Pub Date : 2026-01-31DOI: 10.1016/j.bioactmat.2025.12.048
Pan Li , Zhuowen Liang , Xianyan Zeng , Runbo Lei , Shuo Guo , Zhao Zhang , Guangwei Zhang , Jianxiong Li , Anhui Qin , Mi Qu , Kangkang Su , Dechen Yu , Wenwen Liu , Zhuojing Luo
Age-related osteoporosis arises from bone tissue with inadequate metabolic support for osteogenesis. We identified that DNA methylation-mediated suppression of glutathione synthetase (GSS) represents an upstream lesion limiting endogenous glutathione (GSH) synthesis and supply in aged bone, thereby constraining osteoblast differentiation. In turn, impaired GSH synthesis exacerbates oxidative stress levels and diminishes osteogenic capacity, and this metabolic bottleneck is independent of substrate availability: cysteine supplementation neither restored GSH synthesis flux in aged bone nor rescued its osteogenic deficits. To overcome this limitation, we developed an exosome-based GSH delivery platform using electroporation to efficiently load GSH. These exosomes are derived from CXCR4-enriched bone marrow mesenchymal stem cells (BMSCs), leveraging CXCR4-mediated homing to the bone marrow niche to enhance bone retention, stabilize GSH during loading and circulation, and elevate local GSH pools at osteogenic sites. In aged bone, this targeted system sustainably delivers GSH, alleviates oxidative stress, improves mitochondrial function, delays cellular senescence, and promotes osteogenesis. In summary, while DNA methylation acts upstream to constrain GSH synthesis in aging bone, therapeutically correcting the resultant metabolic deficit via bone-homing exosome–mediated GSH delivery restores osteogenic function and improves bone metabolism in aged individuals.
{"title":"Age-related GSS promoter methylation in BMSCs drives osteoporosis and the reversal by targeted GSH delivery","authors":"Pan Li , Zhuowen Liang , Xianyan Zeng , Runbo Lei , Shuo Guo , Zhao Zhang , Guangwei Zhang , Jianxiong Li , Anhui Qin , Mi Qu , Kangkang Su , Dechen Yu , Wenwen Liu , Zhuojing Luo","doi":"10.1016/j.bioactmat.2025.12.048","DOIUrl":"10.1016/j.bioactmat.2025.12.048","url":null,"abstract":"<div><div>Age-related osteoporosis arises from bone tissue with inadequate metabolic support for osteogenesis. We identified that DNA methylation-mediated suppression of glutathione synthetase (GSS) represents an upstream lesion limiting endogenous glutathione (GSH) synthesis and supply in aged bone, thereby constraining osteoblast differentiation. In turn, impaired GSH synthesis exacerbates oxidative stress levels and diminishes osteogenic capacity, and this metabolic bottleneck is independent of substrate availability: cysteine supplementation neither restored GSH synthesis flux in aged bone nor rescued its osteogenic deficits. To overcome this limitation, we developed an exosome-based GSH delivery platform using electroporation to efficiently load GSH. These exosomes are derived from CXCR4-enriched bone marrow mesenchymal stem cells (BMSCs), leveraging CXCR4-mediated homing to the bone marrow niche to enhance bone retention, stabilize GSH during loading and circulation, and elevate local GSH pools at osteogenic sites. In aged bone, this targeted system sustainably delivers GSH, alleviates oxidative stress, improves mitochondrial function, delays cellular senescence, and promotes osteogenesis. In summary, while DNA methylation acts upstream to constrain GSH synthesis in aging bone, therapeutically correcting the resultant metabolic deficit via bone-homing exosome–mediated GSH delivery restores osteogenic function and improves bone metabolism in aged individuals.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 472-491"},"PeriodicalIF":18.0,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075129","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 : 2026-01-31DOI: 10.1016/j.bioactmat.2026.01.032
Yingzi Li , Qian Li , Zhaoming Deng , Xiaohua Liu
Regeneration of the alveolar bone remains a major clinical challenge due to the complex oral microenvironment and the need for coordinated restoration of multiple tissue types. To overcome these hurdles, biomaterials designed for periodontal regeneration must meet a rigorous set of criteria, including excellent injectability, mechanical stability, selective cell repopulation, and strong osteoinductive capacity. In this study, we developed a bioinspired, multifunctional microsphere system that fulfills these requirements. The system is injectable, mechanically robust, selectively binds bone marrow-derived stem cells (BMSCs), and exhibits potent osteoinductivity. These multifunctional properties were achieved by UV-assembling nanofibrous hollow microspheres (NFH-MS), conjugating the BMSC-specific E7 peptide to the nanofibrous shell, and encapsulating a bone-forming peptide (BFP) within the hollow core. UV-assembly enhanced the scaffold's mechanical integrity, generated interconnected macropores to support cell infiltration, and promoted intercellular communication. Notably, it significantly upregulated Connexin 43 and N-cadherin-mediated junctions, further facilitating cellular interactions. In synergy with E7 and BFP, the UV-assembled NFH-MS scaffold markedly improved BMSC adhesion, osteogenic differentiation, and biomineralization. This bioinspired multifunctional NFH-MS platform demonstrated superior alveolar bone regeneration in a rat fenestration defect model, offering a promising and minimally invasive strategy for periodontal tissue engineering.
