Pub Date : 2026-01-08DOI: 10.1016/j.bmt.2025.100131
Zhe Wang , Xiang Lin , Yunpeng Shi , Hong Yan , Yixuan Shang , Haozhen Ren
Background
In recent years, tissue engineering has experienced rapid development, with bioscaffolds emerging as a focal point of research due to their favorable bioactivity, biocompatibility, and capacity to provide mechanical support for cellular growth. The bioscaffolds have great potential in tissue regeneration. However, conventional natural scaffolds and polymer scaffolds pose risks of immunogenicity, while also face challenges in mimicking the in vivo microenvironment and the biochemical and mechanical properties of natural organs/tissues, which collectively limit their repair capability. The development of decellularized extracellular matrix (dECM) technology offers a viable solution to these challenges, demonstrating considerable potential for advancing organ and tissue regeneration.
Technology
This reviews the classification of dECM, outlines various current methods for its preparation, and comprehensively examines its latest advances in tissue repair and regenerative medicine, including applications in skin, bone, nerve, heart, lung, liver, and kidney tissues.
Results
This review systematically examines recent advances in dECM production and regenerative medicine applications. We classify dECM subtypes, detail contemporary decellularization protocols, and highlight their biomedical utility. Superior biocompatibility substantially mitigates post-transplant immune rejection risk, underscoring strong clinical translation potential for tissue engineering.
{"title":"Decellularized extracellular matrix: Advanced bioplatforms for functional tissue restoration via innovative decellularization techniques","authors":"Zhe Wang , Xiang Lin , Yunpeng Shi , Hong Yan , Yixuan Shang , Haozhen Ren","doi":"10.1016/j.bmt.2025.100131","DOIUrl":"10.1016/j.bmt.2025.100131","url":null,"abstract":"<div><h3>Background</h3><div>In recent years, tissue engineering has experienced rapid development, with bioscaffolds emerging as a focal point of research due to their favorable bioactivity, biocompatibility, and capacity to provide mechanical support for cellular growth. The bioscaffolds have great potential in tissue regeneration. However, conventional natural scaffolds and polymer scaffolds pose risks of immunogenicity, while also face challenges in mimicking the <em>in vivo</em> microenvironment and the biochemical and mechanical properties of natural organs/tissues, which collectively limit their repair capability. The development of decellularized extracellular matrix (dECM) technology offers a viable solution to these challenges, demonstrating considerable potential for advancing organ and tissue regeneration.</div></div><div><h3>Technology</h3><div>This reviews the classification of dECM, outlines various current methods for its preparation, and comprehensively examines its latest advances in tissue repair and regenerative medicine, including applications in skin, bone, nerve, heart, lung, liver, and kidney tissues.</div></div><div><h3>Results</h3><div>This review systematically examines recent advances in dECM production and regenerative medicine applications. We classify dECM subtypes, detail contemporary decellularization protocols, and highlight their biomedical utility. Superior biocompatibility substantially mitigates post-transplant immune rejection risk, underscoring strong clinical translation potential for tissue engineering.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"13 ","pages":"Article 100131"},"PeriodicalIF":0.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><div>Fracture healing remains a significant clinical challenge, particularly in cases of delayed or impaired recovery, often hindered by inadequate vascularization, patient variability. Conventional stimulation methods relying on implanted electrodes or external coils are constrained by invasiveness, complexity, and patient discomfort. Smart biomaterials capable of providing wireless, localized bioelectric stimulation represent a promising alternative. Among these, magnetoelectric (ME) laminates can convert externally applied magnetic fields into localized therapeutic voltages, enabling non-invasive and patient-specific bone regeneration. Although magnetoelectric systems have shown potential in biomedical stimulation, their electromechanical coupling behavior, tunability, and optimization for orthopedic applications remain insufficiently explored. Understanding these mechanisms through computational modeling is crucial for developing clinically translatable ME-based bone regeneration systems. This study introduces a next-generation trilayer ME laminate integrating a new material pairing: magnetostrictive Galfenol (Fe<sub>80</sub>Ga<sub>20</sub>) with a piezoelectric layer of either poly(vinylidene fluoride)(PVDF) or Barium Titanate (BaTiO<sub>3</sub>). A fully coupled 3D finite-element model was developed in COMSOL Multiphysics 6.0 to simulate magnetostrictive deformation, interfacial strain transfer, and piezoelectric voltage generation under physiologically relevant magnetic field strengths and frequencies. Parametric studies assessed tunability across varying excitation conditions, while comparative analyses evaluated the performance trade-offs between PVDF- and BaTiO<sub>3</sub>-based laminates. Simulations revealed that the proposed trilayer laminate could generate sustained voltage outputs within the osteogenesis-relevant range (100 nV–5 V) without implanted electrodes. Resonance-dependent voltage peaks were sensitive to excitation frequency and adaptable to bone geometry, supporting personalized stimulation protocols. PVDF-based laminates provided higher flexibility and biocompatibility, whereas BaTiO<sub>3</sub>-based laminates achieved superior voltage outputs, highlighting design trade-offs relevant for clinical optimization. This work establishes the engineering feasibility and fundamental electromechanical characteristics of magnetoelectric trilayer laminates for wireless bone stimulation. The deterministic modeling approach, incorporating parameter sweeps for laminate thickness, field amplitude, and excitation frequency, provides a first-level sensitivity framework for device design. Overall, the study bridges computational modeling and translational potential, positioning ME laminates as a next-generation platform for non-invasive, customizable, and patient-centered bone regeneration. These findings lay the groundwork for forthcoming <em>in-vitro</em> and <em>in-vivo</em> validations, advancing the integration of smart magnetoe
