Sorel E. De León, Simon Higham, Young Jun Jung, Wei Tong, David J. Garrett
Brain–machine interfaces (BMIs) have experienced remarkable advancements in recent years, marked by multiple companies initiating human trials. Consequently, the interface between the brain and electrodes has become more critical than ever, requiring implanted electrodes to be not only biocompatible and minimally invasive but also capable of remaining functioning in the brain for a lifetime. While significant progress has been made in the manufacturing of intracortical electrodes, challenges persist in ensuring longevity and minimizing tissue damage. Additionally, the reliance on manual labor in fabrication techniques poses obstacles to large‐scale production for commercialization. In this review, we explore recent breakthroughs and obstacles in the fabrication of microwire‐structured electrode arrays, wherein single wires are arranged in an xy matrix for cortical penetration. We discuss the impact of various fabrication strategies and materials on implant longevity, as well as the remaining challenges in this field.
{"title":"Recent developments in microwire‐structured intracortical electrode arrays for brain–machine interfaces","authors":"Sorel E. De León, Simon Higham, Young Jun Jung, Wei Tong, David J. Garrett","doi":"10.1002/btm2.10742","DOIUrl":"https://doi.org/10.1002/btm2.10742","url":null,"abstract":"Brain–machine interfaces (BMIs) have experienced remarkable advancements in recent years, marked by multiple companies initiating human trials. Consequently, the interface between the brain and electrodes has become more critical than ever, requiring implanted electrodes to be not only biocompatible and minimally invasive but also capable of remaining functioning in the brain for a lifetime. While significant progress has been made in the manufacturing of intracortical electrodes, challenges persist in ensuring longevity and minimizing tissue damage. Additionally, the reliance on manual labor in fabrication techniques poses obstacles to large‐scale production for commercialization. In this review, we explore recent breakthroughs and obstacles in the fabrication of microwire‐structured electrode arrays, wherein single wires are arranged in an <jats:italic>xy</jats:italic> matrix for cortical penetration. We discuss the impact of various fabrication strategies and materials on implant longevity, as well as the remaining challenges in this field.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juan Deng, Juan Qin, Guolin Song, Chenghai Li, Wentao Tang, Yilin Tang, Xinfang Xiao, Liu Wu, Sicheng He, Yiqing Zhou, Junfen Li, Yan Wang
The potential of low‐intensity pulsed ultrasound (LIPUS) in regulating ovarian function has been demonstrated; however, there is a lack of scientific evidence regarding the long‐term efficacy of LIPUS in treating ovarian injury and understanding its regulatory mechanisms. In this study, 4‐vinylcyclohexene diepoxide (VCD) was used to induce ovarian injury in rats, and LIPUS was applied to target the damaged ovarian tissues. The research aimed to investigate the long‐term protective effect of LIPUS against ovum toxicity induced by VCD and elucidate the associated molecular mechanisms. During the experiment, HE staining was employed for observing the morphology and structure of the ovary, while protein sequencing was utilized for identifying and confirming the molecular mechanism through which LIPUS restores the damaged ovarian structure. The long‐term effectiveness of LIPUS in protecting against ovarian injury was evaluated through ELISA, estrous cycle monitoring, fertility testing, and behavioral analysis. The results indicated that LIPUS effectively restored the structure of damaged ovaries. Both in vivo and in vitro studies revealed that this protective effect may be attributed to LIPUS inhibiting apoptosis of ovarian granulosa cells (GCs) by regulating Daxx‐mediated ASK1/JNK signaling pathway. Subsequent functional tests demonstrated significant improvements in sex hormone secretion and regulation of estrous cycle within 6 cycles following LIPUS treatment. Additionally, there was a notable increase in offspring numbers after mating. Behavioral analysis revealed that LIPUS effectively alleviated menopausal symptoms resulting from ovarian injury including mood fluctuations, cognitive behavior changes, and reduced muscle excitability levels. These findings suggest that beneficial effects of LIPUS may help reduce VCD‐induced ovarian damage with long‐term efficacy.