{"title":"Assembly of bioinspired multifunctional microspheres for enhanced alveolar bone regeneration","authors":"Yingzi Li , Qian Li , Zhaoming Deng , Xiaohua Liu","doi":"10.1016/j.bioactmat.2026.01.032","DOIUrl":"10.1016/j.bioactmat.2026.01.032","url":null,"abstract":"<div><div>Regeneration of the alveolar bone remains a major clinical challenge due to the complex oral microenvironment and the need for coordinated restoration of multiple tissue types. To overcome these hurdles, biomaterials designed for periodontal regeneration must meet a rigorous set of criteria, including excellent injectability, mechanical stability, selective cell repopulation, and strong osteoinductive capacity. In this study, we developed a bioinspired, multifunctional microsphere system that fulfills these requirements. The system is injectable, mechanically robust, selectively binds bone marrow-derived stem cells (BMSCs), and exhibits potent osteoinductivity. These multifunctional properties were achieved by UV-assembling nanofibrous hollow microspheres (NFH-MS), conjugating the BMSC-specific E7 peptide to the nanofibrous shell, and encapsulating a bone-forming peptide (BFP) within the hollow core. UV-assembly enhanced the scaffold's mechanical integrity, generated interconnected macropores to support cell infiltration, and promoted intercellular communication. Notably, it significantly upregulated Connexin 43 and N-cadherin-mediated junctions, further facilitating cellular interactions. In synergy with E7 and BFP, the UV-assembled NFH-MS scaffold markedly improved BMSC adhesion, osteogenic differentiation, and biomineralization. This bioinspired multifunctional NFH-MS platform demonstrated superior alveolar bone regeneration in a rat fenestration defect model, offering a promising and minimally invasive strategy for periodontal tissue engineering.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 781-795"},"PeriodicalIF":18.0,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074041","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 : 2026-01-31DOI: 10.1016/j.bioactmat.2026.01.030
Chen Cheng , Ru Li , Tianwang Guan , Haowei Li , Luping Cheng , Min Zou , Shuwen Liu , Caiwen Ou
Zika virus (ZIKV) can traverse the placental barrier, leading to fetal microcephaly and congenital zika syndrome (CZS). The viral E protein mediates host-cell interactions and infection. Here, we demonstrated that cord blood natural killer cell-derived extracellular vesicles (CBNK-EVs) potently inhibit ZIKV infection in vitro without compromising cellular viability. Mechanistically, CBNK-EVs engage ZIKV through ITGB2, a surface-enriched integrin that interacts with the viral E protein, facilitating nanoparticle-virion contact or membrane fusion. This interaction triggers antiviral activity via perforins within extracellular vesicles (EVs), resulting in diminished viral infectivity. Notably, CBNK-EVs not only effectively crossed the placental barrier to protect fetuses from ZIKV-induced pathologies, but also reduced the ZIKV burden in IFN-deficient murine models and decreased CZS incidence and mortality. Additionally, either blockade of ITGB2 with a monoclonal antibody or chelation of Ca2+ with EGTA impaired the anti-ZIKV activity of CBNK-EVs. Collectively, our findings identified CBNK-EVs as natural antiviral nanoparticles that play a pivotal role in curbing ZIKV infection and vertical transmission, offering a promising therapeutic strategy against congenital ZIKV-related complications.
