Pub Date : 2025-02-01DOI: 10.1016/j.mtbio.2024.101385
Yuzhao Cheng , Xin Dong , Jing Shi , Guangsheng Wu , Pei Tao , Nan Ren , Yimin Zhao , Fenglan Li , Zhongshan Wang
M2 macrophage–derived extracellular vesicles (M2-EVs) demonstrate the capacity to reduce pro-inflammatory M1 macrophage formation, thereby restoring the M1–M2 macrophage balance and promoting immunoregulation. However, the efficacy of M2-EVs in regulating macrophage polarization and subsequently enhancing osseointegration around titanium (Ti) implants in patients with diabetes mellitus (DM) remains to be elucidated. In this study, Ti implants were coated with polydopamine to facilitate M2-EVs adherence. In vitro experiment results demonstrated that M2-EVs could carry miR-23a-3p, inhibiting NOD-like receptor protein3(NLRP3) inflammasome activation in M1 macrophage and reducing the levels of inflammatory cytokines such as IL-1β by targeting NEK7. This improved the M1–M2 macrophage balance and enhanced mineralization on the Ti implant surfaces. The in vivo experiment results demonstrated that in diabetic conditions, the nanocoated M2-EVs significantly promoted high-quality bone deposition around the Ti implants. The current results provide a novel perspective for simple and effective decoration of M2-EVs on Ti implants; clinically, the method may afford osteoimmunomodulatory effects enhancing implant osseointegration in patients with DM.
{"title":"Immunomodulation with M2 macrophage–derived extracellular vesicles for enhanced titanium implant osseointegration under diabetic conditions","authors":"Yuzhao Cheng , Xin Dong , Jing Shi , Guangsheng Wu , Pei Tao , Nan Ren , Yimin Zhao , Fenglan Li , Zhongshan Wang","doi":"10.1016/j.mtbio.2024.101385","DOIUrl":"10.1016/j.mtbio.2024.101385","url":null,"abstract":"<div><div>M2 macrophage–derived extracellular vesicles (M2-EVs) demonstrate the capacity to reduce pro-inflammatory M1 macrophage formation, thereby restoring the M1–M2 macrophage balance and promoting immunoregulation. However, the efficacy of M2-EVs in regulating macrophage polarization and subsequently enhancing osseointegration around titanium (Ti) implants in patients with diabetes mellitus (DM) remains to be elucidated. In this study, Ti implants were coated with polydopamine to facilitate M2-EVs adherence. In vitro experiment results demonstrated that M2-EVs could carry miR-23a-3p, inhibiting NOD-like receptor protein3(NLRP3) inflammasome activation in M1 macrophage and reducing the levels of inflammatory cytokines such as IL-1β by targeting NEK7. This improved the M1–M2 macrophage balance and enhanced mineralization on the Ti implant surfaces. The in vivo experiment results demonstrated that in diabetic conditions, the nanocoated M2-EVs significantly promoted high-quality bone deposition around the Ti implants. The current results provide a novel perspective for simple and effective decoration of M2-EVs on Ti implants; clinically, the method may afford osteoimmunomodulatory effects enhancing implant osseointegration in patients with DM.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101385"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914868","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 : 2025-02-01DOI: 10.1016/j.mtbio.2024.101401
Lorenz Isert , Mehak Passi , Benedikt Freystetter , Maximilian Grab , Andreas Roidl , Christoph Müller , Aditi Mehta , Harini G. Sundararaghavan , Stefan Zahler , Olivia M. Merkel
In this study, an advanced nanofiber breast cancer in vitro model was developed and systematically characterized including physico-chemical, cell-biological and biophysical parameters. Using electrospinning, the architecture of tumor-associated collagen signatures (TACS5 and TACS6) was mimicked. By employing a rotating cylinder or static plate collector set-up, aligned fibers (TACS5-like structures) and randomly orientated fibers (TACS6-like structures) fibers were produced, respectively. The biocompatibility of these fibers was enhanced by collagen coating, ensuring minimal toxicity and improved cell attachment. Various breast cancer cell lines (MCF7, HCC1954, MDA-MB-468, and MDA-MB-231) were cultured on these fibers to assess epithelial-to-mesenchymal transition (EMT) markers, cellular morphology, and migration.
Aligned fibers (TACS5) significantly influenced EMT-related changes, promoting cellular alignment, spindle-shaped morphology and a highly migratory phenotype in mesenchymal and hybrid EMT cells (MDA-MB-468, MDA-MB-231). Conversely, epithelial cells (MCF7, HCC1954) showed limited response, but - under growth factor treatment - started to infiltrate the fibrous scaffold and underwent EMT-like changes, particularly on TACS5-mimicks, emphasizing the interplay of topographical cues and EMT induction.
