulose (BC) nanofibers into a gelatin methacryloyl (GelMA) hydrogel network. Additionally, a biomaterial system was developed based on this composite, featuring dual-release functionality of fibroblast growth factor (FGF) and transforming growth factor beta (TGF-β) to facilitate step-wise maturation of neo-cartilage tissue. This process includes early-stage proliferation followed by second-stage extracellular matrix (ECM) deposition, driving the transition from proliferation to chondrogenesis. By encapsulating chondrocytes within the biomaterial system, mature neo-cartilage tissues with typical cartilage lacunae structures and abundant homogeneous cartilage-specific ECM deposition were successfully regenerated <em>in vitro</em> and <em>in vivo</em>. Furthermore, with a tailor-made growth factor-releasing strategy, the biomaterial system with low cell seeding density achieved biochemically and biomechanically functional neo-cartilage tissue regeneration, comparable to that achieved with high cell seeding density in the nanofiber-hydrogel composite. Based on the current biomaterial system, mature and functional cartilage-ring analogs were successfully constructed and applied to repair tracheal defects. Overall, the biomaterial system developed in this study provides a promising strategy for engineering transplantable, high-quality cartilage substitutes, with translational potential for artificial trachea construction.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 136-151"},"PeriodicalIF":18.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078449","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}
Pub Date : 2025-01-19DOI: 10.1016/j.bioactmat.2025.01.009
Kanghyeon Kim , Sunhong Min , Ramar Thangam , Kyong-Ryol Tag , Hyun-Jeong Lee , Jeongyun Heo , Hwapyung Jung , Thet Thet Swe , Iman Zare , Guosheng Song , Alireza Hassani Najafabadi , Junmin Lee , Hyun-Do Jung , Jong Seung Kim , Sunghoon Hur , Hyun-Cheol Song , Sung-Gyu Park , Kunyu Zhang , Pengchao Zhao , Liming Bian , Heemin Kang
Diverse connective tissues exhibit hierarchical anisotropic structures that intricately regulate homeostasis and tissue functions for dynamic immune response modulation. In this study, remotely manipulable hierarchical nanostructures are tailored to exhibit multi-scale ligand anisotropy. Hierarchical nanostructure construction involves coupling liganded nanoscale isotropic/anisotropic Au (comparable to few integrin molecules-scale) to the surface of microscale isotropic/anisotropic magnetic Fe3O4 (comparable to integrin cluster-scale) and then elastically tethering them to a substrate. Systematic independent tailoring of nanoscale or microscale ligand isotropy versus anisotropy in four different hierarchical nanostructures with constant liganded surface area demonstrates similar levels of integrin molecule bridging and macrophage adhesion on the nanoscale ligand isotropy versus anisotropy. Conversely, the levels of integrin cluster bridging across hierarchical nanostructures and macrophage adhesion are significantly promoted by microscale ligand anisotropy compared with microscale ligand isotropy. Furthermore, microscale ligand anisotropy dominantly activates the host macrophage adhesion and pro-regenerative M2 polarization in vivo over the nanoscale ligand anisotropy, which can be cyclically reversed by substrate-proximate versus substrate-distant magnetic manipulation. This unprecedented scale-specific regulation of cells can be diversified by unlimited tuning of the scale, anisotropy, dimension, shape, and magnetism of hierarchical structures to decipher scale-specific dynamic cell-material interactions to advance immunoengineering strategies.
{"title":"Dynamic hierarchical ligand anisotropy for competing macrophage regulation in vivo","authors":"Kanghyeon Kim , Sunhong Min , Ramar Thangam , Kyong-Ryol Tag , Hyun-Jeong Lee , Jeongyun Heo , Hwapyung Jung , Thet Thet Swe , Iman Zare , Guosheng Song , Alireza Hassani Najafabadi , Junmin Lee , Hyun-Do Jung , Jong Seung Kim , Sunghoon Hur , Hyun-Cheol Song , Sung-Gyu Park , Kunyu Zhang , Pengchao Zhao , Liming Bian , Heemin Kang","doi":"10.1016/j.bioactmat.2025.01.009","DOIUrl":"10.1016/j.bioactmat.2025.01.009","url":null,"abstract":"<div><div>Diverse connective tissues exhibit hierarchical anisotropic structures that intricately regulate homeostasis and tissue functions for dynamic immune response modulation. In this study, remotely manipulable hierarchical nanostructures are tailored to exhibit multi-scale ligand anisotropy. Hierarchical nanostructure construction involves coupling liganded nanoscale isotropic/anisotropic Au (comparable to few integrin molecules-scale) to the surface of microscale isotropic/anisotropic magnetic Fe<sub>3</sub>O<sub>4</sub> (comparable to integrin cluster-scale) and then elastically tethering them to a substrate. Systematic independent tailoring of nanoscale or microscale ligand isotropy versus anisotropy in four different hierarchical nanostructures with constant liganded surface area demonstrates similar levels of integrin molecule bridging and macrophage adhesion on the nanoscale ligand isotropy versus anisotropy. Conversely, the levels of integrin cluster bridging across hierarchical nanostructures and macrophage adhesion are significantly promoted by microscale ligand anisotropy compared with microscale ligand isotropy. Furthermore, microscale ligand anisotropy dominantly activates the host macrophage adhesion and pro-regenerative M2 polarization <em>in vivo</em> over the nanoscale ligand anisotropy, which can be cyclically reversed by substrate-proximate versus substrate-distant magnetic manipulation. This unprecedented scale-specific regulation of cells can be diversified by unlimited tuning of the scale, anisotropy, dimension, shape, and magnetism of hierarchical structures to decipher scale-specific dynamic cell-material interactions to advance immunoengineering strategies.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 121-135"},"PeriodicalIF":18.0,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078450","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}
