Pub Date : 2026-01-25DOI: 10.1016/j.mtbio.2026.102849
Lijing Qin , Xiu Wang , Tongjuan Liang , Yongyi Bi , Zhijun Guo , Wenzhong Li , Wanjun Liang
Brain diseases are one of the most critical threats to human health. The blood-brain barrier (BBB) prevents drugs from entering the brain, rendering standard treatments for neurological illnesses ineffective. In recent years, there has been an increase in interest in nanotechnology-based research to develop innovative drug delivery systems (NDDS) for drug loading, BBB penetration, and precision delivery to diseased areas. Nanocarriers made from natural biomaterials, in particular, solve the drawbacks of standard nanocarriers, such as low stability and inadequate targeting, while simultaneously providing benefits such as simplicity of modification and good biodegradability. This review focuses on the most recent advances in NDDS based on natural biomaterials for overcoming the BBB in treating brain diseases, with a particular emphasis on the methods and mechanisms by which natural biopolymers—such as polysaccharides, peptides, and polynucleotides—break through the BBB and enhance brain-targeted delivery. We explore current challenges and future application prospects of natural biopolymers in permeable nanomedicine delivery systems for the BBB, aiming to provide key insights for advancing cross-BBB delivery platforms toward smarter, multifunctional development, subsequent research, and translational applications.
{"title":"Research progress of blood-brain barrier penetrating and brain diseases therapy by natural biopolymer - based nanomedicine delivery systems","authors":"Lijing Qin , Xiu Wang , Tongjuan Liang , Yongyi Bi , Zhijun Guo , Wenzhong Li , Wanjun Liang","doi":"10.1016/j.mtbio.2026.102849","DOIUrl":"10.1016/j.mtbio.2026.102849","url":null,"abstract":"<div><div>Brain diseases are one of the most critical threats to human health. The blood-brain barrier (BBB) prevents drugs from entering the brain, rendering standard treatments for neurological illnesses ineffective. In recent years, there has been an increase in interest in nanotechnology-based research to develop innovative drug delivery systems (NDDS) for drug loading, BBB penetration, and precision delivery to diseased areas. Nanocarriers made from natural biomaterials, in particular, solve the drawbacks of standard nanocarriers, such as low stability and inadequate targeting, while simultaneously providing benefits such as simplicity of modification and good biodegradability. This review focuses on the most recent advances in NDDS based on natural biomaterials for overcoming the BBB in treating brain diseases, with a particular emphasis on the methods and mechanisms by which natural biopolymers—such as polysaccharides, peptides, and polynucleotides—break through the BBB and enhance brain-targeted delivery. We explore current challenges and future application prospects of natural biopolymers in permeable nanomedicine delivery systems for the BBB, aiming to provide key insights for advancing cross-BBB delivery platforms toward smarter, multifunctional development, subsequent research, and translational applications.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102849"},"PeriodicalIF":10.2,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-24DOI: 10.1016/j.mtbio.2026.102840
Shu Feng , Ying Xuan , Hong Jin , Meng Cui , Xinyue Meng , Jun Liao , Jianwei Feng
Hepatocellular carcinoma (HCC) remains a formidable challenge due to profound heterogeneity, recurrence, and pervasive therapeutic resistance, creating a significant unmet clinical need. Engineered nanozymes, nanomaterials with intrinsic catalytic activities, have emerged as a transformative paradigm. Unlike passive nanocarriers, nanozymes function as active therapeutic agents. Their prowess is predicated on catalytically manipulating the tumor microenvironment (TME), enabling localized ROS generation, inducing regulated cell death, and remodeling the immunosuppressive TME. This review systematically delineates the principles and potential of nanozyme strategies for HCC, focusing on catalytic therapy, nanozyme-enhanced immunotherapy, photothermal therapy, and integrated combination platforms, highlighting their capacity for synergistic antitumor effects. The review also critically discusses formidable challenges spanning metabolic heterogeneity, TME-driven immunosuppression, and biocompatibility hurdles that impede clinical translation. This work provides critical insights for the rational design of next-generation nanozymes and accelerating their integration into future multidisciplinary HCC treatment frameworks.