The biophysical analysis revealed a clear correlation between cellular EMT status and cell mechanics, with increased EMT correlating to decreased total cellular stiffness. Cancer cell mechanics, however, were found to be dynamic during biochemical and topographical EMT-induction, exceeding initial stiffness by up to 2-fold. These findings highlight the potential of TACS5-like nanofiber scaffolds in modeling the tumor microenvironment and studying cancer cell behavior and mechanics.
{"title":"Cellular EMT-status governs contact guidance in an electrospun TACS-mimicking in vitro model","authors":"Lorenz Isert , Mehak Passi , Benedikt Freystetter , Maximilian Grab , Andreas Roidl , Christoph Müller , Aditi Mehta , Harini G. Sundararaghavan , Stefan Zahler , Olivia M. Merkel","doi":"10.1016/j.mtbio.2024.101401","DOIUrl":"10.1016/j.mtbio.2024.101401","url":null,"abstract":"<div><div>In this study, an advanced nanofiber breast cancer <em>in vitro</em> model was developed and systematically characterized including physico-chemical, cell-biological and biophysical parameters. Using electrospinning, the architecture of tumor-associated collagen signatures (TACS5 and TACS6) was mimicked. By employing a rotating cylinder or static plate collector set-up, aligned fibers (TACS5-like structures) and randomly orientated fibers (TACS6-like structures) fibers were produced, respectively. The biocompatibility of these fibers was enhanced by collagen coating, ensuring minimal toxicity and improved cell attachment. Various breast cancer cell lines (MCF7, HCC1954, MDA-MB-468, and MDA-MB-231) were cultured on these fibers to assess epithelial-to-mesenchymal transition (EMT) markers, cellular morphology, and migration.</div><div>Aligned fibers (TACS5) significantly influenced EMT-related changes, promoting cellular alignment, spindle-shaped morphology and a highly migratory phenotype in mesenchymal and hybrid EMT cells (MDA-MB-468, MDA-MB-231). Conversely, epithelial cells (MCF7, HCC1954) showed limited response, but - under growth factor treatment - started to infiltrate the fibrous scaffold and underwent EMT-like changes, particularly on TACS5-mimicks, emphasizing the interplay of topographical cues and EMT induction.</div><div>The biophysical analysis revealed a clear correlation between cellular EMT status and cell mechanics, with increased EMT correlating to decreased total cellular stiffness. Cancer cell mechanics, however, were found to be dynamic during biochemical and topographical EMT-induction, exceeding initial stiffness by up to 2-fold. These findings highlight the potential of TACS5-like nanofiber scaffolds in modeling the tumor microenvironment and studying cancer cell behavior and mechanics.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101401"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932121","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 : 2025-02-01DOI: 10.1016/j.mtbio.2024.101403
Teng Wan , Qi-Cheng Li , Feng-Shi Zhang , Xiao-Meng Zhang , Na Han , Pei-Xun Zhang
Recent advancements in tissue engineering have promoted the development of nerve guidance conduits (NGCs) that significantly enhance peripheral nerve injury treatment, improving outcomes and recovery rates. However, utilising tailored biomimetic three-dimensional (3D) topological porous structures combined with multiple bio-effect neurotrophic factors to create environments similar to neural tissues, regulate local immune responses, and develop a supportive microenvironment to promote peripheral nerve regeneration and repair poses significant challenges. Herein, a biomimetic extracellular matrix (ECM) NGC featuring an interconnected 3D porous network and sustained delivery of insulin-like growth factor-1 (IGF-1) is designed using multi-functional gelatine microcapsules (GMs). Nerve conduits made by blending chitosan (CS) with GMs demonstrate suitable degradation rates, reduced swelling rates, increased suture tensile strength, improved elongation at break, and 50 % radial compression performance that meet clinical application requirements. In vitro cytological studies indicate that biomimetic ECM NGCs exhibit good biocompatibility, promote early survival, proliferation, and remyelination potential of Schwann cells (SCs), and support neurite outgrowth. The biomimetic ECM NGCs comprising a 3D interconnected porous network in a 10-mm sciatic nerve defect rat model sustain IGF-1 delivery, promoting early infiltration of macrophages and polarisation towards M2-type macrophages. Furthermore, observations at 12 weeks post-implantation revealed improvements in electrophysiological performance, alleviation of gastrocnemius muscle atrophy, increased peripheral nerve regeneration, and motor function restoration. Thus, biomimetic ECM NGCs offer a therapeutic strategy for peripheral nerve regeneration with promising clinical applications and transformation prospects to regulate immune microenvironments, promoting SC proliferation and differentiation with nerve axon growth.