{"title":"The potential of low‐intensity pulsed ultrasound to apply the long‐term ovary protection from injury induced by 4‐vinylcyclohexene diepoxide through inhibiting granulosa cell apoptosis","authors":"Juan Deng, Juan Qin, Guolin Song, Chenghai Li, Wentao Tang, Yilin Tang, Xinfang Xiao, Liu Wu, Sicheng He, Yiqing Zhou, Junfen Li, Yan Wang","doi":"10.1002/btm2.10744","DOIUrl":"https://doi.org/10.1002/btm2.10744","url":null,"abstract":"The potential of low‐intensity pulsed ultrasound (LIPUS) in regulating ovarian function has been demonstrated; however, there is a lack of scientific evidence regarding the long‐term efficacy of LIPUS in treating ovarian injury and understanding its regulatory mechanisms. In this study, 4‐vinylcyclohexene diepoxide (VCD) was used to induce ovarian injury in rats, and LIPUS was applied to target the damaged ovarian tissues. The research aimed to investigate the long‐term protective effect of LIPUS against ovum toxicity induced by VCD and elucidate the associated molecular mechanisms. During the experiment, HE staining was employed for observing the morphology and structure of the ovary, while protein sequencing was utilized for identifying and confirming the molecular mechanism through which LIPUS restores the damaged ovarian structure. The long‐term effectiveness of LIPUS in protecting against ovarian injury was evaluated through ELISA, estrous cycle monitoring, fertility testing, and behavioral analysis. The results indicated that LIPUS effectively restored the structure of damaged ovaries. Both in vivo and in vitro studies revealed that this protective effect may be attributed to LIPUS inhibiting apoptosis of ovarian granulosa cells (GCs) by regulating Daxx‐mediated ASK1/JNK signaling pathway. Subsequent functional tests demonstrated significant improvements in sex hormone secretion and regulation of estrous cycle within 6 cycles following LIPUS treatment. Additionally, there was a notable increase in offspring numbers after mating. Behavioral analysis revealed that LIPUS effectively alleviated menopausal symptoms resulting from ovarian injury including mood fluctuations, cognitive behavior changes, and reduced muscle excitability levels. These findings suggest that beneficial effects of LIPUS may help reduce VCD‐induced ovarian damage with long‐term efficacy.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"91 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simone Capuani, Jocelyn Nikita Campa‐Carranza, Nathanael Hernandez, Renuka T. R. Menon, Rohan Bhavane, Gabrielle E. Rome, Laxman Devkota, Ketan B. Ghaghada, Ananth V. Annapragada, Corrine Ying Xuan Chua, Andrew A. Badachhape, Alessandro Grattoni
Revascularization plays a critical role in the successful engraftment of transplanted pancreatic islets, which are inherently rich in capillaries to meet their high metabolic demands. Innovative islet encapsulation strategies such as the NICHE (neovascularized implantable cell homing and encapsulation), generate a prevascularized transplantation site that allows for direct integration of the graft with the systemic circulation. Timing the transplantation is key to maximizing islet engraftment and survival, especially in diabetic individuals, who exhibit impaired wound healing. Therefore, in this study, we explored different methods to assess vascular development within NICHE in vivo in a non‐invasive fashion. We effectively tracked neoangiogenesis using nanoparticle contrast‐enhanced computed tomography (nCECT), observing a steady increase in vascularization over an 8‐week period, which was confirmed histologically. Next, we estimated relative vascularization changes via T2 mapping with magnetic resonance imaging (MRI) before and after islet transplantation. On the first day post‐transplantation, we measured a slight decrease in T2 values followed by a significant increase by day 14 attributable to islet revascularization. Our findings underscore the potential of non‐invasive imaging techniques to provide insightful information on the readiness of the transplant site within cell encapsulation systems to support cell graft transplantation.