{"title":"Nanozyme for precision treatment of hepatocellular carcinoma","authors":"Shu Feng , Ying Xuan , Hong Jin , Meng Cui , Xinyue Meng , Jun Liao , Jianwei Feng","doi":"10.1016/j.mtbio.2026.102840","DOIUrl":"10.1016/j.mtbio.2026.102840","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) remains a formidable challenge due to profound heterogeneity, recurrence, and pervasive therapeutic resistance, creating a significant unmet clinical need. Engineered nanozymes, nanomaterials with intrinsic catalytic activities, have emerged as a transformative paradigm. Unlike passive nanocarriers, nanozymes function as active therapeutic agents. Their prowess is predicated on catalytically manipulating the tumor microenvironment (TME), enabling localized ROS generation, inducing regulated cell death, and remodeling the immunosuppressive TME. This review systematically delineates the principles and potential of nanozyme strategies for HCC, focusing on catalytic therapy, nanozyme-enhanced immunotherapy, photothermal therapy, and integrated combination platforms, highlighting their capacity for synergistic antitumor effects. The review also critically discusses formidable challenges spanning metabolic heterogeneity, TME-driven immunosuppression, and biocompatibility hurdles that impede clinical translation. This work provides critical insights for the rational design of next-generation nanozymes and accelerating their integration into future multidisciplinary HCC treatment frameworks.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102840"},"PeriodicalIF":10.2,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-24DOI: 10.1016/j.mtbio.2026.102838
Luke Hipwood , Minne Dekker , Dietmar W. Hutmacher , Christoph Meinert , Jacqui A. McGovern
Decellularized extracellular matrices (dECMs) are promising biomaterials for generating tissue-specific in vitro models due to their organotypic extracellular matrix (ECM) protein profiles compared to natural and synthetic alternatives. However, most dECM-based hydrogels rely on collagen fibrillogenesis, resulting in limited mechanical tuneability and cell instructivity. Here, we developed LungMA, a photocrosslinkable, methacrylated lung dECM hydrogel engineered for precise stiffness modulation and tissue-specific lung cancer modelling. The decellularization process removed >99 % of native DNA, ensuring minimal cellular remnants while preserving key ECM components including laminin-332, collagen VI, and heparan sulfate proteoglycan 2 (HSPG2). Methacrylation and photoinitiation enabled formation of stable LungMA hydrogels with tunable stiffnesses ranging from 1 kPa (healthy lung) to 4 kPa (fibrotic lung).
Using A549 non-small-cell lung cancer (NSCLC) cells, we demonstrated that matrix composition and stiffness influenced cell morphology, proliferation, and drug response. Soft LungMA (1 kPa) promoted motile, sheet-like cellular organization, whereas stiff LungMA (>4 kPa) induced compact spheroids associated with chemoresistance. Increasing matrix stiffness resulted in an increase in doxorubicin IC50 from 0.40 μM (soft LungMA) to 1.23 μM (stiff LungMA), and cisplatin IC50 from 0.03 μM to 8.34 μM, reflecting clinical observations where fibrosis correlates with poor prognosis.
In contrast, gelatin methacryloyl (GelMA) and basement membrane extract (BME)-based hydrogels failed to induce these stiffness-dependent effects during cisplatin treatment underscoring the instructive role of lung-specific ECM components and matrix stiffness on chemotherapeutic outcomes.
LungMA provides a physiologically relevant, mechanically tunable, lung-specific platform that replicates in vivo-like cancer phenotypes and drug responses. This work supports the application of LungMA for oncology research, disease modelling, and high-throughput drug screening as a clinically relevant, non-animal alternative for lung cancer studies.
{"title":"Photocrosslinkable lung dECM hydrogels promote stiffness-dependent lung cancer growth and chemoresistance","authors":"Luke Hipwood , Minne Dekker , Dietmar W. Hutmacher , Christoph Meinert , Jacqui A. McGovern","doi":"10.1016/j.mtbio.2026.102838","DOIUrl":"10.1016/j.mtbio.2026.102838","url":null,"abstract":"<div><div>Decellularized extracellular matrices (dECMs) are promising biomaterials for generating tissue-specific <em>in vitro</em> models due to their organotypic extracellular matrix (ECM) protein profiles compared to natural and synthetic alternatives. However, most dECM-based hydrogels rely on collagen fibrillogenesis, resulting in limited mechanical tuneability and cell instructivity. Here, we developed LungMA, a photocrosslinkable, methacrylated lung dECM hydrogel engineered for precise stiffness modulation and tissue-specific lung cancer modelling. The decellularization process removed >99 % of native DNA, ensuring minimal cellular remnants while preserving key ECM components including laminin-332, collagen VI, and heparan sulfate proteoglycan 2 (HSPG2). Methacrylation and photoinitiation enabled formation of stable LungMA hydrogels with tunable stiffnesses ranging from 1 kPa (healthy lung) to 4 kPa (fibrotic lung).</div><div>Using A549 non-small-cell lung cancer (NSCLC) cells, we demonstrated that matrix composition and stiffness influenced cell morphology, proliferation, and drug response. Soft LungMA (1 kPa) promoted motile, sheet-like cellular organization, whereas stiff LungMA (>4 kPa) induced compact spheroids associated with chemoresistance. Increasing matrix stiffness resulted in an increase in doxorubicin IC<sub>50</sub> from 0.40 μM (soft LungMA) to 1.23 μM (stiff LungMA), and cisplatin IC<sub>50</sub> from 0.03 μM to 8.34 μM, reflecting clinical observations where fibrosis correlates with poor prognosis.