{"title":"Biomimetic ECM nerve guidance conduit with dynamic 3D interconnected porous network and sustained IGF-1 delivery for enhanced peripheral nerve regeneration and immune modulation","authors":"Teng Wan , Qi-Cheng Li , Feng-Shi Zhang , Xiao-Meng Zhang , Na Han , Pei-Xun Zhang","doi":"10.1016/j.mtbio.2024.101403","DOIUrl":"10.1016/j.mtbio.2024.101403","url":null,"abstract":"<div><div>Recent advancements in tissue engineering have promoted the development of nerve guidance conduits (NGCs) that significantly enhance peripheral nerve injury treatment, improving outcomes and recovery rates. However, utilising tailored biomimetic three-dimensional (3D) topological porous structures combined with multiple bio-effect neurotrophic factors to create environments similar to neural tissues, regulate local immune responses, and develop a supportive microenvironment to promote peripheral nerve regeneration and repair poses significant challenges. Herein, a biomimetic extracellular matrix (ECM) NGC featuring an interconnected 3D porous network and sustained delivery of insulin-like growth factor-1 (IGF-1) is designed using multi-functional gelatine microcapsules (GMs). Nerve conduits made by blending chitosan (CS) with GMs demonstrate suitable degradation rates, reduced swelling rates, increased suture tensile strength, improved elongation at break, and 50 % radial compression performance that meet clinical application requirements. In vitro cytological studies indicate that biomimetic ECM NGCs exhibit good biocompatibility, promote early survival, proliferation, and remyelination potential of Schwann cells (SCs), and support neurite outgrowth. The biomimetic ECM NGCs comprising a 3D interconnected porous network in a 10-mm sciatic nerve defect rat model sustain IGF-1 delivery, promoting early infiltration of macrophages and polarisation towards M2-type macrophages. Furthermore, observations at 12 weeks post-implantation revealed improvements in electrophysiological performance, alleviation of gastrocnemius muscle atrophy, increased peripheral nerve regeneration, and motor function restoration. Thus, biomimetic ECM NGCs offer a therapeutic strategy for peripheral nerve regeneration with promising clinical applications and transformation prospects to regulate immune microenvironments, promoting SC proliferation and differentiation with nerve axon growth.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101403"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951249","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 : 2025-02-01DOI: 10.1016/j.mtbio.2024.101396
Jinli Li , Yang Li , Guangtao Song , Haiying Wang , Qing Zhang , Min Wang , Muxue Zhao , Bei Wang , HuiGuo Zhu , Liu Ranzhi , Qiang Wang , Yuyan Xiong
Organoids, exhibiting the capability to undergo differentiation in specific in vitro growth environments, have garnered significant attention in recent years due to their capacity to recapitulate human organs with resemblant in vivo structures and physiological functions. This groundbreaking technology offers a unique opportunity to study human diseases and address the limitations of traditional animal models. Cardiovascular diseases (CVDs), a leading cause of mortality worldwide, have spurred an increasing number of researchers to explore the great potential of human cardiovascular organoids for cardiovascular research. This review initiates by elaborating on the development and manufacture of human cardiovascular organoids, including cardiac organoids and blood vessel organoids. Next, we provide a comprehensive overview of their applications in modeling various cardiovascular disorders. Furthermore, we shed light on the prospects of cardiovascular organoids in CVDs therapy, and unfold an in-depth discussion of the current challenges of human cardiovascular organoids in the development and application for understanding and treating CVDs.
{"title":"Revolutionizing cardiovascular research: Human organoids as a Beacon of hope for understanding and treating cardiovascular diseases","authors":"Jinli Li , Yang Li , Guangtao Song , Haiying Wang , Qing Zhang , Min Wang , Muxue Zhao , Bei Wang , HuiGuo Zhu , Liu Ranzhi , Qiang Wang , Yuyan Xiong","doi":"10.1016/j.mtbio.2024.101396","DOIUrl":"10.1016/j.mtbio.2024.101396","url":null,"abstract":"<div><div>Organoids, exhibiting the capability to undergo differentiation in specific in vitro growth environments, have garnered significant attention in recent years due to their capacity to recapitulate human organs with resemblant in vivo structures and physiological functions. This groundbreaking technology offers a unique opportunity to study human diseases and address the limitations of traditional animal models. Cardiovascular diseases (CVDs), a leading cause of mortality worldwide, have spurred an increasing number of researchers to explore the great potential of human cardiovascular organoids for cardiovascular research. This review initiates by elaborating on the development and manufacture of human cardiovascular organoids, including cardiac organoids and blood vessel organoids. Next, we provide a comprehensive overview of their applications in modeling various cardiovascular disorders. Furthermore, we shed light on the prospects of cardiovascular organoids in CVDs therapy, and unfold an in-depth discussion of the current challenges of human cardiovascular organoids in the development and application for understanding and treating CVDs.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101396"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971608","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 : 2025-02-01DOI: 10.1016/j.mtbio.2024.101411
Jie Gao , Yiduo Zhou , Gang Xu , Zhongqing Wei , Liucheng Ding , Wei Zhang , Yi Huang
Currently, most peripheral nerve injuries are incurable mainly due to excessive reactive oxygen species (ROS) generation in inflammatory tissues, which can further exacerbate localized tissue injury and cause chronic diseases. Although promising for promoting nerve regeneration, stem cell therapy still suffers from abundant intrinsic limitations, mainly including excessive ROS in lesions and inefficient production of growth factors (GFs). Biomaterials that scavenge endogenous ROS and promote GFs secretion might overcome such limitations and thus are being increasingly investigated. Herein, firstly reported as specific ROS scavenging agents and paracrine stimulators, gold nanoparticles (GNPs) were incorporated in the chitosan/polyvinyl alcohol hydrogel networks. The GNPs/hydrogel composite can support the survival of mesenchymal stem cells (MSCs) with excellent expansion efficiency and protect MSCs in a simulated ROS microenvironment, decreasing the intracellular ROS levels and simultaneously enhancing cell viability. Moreover, biodegradable scaffolds, along with MSCs, were implanted into sciatic nerve defects in a rat model to show good application value in vivo. Our work demonstrated that the GNPs/hydrogel shows great promise in MSCs therapy for peripheral nerve injury with convincing biological evidence.