{"title":"Cord blood natural killer cell-derived extracellular vesicles inhibit Zika virus infectivity through ITGB2/perforin-mediated envelope disruption in vitro and in vivo","authors":"Chen Cheng , Ru Li , Tianwang Guan , Haowei Li , Luping Cheng , Min Zou , Shuwen Liu , Caiwen Ou","doi":"10.1016/j.bioactmat.2026.01.030","DOIUrl":"10.1016/j.bioactmat.2026.01.030","url":null,"abstract":"<div><div>Zika virus (ZIKV) can traverse the placental barrier, leading to fetal microcephaly and congenital zika syndrome (CZS). The viral E protein mediates host-cell interactions and infection. Here, we demonstrated that cord blood natural killer cell-derived extracellular vesicles (CBNK-EVs) potently inhibit ZIKV infection in vitro without compromising cellular viability. Mechanistically, CBNK-EVs engage ZIKV through ITGB2, a surface-enriched integrin that interacts with the viral E protein, facilitating nanoparticle-virion contact or membrane fusion. This interaction triggers antiviral activity via perforins within extracellular vesicles (EVs), resulting in diminished viral infectivity. Notably, CBNK-EVs not only effectively crossed the placental barrier to protect fetuses from ZIKV-induced pathologies, but also reduced the ZIKV burden in IFN-deficient murine models and decreased CZS incidence and mortality. Additionally, either blockade of ITGB2 with a monoclonal antibody or chelation of Ca<sup>2+</sup> with EGTA impaired the anti-ZIKV activity of CBNK-EVs. Collectively, our findings identified CBNK-EVs as natural antiviral nanoparticles that play a pivotal role in curbing ZIKV infection and vertical transmission, offering a promising therapeutic strategy against congenital ZIKV-related complications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 456-471"},"PeriodicalIF":18.0,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074954","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 : 2026-01-30DOI: 10.1016/j.bioactmat.2026.01.024
Jie Ren , Junjin Li , Hongda Wang , Haiwen Feng , Huaying Hao , Junyu Chen , Yuanquan Li , Zhengyu Xu , Chuanhao Li , Wang Jiang , Yan Wang , Xiaoyang Zhang , Xiaomeng Song , Guangzhi Ning , Jun Liang , Shiqing Feng
Spinal cord injury (SCI) repair lacks clinically validated restorative therapies. Transplantation of exogenous neural stem cells (NSCs) offers significant potential for therapeutic applications; however, challenges remain, including substantial cell loss, uncontrolled differentiation, and limited tissue integration within inflammatory microenvironments. Furthermore, the workflow associated with traditional NSC transplantation—including cryopreservation, thawing, transportation, and injection—remains fragmented, resulting in systemic limitations. These issues manifest as reduced cell viability and stemness, an elevated risk of contamination, and dosing inaccuracies. All these significantly impede clinical translation. An integrated system for NSC preservation, transport, and transplantation is required to meet the following criteria: (i) maintenance of high cell viability and stemness post-cryopreservation and thawing; (ii) modulation of the acute-phase immune microenvironment; (iii) regulation of the differentiation fate of transplanted NSCs; (iv) injectable, standardized, and closed-system operation. To meet these requirements, we established a comprehensive cryopreservation, thawing, and transplant (CTT) integrated platform. Utilizing the bioactive material PM-BMH@Exo, this platform enables seamless end-to-end workflow integration through a mechanism that preserves bioactivity. It not only ensures high viability retention and directed differentiation of NSCs but also effectively mitigates the rapid viability decline of cells observed after traditional cryopreservation. Furthermore, the system enables closed-loop operations spanning cryopreservation, thawing, and minimally invasive injection. It breaks through systemic bottlenecks from multi-step procedures, comprehensively enhancing the timeliness and standardization of therapeutic interventions. We systematically evaluated the system's feasibility and efficacy via in vitro and in vivo experiments. This study presents a technologically viable and clinically compatible pathway with potential applications for SCI repair.