</div><div>In contrast, gelatin methacryloyl (GelMA) and basement membrane extract (BME)-based hydrogels failed to induce these stiffness-dependent effects during cisplatin treatment underscoring the instructive role of lung-specific ECM components and matrix stiffness on chemotherapeutic outcomes.</div><div>LungMA provides a physiologically relevant, mechanically tunable, lung-specific platform that replicates <em>in vivo</em>-like cancer phenotypes and drug responses. This work supports the application of LungMA for oncology research, disease modelling, and high-throughput drug screening as a clinically relevant, non-animal alternative for lung cancer studies.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102838"},"PeriodicalIF":10.2,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.mtbio.2026.102847
Yang Wu, Chengfeng Wang , Kai Fang , Ruofei Zu, Yangyang Deng, Chenchen Hu, Keang Cao, Yuqing Fang, Xue Chen, Yong Liu, Yongli Zhang, Bin Sun, Lu Wang, Wang Shen, Hongmei Xia
Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra of the midbrain, leading to a spectrum of motor and non-motor symptoms. Current pharmacological interventions for PD offer limited efficacy and are associated with significant adverse effects, thereby driving the development of novel drug delivery systems. This study aimed to enhance the therapeutic potential of paeonol by innovatively constructing paeonol-loaded liposome-exosome (Lip-Exo/Pae) hybrid nanoparticles, thereby synergistically leveraging the advantages of both liposomes and exosomes. To achieve this, we meticulously prepared paeonol-loaded liposomes using the ethanol injection method. Exosomes were successfully extracted from Salvia miltiorrhiza rhizomes via PEG co-precipitation. Subsequently, these components were integrated through freeze-thaw cycling to form the uniquely structured Lip-Exo/Pae hybrid nanoparticles. Comprehensive characterization confirmed that these hybrid nanoparticles exhibited uniform particle size and good dispersion stability, maintaining excellent colloidal stability for 28 days under refrigeration at 4 °C. In vivo fluorescence imaging demonstrated their efficient traversal of the blood-brain barrier, with targeted accumulation and sustained retention within brain tissue. In MPTP-induced PD mice, Lip-Exo/Pae significantly ameliorated behavioral deficits, including spontaneous activity, motor coordination, and balance. Furthermore, it effectively attenuated neuronal damage and iron deposition in the substantia nigra, protected dopaminergic neurons, increased the number and protein expression of tyrosine hydroxylase (TH) positive cells, and reduced oxidative stress and inflammation. The nanoparticles also exhibited favorable biocompatibility and safety profiles. This research not only provided a novel strategy for PD treatment but also overcame the limitations of single nanocarriers in drug delivery by integrating the benefits of liposomes and exosomes. Looking ahead, this study will further explore the clinical application potential of Lip-Exo/Pae hybrid nanoparticles and continuously optimize their preparation process to achieve broader applications and stronger therapeutic effects, thereby contributing to breakthroughs in the treatment of neurodegenerative diseases.
{"title":"Bionic design based on liposome-exosome hybrid nanoparticles for synergistic delivery of paeonol to achieve neuroprotection and improvement of motor function in Parkinson's disease model mice","authors":"Yang Wu, Chengfeng Wang , Kai Fang , Ruofei Zu, Yangyang Deng, Chenchen Hu, Keang Cao, Yuqing Fang, Xue Chen, Yong Liu, Yongli Zhang, Bin Sun, Lu Wang, Wang Shen, Hongmei Xia","doi":"10.1016/j.mtbio.2026.102847","DOIUrl":"10.1016/j.mtbio.2026.102847","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra of the midbrain, leading to a spectrum of motor and non-motor symptoms. Current pharmacological interventions for PD offer limited efficacy and are associated with significant adverse effects, thereby driving the development of novel drug delivery systems. This study aimed to enhance the therapeutic potential of paeonol by innovatively constructing paeonol-loaded liposome-exosome (Lip-Exo/Pae) hybrid nanoparticles, thereby synergistically leveraging the advantages of both liposomes and exosomes. To achieve this, we meticulously prepared paeonol-loaded liposomes using the ethanol injection method. Exosomes were successfully extracted from <em>Salvia miltiorrhiza</em> rhizomes via PEG co-precipitation. Subsequently, these components were integrated through freeze-thaw cycling to form the uniquely structured Lip-Exo/Pae hybrid nanoparticles. Comprehensive characterization confirmed that these hybrid nanoparticles exhibited uniform particle size and good dispersion stability, maintaining excellent colloidal stability for 28 days under refrigeration at 4 °C. In vivo fluorescence imaging demonstrated their efficient traversal of the blood-brain barrier, with targeted accumulation and sustained retention within brain tissue. In MPTP-induced PD mice, Lip-Exo/Pae significantly ameliorated behavioral deficits, including spontaneous activity, motor coordination, and balance. Furthermore, it effectively attenuated neuronal damage and iron deposition in the substantia nigra, protected dopaminergic neurons, increased the number and protein expression of tyrosine hydroxylase (TH) positive cells, and reduced oxidative stress and inflammation. The nanoparticles also exhibited favorable biocompatibility and safety profiles. This research not only provided a novel strategy for PD treatment but also overcame the limitations of single nanocarriers in drug delivery by integrating the benefits of liposomes and exosomes. Looking ahead, this study will further explore the clinical application potential of Lip-Exo/Pae hybrid nanoparticles and continuously optimize their preparation process to achieve broader applications and stronger therapeutic effects, thereby contributing to breakthroughs in the treatment of neurodegenerative diseases.