Pub Date : 2025-01-18DOI: 10.1016/j.bioactmat.2025.01.011
Mingyang Li , Tao Deng , Quan Chen , Shenghu Jiang , Hang Li , Jiayi Li , Shenglan You , Hui-qi Xie , Bin Shen
Matrix metalloproteinases (MMPs), coupled with other proteinases and glycanases, can degrade proteoglycans, collagens, and other extracellular matrix (ECM) components in inflammatory and non-inflammatory arthritis, making them important pathogenic molecules and ideal disease indicators and pharmaceutical intervention triggers. For MMP responsiveness, MMP-sensitive peptides (MSPs) are among the most easily synthesized and cost-effective substrates, with free terminal amine and/or carboxyl groups extensively employed in multiple designs. We hereby provide a comprehensive review over the mechanisms and advances in MSP applications for the management of arthritis. These applications include early and precise diagnosis of MMP activity via fluorescence probe technologies; acting as nanodrug carriers to enable on-demand drug release triggered by pathological microenvironments; and facilitating cartilage engineering through MMP-mediated degradation, which promotes cell migration, matrix synthesis, and tissue integration. Specifically, the ultra-sensitive MSP diagnostic probes could significantly advance the early diagnosis and detection of osteoarthritis (OA), while MSP-based drug carriers for rheumatoid arthritis (RA) can intelligently release anti-inflammatory drugs effectively during flare-ups, or even before symptoms manifest. The continuous progress in MSP development may acceleratedly lead to novel management regimens for arthropathy in the future.
{"title":"A versatile platform based on matrix metalloproteinase-sensitive peptides for novel diagnostic and therapeutic strategies in arthritis","authors":"Mingyang Li , Tao Deng , Quan Chen , Shenghu Jiang , Hang Li , Jiayi Li , Shenglan You , Hui-qi Xie , Bin Shen","doi":"10.1016/j.bioactmat.2025.01.011","DOIUrl":"10.1016/j.bioactmat.2025.01.011","url":null,"abstract":"<div><div>Matrix metalloproteinases (MMPs), coupled with other proteinases and glycanases, can degrade proteoglycans, collagens, and other extracellular matrix (ECM) components in inflammatory and non-inflammatory arthritis, making them important pathogenic molecules and ideal disease indicators and pharmaceutical intervention triggers. For MMP responsiveness, MMP-sensitive peptides (MSPs) are among the most easily synthesized and cost-effective substrates, with free terminal amine and/or carboxyl groups extensively employed in multiple designs. We hereby provide a comprehensive review over the mechanisms and advances in MSP applications for the management of arthritis. These applications include early and precise diagnosis of MMP activity via fluorescence probe technologies; acting as nanodrug carriers to enable on-demand drug release triggered by pathological microenvironments; and facilitating cartilage engineering through MMP-mediated degradation, which promotes cell migration, matrix synthesis, and tissue integration. Specifically, the ultra-sensitive MSP diagnostic probes could significantly advance the early diagnosis and detection of osteoarthritis (OA), while MSP-based drug carriers for rheumatoid arthritis (RA) can intelligently release anti-inflammatory drugs effectively during flare-ups, or even before symptoms manifest. The continuous progress in MSP development may acceleratedly lead to <span><span>novel</span><svg><path></path></svg></span> management regimens for arthropathy in the future.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 100-120"},"PeriodicalIF":18.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078519","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}
Pub Date : 2025-01-14DOI: 10.1016/j.bioactmat.2025.01.006
Yichao Ma , Peng Lai , Zhou Sha , Bing Li , Jiangpeng Wu , Xiaojun Zhou , Chuanglong He , Xiaojun Ma
The oncogene MYC is one of the most commonly activated oncogenic proteins in human tumors, with nearly one-fourth of osteosarcoma showing MYC amplification and exhibiting the worst clinical outcomes. The clinical efficacy of single radiotherapy, chemotherapy, and immunotherapy for such osteosarcoma is poor, and the dysregulation of MYC amplification and immune-suppressive tumor microenvironment (TME) may be potential causes of anti-tumor failure. To address the above issues, we developed an injectable TME-responsive nanocomposite hydrogel to simultaneously deliver an effective MYC inhibitor (NHWD-870) and IL11Rα-targeted liposomes containing cisplatin-loaded MnO2 (Cis/Mn@Lipo-IL11). After in situ administration, NHWD-870 effectively degrades MYC and downregulates CCL2 and IL13 cytokines to trigger M1 type activation of macrophages. Meanwhile, targeted delivery of Cis/Mn@Lipo-IL11 reacts with excess intratumoral GSH to generate Mn2+ and thus inducing excess active oxygen species (ROS) production through Fenton-like reaction, along with cisplatin, thereby inducing immunogenic cell death (ICD) to promote dendritic cell maturation. Through synergistic regulation of MYC and ICD levels, the immune microenvironment was reshaped to enhance immune infiltration. In the osteosarcoma-bearing model, the nanocomposite hydrogel significantly enhanced tumor T cell infiltration, induced effective anti-tumor immunity and attenuated lung metastasis. Therefore, our results reveal a powerful strategy for targeted combination therapy of MYC-amplified osteosarcoma.