{"title":"Nanoparticle contrast‐enhanced computed tomography and magnetic resonance imaging of vascularization of a subcutaneous niche for islet transplantation","authors":"Simone Capuani, Jocelyn Nikita Campa‐Carranza, Nathanael Hernandez, Renuka T. R. Menon, Rohan Bhavane, Gabrielle E. Rome, Laxman Devkota, Ketan B. Ghaghada, Ananth V. Annapragada, Corrine Ying Xuan Chua, Andrew A. Badachhape, Alessandro Grattoni","doi":"10.1002/btm2.10740","DOIUrl":"https://doi.org/10.1002/btm2.10740","url":null,"abstract":"Revascularization plays a critical role in the successful engraftment of transplanted pancreatic islets, which are inherently rich in capillaries to meet their high metabolic demands. Innovative islet encapsulation strategies such as the NICHE (neovascularized implantable cell homing and encapsulation), generate a prevascularized transplantation site that allows for direct integration of the graft with the systemic circulation. Timing the transplantation is key to maximizing islet engraftment and survival, especially in diabetic individuals, who exhibit impaired wound healing. Therefore, in this study, we explored different methods to assess vascular development within NICHE in vivo in a non‐invasive fashion. We effectively tracked neoangiogenesis using nanoparticle contrast‐enhanced computed tomography (nCECT), observing a steady increase in vascularization over an 8‐week period, which was confirmed histologically. Next, we estimated relative vascularization changes via T2 mapping with magnetic resonance imaging (MRI) before and after islet transplantation. On the first day post‐transplantation, we measured a slight decrease in T2 values followed by a significant increase by day 14 attributable to islet revascularization. Our findings underscore the potential of non‐invasive imaging techniques to provide insightful information on the readiness of the transplant site within cell encapsulation systems to support cell graft transplantation.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"3 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amy Simpson, Teresa DiColandrea, Stefan Przyborski
Air pollution is an exogenous stressor known to have a detrimental impact on skin health through the induction of inflammation; however, the direct effect of topical pollution exposure is still being elucidated. Human skin equivalents (HSE) aim to reproduce in vitro the structure and function of the native skin tissue. However, HSEs typically lack skin‐resident immune cells, which could play a key role in the inflammatory response induced by pollution exposure. We outline the development of a HSE‐containing MUTZ‐3‐derived Langerhans cells (MUTZ‐3‐LCs), which show dendritic morphology and Langerhans cell marker expression. We demonstrated that HSE‐containing MUTZ‐3‐LC have lower basal levels of proinflammatory cytokines, but topical stimulation with allergens and irritant compounds induced a greater inflammatory response in these models compared to HSE without immune cells. To study the effect of pollution, we created a technique to apply diesel particulate matter (DPM) to HSEs. Though our microscopic analysis demonstrated that DPM does not penetrate the stratum corneum, we showed that DPM did induce production of proinflammatory cytokines, but notably only in HSEs containing MUTZ‐3‐LCs. These data suggest that topical exposure to air pollution can induce cutaneous inflammation and that skin‐resident immune cells contribute to this response. This highlights the significance of immune‐competent HSEs to the study of exogenous stressors in vitro.
{"title":"Assessing the impact of airborne particulate pollution on human skin utilizing a novel human skin equivalent containing MUTZ‐3‐derived Langerhans cells","authors":"Amy Simpson, Teresa DiColandrea, Stefan Przyborski","doi":"10.1002/btm2.10738","DOIUrl":"https://doi.org/10.1002/btm2.10738","url":null,"abstract":"Air pollution is an exogenous stressor known to have a detrimental impact on skin health through the induction of inflammation; however, the direct effect of topical pollution exposure is still being elucidated. Human skin equivalents (HSE) aim to reproduce in vitro the structure and function of the native skin tissue. However, HSEs typically lack skin‐resident immune cells, which could play a key role in the inflammatory response induced by pollution exposure. We outline the development of a HSE‐containing MUTZ‐3‐derived Langerhans cells (MUTZ‐3‐LCs), which show dendritic morphology and Langerhans cell marker expression. We demonstrated that HSE‐containing MUTZ‐3‐LC have lower basal levels of proinflammatory cytokines, but topical stimulation with allergens and irritant compounds induced a greater inflammatory response in these models compared to HSE without immune cells. To study the effect of pollution, we created a technique to apply diesel particulate matter (DPM) to HSEs. Though our microscopic analysis demonstrated that DPM does not penetrate the stratum corneum, we showed that DPM did induce production of proinflammatory cytokines, but notably only in HSEs containing MUTZ‐3‐LCs. These data suggest that topical exposure to air pollution can induce cutaneous inflammation and that skin‐resident immune cells contribute to this response. This highlights the significance of immune‐competent HSEs to the study of exogenous stressors in vitro.