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102847"},"PeriodicalIF":10.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.mtbio.2026.102846
Huxin Tang , Mingyang Hu , Xinying Huang , Jianan Chen , Yesheng Jin , Shuo Chen , Ke Li , Yong Xu
Biomineralization is a critical process wherein organisms form mineral composites via organic-inorganic synergistic interactions, which are essential for maintaining and repairing bone tissue homeostasis. Polysaccharides, as a class of natural biological macromolecules, play a crucial role in regulating biomineralization processes. This may be ascribed to their distinctive physical and chemical characteristics, in addition to their biological functions. These molecules effectively alter the crystalline structure and mechanical attributes of minerals like hydroxyapatite by adjusting ion levels, supplying sites for nucleation during mineral formation, and interacting with other biomolecules such as collagen to direct the deposition of minerals. Chitosan, alginate, hyaluronic acid, and sulfated polysaccharides have shown significant biomimetic properties through the creation of biomimetic scaffolds, improvement of cell attachment and differentiation, and facilitation of bone defect healing. This article systematically reviews the molecular mechanisms of polysaccharides in biomineralization and discusses their applications in bone tissue engineering from a biomineralization perspective, thereby offering novel insights for clinical treatment.
{"title":"Harnessing polysaccharide-mediated biomineralization for advanced bone tissue engineering","authors":"Huxin Tang , Mingyang Hu , Xinying Huang , Jianan Chen , Yesheng Jin , Shuo Chen , Ke Li , Yong Xu","doi":"10.1016/j.mtbio.2026.102846","DOIUrl":"10.1016/j.mtbio.2026.102846","url":null,"abstract":"<div><div>Biomineralization is a critical process wherein organisms form mineral composites via organic-inorganic synergistic interactions, which are essential for maintaining and repairing bone tissue homeostasis. Polysaccharides, as a class of natural biological macromolecules, play a crucial role in regulating biomineralization processes. This may be ascribed to their distinctive physical and chemical characteristics, in addition to their biological functions. These molecules effectively alter the crystalline structure and mechanical attributes of minerals like hydroxyapatite by adjusting ion levels, supplying sites for nucleation during mineral formation, and interacting with other biomolecules such as collagen to direct the deposition of minerals. Chitosan, alginate, hyaluronic acid, and sulfated polysaccharides have shown significant biomimetic properties through the creation of biomimetic scaffolds, improvement of cell attachment and differentiation, and facilitation of bone defect healing. This article systematically reviews the molecular mechanisms of polysaccharides in biomineralization and discusses their applications in bone tissue engineering from a biomineralization perspective, thereby offering novel insights for clinical treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102846"},"PeriodicalIF":10.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1016/j.mtbio.2026.102845
Tang Deng , Zhanli Peng , Jinxi Liang , Qinghui Kan , Jin Peng , Zhihao Zhou , Lin Huang , Heng Liu , Guiyun Jin , Chen Yao
Although reactive oxygen species (ROS)-mediated PANoptosis plays a pivotal role in the pathological dysfunction of lower limb ischemia/reperfusion injury (LL-IRI), its exact mechanism remains unclear. Real-time detection of H2O2 will help to reveal the complicated relationship between ROS, PANoptosis and LL-IRI. In this work, we designed and synthesized a novel near-infrared fluorogenic (NIRF) probe, BFP-H2O2, which exhibited a pronounced fluorescence-enhanced response to H2O2 at 650 nm. BFP-H2O2 was successfully applied to a TAK1i/LPS-induced PANoptosis cell model, revealing up-regulation of H2O2 during PANoptosis. To the best of our knowledge, there were no suitable chemical tools available for high-throughput screening of anti-PANoptosis compounds from Plantagodepressa Willd (PW). Leveraging BFP-H2O2, aucubin (AU) from PW was identified for the first time as the most promising anti-PANoptosis active ingredient. Additionally, BFP-H2O2 enabled visual imaging of the dynamic changes of H2O2 in the LL-IRI mice model. Particularly importantly, it was confirmed that AU could effectively inhibit H2O2-mediated oxidative stress and attenuate PANoptosis in gastrocnemius muscle tissues during LL-IRI. This work not only afforded a reliable chemical tool for screening anti-PANoptosis drugs, but also further elucidated the mechanism of PANoptosis and LL-IRI and advanced the development of therapeutic drugs for PANoptosis-related diseases.