{"title":"Integrated cryopreservation-thawing-transplantation platform for neural stem cell-based spinal cord injury repair","authors":"Jie Ren , Junjin Li , Hongda Wang , Haiwen Feng , Huaying Hao , Junyu Chen , Yuanquan Li , Zhengyu Xu , Chuanhao Li , Wang Jiang , Yan Wang , Xiaoyang Zhang , Xiaomeng Song , Guangzhi Ning , Jun Liang , Shiqing Feng","doi":"10.1016/j.bioactmat.2026.01.024","DOIUrl":"10.1016/j.bioactmat.2026.01.024","url":null,"abstract":"<div><div>Spinal cord injury (SCI) repair lacks clinically validated restorative therapies. Transplantation of exogenous neural stem cells (NSCs) offers significant potential for therapeutic applications; however, challenges remain, including substantial cell loss, uncontrolled differentiation, and limited tissue integration within inflammatory microenvironments. Furthermore, the workflow associated with traditional NSC transplantation—including cryopreservation, thawing, transportation, and injection—remains fragmented, resulting in systemic limitations. These issues manifest as reduced cell viability and stemness, an elevated risk of contamination, and dosing inaccuracies. All these significantly impede clinical translation. An integrated system for NSC preservation, transport, and transplantation is required to meet the following criteria: (i) maintenance of high cell viability and stemness post-cryopreservation and thawing; (ii) modulation of the acute-phase immune microenvironment; (iii) regulation of the differentiation fate of transplanted NSCs; (iv) injectable, standardized, and closed-system operation. To meet these requirements, we established a comprehensive cryopreservation, thawing, and transplant (CTT) integrated platform. Utilizing the bioactive material PM-BMH@Exo, this platform enables seamless end-to-end workflow integration through a mechanism that preserves bioactivity. It not only ensures high viability retention and directed differentiation of NSCs but also effectively mitigates the rapid viability decline of cells observed after traditional cryopreservation. Furthermore, the system enables closed-loop operations spanning cryopreservation, thawing, and minimally invasive injection. It breaks through systemic bottlenecks from multi-step procedures, comprehensively enhancing the timeliness and standardization of therapeutic interventions. We systematically evaluated the system's feasibility and efficacy via in vitro and in vivo experiments. This study presents a technologically viable and clinically compatible pathway with potential applications for SCI repair.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 401-424"},"PeriodicalIF":18.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075128","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 : 2026-01-30DOI: 10.1016/j.bioactmat.2026.01.036
Donya Esmaeilpour , Michael R. Hamblin , Jianlin Cheng , Arezoo Khosravi , Jian Liu , Atefeh Zarepour , Ali Zarrabi , Mika Sillanpää , Ehsan Nazarzadeh Zare , Jianliang Shen , Hassan Karimi-Maleh
The integration of artificial intelligence, protein engineering, and sustainable nanomedicine is driving a paradigm shift in theranostics by enabling highly precise disease diagnosis and targeted therapy. AI-driven methodologies, including machine learning and deep learning, facilitate the rapid analysis of complex biological and chemical datasets, accelerating protein structure prediction, molecular docking, and structure-activity relationship modeling. These capabilities support the rational design of proteins and peptides with enhanced specificity, therapeutic efficacy, and safety, while enabling personalized treatment strategies tailored to individual molecular profiles. In parallel, sustainable nanomedicine focuses on the development of biodegradable, biocompatible, and environmentally benign nanomaterials to improve drug bioavailability, stability, and controlled release. AI-assisted optimization further refines nanocarrier design by balancing therapeutic performance with safety and environmental impact. Advanced intelligent nanocarriers capable of real-time monitoring, adaptive drug release, and degradation into non-toxic by-products represent a significant advancement over conventional static systems. The theranostic paradigm has become central to precision medicine, particularly in oncology, especially where AI-designed nanoplatforms enable targeted delivery of imaging agents and therapeutics to tumors, while allowing continuous treatment monitoring and minimizing off-target effects. Emerging applications in neurological, infectious, and cardiovascular diseases further highlight the broad clinical potential of this approach. Accordingly, this review summarizes AI-driven protein design strategies, sustainable nanocarrier engineering, and their convergence in next-generation theranostic systems, critically discussing mechanistic insights, translational challenges, and design principles required for developing safe, scalable, and clinically adaptable intelligent nanomedicines.