{"title":"Wireless bioelectric stimulation for bone regeneration using magnetoelectric PVDF/BaTiO3 – Fe80Ga20 laminates","authors":"H.A. Viraji , Aravinda Abeygunawardane , S.U. Adikary , Sajith Edirisinghe , Aadil Faleel","doi":"10.1016/j.bmt.2025.100121","DOIUrl":"10.1016/j.bmt.2025.100121","url":null,"abstract":"<div><div>Fracture healing remains a significant clinical challenge, particularly in cases of delayed or impaired recovery, often hindered by inadequate vascularization, patient variability. Conventional stimulation methods relying on implanted electrodes or external coils are constrained by invasiveness, complexity, and patient discomfort. Smart biomaterials capable of providing wireless, localized bioelectric stimulation represent a promising alternative. Among these, magnetoelectric (ME) laminates can convert externally applied magnetic fields into localized therapeutic voltages, enabling non-invasive and patient-specific bone regeneration. Although magnetoelectric systems have shown potential in biomedical stimulation, their electromechanical coupling behavior, tunability, and optimization for orthopedic applications remain insufficiently explored. Understanding these mechanisms through computational modeling is crucial for developing clinically translatable ME-based bone regeneration systems. This study introduces a next-generation trilayer ME laminate integrating a new material pairing: magnetostrictive Galfenol (Fe<sub>80</sub>Ga<sub>20</sub>) with a piezoelectric layer of either poly(vinylidene fluoride)(PVDF) or Barium Titanate (BaTiO<sub>3</sub>). A fully coupled 3D finite-element model was developed in COMSOL Multiphysics 6.0 to simulate magnetostrictive deformation, interfacial strain transfer, and piezoelectric voltage generation under physiologically relevant magnetic field strengths and frequencies. Parametric studies assessed tunability across varying excitation conditions, while comparative analyses evaluated the performance trade-offs between PVDF- and BaTiO<sub>3</sub>-based laminates. Simulations revealed that the proposed trilayer laminate could generate sustained voltage outputs within the osteogenesis-relevant range (100 nV–5 V) without implanted electrodes. Resonance-dependent voltage peaks were sensitive to excitation frequency and adaptable to bone geometry, supporting personalized stimulation protocols. PVDF-based laminates provided higher flexibility and biocompatibility, whereas BaTiO<sub>3</sub>-based laminates achieved superior voltage outputs, highlighting design trade-offs relevant for clinical optimization. This work establishes the engineering feasibility and fundamental electromechanical characteristics of magnetoelectric trilayer laminates for wireless bone stimulation. The deterministic modeling approach, incorporating parameter sweeps for laminate thickness, field amplitude, and excitation frequency, provides a first-level sensitivity framework for device design. Overall, the study bridges computational modeling and translational potential, positioning ME laminates as a next-generation platform for non-invasive, customizable, and patient-centered bone regeneration. These findings lay the groundwork for forthcoming <em>in-vitro</em> and <em>in-vivo</em> validations, advancing the integration of smart magnetoe","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100121"},"PeriodicalIF":0.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1016/j.bmt.2025.100120
Zixuan Tang , Qingquan Xia , Jian Li , Jun Chen , Xuhua Wu , Jiang Li , Jiangyi Liu , Wei Liu , Ke Rong , Xiangchao Meng
The healing of acute infected wounds is a multi-stage and sequential biological process. Traditional antibacterial dressings are usually a simple superposition of antibacterial properties and active ingredients, lacking effective coupling with the wound microenvironment, and it is difficult to accurately match the continuous process of infected wound healing. In this study, a pH-responsive hydrogel of sodium alginate and carboxymethyl chitosan interpenetrating network was constructed, and tannic acid (TA) and zinc-doped bioglass (BAG) were loaded through hydrogen bonding and hydrophobic interactions. In the acidic environment of infection, the enhancement of intermolecular non-covalent interaction leads to the contraction of hydrogel network and the rapid release of TA. In the alkaline environment of healing, the weakening of intermolecular interaction leads to the expansion of hydrogel network and the continuous release of Zn2+ and Ca2+. In vitro biological evaluation showed that the hydrogel had an effective antibacterial effects against E.coli and S.aureus, and effectively regulated immune response. In addition, the hydrogel effectively removed excessive ROS and significantly increase the activity of cellular antioxidant enzymes, thereby accelerating the wound healing process in animal experiment. This microenvironment-responsive hydrogel provides a new therapeutic strategy for precise sequential repair of acute infectious wounds.