{"title":"Unveiling aucubin-mediated inhibition of PANoptosis in lower limb ischemia-reperfusion injury with a near-infrared H2O2 fluorogenic probe","authors":"Tang Deng , Zhanli Peng , Jinxi Liang , Qinghui Kan , Jin Peng , Zhihao Zhou , Lin Huang , Heng Liu , Guiyun Jin , Chen Yao","doi":"10.1016/j.mtbio.2026.102845","DOIUrl":"10.1016/j.mtbio.2026.102845","url":null,"abstract":"<div><div>Although reactive oxygen species (ROS)-mediated PANoptosis plays a pivotal role in the pathological dysfunction of lower limb ischemia/reperfusion injury (LL-IRI), its exact mechanism remains unclear. Real-time detection of H<sub>2</sub>O<sub>2</sub> will help to reveal the complicated relationship between ROS, PANoptosis and LL-IRI. In this work, we designed and synthesized a novel near-infrared fluorogenic (NIRF) probe, BFP-H<sub>2</sub>O<sub>2</sub>, which exhibited a pronounced fluorescence-enhanced response to H<sub>2</sub>O<sub>2</sub> at 650 nm. BFP-H<sub>2</sub>O<sub>2</sub> was successfully applied to a TAK1i/LPS-induced PANoptosis cell model, revealing up-regulation of H<sub>2</sub>O<sub>2</sub> during PANoptosis. To the best of our knowledge, there were no suitable chemical tools available for high-throughput screening of anti-PANoptosis compounds from Plantagodepressa Willd (PW). Leveraging BFP-H<sub>2</sub>O<sub>2</sub>, aucubin (AU) from PW was identified for the first time as the most promising anti-PANoptosis active ingredient. Additionally, BFP-H<sub>2</sub>O<sub>2</sub> enabled visual imaging of the dynamic changes of H<sub>2</sub>O<sub>2</sub> in the LL-IRI mice model. Particularly importantly, it was confirmed that AU could effectively inhibit H<sub>2</sub>O<sub>2</sub>-mediated oxidative stress and attenuate PANoptosis in gastrocnemius muscle tissues during LL-IRI. This work not only afforded a reliable chemical tool for screening anti-PANoptosis drugs, but also further elucidated the mechanism of PANoptosis and LL-IRI and advanced the development of therapeutic drugs for PANoptosis-related diseases.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102845"},"PeriodicalIF":10.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1016/j.mtbio.2026.102842
Jae-Hun Kim , Guolong Jin , Jaehyeon Kim , Chanhyeock Kim , Chanhan Kang , Sunwoo Lee , Jin-Hyung Shim , Won-Soo Yun , Songwan Jin
Damage or functional failure of vital organs remains a major clinical challenge, while the availability of donor organs for transplantation is severely limited. As a result, tissue engineering has emerged as a promising strategy for organ replacement; however, conventional top-down tissue engineering, which employs scaffolds to provide three-dimensional growth environments, cannot ensure precise cell positioning, restricting its applicability to complex and heterogeneous tissues. In contrast, bottom-up strategies that assemble spheroids or organoids as modular building blocks offer a more effective route to organ-like constructs. Nevertheless, they suffer from low reproducibility because of spontaneous cell self-assembly. Three-dimensional bioprinting provides a promising solution for the reproducible fabrication of multicellular organ building blocks (OBBs). At the same time, while extrusion-based bioprinting offers high reproducibility, its limited dimensional accuracy has restricted its use for fabricating OBBs that require both precise microarchitectures and reliable assembly. Here, we address this limitation by introducing a strategy in which bioinks are directly bioprinted within three-dimensionally printed molds, enabling the formation of OBBs with well-defined geometries and controlled spatial organization. By combining mold-guided bioprinting with multimaterial preset extrusion, we demonstrated the fabrication of heterogeneous OBBs with microscale architectures while preserving the modularity essential for bottom-up assembly. This approach resolves the conventional trade-off between structural precision and assembly-based scalability, allowing the construction of large tissue constructs with hierarchical vascular networks. Overall, this work presents a 3D bioprinting-based OBB fabrication strategy that integrates precision manufacturing with bottom-up tissue assembly, offering a reproducible and scalable framework for bioartificial organ engineering.