{"title":"Hybrid hydrogels containing gradients in gold nanoparticles for localized delivery of mesenchymal stem cells and enhanced nerve tissues remodeling in vivo","authors":"Jie Gao , Yiduo Zhou , Gang Xu , Zhongqing Wei , Liucheng Ding , Wei Zhang , Yi Huang","doi":"10.1016/j.mtbio.2024.101411","DOIUrl":"10.1016/j.mtbio.2024.101411","url":null,"abstract":"<div><div>Currently, most peripheral nerve injuries are incurable mainly due to excessive reactive oxygen species (ROS) generation in inflammatory tissues, which can further exacerbate localized tissue injury and cause chronic diseases. Although promising for promoting nerve regeneration, stem cell therapy still suffers from abundant intrinsic limitations, mainly including excessive ROS in lesions and inefficient production of growth factors (GFs). Biomaterials that scavenge endogenous ROS and promote GFs secretion might overcome such limitations and thus are being increasingly investigated. Herein, firstly reported as specific ROS scavenging agents and paracrine stimulators, gold nanoparticles (GNPs) were incorporated in the chitosan/polyvinyl alcohol hydrogel networks. The GNPs/hydrogel composite can support the survival of mesenchymal stem cells (MSCs) with excellent expansion efficiency and protect MSCs in a simulated ROS microenvironment, decreasing the intracellular ROS levels and simultaneously enhancing cell viability. Moreover, biodegradable scaffolds, along with MSCs, were implanted into sciatic nerve defects in a rat model to show good application value <em>in vivo</em>. Our work demonstrated that the GNPs/hydrogel shows great promise in MSCs therapy for peripheral nerve injury with convincing biological evidence.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101411"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983831","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 : 2025-02-01DOI: 10.1016/j.mtbio.2024.101421
Wenjie Xi , Weijie Wu , Lili Zhou , Qi Zhang , Shushu Yang , Lihong Huang , Yijun Lu , Jing Wang , Xinjin Chi , Yang Kang
Sepsis is a serious and life-threatening condition, which can lead to organ failure and death clinically. Abnormally increased cell-free DNA (cfDNA) and inflammatory cytokines are involved in the development and progression of sepsis. Thus, cfDNA clearance and down-regulation of inflammatory factors are essential for the effective treatment of sepsis. Here we designed and constructed a polydopamine-based multifunctional nanoparticle for the treatment of sepsis. These nanoparticles (NPs) are composed of polydopamine (PDA) grafted with cationic polyethyleneimine (PEI). On the one hand, the NPs can utilize the electrostatic interaction to effectively adsorb cfDNA in blood, then effectively inhibiting the activation of toll like receptors (TLRs) and nuclear factor kappa B (NF-κB) pathways induced by cfDNA. On the other hand, the NPs have an immunomodulatory function, which can effectively convert pro-inflammatory macrophage (M1) into anti-inflammatory macrophage (M2), thus reduce the release of inflammatory cytokines and slow down the inflammatory storm of sepsis. In addition, the NPs possess good reactive oxygen species (ROS) scavenging ability. Briefly, the effective treatment of sepsis can be achieved by multiple strategies of effectively capturing the inflammatory triggering factor cfDNA, modulating the polarization of M1 macrophage to M2 macrophage and scavenging ROS, which has a promising clinical application.