{"title":"Artificial intelligence driven protein design and sustainable nanomedicine for advanced theranostics","authors":"Donya Esmaeilpour , Michael R. Hamblin , Jianlin Cheng , Arezoo Khosravi , Jian Liu , Atefeh Zarepour , Ali Zarrabi , Mika Sillanpää , Ehsan Nazarzadeh Zare , Jianliang Shen , Hassan Karimi-Maleh","doi":"10.1016/j.bioactmat.2026.01.036","DOIUrl":"10.1016/j.bioactmat.2026.01.036","url":null,"abstract":"<div><div>The integration of artificial intelligence, protein engineering, and sustainable nanomedicine is driving a paradigm shift in theranostics by enabling highly precise disease diagnosis and targeted therapy. AI-driven methodologies, including machine learning and deep learning, facilitate the rapid analysis of complex biological and chemical datasets, accelerating protein structure prediction, molecular docking, and structure-activity relationship modeling. These capabilities support the rational design of proteins and peptides with enhanced specificity, therapeutic efficacy, and safety, while enabling personalized treatment strategies tailored to individual molecular profiles. In parallel, sustainable nanomedicine focuses on the development of biodegradable, biocompatible, and environmentally benign nanomaterials to improve drug bioavailability, stability, and controlled release. AI-assisted optimization further refines nanocarrier design by balancing therapeutic performance with safety and environmental impact. Advanced intelligent nanocarriers capable of real-time monitoring, adaptive drug release, and degradation into non-toxic by-products represent a significant advancement over conventional static systems. The theranostic paradigm has become central to precision medicine, particularly in oncology, especially where AI-designed nanoplatforms enable targeted delivery of imaging agents and therapeutics to tumors, while allowing continuous treatment monitoring and minimizing off-target effects. Emerging applications in neurological, infectious, and cardiovascular diseases further highlight the broad clinical potential of this approach. Accordingly, this review summarizes AI-driven protein design strategies, sustainable nanocarrier engineering, and their convergence in next-generation theranostic systems, critically discussing mechanistic insights, translational challenges, and design principles required for developing safe, scalable, and clinically adaptable intelligent nanomedicines.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 425-455"},"PeriodicalIF":18.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074953","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 : 2026-01-29DOI: 10.1016/j.bioactmat.2025.12.034
Alvile Kasarinaite , Junhan Ou , Kailin Chen , Dayang Peng , Wendi Jia , Chenyang Ding , Wenwen Huang , David C. Hay , Yishan Chen
Tissue regeneration is orchestrated by both intracellular signaling programs and extracellular matrix remodeling. Glycosaminoglycans (GAGs) are essential sugar chains ubiquitously expressed throughout the body. Their spatiotemporal turnover is an important part of normal organ biology and essential to tissue repair following injury. Glycoscience is a hot topic and is its role in organ physiology is being increasingly unraveled due to both scientific and technological advances. The mechanistic understanding of GAG regulation and manipulation is multidisciplinary effort, spanning biology, chemistry, materials science and translational medicine. This review broadly examines how GAG biology is naturally regulated and precisely controlled in health and disease, including data analysis from a stem cell-based model of liver disease. Despite being limited in types, GAGs successfully regulate complex cell and tissue level biology. We also discuss preclinical and clinical applications of GAGs, with a focus on biomaterials for tissue engineering and precision drug delivery, stressing their importance in biomedical engineering and clinical therapy. In addition, we outline state-of-art detection techniques and molecular modeling tools for analyzing GAG quantity, structure and interactions with other molecules. This review provides a timely and comprehensive overview of GAG biology highlighting their role in tissue repair and engineering, and outlines future directions for their design and next-generation therapies.