{"title":"Bioprinting and assembly of organ building blocks for tissue engineering applications","authors":"Jae-Hun Kim , Guolong Jin , Jaehyeon Kim , Chanhyeock Kim , Chanhan Kang , Sunwoo Lee , Jin-Hyung Shim , Won-Soo Yun , Songwan Jin","doi":"10.1016/j.mtbio.2026.102842","DOIUrl":"10.1016/j.mtbio.2026.102842","url":null,"abstract":"<div><div>Damage or functional failure of vital organs remains a major clinical challenge, while the availability of donor organs for transplantation is severely limited. As a result, tissue engineering has emerged as a promising strategy for organ replacement; however, conventional top-down tissue engineering, which employs scaffolds to provide three-dimensional growth environments, cannot ensure precise cell positioning, restricting its applicability to complex and heterogeneous tissues. In contrast, bottom-up strategies that assemble spheroids or organoids as modular building blocks offer a more effective route to organ-like constructs. Nevertheless, they suffer from low reproducibility because of spontaneous cell self-assembly. Three-dimensional bioprinting provides a promising solution for the reproducible fabrication of multicellular organ building blocks (OBBs). At the same time, while extrusion-based bioprinting offers high reproducibility, its limited dimensional accuracy has restricted its use for fabricating OBBs that require both precise microarchitectures and reliable assembly. Here, we address this limitation by introducing a strategy in which bioinks are directly bioprinted within three-dimensionally printed molds, enabling the formation of OBBs with well-defined geometries and controlled spatial organization. By combining mold-guided bioprinting with multimaterial preset extrusion, we demonstrated the fabrication of heterogeneous OBBs with microscale architectures while preserving the modularity essential for bottom-up assembly. This approach resolves the conventional trade-off between structural precision and assembly-based scalability, allowing the construction of large tissue constructs with hierarchical vascular networks. Overall, this work presents a 3D bioprinting-based OBB fabrication strategy that integrates precision manufacturing with bottom-up tissue assembly, offering a reproducible and scalable framework for bioartificial organ engineering.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102842"},"PeriodicalIF":10.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1016/j.mtbio.2026.102833
Ru Feng , Tao Yue , Xuhui Zhao , Jie Dong , Jin Zhang , Xiaoyang Peng , Huifang Zhao , Jinghua Sun , Ruiping Zhang
Diabetic nephropathy (DN) is a serious complication of diabetes and a leading cause of end-stage renal disease. Current treatments using anti-inflammatory, antioxidant, and antifibrotic drugs are limited by rapid systemic clearance and poor renal retention. Here, we developed a urine-microenvironment responsive nanocapsule, MNP-THA@MnCaP, composed of a MnCaP nanoshell co-loaded with functionalized melanin (MNP) nanoparticles and thalidomide (THA) for synergistic therapy of DN. The nanocapsules preferentially accumulate in the kidneys via passive targeting and degrade under acidic urinary conditions, enabling controlled release of therapeutic agents. In vitro, MNP-THA@MnCaP alleviated oxidative stress, suppressed epithelial-mesenchymal transition, and reduced apoptosis in renal tubular cells. In vivo, the formulation targeted DN kidneys, attenuated oxidative injury, inflammation, and fibrosis, and restored renal function. Moreover, the released Mn2+ allowed T1-weighted magnetic resonance imaging, while MNP supported photoacoustic imaging, facilitating real-time tracking of the treatment process. With excellent biocompatibility and biodegradability, MNP-THA@MnCaP represents a promising theranostic platform with strong translational potential for DN treatment.