{"title":"Multifunctional nanoparticles confers both multiple inflammatory mediators scavenging and macrophage polarization for sepsis therapy","authors":"Wenjie Xi , Weijie Wu , Lili Zhou , Qi Zhang , Shushu Yang , Lihong Huang , Yijun Lu , Jing Wang , Xinjin Chi , Yang Kang","doi":"10.1016/j.mtbio.2024.101421","DOIUrl":"10.1016/j.mtbio.2024.101421","url":null,"abstract":"<div><div>Sepsis is a serious and life-threatening condition, which can lead to organ failure and death clinically. Abnormally increased cell-free DNA (cfDNA) and inflammatory cytokines are involved in the development and progression of sepsis. Thus, cfDNA clearance and down-regulation of inflammatory factors are essential for the effective treatment of sepsis. Here we designed and constructed a polydopamine-based multifunctional nanoparticle for the treatment of sepsis. These nanoparticles (NPs) are composed of polydopamine (PDA) grafted with cationic polyethyleneimine (PEI). On the one hand, the NPs can utilize the electrostatic interaction to effectively adsorb cfDNA in blood, then effectively inhibiting the activation of toll like receptors (TLRs) and nuclear factor kappa B (NF-κB) pathways induced by cfDNA. On the other hand, the NPs have an immunomodulatory function, which can effectively convert pro-inflammatory macrophage (M1) into anti-inflammatory macrophage (M2), thus reduce the release of inflammatory cytokines and slow down the inflammatory storm of sepsis. In addition, the NPs possess good reactive oxygen species (ROS) scavenging ability. Briefly, the effective treatment of sepsis can be achieved by multiple strategies of effectively capturing the inflammatory triggering factor cfDNA, modulating the polarization of M1 macrophage to M2 macrophage and scavenging ROS, which has a promising clinical application.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101421"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983860","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 : 2025-02-01DOI: 10.1016/j.mtbio.2024.101426
Minzheng Guo , Baochuang Qi , Zijie Pei , Haonan Ni , Junxiao Ren , Huan Luo , Hongxin Shi , Chen Meng , Yang Yu , Zhifang Tang , Yongqing Xu , Qingyun Xue , Chuan Li
The early treatment of Osteonecrosis of Femoral Head (ONFH) remains a clinical challenge. Conventional Bone Marrow Mesenchymal Stem Cell (BMSC) injection methods often result in unsatisfactory outcomes due to mechanical cell damage, low cell survival and retention rates, inadequate cell matrix accumulation, and poor intercellular interaction. In this study, we employed a novel cell carrier material termed "3D Microscaffold" to deliver BMSCs, addressing these issues and enhancing the therapeutic effects of cell therapy for ONFH. We injected 3D microscaffold loaded with low-dose BMSCs or free high-dose BMSCs into the femoral heads of ONFH rats and assessed therapeutic effects using imaging, serology, histology, and immunohistochemistry. To understand the mechanism of efficacy, we established a co-culture model of human osteoblasts and BMSCs, followed by cell proliferation and activity detection, flow cytometry analysis, Quantitative RT-PCR, and Western blotting. Additionally, RNA sequencing was performed on femoral head tissues. Results showed that the 3D microscaffold with low-dose BMSCs had a therapeutic effect comparable to high-dose free BMSCs. Osteoblasts in the 3D microscaffold group exhibited superior phenotypes compared to the non-3D microscaffold group. Furthermore, we have, for the first time, preliminarily validated that the low-dose BMSCs-loaded 3D microscaffolds may promote the repair of femoral head necrosis through the synergistic action of the MAPK and Hippo signaling pathways.