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"29 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reduced glutathione (GSH) could reduce oxidative stress to improve adipose tissue‐derived mesenchymal stem cell (ADSC) engraftment efficiency in vivo. However, the underlying mechanisms remain unclear. Our goal is to investigate whether GSH enhances ADSC engraftment through targeting the TGFβ/SMAD3/NOX4 pathway. Liver fibrotic male mice were administrated GSH, setanaxib (STX), and SIS3 during ADSC transplantation. ADSC engraftment efficiency and reactive oxygen species (ROS) level were detected both in vivo and ex vivo. Biochemical analysis was used to analyze the content of superoxide and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) in liver tissues. Immunohistochemistry and western blotting were used to examine the protein level of NOX1, NOX2, NOX4, transforming growth factor‐β1 (TGFβ1), SMAD3, and p‐SMAD3 in liver tissues. Additionally, the therapeutic efficacy of the ADSC transplantation was further investigated. We found that GSH significantly improved ADSC engraftment efficiency, which was closely related to the reduced ROS generation in liver tissues. However, the enhanced cell engraftment was abolished after the combined treatment with STX or SIS3. GSH could effectively reduce superoxide and NOXs content, and selectively inhibit NOX4 expression in liver tissues. The co‐localization results showed that GSH could reduce NOX4 expressed in activated hepatic stellate cells. Mechanistically, GSH down‐regulated TGFβ/SMAD3 signaling. More importantly, GSH enhanced the therapeutic efficacy of ADSC therapy in liver fibrotic mice. Taken together, GSH could improve the engraftment efficiency of ADSCs in liver fibrosis by targeting TGFβ1/SMAD3/NOX4 signaling pathway, which provides a new theoretical basis for GSH enhancing ADSC engraftment efficiency in liver diseases.
{"title":"Reduced glutathione enhances adipose tissue‐derived mesenchymal stem cell engraftment efficiency for liver fibrosis by targeting TGFβ1/SMAD3/NOX4 pathway","authors":"Shaoxiong Yu, Yingchao Wang, Yingjun Shi, Saihua Yu, Bixing Zhao, Naishun Liao, Xiaolong Liu","doi":"10.1002/btm2.10735","DOIUrl":"https://doi.org/10.1002/btm2.10735","url":null,"abstract":"Reduced glutathione (GSH) could reduce oxidative stress to improve adipose tissue‐derived mesenchymal stem cell (ADSC) engraftment efficiency in vivo. However, the underlying mechanisms remain unclear. Our goal is to investigate whether GSH enhances ADSC engraftment through targeting the TGFβ/SMAD3/NOX4 pathway. Liver fibrotic male mice were administrated GSH, setanaxib (STX), and SIS3 during ADSC transplantation. ADSC engraftment efficiency and reactive oxygen species (ROS) level were detected both in vivo and ex vivo. Biochemical analysis was used to analyze the content of superoxide and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) in liver tissues. Immunohistochemistry and western blotting were used to examine the protein level of NOX1, NOX2, NOX4, transforming growth factor‐β1 (TGFβ1), SMAD3, and p‐SMAD3 in liver tissues. Additionally, the therapeutic efficacy of the ADSC transplantation was further investigated. We found that GSH significantly improved ADSC engraftment efficiency, which was closely related to the reduced ROS generation in liver tissues. However, the enhanced cell engraftment was abolished after the combined treatment with STX or SIS3. GSH could effectively reduce superoxide and NOXs content, and selectively inhibit NOX4 expression in liver tissues. The co‐localization results showed that GSH could reduce NOX4 expressed in activated hepatic stellate cells. Mechanistically, GSH down‐regulated TGFβ/SMAD3 signaling. More importantly, GSH enhanced the therapeutic efficacy of ADSC therapy in liver fibrotic mice. Taken together, GSH could improve the engraftment efficiency of ADSCs in liver fibrosis by targeting TGFβ1/SMAD3/NOX4 signaling pathway, which provides a new theoretical basis for GSH enhancing ADSC engraftment efficiency in liver diseases.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"97 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maytal Avrashami, Danna Niezni, Dana Meron Azagury, Hagit Sason, Yosi Shamay