{"title":"Glycosaminoglycans in tissue regeneration: Insights into glycobiology and their biomedical application","authors":"Alvile Kasarinaite , Junhan Ou , Kailin Chen , Dayang Peng , Wendi Jia , Chenyang Ding , Wenwen Huang , David C. Hay , Yishan Chen","doi":"10.1016/j.bioactmat.2025.12.034","DOIUrl":"10.1016/j.bioactmat.2025.12.034","url":null,"abstract":"<div><div>Tissue regeneration is orchestrated by both intracellular signaling programs and extracellular matrix remodeling. Glycosaminoglycans (GAGs) are essential sugar chains ubiquitously expressed throughout the body. Their spatiotemporal turnover is an important part of normal organ biology and essential to tissue repair following injury. Glycoscience is a hot topic and is its role in organ physiology is being increasingly unraveled due to both scientific and technological advances. The mechanistic understanding of GAG regulation and manipulation is multidisciplinary effort, spanning biology, chemistry, materials science and translational medicine. This review broadly examines how GAG biology is naturally regulated and precisely controlled in health and disease, including data analysis from a stem cell-based model of liver disease. Despite being limited in types, GAGs successfully regulate complex cell and tissue level biology. We also discuss preclinical and clinical applications of GAGs, with a focus on biomaterials for tissue engineering and precision drug delivery, stressing their importance in biomedical engineering and clinical therapy. In addition, we outline state-of-art detection techniques and molecular modeling tools for analyzing GAG quantity, structure and interactions with other molecules. This review provides a timely and comprehensive overview of GAG biology highlighting their role in tissue repair and engineering, and outlines future directions for their design and next-generation therapies.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 320-337"},"PeriodicalIF":18.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074957","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 : 2026-01-29DOI: 10.1016/j.bioactmat.2026.01.034
Shuaimei Zhang , Hong Xu , Feifan Xiang , Yiqi Ma , Beibei Liu , Gaocan Li , Yunbing Wang , Min Wu
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults, with inevitable postoperative recurrence due to incomplete resection and limited chemotherapy efficacy. Temozolomide (TMZ), the first-line therapy, is hindered by rapid degradation of its active metabolite 3-methyl-(triazene-1-yl)-imidazole-4-carboxamide (MTIC), systemic toxicity, and frequent resistance driven by DNA repair. These shortcomings underscore the urgent need for localized strategies to achieve sustained stability and improve therapeutic outcomes. To address these limitations, we have developed an injectable extracellular matrix–mimicking hydrogel incorporating mesoporous polydopamine nanoparticles loaded with cobalt-stabilized MTIC complexes (MPDA@MTIC–Co). This hydrogel provides mechanical robustness, prolonged intratumoral retention, and sustained on-demand release, while enabling efficient cellular uptake, robust near-infrared–triggered photothermal conversion, and induction of apoptosis through PI3K/AKT pathway suppression. In orthotopic postoperative GBM models, local MPDA@MTIC–Co administration achieves synergistic chemo–photothermal therapy, markedly suppressed recurrence, prolonged survival, and demonstrated excellent biosafety. Collectively, this work establishes a materials-driven localized platform that remodels the postsurgical tumor microenvironment, overcomes the intrinsic limitations of TMZ, and provides a promising strategy for improving patient outcomes in GBM.
{"title":"A multifunctional injectable MPDA@MTIC–Co hydrogel platform for synergistic chemotherapy–photothermal therapy of postoperative glioblastoma","authors":"Shuaimei Zhang , Hong Xu , Feifan Xiang , Yiqi Ma , Beibei Liu , Gaocan Li , Yunbing Wang , Min Wu","doi":"10.1016/j.bioactmat.2026.01.034","DOIUrl":"10.1016/j.bioactmat.2026.01.034","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults, with inevitable postoperative recurrence due to incomplete resection and limited chemotherapy efficacy. Temozolomide (TMZ), the first-line therapy, is hindered by rapid degradation of its active metabolite 3-methyl-(triazene-1-yl)-imidazole-4-carboxamide (MTIC), systemic toxicity, and frequent resistance driven by DNA repair. These shortcomings underscore the urgent need for localized strategies to achieve sustained stability and improve therapeutic outcomes. To address these limitations, we have developed an injectable extracellular matrix–mimicking hydrogel incorporating mesoporous polydopamine nanoparticles loaded with cobalt-stabilized MTIC complexes (MPDA@MTIC–Co). This hydrogel provides mechanical robustness, prolonged intratumoral retention, and sustained on-demand release, while enabling efficient cellular uptake, robust near-infrared–triggered photothermal conversion, and induction of apoptosis through PI3K/AKT pathway suppression. In orthotopic postoperative GBM models, local MPDA@MTIC–Co administration achieves synergistic chemo–photothermal therapy, markedly suppressed recurrence, prolonged survival, and demonstrated excellent biosafety. Collectively, this work establishes a materials-driven localized platform that remodels the postsurgical tumor microenvironment, overcomes the intrinsic limitations of TMZ, and provides a promising strategy for improving patient outcomes in GBM.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 387-400"},"PeriodicalIF":18.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074951","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 : 2026-01-29DOI: 10.1016/j.bioactmat.2025.12.054
Ebrahim Tajik , Nima Reihani , Vahid Karamzadeh , Guosheng Tang , Hossein Ravanbakhsh
Shape memory polymers (SMPs) have emerged as versatile and adaptive materials in healthcare, offering transformative solutions for tissue repair and biomedical device interfaces. Their ability to undergo controlled shape changes in response to external stimuli has driven significant interest in developing smart implants for minimally invasive procedures. Precise material design and engineering that leverage physiological conditions, such as body temperature and bodily fluids, can unlock their potential for biomedical applications. This review focuses explicitly on SMPs activated by physiological stimuli, referred to here as “body-responsive” SMPs. By categorizing SMPs into temperature-responsive, water-responsive, and dual-responsive variants, their shape memory behavior is analyzed, with an emphasis on how the structural design governs the body-responsiveness of the SMPs. Current biomedical applications, including tissue engineering, vascular interventions, bioelectronic devices, and targeted drug delivery, are also highlighted to demonstrate the practical relevance and versatility of body-responsive SMPs. Additionally, emerging fabrication technologies are discussed to provide insight into current scalable production methods suitable for SMPs. Finally, challenges in the design and performance of SMPs are explored, and a vision for future advancements is presented, outlining a roadmap for translating SMPs into biomedical applications within clinical settings.