{"title":"Microenvironment-feedback hydrogel for precise sequential repair of acute infectious wounds","authors":"Zixuan Tang , Qingquan Xia , Jian Li , Jun Chen , Xuhua Wu , Jiang Li , Jiangyi Liu , Wei Liu , Ke Rong , Xiangchao Meng","doi":"10.1016/j.bmt.2025.100120","DOIUrl":"10.1016/j.bmt.2025.100120","url":null,"abstract":"<div><div>The healing of acute infected wounds is a multi-stage and sequential biological process. Traditional antibacterial dressings are usually a simple superposition of antibacterial properties and active ingredients, lacking effective coupling with the wound microenvironment, and it is difficult to accurately match the continuous process of infected wound healing. In this study, a pH-responsive hydrogel of sodium alginate and carboxymethyl chitosan interpenetrating network was constructed, and tannic acid (TA) and zinc-doped bioglass (BAG) were loaded through hydrogen bonding and hydrophobic interactions. In the acidic environment of infection, the enhancement of intermolecular non-covalent interaction leads to the contraction of hydrogel network and the rapid release of TA. In the alkaline environment of healing, the weakening of intermolecular interaction leads to the expansion of hydrogel network and the continuous release of Zn<sup>2+</sup> and Ca<sup>2+</sup>. <em>In vitro</em> biological evaluation showed that the hydrogel had an effective antibacterial effects against <em>E.coli</em> and <em>S.aureus</em>, and effectively regulated immune response. In addition, the hydrogel effectively removed excessive ROS and significantly increase the activity of cellular antioxidant enzymes, thereby accelerating the wound healing process in animal experiment. This microenvironment-responsive hydrogel provides a new therapeutic strategy for precise sequential repair of acute infectious wounds.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100120"},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1016/j.bmt.2025.100118
Wei Xu , Liwen Song , Qifeng Yu , Shichao Tong , Yi Wang , Yifan Li , Jin Qiu , Zhikun Li
Chemotherapy-induced bone loss in patients with osteosarcoma (OS) has attracted increasing attention worldwide. Previous studies have revealed the interactions between OS cells and osteoclasts via secretion of various cytokines. However, the specific impacts of chemically injured OS cells on osteoclast functions remain unknown. Untargeted metabolomics is a high-throughput analytical technique used to screen potential biomarkers and identify unknown metabolites in various biological samples. In this study, cisplatin (CDDP)-injured OS cell supernatant promoted the osteoclast differentiation of bone marrow macrophages (BMMs). Untargeted metabolomic analysis revealed the metabolic profile of injured OS cells, and FAPy-adenine (FA), which was upregulated by approximately 2000-fold, was identified in the supernatant. FA promoted the osteoclast differentiation of BMMs in a dose-dependent manner. RNA sequencing revealed increased Fc gamma receptor 1 (Fcgr1) expression levels in FA-treated BMMs. Fcgr1 overexpression promoted the osteoclast differentiation of BMMs and Cathepsin K expression, whereas its knockdown inhibited the pro-osteoclast differentiation effect of FA. Furthermore, FA accelerated osteoporosis progression in ovariectomy model rats. Upregulation of Fcgr1 levels promoted bone loss, whereas its silencing inhibited the bone loss induced by FA in ovariectomy model rats. Collectively, these findings suggest that FA released from CDDP-injured OS cells contributes to osteoporosis progression by upregulating Fcgr1 levels, providing new insights into chemotherapy-induced bone loss in patients with OS.