Three‐dimensional (3D) spheroid models offer a more physiologically relevant and complex environment compared to traditional two‐dimensional cultures, making them a promising tool for studying tumor biology and drug response. However, these models often face challenges in real‐time monitoring of drug diffusion, penetration, and target engagement, limiting their predictive power for in vivo and clinical outcomes. This study introduces a novel approach for real‐time tracking of drug permeability using small molecule drugs with GFP/RFP‐disrupting properties that correlate with their efficacy. We developed a reproducible 3D spheroid model with various cancer cell lines expressing GFP/RFP for efficient drug screening. Through screening over 20 FDA‐approved enzyme inhibitors, we identified three covalent kinase inhibitors—osimertinib, afatinib, and neratinib—that irreversibly disrupt GFP and RFP fluorescence. Our results reveal distinct drug diffusion and penetration profiles within GFP/RFP‐expressing spheroids, varying with drug concentration and formulation, and correlating with clinical volume of distribution (Vd) values. Additionally, we demonstrate that our approach is useful for evaluating different drug formulations as well as screening penetration enhancers for solid tumors. These findings offer a valuable 3D model for studying kinetics of drug permeability and efficacy in tumor‐like environments, with potential implications for drug delivery research and formulation development.
{"title":"Green/red fluorescent protein disrupting drugs for real‐time permeability tracking in three‐dimensional tumor spheroids","authors":"Maytal Avrashami, Danna Niezni, Dana Meron Azagury, Hagit Sason, Yosi Shamay","doi":"10.1002/btm2.10731","DOIUrl":"https://doi.org/10.1002/btm2.10731","url":null,"abstract":"Three‐dimensional (3D) spheroid models offer a more physiologically relevant and complex environment compared to traditional two‐dimensional cultures, making them a promising tool for studying tumor biology and drug response. However, these models often face challenges in real‐time monitoring of drug diffusion, penetration, and target engagement, limiting their predictive power for in vivo and clinical outcomes. This study introduces a novel approach for real‐time tracking of drug permeability using small molecule drugs with GFP/RFP‐disrupting properties that correlate with their efficacy. We developed a reproducible 3D spheroid model with various cancer cell lines expressing GFP/RFP for efficient drug screening. Through screening over 20 FDA‐approved enzyme inhibitors, we identified three covalent kinase inhibitors—osimertinib, afatinib, and neratinib—that irreversibly disrupt GFP and RFP fluorescence. Our results reveal distinct drug diffusion and penetration profiles within GFP/RFP‐expressing spheroids, varying with drug concentration and formulation, and correlating with clinical volume of distribution (Vd) values. Additionally, we demonstrate that our approach is useful for evaluating different drug formulations as well as screening penetration enhancers for solid tumors. These findings offer a valuable 3D model for studying kinetics of drug permeability and efficacy in tumor‐like environments, with potential implications for drug delivery research and formulation development.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"20 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seung Jin Eo, Dae Sung Ryu, Hyeonseung Lee, Ji Won Kim, Song Hee Kim, Jin Hee Noh, Yuri Kim, Seokin Kang, Kun Na, Jung‐Hoon Park, Do Hoon Kim
Photodynamic therapy (PDT) using photosensitizer (PS)‐embedded silicone membrane‐covered self‐expandable metallic stents (SEMSs) can function in palliative therapeutic option for malignant gastrointestinal tract obstruction. However, stent‐related complications should be considered, and accurate delivery of light sources is technically difficult. Here, a Chlorin e6 (Ce6)‐an embedded stent‐based catheter is developed to improve its therapeutic efficacy and safety. PDT using Ce6‐embedded stent successfully induced cell death of colorectal cancer cell line. PDT‐treated liver tissues showed an increase in ablation depth in proportion to irradiation energy, and 600 J/cm2 demonstrates an even and sufficient ablation depth. Endoluminal PDT using the Ce6‐embedded stent‐based catheter was technically successful in a rat colon model without procedure‐related complications such as colonic perforation or stricture formation. The results in colonoscopy, colonography, and histological examination, along with statistical analysis, suggest that a novel PDT modality using a Ce6‐embedded stent‐based catheter was safely conducted and demonstrated apoptotic cell death at 12 h after PDT, and it gradually recovered from 2 to 4 weeks. Thus, the PDT using the Ce6‐embedded stent‐based catheter may represent a promising new approach for the treatment of malignant colorectal obstruction.
