Pub Date : 2026-04-01Epub Date: 2026-02-01DOI: 10.1016/j.mtbio.2026.102885
Qiufang Gong , Lutong Wen , Qiuchen Wang , Yiheng Xia , Mei Zhang , Bo Sun , Tianqing Zhang , Hongyu Zhang , Dongliang Yang , Xuejiao Song , Jingbo Dong , Chao Liang
Diabetic abscesses represent a severe and challenging complication of chronic wounds, characterized by impaired healing due to hyperglycemia-induced oxidative stress, persistent inflammation, and susceptibility to infection. Despite advances in wound care, effective therapeutic strategies that simultaneously address these multifactorial pathologies remain lacking. Herein, we developed cerium molybdate nanoparticles (CeMo) through a green one-pot method as multifunctional therapeutic platforms for diabetic abscess treatment. CeMo exhibited dual enzyme-mimetic activities, serving as superoxide dismutase and catalase to catalytically eliminate reactive oxygen species (ROS) with over 90% scavenging efficiency at 100 μg/mL. Furthermore, they demonstrated exceptional photothermal conversion efficiency with a 30% conversion efficiency under 808 nm laser irradiation, enabling effective disruption of methicillin-resistant Staphylococcus aureus (MRSA). In vitro studies validated their ability to alleviate oxidative stress, facilitate macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype. In a diabetic murine abscess model, CeMo synergistically combined stable photothermal antibacterial activity, broad-spectrum ROS scavenging capability, and efficient immunomodulation to accelerate wound closure, achieving 90% healing within 12 days versus 35% in controls, while promoting collagen deposition and tissue remodeling. This work presents a promising strategy for managing infected diabetic wounds through multimodal microenvironment reprogramming.
{"title":"Rewiring diabetic abscess microenvironment for healing via CeMo-mediated photothermal antibacterial, ROS scavenging and immunomodulatory","authors":"Qiufang Gong , Lutong Wen , Qiuchen Wang , Yiheng Xia , Mei Zhang , Bo Sun , Tianqing Zhang , Hongyu Zhang , Dongliang Yang , Xuejiao Song , Jingbo Dong , Chao Liang","doi":"10.1016/j.mtbio.2026.102885","DOIUrl":"10.1016/j.mtbio.2026.102885","url":null,"abstract":"<div><div>Diabetic abscesses represent a severe and challenging complication of chronic wounds, characterized by impaired healing due to hyperglycemia-induced oxidative stress, persistent inflammation, and susceptibility to infection. Despite advances in wound care, effective therapeutic strategies that simultaneously address these multifactorial pathologies remain lacking. Herein, we developed cerium molybdate nanoparticles (CeMo) through a green one-pot method as multifunctional therapeutic platforms for diabetic abscess treatment. CeMo exhibited dual enzyme-mimetic activities, serving as superoxide dismutase and catalase to catalytically eliminate reactive oxygen species (ROS) with over 90% scavenging efficiency at 100 μg/mL. Furthermore, they demonstrated exceptional photothermal conversion efficiency with a 30% conversion efficiency under 808 nm laser irradiation, enabling effective disruption of methicillin-resistant <em>Staphylococcus aureus</em> (MRSA). In vitro studies validated their ability to alleviate oxidative stress, facilitate macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype. In a diabetic murine abscess model, CeMo synergistically combined stable photothermal antibacterial activity, broad-spectrum ROS scavenging capability, and efficient immunomodulation to accelerate wound closure, achieving 90% healing within 12 days versus 35% in controls, while promoting collagen deposition and tissue remodeling. This work presents a promising strategy for managing infected diabetic wounds through multimodal microenvironment reprogramming.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102885"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146169946","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 : 2026-04-01Epub Date: 2026-01-13DOI: 10.1016/j.mtbio.2026.102801
Zi-Zhan Li , Li-Ya Wei , Lei-Ming Cao , Guang-Rui Wang , Han-Yue Luo , Kan Zhou , Xing-Zhong Zhao , Bing Liu , Ming-Xue Zheng , Chun Xu , Bo Cai , Lin-Lin Bu
Oral cancer remains a global health burden, with limited improvements in long-term survival despite advances in multimodal therapy. Advances in early diagnosis and treatment strategies for oral cancer patients will significantly improve survival outcomes. Microfluidic technology, with its capacity for precise fluid manipulation, high-throughput analysis, and experimental miniaturization, has emerged as a powerful tool to accelerate innovations in cancer research and has become a pivotal pathway in oral cancer investigation and clinical translation. This review systematically examines the expanding roles of microfluidics in oral cancer research, with a particular focus on microfluidics-based liquid biopsy for early detection and prognosis, and microfluidics-enabled therapeutic strategies for treatment development and optimization. By bridging basic research with clinical application, microfluidics holds the potential to revolutionize early diagnosis, precision therapeutics, and functional outcome-oriented management in oral cancer, ultimately improving patient survival and quality of life.