{"title":"Targeting Fcgr1 to repress FAPy-adenine-induced osteoporosis in osteosarcoma receiving chemotherapy","authors":"Wei Xu , Liwen Song , Qifeng Yu , Shichao Tong , Yi Wang , Yifan Li , Jin Qiu , Zhikun Li","doi":"10.1016/j.bmt.2025.100118","DOIUrl":"10.1016/j.bmt.2025.100118","url":null,"abstract":"<div><div>Chemotherapy-induced bone loss in patients with osteosarcoma (OS) has attracted increasing attention worldwide. Previous studies have revealed the interactions between OS cells and osteoclasts via secretion of various cytokines. However, the specific impacts of chemically injured OS cells on osteoclast functions remain unknown. Untargeted metabolomics is a high-throughput analytical technique used to screen potential biomarkers and identify unknown metabolites in various biological samples. In this study, cisplatin (CDDP)-injured OS cell supernatant promoted the osteoclast differentiation of bone marrow macrophages (BMMs). Untargeted metabolomic analysis revealed the metabolic profile of injured OS cells, and FAPy-adenine (FA), which was upregulated by approximately 2000-fold, was identified in the supernatant. FA promoted the osteoclast differentiation of BMMs in a dose-dependent manner. RNA sequencing revealed increased Fc gamma receptor 1 (Fcgr1) expression levels in FA-treated BMMs. Fcgr1 overexpression promoted the osteoclast differentiation of BMMs and Cathepsin K expression, whereas its knockdown inhibited the pro-osteoclast differentiation effect of FA. Furthermore, FA accelerated osteoporosis progression in ovariectomy model rats. Upregulation of Fcgr1 levels promoted bone loss, whereas its silencing inhibited the bone loss induced by FA in ovariectomy model rats. Collectively, these findings suggest that FA released from CDDP-injured OS cells contributes to osteoporosis progression by upregulating Fcgr1 levels, providing new insights into chemotherapy-induced bone loss in patients with OS.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100118"},"PeriodicalIF":0.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145528855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1016/j.bmt.2025.100119
Xuechao Liu , Kunpeng Wei , Enyu Lin , Yi Li , Pengzhen Zhuang , Yanbing Zhou , Guilai Zuo , Zhaojian Niu
Cancer drug resistance presents a significant challenge in modern oncology, necessitating detailed exploration of its underlying mechanisms and the development of effective counterstrategies. This review aims to systematically evaluate the most recent applications and advancements of multi-omics technologies in elucidating the mechanisms of cancer drug resistance. Multi-omics includes genomics, transcriptomics, proteomics, microbiomics, metabolomics, and epigenomics. Notably, emerging methodologies such as single-cell and spatial omics have been instrumental in revealing the biological characteristics and resistance mechanisms of tumor cells across various layers and dimensions. The review highlights resistance mechanisms uncovered through the combined application of multi-omics, including gene mutations and epigenetic modifications, reprogramming of signaling pathways, drug efflux and cytoskeletal reorganization, and DNA repair mechanisms. It also explores novel mechanisms in the tumor immune microenvironment (TIME), metabolic reprogramming, and microbiome interactions. The review assesses the benefits of integrating multi-omics data, the application of these technologies in identifying key genes and pathways, and their role in personalized treatment strategies. It provides a comprehensive understanding of the dynamic changes and heterogeneity in cancer drug resistance to aid precision treatment strategies. Additionally, the article offers insights into the future directions of multi-omics technologies in oncology drug resistance research and discusses the primary challenges ahead. We aim to provide novel perspectives and directions for innovation and optimization in cancer treatment, ultimately enhancing patient prognosis and quality of life in oncology.
{"title":"Multi-omics advances in understanding cancer drug resistance","authors":"Xuechao Liu , Kunpeng Wei , Enyu Lin , Yi Li , Pengzhen Zhuang , Yanbing Zhou , Guilai Zuo , Zhaojian Niu","doi":"10.1016/j.bmt.2025.100119","DOIUrl":"10.1016/j.bmt.2025.100119","url":null,"abstract":"<div><div>Cancer drug resistance presents a significant challenge in modern oncology, necessitating detailed exploration of its underlying mechanisms and the development of effective counterstrategies. This review aims to systematically evaluate the most recent applications and advancements of multi-omics technologies in elucidating the mechanisms of cancer drug resistance. Multi-omics includes genomics, transcriptomics, proteomics, microbiomics, metabolomics, and epigenomics. Notably, emerging methodologies such as single-cell and spatial omics have been instrumental in revealing the biological characteristics and resistance mechanisms of tumor cells across various layers and dimensions. The review highlights resistance mechanisms uncovered through the combined application of multi-omics, including gene mutations and epigenetic modifications, reprogramming of signaling pathways, drug efflux and cytoskeletal reorganization, and DNA repair mechanisms. It also explores novel mechanisms in the tumor immune microenvironment (TIME), metabolic reprogramming, and microbiome interactions. The review assesses the benefits of integrating multi-omics data, the application of these technologies in identifying key genes and pathways, and their role in personalized treatment strategies. It provides a comprehensive understanding of the dynamic changes and heterogeneity in cancer drug resistance to aid precision treatment strategies. Additionally, the article offers insights into the future directions of multi-omics technologies in oncology drug resistance research and discusses the primary challenges ahead. We aim to provide novel perspectives and directions for innovation and optimization in cancer treatment, ultimately enhancing patient prognosis and quality of life in oncology.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100119"},"PeriodicalIF":0.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145528256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-06DOI: 10.1016/j.bmt.2025.100117