{"title":"Urinary microenvironment-degradable nanocapsules for traceable therapy of diabetic nephropathy","authors":"Ru Feng , Tao Yue , Xuhui Zhao , Jie Dong , Jin Zhang , Xiaoyang Peng , Huifang Zhao , Jinghua Sun , Ruiping Zhang","doi":"10.1016/j.mtbio.2026.102833","DOIUrl":"10.1016/j.mtbio.2026.102833","url":null,"abstract":"<div><div>Diabetic nephropathy (DN) is a serious complication of diabetes and a leading cause of end-stage renal disease. Current treatments using anti-inflammatory, antioxidant, and antifibrotic drugs are limited by rapid systemic clearance and poor renal retention. Here, we developed a urine-microenvironment responsive nanocapsule, MNP-THA@MnCaP, composed of a MnCaP nanoshell co-loaded with functionalized melanin (MNP) nanoparticles and thalidomide (THA) for synergistic therapy of DN. The nanocapsules preferentially accumulate in the kidneys via passive targeting and degrade under acidic urinary conditions, enabling controlled release of therapeutic agents. In vitro, MNP-THA@MnCaP alleviated oxidative stress, suppressed epithelial-mesenchymal transition, and reduced apoptosis in renal tubular cells. <em>In vivo</em>, the formulation targeted DN kidneys, attenuated oxidative injury, inflammation, and fibrosis, and restored renal function. Moreover, the released Mn<sup>2+</sup> allowed T<sub>1</sub>-weighted magnetic resonance imaging, while MNP supported photoacoustic imaging, facilitating real-time tracking of the treatment process. With excellent biocompatibility and biodegradability, MNP-THA@MnCaP represents a promising theranostic platform with strong translational potential for DN treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102833"},"PeriodicalIF":10.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1016/j.mtbio.2026.102827
Rui Hu , Kaiwen Liu , Wenzhao Wang , Wencan Zhang , Liang Wang , Yuanqiang Zhang , Hecheng Ma , Menglin Cong , Chuanxi Chi , Jiankang Cao , Baoliang Zhang , Liang Liu , Qunbo Meng , Xiangzhen Kong , Bin Shi , Liming Li , Lei Cheng , Zhijian Wei
Intervertebral disc degeneration (IDD) is characterized by an imbalance between nucleus pulposus catabolism and anabolism, driven by metabolic dysfunction of nucleus pulposus cells (NPCs) and a chronic inflammatory microenvironment. Effective treatments for IDD are lacking. Here, we report an injectable hydrogel that achieves reactive oxygen species (ROS)-triggered self-stabilization within the degenerative microenvironment for adaptive intradiscal therapy. The CAD hydrogel is constructed from chitosan-phenylboronic acid (CS-PBA), aldehyde-β-cyclodextrin (A-β-CD), and hyaluronic acid-dopamine (HA-DA), forming a dynamic multinetwork. The dopamine moieties are preorganized within the network via both boronate ester bonds and host‒guest interactions with β-CD. Upon encountering pathological ROS in the oxidative IDD microenvironment, the cleavage of boronate esters triggers the release of sinigrin (SIN). Moreover, in situ polymerization of the dopamine moieties occurs simultaneously, which is facilitated by the spatial confinement of dopamine by β-CD. Polymerization converts the dynamic network into a covalently stabilized matrix, effectively self-solidifying the hydrogel to counteract mechanical decay and enabling the sustainable release of dabigatran (DAB) encapsulated in β-CD. This process ensures long-term structural support while enabling intelligent dual drug delivery. In a puncture-induced IDD model, the hydrogel demonstrated significant efficacy. In vitro, the dual-drug-loaded DS@CAD hydrogel mitigated NPC inflammatory catabolism and promoted anabolism. Mechanistically, the rapid release of SIN attenuated inflammation by targeting MAPK signalling, while sustained DAB release inhibited inflammation via RELA and promoted extracellular matrix anabolism by activating AMPK. This reconfigurable hydrogel platform offers an innovative strategy for developing next-generation biomaterials that respond to complex disease microenvironments for adaptive therapy.