{"title":"Emerging roles of microfluidics in oral cancer research and clinical translation","authors":"Zi-Zhan Li , Li-Ya Wei , Lei-Ming Cao , Guang-Rui Wang , Han-Yue Luo , Kan Zhou , Xing-Zhong Zhao , Bing Liu , Ming-Xue Zheng , Chun Xu , Bo Cai , Lin-Lin Bu","doi":"10.1016/j.mtbio.2026.102801","DOIUrl":"10.1016/j.mtbio.2026.102801","url":null,"abstract":"<div><div>Oral cancer remains a global health burden, with limited improvements in long-term survival despite advances in multimodal therapy. Advances in early diagnosis and treatment strategies for oral cancer patients will significantly improve survival outcomes. Microfluidic technology, with its capacity for precise fluid manipulation, high-throughput analysis, and experimental miniaturization, has emerged as a powerful tool to accelerate innovations in cancer research and has become a pivotal pathway in oral cancer investigation and clinical translation. This review systematically examines the expanding roles of microfluidics in oral cancer research, with a particular focus on microfluidics-based liquid biopsy for early detection and prognosis, and microfluidics-enabled therapeutic strategies for treatment development and optimization. By bridging basic research with clinical application, microfluidics holds the potential to revolutionize early diagnosis, precision therapeutics, and functional outcome-oriented management in oral cancer, ultimately improving patient survival and quality of life.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102801"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981375","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 : 2026-04-01Epub Date: 2026-02-01DOI: 10.1016/j.mtbio.2026.102863
Jing Sun, Xi Wang, Xiaoxue Wang, Wenhui Yu, Yang Yu, Shaohua Ge, Zheqin Dong
Guided bone regeneration (GBR) membranes are widely used for the treatment of bone defects. Natural hydrogels are promising candidates for GBR membranes owing to their excellent bioactivity and controllable degradability, but their clinical translation is restricted by inherent mechanical weakness. Inspired by tendon-strengthening mechanisms in athletes, we propose a tannic acid (TA)-assisted wet-stretching (TAWS) strategy to transform gelatin methacryloyl (GelMA) hydrogels into mechanically robust GBR membranes. During stretching, GelMA chains are directionally aligned while TA establishes multivalent hydrogen bonds between adjacent fibers, synergistically reinforcing the network. The resulting TA-trained (GHT) membranes achieved a 22.16-fold increase in Young's modulus and a 12.31-fold enhancement in toughness. In parallel, TAWS markedly slowed degradation kinetics and enhanced physiological stability, enabling GHT membranes to retain ∼80 % of their initial mass after 28 days in SBF. Beyond reinforcement, TA imparted potent ROS-scavenging and immunomodulatory activity. In vitro, GHT membranes enhanced stem cell survival, proliferation, and osteogenic differentiation under oxidative stress. In a mandibular defect model under elevated oxidative and inflammatory challenge, GHT reduced ROS levels (DHE fluorescence) to 53.76 % of the untreated ROS-upregulated group and increased bone volume fraction (BV/TV) by approximately 2.68-fold at 4 weeks and 2.21-fold at 8 weeks, outperforming the Bio-Gide® membrane. Collectively, TAWS provides a scalable platform to engineer multifunctional hydrogel membranes that integrate mechanics, stability, and regenerative performance for advanced GBR.