{"title":"Therapeutic effect of low-dose BMSCs-Loaded 3D microscaffold on early osteonecrosis of the femoral head","authors":"Minzheng Guo , Baochuang Qi , Zijie Pei , Haonan Ni , Junxiao Ren , Huan Luo , Hongxin Shi , Chen Meng , Yang Yu , Zhifang Tang , Yongqing Xu , Qingyun Xue , Chuan Li","doi":"10.1016/j.mtbio.2024.101426","DOIUrl":"10.1016/j.mtbio.2024.101426","url":null,"abstract":"<div><div>The early treatment of Osteonecrosis of Femoral Head (ONFH) remains a clinical challenge. Conventional Bone Marrow Mesenchymal Stem Cell (BMSC) injection methods often result in unsatisfactory outcomes due to mechanical cell damage, low cell survival and retention rates, inadequate cell matrix accumulation, and poor intercellular interaction. In this study, we employed a novel cell carrier material termed \"3D Microscaffold\" to deliver BMSCs, addressing these issues and enhancing the therapeutic effects of cell therapy for ONFH. We injected 3D microscaffold loaded with low-dose BMSCs or free high-dose BMSCs into the femoral heads of ONFH rats and assessed therapeutic effects using imaging, serology, histology, and immunohistochemistry. To understand the mechanism of efficacy, we established a co-culture model of human osteoblasts and BMSCs, followed by cell proliferation and activity detection, flow cytometry analysis, Quantitative RT-PCR, and Western blotting. Additionally, RNA sequencing was performed on femoral head tissues. Results showed that the 3D microscaffold with low-dose BMSCs had a therapeutic effect comparable to high-dose free BMSCs. Osteoblasts in the 3D microscaffold group exhibited superior phenotypes compared to the non-3D microscaffold group. Furthermore, we have, for the first time, preliminarily validated that the low-dose BMSCs-loaded 3D microscaffolds may promote the repair of femoral head necrosis through the synergistic action of the MAPK and Hippo signaling pathways.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101426"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029155","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 : 2025-02-01DOI: 10.1016/j.mtbio.2024.101377
Joyce L.Y. Tang , Shehzahdi S. Moonshi , Yuao Wu , Gary Cowin , Karla X. Vazquez- Prada , Huong D.N. Tran , Andrew C. Bulmer , Hang Thu Ta
We explored the feasibility of a self-assembled chitosan nanocomposite incorporating cerium oxide/nanoceria and superparamagnetic iron oxide nanoparticles (Chit−IOCO NPs), conjugated with methotrexate (MTX) and Cy5 dye, as an integrated cancer theranostic nanosystem (Chit-IOCO-MTX-Cy5). In this system, nanoceria serves as an anti-cancer agent, while the superparamagnetic iron oxide nanoparticles function as a negative contrast agent for MR imaging. This dual metal oxide nanocomposite is conjugated with MTX which is a structural analogue of folate, serving both as a targeting mechanism for folate receptors on cancer cells and as a chemotherapeutic drug. Chit−IOCO-MTX-Cy5 exhibited exceptional negative contrast in T2 and T2∗-weighted MRI, achieving a high relaxivity of 409.5 mM⁻1 s⁻1 which is superior to clinically approved agents. The nanocomposite demonstrated both pro-oxidative and antioxidative properties, significantly increasing reactive oxygen species (ROS) production in U87MG cells (1.4-fold change), which triggered apoptosis in these cancer cells. Simultaneously, it exhibited ROS scavenging activity in non-malignant endothelial cells (0.8-fold change). Intravenous infusion of Chit-IOCO-MTX-Cy5 (5 mg/kg MTX) led to significant tumor growth inhibition, indicating a synergistic enhancement of anti-cancer effects when combining MTX and nanoceria, compared to free MTX or nanoceria without MTX conjugation. Importantly, after treatment cessation, tumours in the nanocomposite group did not re-grow, while those in the free MTX group rapidly did. In vivo MR and fluorescence imaging revealed improved uptake and retention of Chit−IOCO-MTX-Cy5 in tumours compared to nanoceria without MTX. Notably, biosafety and biochemical analyses in mice showed no significant differences between the Chit−IOCO-MTX-Cy5 treatment group and control groups.
我们探索了一种自组装的壳聚糖纳米复合材料的可行性，该纳米复合材料包含氧化铈/纳米粒和超顺磁性氧化铁纳米颗粒（Chit-IOCO NPs），结合甲氨蝶呤（MTX）和Cy5染料，作为综合癌症治疗纳米系统（Chit-IOCO-MTX-Cy5）。在这个系统中，纳米二氧化硅作为抗癌剂，而超顺磁性氧化铁纳米颗粒作为磁共振成像的负造影剂。这种双金属氧化物纳米复合材料与叶酸的结构类似物MTX偶联，既可以作为叶酸受体在癌细胞上的靶向机制，也可以作为化疗药物。Chit-IOCO-MTX-Cy5在T2和T2 *加权MRI中表现出异常的负性对比，达到409.5 mM - 1 s - 1的高松弛度，优于临床批准的药物。纳米复合材料显示出促氧化和抗氧化特性，显著增加U87MG细胞的活性氧（ROS）产生（变化1.4倍），从而引发这些癌细胞的凋亡。同时，在非恶性内皮细胞中显示ROS清除活性（变化0.8倍）。静脉输注Chit-IOCO-MTX-Cy5 （5 mg/kg MTX）可显著抑制肿瘤生长，表明与游离MTX或未结合MTX的纳米ceria相比，MTX与纳米ceria联合使用可协同增强抗癌效果。重要的是，在治疗停止后，纳米复合材料组的肿瘤没有重新生长，而游离MTX组的肿瘤迅速生长。体内MR和荧光成像显示，与不含MTX的纳米粒相比，Chit-IOCO-MTX-Cy5在肿瘤中的摄取和保留有所改善。值得注意的是，小鼠的生物安全性和生化分析显示，Chit-IOCO-MTX-Cy5治疗组与对照组之间没有显著差异。