Junxian Cao , Xiao Chang , Shiwen Deng , Hongjun Yang , Gang Guo , Peng Chen
Tuberous sclerosis complex mutation renal angiomyolipomas (TSC-RAML) are benign tumors driven by abnormal growth of mesenchymal-derived cells. Although mTOR inhibitors are clinically used, drug resistance and incomplete tumour shrinkage highlight the need for new treatment approaches. Here, we developed a new strategy combining single-cell transcriptomics, network pharmacology, and functional experiments to identify targeted therapies for TSC-RAMLs. Single-cell RNA sequencing of tumour tissues from 4 TSC-RAML patients uncovered a distinct mesenchymal subpopulation (TSC-RAML-Cells) with upregulated pathways in adipogenesis and mTOR signalling. Using high-dimensional weighted gene co-expression network analysis (hdWGCNA) on TSC-RAML-Cells, we identified three disease-associated modules containing hub genes critical for tumour survival. Cross-referencing these modules with the Connectivity Map (CMAP) drug database prioritized AS-605240 as a potential therapeutic candidate. Protein-protein interaction (PPI) network analysis further revealed PI3KCA as a central target, and molecular dynamics simulations confirmed stable binding between AS-605240 and PI3KCA, with a binding free energy of −7.8 kcal/mol, supporting its mechanism of action. In vitro experiments using patient-derived TSC-RAML cells showed that AS-605240 suppressed cell growth in a dose-dependent manner (IC50 = 7.8 μM) and increased apoptosis rates through inhibition of the PI3K/AKT pathway. This work not only proposes AS-605240 as a promising therapy for TSC-RAMLs but also provides a scalable “cell subtype-to-drug" discovery framework. By integrating single-cell omics and computational drug repurposing, this approach accelerates precision medicine development for rare diseases.
{"title":"Integrative cell subtype-to-drug discovery technology for angiomyolipomas treatment","authors":"Junxian Cao , Xiao Chang , Shiwen Deng , Hongjun Yang , Gang Guo , Peng Chen","doi":"10.1016/j.bmt.2025.100117","DOIUrl":"10.1016/j.bmt.2025.100117","url":null,"abstract":"<div><div>Tuberous sclerosis complex mutation renal angiomyolipomas (TSC-RAML) are benign tumors driven by abnormal growth of mesenchymal-derived cells. Although mTOR inhibitors are clinically used, drug resistance and incomplete tumour shrinkage highlight the need for new treatment approaches. Here, we developed a new strategy combining single-cell transcriptomics, network pharmacology, and functional experiments to identify targeted therapies for TSC-RAMLs. Single-cell RNA sequencing of tumour tissues from 4 TSC-RAML patients uncovered a distinct mesenchymal subpopulation (TSC-RAML-Cells) with upregulated pathways in adipogenesis and mTOR signalling. Using high-dimensional weighted gene co-expression network analysis (hdWGCNA) on TSC-RAML-Cells, we identified three disease-associated modules containing hub genes critical for tumour survival. Cross-referencing these modules with the Connectivity Map (CMAP) drug database prioritized AS-605240 as a potential therapeutic candidate. Protein-protein interaction (PPI) network analysis further revealed PI3KCA as a central target, and molecular dynamics simulations confirmed stable binding between AS-605240 and PI3KCA, with a binding free energy of −7.8 kcal/mol, supporting its mechanism of action. In vitro experiments using patient-derived TSC-RAML cells showed that AS-605240 suppressed cell growth in a dose-dependent manner (IC50 = 7.8 μM) and increased apoptosis rates through inhibition of the PI3K/AKT pathway. This work not only proposes AS-605240 as a promising therapy for TSC-RAMLs but also provides a scalable “cell subtype-to-drug\" discovery framework. By integrating single-cell omics and computational drug repurposing, this approach accelerates precision medicine development for rare diseases.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100117"},"PeriodicalIF":0.0,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chronic infection with the hepatitis B virus (HBV) is a common cause of liver disease worldwide, particularly in Asia and Africa, where it is highly prevalent. Currently, therapies for chronic HBV infection, such as nucleoside analogs (NAs), mainly suppress viral replication but rarely achieve a lasting cure. Recently, emerging adoptive cell therapy (ACT), represented by chimeric antigen receptor (CAR)-T, T cell receptor (TCR)-T, and CAR-NK (Natural Killer) cell therapy, have provided new opportunities for the treatment of numerous diseases. For instance, CAR-T cells can be designed to target HBV antigens and kill HBV-infected cells with safety concerns regarding potential side effects and limitations of CAR-T cell exhaustion. TCR-T cells mainly exert their immune activation effects by recognizing antigen peptide-MHC complexes in HBV-infected hepatocytes. Although the antiviral effects of TCR-T are evident in preclinical studies, they are limited by on-target toxicity and carry a risk of transient liver damage. In addition to CAR-T and TCR-T therapies, CAR-NK cell therapy has shown promising prospects in treating HBV-associated liver diseases. To enhance the safety and efficiency of ACT applications in clinical settings, CAR and TCR structures should be rationally optimized, and combined treatment strategies need to be explored. In this review, we summarize the structure and mechanism of ACT, including CAR-T, TCR-T, and CAR-NK cell therapies, as well as their research progress and challenges in the treatment of HBV-associated liver diseases.