{"title":"Endoluminal photodynamic therapy with a photoreactive stent‐based catheter system to treat malignant colorectal obstruction","authors":"Seung Jin Eo, Dae Sung Ryu, Hyeonseung Lee, Ji Won Kim, Song Hee Kim, Jin Hee Noh, Yuri Kim, Seokin Kang, Kun Na, Jung‐Hoon Park, Do Hoon Kim","doi":"10.1002/btm2.10732","DOIUrl":"https://doi.org/10.1002/btm2.10732","url":null,"abstract":"Photodynamic therapy (PDT) using photosensitizer (PS)‐embedded silicone membrane‐covered self‐expandable metallic stents (SEMSs) can function in palliative therapeutic option for malignant gastrointestinal tract obstruction. However, stent‐related complications should be considered, and accurate delivery of light sources is technically difficult. Here, a Chlorin e6 (Ce6)‐an embedded stent‐based catheter is developed to improve its therapeutic efficacy and safety. PDT using Ce6‐embedded stent successfully induced cell death of colorectal cancer cell line. PDT‐treated liver tissues showed an increase in ablation depth in proportion to irradiation energy, and 600 J/cm<jats:sup>2</jats:sup> demonstrates an even and sufficient ablation depth. Endoluminal PDT using the Ce6‐embedded stent‐based catheter was technically successful in a rat colon model without procedure‐related complications such as colonic perforation or stricture formation. The results in colonoscopy, colonography, and histological examination, along with statistical analysis, suggest that a novel PDT modality using a Ce6‐embedded stent‐based catheter was safely conducted and demonstrated apoptotic cell death at 12 h after PDT, and it gradually recovered from 2 to 4 weeks. Thus, the PDT using the Ce6‐embedded stent‐based catheter may represent a promising new approach for the treatment of malignant colorectal obstruction.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"50 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To review the theoretical basis and therapeutic effects of fecal microbiota transplantation (FMT) in various diseases in animal experiments and clinical studies, as well as the limitations and current standards of FMT application. PubMed and Web of Science databases were searched for articles published only in English between 1975 and 2023 on reliable results of animal experiments and clinical treatment of FMT. The properties of the gut microbiota and its interactions with the host metabolism are critical to human health, and microbiome disturbance is closely associated with human intestinal and extra‐intestinal diseases. Therefore, therapeutic tools targeting on the modulation of gut microbiota have attracted increasing attention, among which FMT represents the most widely studied intervention strategy. This review gathered and summarized application of FMT in intestinal diseases, metabolic diseases, hypertension, cancer, nervous system diseases and arthritis, and elaborated the beneficial effects that can be achieved by altering the microbiota with FMT and the mechanisms of action. In addition, the potential risks and side effects of FMT approach are discussed, as well as current efforts to standardize the development of FMT. Through a systemic review of the outcome and mechanism of FMT in the treatment of intestinal diseases and extra‐intestinal diseases, we aimed to provide a theoretical basis for the construction of an optimized FMT framework, so as to better exert its application prospects.