{"title":"TME-responsive nanocomposite hydrogel with targeted capacity for enhanced synergistic chemoimmunotherapy of MYC-amplified osteosarcoma","authors":"Yichao Ma , Peng Lai , Zhou Sha , Bing Li , Jiangpeng Wu , Xiaojun Zhou , Chuanglong He , Xiaojun Ma","doi":"10.1016/j.bioactmat.2025.01.006","DOIUrl":"10.1016/j.bioactmat.2025.01.006","url":null,"abstract":"<div><div>The oncogene MYC is one of the most commonly activated oncogenic proteins in human tumors, with nearly one-fourth of osteosarcoma showing MYC amplification and exhibiting the worst clinical outcomes. The clinical efficacy of single radiotherapy, chemotherapy, and immunotherapy for such osteosarcoma is poor, and the dysregulation of MYC amplification and immune-suppressive tumor microenvironment (TME) may be potential causes of anti-tumor failure. To address the above issues, we developed an injectable TME-responsive nanocomposite hydrogel to simultaneously deliver an effective MYC inhibitor (NHWD-870) and IL11Rα-targeted liposomes containing cisplatin-loaded MnO<sub>2</sub> (Cis/Mn@Lipo-IL11). After <em>in situ</em> administration, NHWD-870 effectively degrades MYC and downregulates CCL2 and IL13 cytokines to trigger M1 type activation of macrophages. Meanwhile, targeted delivery of Cis/Mn@Lipo-IL11 reacts with excess intratumoral GSH to generate Mn<sup>2+</sup> and thus inducing excess active oxygen species (ROS) production through Fenton-like reaction, along with cisplatin, thereby inducing immunogenic cell death (ICD) to promote dendritic cell maturation. Through synergistic regulation of MYC and ICD levels, the immune microenvironment was reshaped to enhance immune infiltration. In the osteosarcoma-bearing model, the nanocomposite hydrogel significantly enhanced tumor T cell infiltration, induced effective anti-tumor immunity and attenuated lung metastasis. Therefore, our results reveal a powerful strategy for targeted combination therapy of MYC-amplified osteosarcoma.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 83-99"},"PeriodicalIF":18.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078451","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}
Pub Date : 2025-01-13DOI: 10.1016/j.bioactmat.2024.12.022
Jinpeng Zhao , Banghui Wang , Mingzhe Yan , Yuxin Liu , Ruizhe Zhao , Xuezhe Wang , Tianyi Shao , Yifei Li , Muhammad Imran , Mingze Ji , Hong Zhao , Carlos F. Guimarães , Guotai Li , Qihui Zhou , Rui L. Reis
Enzyme-powered micro/nanomotors (EMNMs) represent cutting-edge research taking advantage of enzymes as biocatalysts to provide a driving force for micro/nanomotors. Up to now, EMNMs have been designed to be powered by catalase, urease, lipase, collagenase, compound enzymes, etc. They not only have good biocompatibility and biosafety but also possess the unique ability to utilize physiologically relevant fuel to achieve autonomous propulsion through in vivo catalytic reactions. This innovation has opened exciting possibilities for medical applications of EMNMs. Given the fact that the human body is naturally abundant with substrates available for enzymatic reactions, EMNMs can effectively exploit the complex microenvironment associated with diseases, enabling the diagnosis and treatment of various medical conditions. In this review, we first introduce different kinds of EMNMs applied in specific environments for the diagnosis and treatment of diseases, while highlighting their advancements for revolutionizing healthcare practices. Then, we address the challenges faced in this rapidly evolving field, and at last, the potential future development directions are discussed. As the potential of EMNMs becomes increasingly evident, continued research and exploration are essential to unlock their full capabilities and to ensure their successful integration into clinical applications.
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