{"title":"A methotrexate labelled dual metal oxide nanocomposite for long-lasting anti-cancer theranostics","authors":"Joyce L.Y. Tang , Shehzahdi S. Moonshi , Yuao Wu , Gary Cowin , Karla X. Vazquez- Prada , Huong D.N. Tran , Andrew C. Bulmer , Hang Thu Ta","doi":"10.1016/j.mtbio.2024.101377","DOIUrl":"10.1016/j.mtbio.2024.101377","url":null,"abstract":"<div><div>We explored the feasibility of a self-assembled chitosan nanocomposite incorporating cerium oxide/nanoceria and superparamagnetic iron oxide nanoparticles (Chit−IOCO NPs), conjugated with methotrexate (MTX) and Cy5 dye, as an integrated cancer theranostic nanosystem (Chit-IOCO-MTX-Cy5). In this system, nanoceria serves as an anti-cancer agent, while the superparamagnetic iron oxide nanoparticles function as a negative contrast agent for MR imaging. This dual metal oxide nanocomposite is conjugated with MTX which is a structural analogue of folate, serving both as a targeting mechanism for folate receptors on cancer cells and as a chemotherapeutic drug. Chit−IOCO-MTX-Cy5 exhibited exceptional negative contrast in T2 and T2∗-weighted MRI, achieving a high relaxivity of 409.5 mM⁻<sup>1</sup> s⁻<sup>1</sup> which is superior to clinically approved agents. The nanocomposite demonstrated both pro-oxidative and antioxidative properties, significantly increasing reactive oxygen species (ROS) production in U87MG cells (1.4-fold change), which triggered apoptosis in these cancer cells. Simultaneously, it exhibited ROS scavenging activity in non-malignant endothelial cells (0.8-fold change). Intravenous infusion of Chit-IOCO-MTX-Cy5 (5 mg/kg MTX) led to significant tumor growth inhibition, indicating a synergistic enhancement of anti-cancer effects when combining MTX and nanoceria, compared to free MTX or nanoceria without MTX conjugation. Importantly, after treatment cessation, tumours in the nanocomposite group did not re-grow, while those in the free MTX group rapidly did. <em>In vivo</em> MR and fluorescence imaging revealed improved uptake and retention of Chit−IOCO-MTX-Cy5 in tumours compared to nanoceria without MTX. Notably, biosafety and biochemical analyses in mice showed no significant differences between the Chit−IOCO-MTX-Cy5 treatment group and control groups.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101377"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915410","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 : 2025-02-01DOI: 10.1016/j.mtbio.2024.101382
Shan An , Claudio Intini , Donagh O'Shea , James E. Dixon , Yiran Zheng , Fergal J. O'Brien
Articular cartilage has limited capacity for repair (or for regeneration) under pathological conditions, given its non-vascularized connective tissue structure and low cellular density. Our group has successfully developed an injectable hydrogel for cartilage repair, composed of collagen type I (Col I), collagen type II (Col II), and methacrylated-hyaluronic acid (MeHA), capable of supporting chondrogenic differentiation of mesenchymal stem cells (MSCs) towards articular cartilage-like phenotypes. Recent studies have demonstrated that silencing miR-221 may be an effective approach in promoting improved MSC chondrogenesis. Thus, this study aimed to develop a miR-activated hydrogel capable of offering a more effective and less invasive therapeutic approach to articular cartilage repair by delivering a pro-chondrogenic miR-221 inhibitor to MSCs using our MeHA-Col I/Col II hydrogel. The MeHA-Col I/Col II hydrogel was cast as previously shown and incorporated with cells transfected with miR-221 inhibitor (using a non-viral peptide delivery vector) to produce the miR-activated hydrogel. Down-regulation of miR-221 did not affect cell viability and enhanced MSCs-mediated chondrogenesis, as evidenced by significantly upregulated expression of key pro-chondrogenic articular cartilage genes (COL2A1 and ACAN) without promoting hypertrophic events (RUNX2 and COL10A1). Furthermore, miR-221 down-regulation improved cartilage-like matrix formation in the MeHA-Col I/Col II hydrogel, with significantly higher levels of sulfated glycosaminoglycans (sGAG) and Col II produced by MSCs in the hydrogel. These results provide evidence of the potential of the miR-activated hydrogel as a minimally invasive therapeutic strategy for articular cartilage repair.