{"title":"Adoptive cell therapy for HBV-associated liver diseases","authors":"Youxi Zhou , Kaizhao Chen , Yang Zhang , Hongwei Cheng , Shuaishuai Zhang","doi":"10.1016/j.bmt.2025.100116","DOIUrl":"10.1016/j.bmt.2025.100116","url":null,"abstract":"<div><div>Chronic infection with the hepatitis B virus (HBV) is a common cause of liver disease worldwide, particularly in Asia and Africa, where it is highly prevalent. Currently, therapies for chronic HBV infection, such as nucleoside analogs (NAs), mainly suppress viral replication but rarely achieve a lasting cure. Recently, emerging adoptive cell therapy (ACT), represented by chimeric antigen receptor (CAR)-T, T cell receptor (TCR)-T, and CAR-NK (Natural Killer) cell therapy, have provided new opportunities for the treatment of numerous diseases. For instance, CAR-T cells can be designed to target HBV antigens and kill HBV-infected cells with safety concerns regarding potential side effects and limitations of CAR-T cell exhaustion. TCR-T cells mainly exert their immune activation effects by recognizing antigen peptide-MHC complexes in HBV-infected hepatocytes. Although the antiviral effects of TCR-T are evident in preclinical studies, they are limited by on-target toxicity and carry a risk of transient liver damage. In addition to CAR-T and TCR-T therapies, CAR-NK cell therapy has shown promising prospects in treating HBV-associated liver diseases. To enhance the safety and efficiency of ACT applications in clinical settings, CAR and TCR structures should be rationally optimized, and combined treatment strategies need to be explored. In this review, we summarize the structure and mechanism of ACT, including CAR-T, TCR-T, and CAR-NK cell therapies, as well as their research progress and challenges in the treatment of HBV-associated liver diseases.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100116"},"PeriodicalIF":0.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28DOI: 10.1016/j.bmt.2025.100115
Shengwen Cheng , Jiaying Wei , Senrui Liu , Junyan Liu , Xiaohong Luo , Yixuan Lan , Mingfei Dong , Liangbin Zhou , Wei Huang , Chen Zhao , Yiting Lei
Coaxial three-dimensional (3D) printing enables precise, multi-material deposition, demonstrating strong potential across diverse fields, including industrial monitoring, health sensing, artificial intelligence (AI) hardware, and food packaging. Its core value is prominently realized in the biomedical domain, where it has revolutionized tissue engineering. The present review consolidates advancements in 3D coaxial bioprinting across diverse biomedical applications, focusing on its transformative potential in vascularized tissue engineering, spatiotemporal drug delivery, and patient-specific disease modeling. This review also explored unresolved challenges, such as bioink optimization and functional vascularization, while proposing integrative solutions that combine coaxial printing with AI and hybrid fabrication strategies. The versatility of coaxial 3D printing is evident in its numerous biomedical applications, such as cardiovascular tissue engineering, skin regeneration, bone repair, and functional muscle constructs. In bone tissue engineering, coaxial printing facilitates vascularization and osteochondral regeneration through spatially controlled bioink and scaffold design. Applications extend to cartilage repair, neuromuscular junction modeling, and tumor microenvironment replication. Despite progress, challenges persist in optimizing bioink rheology, achieving functional vascularization, and scaling production for clinical application. Notably, the integration of advanced materials, such as hydrogels and inorganic salts, with hybrid strategies, including electrospinning and sacrificial printing, highlights the synergistic potential of coaxial bioprinting to transform regenerative medicine, drug screening, and personalized therapies. Ongoing innovations in multi-scale, multi-cellular printing can bridge the gap between engineered constructs and biological functional tissues.