{"title":"Fecal microbiota transplantation for the treatment of intestinal and extra‐intestinal diseases: Mechanism basis, clinical application, and potential prospect","authors":"Dongxin Yi, Tao Li, Yuji Xiao, Xue Zhang, Qiangqiang Hao, Feng Zhang, Tianming Qiu, Guang Yang, Xiance Sun, Ying Dong, Ningning Wang","doi":"10.1002/btm2.10728","DOIUrl":"https://doi.org/10.1002/btm2.10728","url":null,"abstract":"To review the theoretical basis and therapeutic effects of fecal microbiota transplantation (FMT) in various diseases in animal experiments and clinical studies, as well as the limitations and current standards of FMT application. PubMed and Web of Science databases were searched for articles published only in English between 1975 and 2023 on reliable results of animal experiments and clinical treatment of FMT. The properties of the gut microbiota and its interactions with the host metabolism are critical to human health, and microbiome disturbance is closely associated with human intestinal and extra‐intestinal diseases. Therefore, therapeutic tools targeting on the modulation of gut microbiota have attracted increasing attention, among which FMT represents the most widely studied intervention strategy. This review gathered and summarized application of FMT in intestinal diseases, metabolic diseases, hypertension, cancer, nervous system diseases and arthritis, and elaborated the beneficial effects that can be achieved by altering the microbiota with FMT and the mechanisms of action. In addition, the potential risks and side effects of FMT approach are discussed, as well as current efforts to standardize the development of FMT. Through a systemic review of the outcome and mechanism of FMT in the treatment of intestinal diseases and extra‐intestinal diseases, we aimed to provide a theoretical basis for the construction of an optimized FMT framework, so as to better exert its application prospects.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"70 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giacomo Cortella, Erwin Pavel Lamparelli, Maria Camilla Ciardulli, Joseph Lovecchio, Emanuele Giordano, Nicola Maffulli, Giovanna Della Porta
The advent of bioprinting has enabled the creation of precise three-dimensional (3D) cell cultures suitable for biomimetic in vitro models. In this study, we developed a novel protocol for 3D printing methacrylated collagen (ColMa, or PhotoCol®) combined with tendon stem/progenitor cells (hTSPCs) derived from human tendon explants. Although pure ColMa has not previously been proposed as a printable hydrogel, this paper outlines a robust and highly reproducible pipeline for bioprinting this material. Indeed, we successfully fabricated a 3D bioengineered scaffold and cultured it for 21 days under perfusion conditions with medium supplemented with growth/differentiation factor-5 (GDF-5). This bioprinting pipeline and the culture conditions created an exceptionally favorable 3D environment, enabling the cells to proliferate, exhibit tenogenic behaviors, and produce a new collagen type I matrix, thereby remodeling the surrounding environment. Indeed, over the 21-day culture period under perfusion condition, tenomodulin expression showed a significant upregulation on day 7, with a 2.3-fold increase, compared to days 14 and 21. Collagen type I gene expression was upregulated nearly 10-fold by day 14. This trend was further confirmed by western blot analysis, which revealed a statistically significant difference in tenomodulin expression between day 21 and both day 7 and day 14. For type I collagen, significant differences were observed between day 0 and day 21, as well as between day 0 and day 14, with a p-value of 0.01. These results indicate a progressive over-expression of type I collagen, reflecting cell differentiation towards a proper tenogenic phenotype. Cytokines, such as IL-8 and IL-6, levels peaked at 8566 and 7636 pg/mL, respectively, on day 7, before decreasing to 54 and 46 pg/mL by day 21. Overall, the data suggest that the novel ColMa bioprinting protocol effectively provided a conducive environment for the growth and proper differentiation of hTSPCs, showcasing its potential for studying cell behavior and tenogenic differentiation.