{"title":"A miR-activated hydrogel for the delivery of a pro-chondrogenic microRNA-221 inhibitor as a minimally invasive therapeutic approach for articular cartilage repair","authors":"Shan An , Claudio Intini , Donagh O'Shea , James E. Dixon , Yiran Zheng , Fergal J. O'Brien","doi":"10.1016/j.mtbio.2024.101382","DOIUrl":"10.1016/j.mtbio.2024.101382","url":null,"abstract":"<div><div>Articular cartilage has limited capacity for repair (or for regeneration) under pathological conditions, given its non-vascularized connective tissue structure and low cellular density. Our group has successfully developed an injectable hydrogel for cartilage repair, composed of collagen type I (Col I), collagen type II (Col II), and methacrylated-hyaluronic acid (MeHA), capable of supporting chondrogenic differentiation of mesenchymal stem cells (MSCs) towards articular cartilage-like phenotypes. Recent studies have demonstrated that silencing <em>miR-221</em> may be an effective approach in promoting improved MSC chondrogenesis. Thus, this study aimed to develop a <em>miR</em>-activated hydrogel capable of offering a more effective and less invasive therapeutic approach to articular cartilage repair by delivering a pro-chondrogenic <em>miR-221</em> inhibitor to MSCs using our MeHA-Col I/Col II hydrogel. The MeHA-Col I/Col II hydrogel was cast as previously shown and incorporated with cells transfected with <em>miR-221</em> inhibitor (using a non-viral peptide delivery vector) to produce the <em>miR</em>-activated hydrogel. Down-regulation of <em>miR-221</em> did not affect cell viability and enhanced MSCs-mediated chondrogenesis, as evidenced by significantly upregulated expression of key pro-chondrogenic articular cartilage genes (<em>COL2A1</em> and <em>ACAN</em>) without promoting hypertrophic events (<em>RUNX2</em> and <em>COL10A1</em>). Furthermore, <em>miR-221</em> down-regulation improved cartilage-like matrix formation in the MeHA-Col I/Col II hydrogel, with significantly higher levels of sulfated glycosaminoglycans (sGAG) and Col II produced by MSCs in the hydrogel. These results provide evidence of the potential of the <em>miR-</em>activated hydrogel as a minimally invasive therapeutic strategy for articular cartilage repair.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101382"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932058","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 : 2025-02-01DOI: 10.1016/j.mtbio.2024.101393
Siqi Gao , Iuliia Golovynska , Jiantao Liu , Zhenlong Huang , Hao Xu , Jinghan Qu , Fangrui Lin , Galyna Ostrovska , Junle Qu , Tymish Y. Ohulchanskyy
Combining photothermal and chemotherapy using single nanoplatform is an emerging direction in cancer nanomedicine. Herein, a magnetic field (MF) induced combination of chemo/photothermal therapy is demonstrated using Fe3O4@mSiO2@Au core@shell@satellites nanoparticles (NPs) loaded with chemotherapeutic drug doxorubicin (DOX), both in vitro and in vivo. An application of an external MF to the NPs dispersion causes magnetophoretic movement and aggregation of the NPs. While the synthesized NPs only slightly absorb light at ∼800 nm, their aggregation results in a significant near infrared (NIR) absorption associated with plasmon resonance coupling between the Au satellites in the NPs aggregates. As a result, the aggregates revealed an enhanced photothermal conversion efficiency (∼67 % versus ∼19 % for NPs in absence of MF) and an enhanced NIR photothermal effect was observed under 808 nm laser irradiation. A combination of the MF induced NIR photothermal therapy (PTT) with DOX chemotherapeutic action resulted in an efficient killing of NPs treated cancer cells in vitro and tumor growth restriction in 4T1-tumor-bearing mice in vivo. Histological studies showed striking differences in development and malignancy between tumors treated with the combination of NPs, MF and an 808 nm laser, and the control treatments, revealing a synergy of the MF-induced NIR PTT and chemotherapy and suggesting a promising strategy for cancer therapy.
{"title":"Magnetic field-induced synergistic therapy of cancer using magnetoplasmonic nanoplatform","authors":"Siqi Gao , Iuliia Golovynska , Jiantao Liu , Zhenlong Huang , Hao Xu , Jinghan Qu , Fangrui Lin , Galyna Ostrovska , Junle Qu , Tymish Y. Ohulchanskyy","doi":"10.1016/j.mtbio.2024.101393","DOIUrl":"10.1016/j.mtbio.2024.101393","url":null,"abstract":"<div><div>Combining photothermal and chemotherapy using single nanoplatform is an emerging direction in cancer nanomedicine. Herein, a magnetic field (MF) induced combination of chemo/photothermal therapy is demonstrated using Fe<sub>3</sub>O<sub>4</sub>@mSiO<sub>2</sub>@Au core@shell@satellites nanoparticles (NPs) loaded with chemotherapeutic drug doxorubicin (DOX), both <em>in vitro</em> and <em>in vivo.</em> An application of an external MF to the NPs dispersion causes magnetophoretic movement and aggregation of the NPs. While the synthesized NPs only slightly absorb light at ∼800 nm, their aggregation results in a significant near infrared (NIR) absorption associated with plasmon resonance coupling between the Au satellites in the NPs aggregates. As a result, the aggregates revealed an enhanced photothermal conversion efficiency (∼67 % versus ∼19 % for NPs in absence of MF) and an enhanced NIR photothermal effect was observed under 808 nm laser irradiation. A combination of the MF induced NIR photothermal therapy (PTT) with DOX chemotherapeutic action resulted in an efficient killing of NPs treated cancer cells <em>in vitro</em> and tumor growth restriction in 4T1-tumor-bearing mice <em>in vivo</em>. Histological studies showed striking differences in development and malignancy between tumors treated with the combination of NPs, MF and an 808 nm laser, and the control treatments, revealing a synergy of the MF-induced NIR PTT and chemotherapy and suggesting a promising strategy for cancer therapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101393"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932156","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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