{"title":"Sequential delivery of sinigrin and dabigatran by an in situ self-stabilizing dynamic hydrogel attenuates intervertebral disc degeneration","authors":"Rui Hu , Kaiwen Liu , Wenzhao Wang , Wencan Zhang , Liang Wang , Yuanqiang Zhang , Hecheng Ma , Menglin Cong , Chuanxi Chi , Jiankang Cao , Baoliang Zhang , Liang Liu , Qunbo Meng , Xiangzhen Kong , Bin Shi , Liming Li , Lei Cheng , Zhijian Wei","doi":"10.1016/j.mtbio.2026.102827","DOIUrl":"10.1016/j.mtbio.2026.102827","url":null,"abstract":"<div><div>Intervertebral disc degeneration (IDD) is characterized by an imbalance between nucleus pulposus catabolism and anabolism, driven by metabolic dysfunction of nucleus pulposus cells (NPCs) and a chronic inflammatory microenvironment. Effective treatments for IDD are lacking. Here, we report an injectable hydrogel that achieves reactive oxygen species (ROS)-triggered self-stabilization within the degenerative microenvironment for adaptive intradiscal therapy. The CAD hydrogel is constructed from chitosan-phenylboronic acid (CS-PBA), aldehyde-β-cyclodextrin (A-β-CD), and hyaluronic acid-dopamine (HA-DA), forming a dynamic multinetwork. The dopamine moieties are preorganized within the network via both boronate ester bonds and host‒guest interactions with β-CD. Upon encountering pathological ROS in the oxidative IDD microenvironment, the cleavage of boronate esters triggers the release of sinigrin (SIN). Moreover, <em>in situ</em> polymerization of the dopamine moieties occurs simultaneously, which is facilitated by the spatial confinement of dopamine by β-CD. Polymerization converts the dynamic network into a covalently stabilized matrix, effectively self-solidifying the hydrogel to counteract mechanical decay and enabling the sustainable release of dabigatran (DAB) encapsulated in β-CD. This process ensures long-term structural support while enabling intelligent dual drug delivery. In a puncture-induced IDD model, the hydrogel demonstrated significant efficacy. <em>In vitro</em>, the dual-drug-loaded DS@CAD hydrogel mitigated NPC inflammatory catabolism and promoted anabolism. Mechanistically, the rapid release of SIN attenuated inflammation by targeting MAPK signalling, while sustained DAB release inhibited inflammation via RELA and promoted extracellular matrix anabolism by activating AMPK. This reconfigurable hydrogel platform offers an innovative strategy for developing next-generation biomaterials that respond to complex disease microenvironments for adaptive therapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102827"},"PeriodicalIF":10.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1016/j.mtbio.2026.102811
Yongkang Lai , Yongliang Ouyang , Xiaojing Yin , Tao Yu , Jianhua Wan , Xueyang Li , Yi Hu , Xu Shu , Huan Wang
Chronic pancreatitis (CP) is a lifelong progressive fibrotic inflammatory disorder for which no effective cure is currently available. Persistent and recurrent inflammatory stimulation induced by reactive oxygen species (ROS) is a key driver of pancreatic fibrogenesis, making oxidative stress a promising therapeutic target to halt disease progression. In this study, we developed a nanosystem, HC@CeMOF, consisting of a small-sized cerium-based metal–organic framework (CeMOF) core loaded with curcumin and coated with hyaluronic acid (HA), enabling precise targeting of inflamed pancreatic tissue. HC@CeMOF exhibits a small-sized particle size along with favorable cellular and biological safety profiles. Once administered in vivo, the nanosystem exploits the specific binding affinity of HA to CD44 receptors on macrophages to selectively accumulate at inflamed pancreatic sites. Subsequently, the cerium-based nanozyme efficiently scavenges ROS through the reversible redox cycling between Ce3+ and Ce4+, while the slow release of curcumin further suppresses the NF-κB signaling pathway and modulates inflammatory cytokine levels, thereby achieving synergistic anti-inflammatory and antioxidant effects. Collectively, these mechanisms substantially attenuate CP progression. This targeted ROS-scavenging and anti-inflammatory strategy holds promise as an alternative therapeutic approach for chronic pancreatitis.
{"title":"Engineered targeted Ce-based MOF nanozymes for ROS scavenging and inflammatory Reprogramming in chronic pancreatitis","authors":"Yongkang Lai , Yongliang Ouyang , Xiaojing Yin , Tao Yu , Jianhua Wan , Xueyang Li , Yi Hu , Xu Shu , Huan Wang","doi":"10.1016/j.mtbio.2026.102811","DOIUrl":"10.1016/j.mtbio.2026.102811","url":null,"abstract":"<div><div>Chronic pancreatitis (CP) is a lifelong progressive fibrotic inflammatory disorder for which no effective cure is currently available. Persistent and recurrent inflammatory stimulation induced by reactive oxygen species (ROS) is a key driver of pancreatic fibrogenesis, making oxidative stress a promising therapeutic target to halt disease progression. In this study, we developed a nanosystem, HC@CeMOF, consisting of a small-sized cerium-based metal–organic framework (CeMOF) core loaded with curcumin and coated with hyaluronic acid (HA), enabling precise targeting of inflamed pancreatic tissue. HC@CeMOF exhibits a small-sized particle size along with favorable cellular and biological safety profiles. Once administered <em>in vivo</em>, the nanosystem exploits the specific binding affinity of HA to CD44 receptors on macrophages to selectively accumulate at inflamed pancreatic sites. Subsequently, the cerium-based nanozyme efficiently scavenges ROS through the reversible redox cycling between Ce<sup>3+</sup> and Ce<sup>4+</sup>, while the slow release of curcumin further suppresses the NF-κB signaling pathway and modulates inflammatory cytokine levels, thereby achieving synergistic anti-inflammatory and antioxidant effects. Collectively, these mechanisms substantially attenuate CP progression. This targeted ROS-scavenging and anti-inflammatory strategy holds promise as an alternative therapeutic approach for chronic pancreatitis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102811"},"PeriodicalIF":10.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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