{"title":"Precision and customization in regenerative medicine: The role of coaxial 3D printing","authors":"Shengwen Cheng , Jiaying Wei , Senrui Liu , Junyan Liu , Xiaohong Luo , Yixuan Lan , Mingfei Dong , Liangbin Zhou , Wei Huang , Chen Zhao , Yiting Lei","doi":"10.1016/j.bmt.2025.100115","DOIUrl":"10.1016/j.bmt.2025.100115","url":null,"abstract":"<div><div>Coaxial three-dimensional (3D) printing enables precise, multi-material deposition, demonstrating strong potential across diverse fields, including industrial monitoring, health sensing, artificial intelligence (AI) hardware, and food packaging. Its core value is prominently realized in the biomedical domain, where it has revolutionized tissue engineering. The present review consolidates advancements in 3D coaxial bioprinting across diverse biomedical applications, focusing on its transformative potential in vascularized tissue engineering, spatiotemporal drug delivery, and patient-specific disease modeling. This review also explored unresolved challenges, such as bioink optimization and functional vascularization, while proposing integrative solutions that combine coaxial printing with AI and hybrid fabrication strategies. The versatility of coaxial 3D printing is evident in its numerous biomedical applications, such as cardiovascular tissue engineering, skin regeneration, bone repair, and functional muscle constructs. In bone tissue engineering, coaxial printing facilitates vascularization and osteochondral regeneration through spatially controlled bioink and scaffold design. Applications extend to cartilage repair, neuromuscular junction modeling, and tumor microenvironment replication. Despite progress, challenges persist in optimizing bioink rheology, achieving functional vascularization, and scaling production for clinical application. Notably, the integration of advanced materials, such as hydrogels and inorganic salts, with hybrid strategies, including electrospinning and sacrificial printing, highlights the synergistic potential of coaxial bioprinting to transform regenerative medicine, drug screening, and personalized therapies. Ongoing innovations in multi-scale, multi-cellular printing can bridge the gap between engineered constructs and biological functional tissues.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100115"},"PeriodicalIF":0.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145424719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-27DOI: 10.1016/j.bmt.2025.100114
Qing Wang , Shiyi Zuo , Xixuan Yang , Yaqi Li , Cuiyun Liu , Yaqiao Li , Shuo Wang , Wenjing Wang , Danping Wang , Jiayu Guo , Jin Sun , Zhonggui He , Zhenbao Li , Bingjun Sun
The clinical efficacy of Irinotecan is constrained by individual variability in its enzymatic conversion to the active metabolite, SN38. While direct administration of SN38 bypasses this enzymatic process and demonstrates potent anti-tumor activity, its clinical application remains hindered by poor physicochemical properties and off-target toxicity. These challenges highlight the necessity for efficient drug delivery strategies. Prodrug nanoassemblies combine the advantages of nano drug delivery technology and prodrug strategy, offering an effective approach to address these limitations. The modification module in prodrug design plays a critical role in imparting prodrugs self-assembly ability. Monomethyl branched-chain fatty acids (mmBCFAs), known for their biocompatibility and metabolite safety, show great potential as a worthy option. In this study, we designed and synthesized SN38-SS-BAc18 by incorporating 16-methylheptanoic acid (BAc18) as the modification module, and a disulfide bond as the responsive module for tumor-specific activation. The resulting SN38-SS-BAc18 significantly improved the undesirable physicochemical properties of SN38 and exhibited enhanced self-assembly performance. Due to its prolonged circulation time, high tumor accumulation, and specific release profiles, the prodrug nanoassemblies (SN38-SS-BAc18 NPs) exhibited superior anti-tumor efficacy and biosafety. This study addressed multiple therapeutic limitations of SN38 and Irinotecan, providing valuable insights for the rational design of efficient prodrug nanoassemblies for colorectal cancer treatment.
伊立替康的临床疗效受到其酶转化为活性代谢物SN38的个体差异的限制。虽然直接给药SN38可以绕过这一酶促过程并显示出强大的抗肿瘤活性,但其物理化学性质差和脱靶毒性仍阻碍了其临床应用。这些挑战突出了制定有效给药战略的必要性。前体药物纳米组件结合了纳米药物传递技术和前体药物策略的优点,为解决这些局限性提供了有效的途径。前体药物设计中的修饰模块对赋予前体药物自组装能力起着至关重要的作用。单甲支链脂肪酸(mmBCFAs)以其生物相容性和代谢安全性而闻名,显示出作为一种有价值的选择的巨大潜力。本研究以16-甲基庚酸(BAc18)为修饰模块,以二硫键为肿瘤特异性激活响应模块,设计合成了SN38-SS-BAc18。所得SN38- ss - bac18显著改善了SN38的理化性质,并表现出增强的自组装性能。SN38-SS-BAc18纳米组件具有循环时间长、肿瘤蓄积大、释放特异性强等特点,具有良好的抗肿瘤疗效和生物安全性。本研究解决了SN38和伊立替康的多重治疗局限性,为合理设计有效的结直肠癌治疗前药纳米组件提供了有价值的见解。