{"title":"Tannic acid-assisted mechanical training transforms natural hydrogels into robust and bioactive membranes for guided bone regeneration","authors":"Jing Sun, Xi Wang, Xiaoxue Wang, Wenhui Yu, Yang Yu, Shaohua Ge, Zheqin Dong","doi":"10.1016/j.mtbio.2026.102863","DOIUrl":"10.1016/j.mtbio.2026.102863","url":null,"abstract":"<div><div>Guided bone regeneration (GBR) membranes are widely used for the treatment of bone defects. Natural hydrogels are promising candidates for GBR membranes owing to their excellent bioactivity and controllable degradability, but their clinical translation is restricted by inherent mechanical weakness. Inspired by tendon-strengthening mechanisms in athletes, we propose a tannic acid (TA)-assisted wet-stretching (TAWS) strategy to transform gelatin methacryloyl (GelMA) hydrogels into mechanically robust GBR membranes. During stretching, GelMA chains are directionally aligned while TA establishes multivalent hydrogen bonds between adjacent fibers, synergistically reinforcing the network. The resulting TA-trained (GHT) membranes achieved a 22.16-fold increase in Young's modulus and a 12.31-fold enhancement in toughness. In parallel, TAWS markedly slowed degradation kinetics and enhanced physiological stability, enabling GHT membranes to retain ∼80 % of their initial mass after 28 days in SBF. Beyond reinforcement, TA imparted potent ROS-scavenging and immunomodulatory activity. In vitro, GHT membranes enhanced stem cell survival, proliferation, and osteogenic differentiation under oxidative stress. In a mandibular defect model under elevated oxidative and inflammatory challenge, GHT reduced ROS levels (DHE fluorescence) to 53.76 % of the untreated ROS-upregulated group and increased bone volume fraction (BV/TV) by approximately 2.68-fold at 4 weeks and 2.21-fold at 8 weeks, outperforming the Bio-Gide® membrane. Collectively, TAWS provides a scalable platform to engineer multifunctional hydrogel membranes that integrate mechanics, stability, and regenerative performance for advanced GBR.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102863"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170389","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 : 2026-04-01Epub 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":"2026-04-01","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 : 2026-04-01Epub Date: 2026-01-30DOI: 10.1016/j.mtbio.2026.102880
Qian Wu , Yisi Liu , Heng Song , Zhicheng Song , Hekai Shi , Dongchao Yang , Xiaoyu Peng , Binbin He , Junliang Ma , Fengxuan Han , Bin Li , Yan Gu
Current clinical approaches for abdominal wall defects (AWD) caused by extensive myofascial tissue loss employ synthetic meshes for fibrotic tissue repair, but fail to restore complete functionality. Under physiological conditions, rhythmic contractions of abdominal wall muscles during respiration generate endogenous bioelectric cues essential for muscle action potentials and cellular behavior. Therefore, we aimed to develop an exercise-mimetic electrical stimulation (ES) triggered by sonopiezoelectric therapy (SPT) to promote functional repair of AWD. To achieve this, a sandwich-like piezoelectric patch (PCP) was fabricated by sandwiching a chitin mat between two polycaprolactone mats. The three-layer structure mimics lateral abdominal muscle microarchitecture and provides topographical cues for myoblast alignment and fusion. Under respiratory-induced mechanical deformation, the PCP patches generate ES, helping restore local electric field homeostasis. Additionally, low-intensity pulsed ultrasound (LIPUS) can be applied to deliver more precise and intensified stimulation, further promoting myogenic differentiation and myoblast fusion in both in vitro and in vivo studies. It was found that ES could activate the Ca2+/CaN/NFAT2 signaling pathway under dual mechanical and LIPUS stimulation, enhancing the functional repair of AWD. This exercise-mimetic ES triggered by SPT establishes an innovative therapeutic strategy for abdominal wall repair, demonstrating broad potential in regenerative medicine.