{"title":"Body-responsive shape-memory polymers for biomedical applications","authors":"Ebrahim Tajik , Nima Reihani , Vahid Karamzadeh , Guosheng Tang , Hossein Ravanbakhsh","doi":"10.1016/j.bioactmat.2025.12.054","DOIUrl":"10.1016/j.bioactmat.2025.12.054","url":null,"abstract":"<div><div>Shape memory polymers (SMPs) have emerged as versatile and adaptive materials in healthcare, offering transformative solutions for tissue repair and biomedical device interfaces. Their ability to undergo controlled shape changes in response to external stimuli has driven significant interest in developing smart implants for minimally invasive procedures. Precise material design and engineering that leverage physiological conditions, such as body temperature and bodily fluids, can unlock their potential for biomedical applications. This review focuses explicitly on SMPs activated by physiological stimuli, referred to here as “body-responsive” SMPs. By categorizing SMPs into temperature-responsive, water-responsive, and dual-responsive variants, their shape memory behavior is analyzed, with an emphasis on how the structural design governs the body-responsiveness of the SMPs. Current biomedical applications, including tissue engineering, vascular interventions, bioelectronic devices, and targeted drug delivery, are also highlighted to demonstrate the practical relevance and versatility of body-responsive SMPs. Additionally, emerging fabrication technologies are discussed to provide insight into current scalable production methods suitable for SMPs. Finally, challenges in the design and performance of SMPs are explored, and a vision for future advancements is presented, outlining a roadmap for translating SMPs into biomedical applications within clinical settings.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 338-386"},"PeriodicalIF":18.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074952","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 : 2026-01-28DOI: 10.1016/j.bioactmat.2026.01.001
Qiji Lu , Yudi Kuang , Jingjing Diao , Jiaqian Zheng , Naru Zhao , Chang Du , Yingjun Wang
The geometric features of bioactive scaffolds are biophysical cues regulate cell fate, but their immunomodulatory potential in bone regeneration is yet to be determined. Growing evidence suggests that surface curvature is a potent regulator of cellular behaviours and osteogenesis. Therefore, we quantitatively decoded this underlying mechanism by identifying Gaussian curvature(K) as a potent geometric regulator of macrophage polarization, creating a pro-regenerative microenvironment for bone repair. Using a high-throughput β-tricalcium phosphate(β-TCP) bioceramic platform (K = −4.91 to +4.82 mm−2), we demonstrate that negative gaussian curvature(K−, K < −1.72 mm−2) promotes M2 macrophage polarization and endothelial CD31 expression. Mechanistically, single-cell transcriptomic RNA sequencing revealed that K− scaffold downregulates hypoxia-inducible factor 1-alpha (HIF-1α) via Ras-mitogen-activated protein kinase (Ras-MAPK) inhibition and thus promotes macrophage M2 polarization, consequently elevating BMP2 and VEGF secretion. In vivo, β-TCP scaffolds with K = −1.72 mm−2 achieved 42.4 % greater bone volume and higher torsional strength at 12 weeks than the scaffolds with K = +4.82 mm−2 in 15 mm critical-sized segmental defects of rabbit radius. This work indicates a quantitative geometry-immunity relationship for bioceramic scaffolds, contributing to the development of topology-mediated immunomodulatory biomaterials.
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