{"title":"Prodrug nanoassembly technology for colorectal cancer therapy","authors":"Qing Wang , Shiyi Zuo , Xixuan Yang , Yaqi Li , Cuiyun Liu , Yaqiao Li , Shuo Wang , Wenjing Wang , Danping Wang , Jiayu Guo , Jin Sun , Zhonggui He , Zhenbao Li , Bingjun Sun","doi":"10.1016/j.bmt.2025.100114","DOIUrl":"10.1016/j.bmt.2025.100114","url":null,"abstract":"<div><div>The clinical efficacy of Irinotecan is constrained by individual variability in its enzymatic conversion to the active metabolite, SN38. While direct administration of SN38 bypasses this enzymatic process and demonstrates potent anti-tumor activity, its clinical application remains hindered by poor physicochemical properties and off-target toxicity. These challenges highlight the necessity for efficient drug delivery strategies. Prodrug nanoassemblies combine the advantages of nano drug delivery technology and prodrug strategy, offering an effective approach to address these limitations. The modification module in prodrug design plays a critical role in imparting prodrugs self-assembly ability. Monomethyl branched-chain fatty acids (mmBCFAs), known for their biocompatibility and metabolite safety, show great potential as a worthy option. In this study, we designed and synthesized SN38-SS-BAc<sub>18</sub> by incorporating 16-methylheptanoic acid (BAc<sub>18</sub>) as the modification module, and a disulfide bond as the responsive module for tumor-specific activation. The resulting SN38-SS-BAc<sub>18</sub> significantly improved the undesirable physicochemical properties of SN38 and exhibited enhanced self-assembly performance. Due to its prolonged circulation time, high tumor accumulation, and specific release profiles, the prodrug nanoassemblies (SN38-SS-BAc<sub>18</sub> NPs) exhibited superior anti-tumor efficacy and biosafety. This study addressed multiple therapeutic limitations of SN38 and Irinotecan, providing valuable insights for the rational design of efficient prodrug nanoassemblies for colorectal cancer treatment.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100114"},"PeriodicalIF":0.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145424718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-27DOI: 10.1016/j.bmt.2025.100112
Jing Chen , Xu Zhu , Jun Huo , Shang Wu , Ting Zhou , Chunyu Cheng , Hao Dong , Yan Li , Xianchi Dong , Yuxin Chen
CD4+ T cells play a pivotal role in adaptive immunity, recognizing peptide antigens presented by MHC II molecules during infections and tumor development. Identifying immunodominant MHC II epitopess is essential for understanding CD4+ T cell responses; however, current methods such as mass spectrometry, suffer from low sensitivity and throughput, while computational algorithms show variable accuracy. To overcome these challenges, we developed EliteMHCII, a high-throughput immunopeptidome profiling platform that identifies antigen-derived MHC II epitopes and measures peptide binding affinity across 24 globally common MHC II alleles. Using EliteMHCII, we assessed the immunodominant epitopes of the SARS-CoV-2 RBD protein. Validation in vaccinated individuals and humanized mouse models revealed a strong correlation between high-affinity peptides and robust CD4+ T cell responses, while low-affinity peptides failed to elicit responses. Therefore, our immunopeptidome profiling platform, EliteMHCII, serves as a rapid, high throughput, feasible platform for CD4+ T cell epitope discovery at a global populational level in the context of infectious diseases and cancer immunotherapy.
{"title":"A high-throughput immunopeptidome platform for MHC II alleles to characterize antigen-specific CD4+ T cells","authors":"Jing Chen , Xu Zhu , Jun Huo , Shang Wu , Ting Zhou , Chunyu Cheng , Hao Dong , Yan Li , Xianchi Dong , Yuxin Chen","doi":"10.1016/j.bmt.2025.100112","DOIUrl":"10.1016/j.bmt.2025.100112","url":null,"abstract":"<div><div>CD4<sup>+</sup> T cells play a pivotal role in adaptive immunity, recognizing peptide antigens presented by MHC II molecules during infections and tumor development. Identifying immunodominant MHC II epitopess is essential for understanding CD4<sup>+</sup> T cell responses; however, current methods such as mass spectrometry, suffer from low sensitivity and throughput, while computational algorithms show variable accuracy. To overcome these challenges, we developed EliteMHCII, a high-throughput immunopeptidome profiling platform that identifies antigen-derived MHC II epitopes and measures peptide binding affinity across 24 globally common MHC II alleles. Using EliteMHCII, we assessed the immunodominant epitopes of the SARS-CoV-2 RBD protein. Validation in vaccinated individuals and humanized mouse models revealed a strong correlation between high-affinity peptides and robust CD4<sup>+</sup> T cell responses, while low-affinity peptides failed to elicit responses. Therefore, our immunopeptidome profiling platform, EliteMHCII, serves as a rapid, high throughput, feasible platform for CD4<sup>+</sup> T cell epitope discovery at a global populational level in the context of infectious diseases and cancer immunotherapy.</div></div>","PeriodicalId":100180,"journal":{"name":"Biomedical Technology","volume":"12 ","pages":"Article 100112"},"PeriodicalIF":0.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}