{"title":"ColMA-based bioprinted 3D scaffold allowed to study tenogenic events in human tendon stem cells","authors":"Giacomo Cortella, Erwin Pavel Lamparelli, Maria Camilla Ciardulli, Joseph Lovecchio, Emanuele Giordano, Nicola Maffulli, Giovanna Della Porta","doi":"10.1002/btm2.10723","DOIUrl":"10.1002/btm2.10723","url":null,"abstract":"<p>The advent of bioprinting has enabled the creation of precise three-dimensional (3D) cell cultures suitable for biomimetic in vitro models. In this study, we developed a novel protocol for 3D printing methacrylated collagen (ColMa, or PhotoCol®) combined with tendon stem/progenitor cells (hTSPCs) derived from human tendon explants. Although pure ColMa has not previously been proposed as a printable hydrogel, this paper outlines a robust and highly reproducible pipeline for bioprinting this material. Indeed, we successfully fabricated a 3D bioengineered scaffold and cultured it for 21 days under perfusion conditions with medium supplemented with growth/differentiation factor-5 (GDF-5). This bioprinting pipeline and the culture conditions created an exceptionally favorable 3D environment, enabling the cells to proliferate, exhibit tenogenic behaviors, and produce a new collagen type I matrix, thereby remodeling the surrounding environment. Indeed, over the 21-day culture period under perfusion condition, tenomodulin expression showed a significant upregulation on day 7, with a 2.3-fold increase, compared to days 14 and 21. Collagen type I gene expression was upregulated nearly 10-fold by day 14. This trend was further confirmed by western blot analysis, which revealed a statistically significant difference in tenomodulin expression between day 21 and both day 7 and day 14. For type I collagen, significant differences were observed between day 0 and day 21, as well as between day 0 and day 14, with a <i>p</i>-value of 0.01. These results indicate a progressive over-expression of type I collagen, reflecting cell differentiation towards a proper tenogenic phenotype. Cytokines, such as IL-8 and IL-6, levels peaked at 8566 and 7636 pg/mL, respectively, on day 7, before decreasing to 54 and 46 pg/mL by day 21. Overall, the data suggest that the novel ColMa bioprinting protocol effectively provided a conducive environment for the growth and proper differentiation of hTSPCs, showcasing its potential for studying cell behavior and tenogenic differentiation.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10723","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Minocycline is a commonly used drug for adjunctive therapy in periodontal disease. However, the current mainstream local medications primarily rely on intra‐pocket administration, which, while avoiding the side effects of traditional systemic drugs, presents challenges such as inconvenience, discomfort, and the need for professional assistance, thus affecting patient compliance. Herein, we introduce a minocycline‐loaded dissolvable microneedle (Mino‐DMN) patch that allows for local and efficient delivery of minocycline to gingiva for the treatment of periodontitis. A two‐step casting micro‐molding process involving vacuum drying and freeze drying is employed to concentrate minocycline in the microneedle part and limit its diffusion into the patch backing. The resulting Mino‐DMN patch features an array of minocycline‐enriched gelatin MNs with a porous HA patch backing. The microneedles can penetrate into gingiva with enough mechanical strength and quickly release minocycline into the gingival tissue, ensuring prolonged local residence of the drug and minimizing its loss to saliva. In vivo experiments show Mino‐DMN inhibits pro‐inflammatory factors, promotes anti‐inflammatory factors, and stimulates bone formation, surpassing topical application and comparable to the inconvenient and discomfort administration of Periocline®. This proposed Mino‐DMN offers a simple, efficient, user‐friendly strategy for the adjunctive treatment of periodontal disease.
{"title":"Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease","authors":"Huimin Li, Xueyu Wen, Xinyi Gong, Yange Wu, Puxuan Zhao, Yun Zhang, Zhuomin Sha, Hao Chang, Xuepeng Chen","doi":"10.1002/btm2.10730","DOIUrl":"https://doi.org/10.1002/btm2.10730","url":null,"abstract":"Minocycline is a commonly used drug for adjunctive therapy in periodontal disease. However, the current mainstream local medications primarily rely on intra‐pocket administration, which, while avoiding the side effects of traditional systemic drugs, presents challenges such as inconvenience, discomfort, and the need for professional assistance, thus affecting patient compliance. Herein, we introduce a minocycline‐loaded dissolvable microneedle (Mino‐DMN) patch that allows for local and efficient delivery of minocycline to gingiva for the treatment of periodontitis. A two‐step casting micro‐molding process involving vacuum drying and freeze drying is employed to concentrate minocycline in the microneedle part and limit its diffusion into the patch backing. The resulting Mino‐DMN patch features an array of minocycline‐enriched gelatin MNs with a porous HA patch backing. The microneedles can penetrate into gingiva with enough mechanical strength and quickly release minocycline into the gingival tissue, ensuring prolonged local residence of the drug and minimizing its loss to saliva. In vivo experiments show Mino‐DMN inhibits pro‐inflammatory factors, promotes anti‐inflammatory factors, and stimulates bone formation, surpassing topical application and comparable to the inconvenient and discomfort administration of Periocline®. This proposed Mino‐DMN offers a simple, efficient, user‐friendly strategy for the adjunctive treatment of periodontal disease.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"33 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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