{"title":"Exercise-mimetic electrical stimulation of muscles triggered by sonopiezoelectric therapy promotes functional repair of abdominal wall defects","authors":"Qian Wu , Yisi Liu , Heng Song , Zhicheng Song , Hekai Shi , Dongchao Yang , Xiaoyu Peng , Binbin He , Junliang Ma , Fengxuan Han , Bin Li , Yan Gu","doi":"10.1016/j.mtbio.2026.102880","DOIUrl":"10.1016/j.mtbio.2026.102880","url":null,"abstract":"<div><div>Current clinical approaches for abdominal wall defects (AWD) caused by extensive myofascial tissue loss employ synthetic meshes for fibrotic tissue repair, but fail to restore complete functionality. Under physiological conditions, rhythmic contractions of abdominal wall muscles during respiration generate endogenous bioelectric cues essential for muscle action potentials and cellular behavior. Therefore, we aimed to develop an exercise-mimetic electrical stimulation (ES) triggered by sonopiezoelectric therapy (SPT) to promote functional repair of AWD. To achieve this, a sandwich-like piezoelectric patch (PCP) was fabricated by sandwiching a chitin mat between two polycaprolactone mats. The three-layer structure mimics lateral abdominal muscle microarchitecture and provides topographical cues for myoblast alignment and fusion. Under respiratory-induced mechanical deformation, the PCP patches generate ES, helping restore local electric field homeostasis. Additionally, low-intensity pulsed ultrasound (LIPUS) can be applied to deliver more precise and intensified stimulation, further promoting myogenic differentiation and myoblast fusion in both <em>in vitro and in vivo</em> studies. It was found that ES could activate the Ca<sup>2+</sup>/CaN/NFAT2 signaling pathway under dual mechanical and LIPUS stimulation, enhancing the functional repair of AWD. This exercise-mimetic ES triggered by SPT establishes an innovative therapeutic strategy for abdominal wall repair, demonstrating broad potential in regenerative medicine.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102880"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170522","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 : 2026-04-01Epub Date: 2026-01-16DOI: 10.1016/j.mtbio.2026.102813
Sophie Anuth , Emely Bortel , Julie Villanova , Jussi-Petteri Suuronen , Sven Geissler , Amaia Cipitria , Peter Fratzl , Tobias Fretwurst , Katja Nelson , Susanne Nahles , Bernhard Hesse
Bone remodeling is a highly regulated, hierarchical process critical for maintaining structural integrity and mineral homeostasis. At the nano-scale, the osteocytes orchestrate mechanosensing, signaling, and nutrient transport across the mineralized matrix utilizing their extensive network of cell dendrites. The lacunar-canalicular network (OLCN) houses the cellular components within the matrix. How this network integrates across bone regions formed during different remodeling cycles remains unresolved. How the cellular network is connected across interfaces between different remodeling regions or cement lines is the focus of this exploration: is the network integration merely stochastical occurrences or result of a cued, directed formation process?
Using synchrotron-based nano computed tomography (nano-CT), we analyze human bone samples of 35 different patients with sub-micron resolution to characterize canalicular structures around cement lines. The results show the network's ability and affinity to integrate, and the strong influence of local tissue conditions on the degree of integration. We novelly include the structural analysis of canalicular network architecture to interpret underlying formation processes. Besides 'cross-generational' canalicular connections, we identify previously overlooked canalicular loops in newly formed bone near cement lines and interpret these as morphological indicators of a directed, adaptive search for reconnection. The study suggests a mechanism combining random outgrowth and directed progression influenced by local cues.
We propose a 'cross-generational' OLCN: a deliberately integrated network that enhances tissue connectivity, functional resilience, and osteocyte survival across temporal remodeling stages. These findings advance the understanding of bone network complexity and introduce canalicular looping as a nano-structural signature of directed formation in bone network architecture.
{"title":"Nano-scale evidence for osteocyte network integration across bone remodeling interfaces in human bone revealed by synchrotron nanoCT","authors":"Sophie Anuth , Emely Bortel , Julie Villanova , Jussi-Petteri Suuronen , Sven Geissler , Amaia Cipitria , Peter Fratzl , Tobias Fretwurst , Katja Nelson , Susanne Nahles , Bernhard Hesse","doi":"10.1016/j.mtbio.2026.102813","DOIUrl":"10.1016/j.mtbio.2026.102813","url":null,"abstract":"<div><div>Bone remodeling is a highly regulated, hierarchical process critical for maintaining structural integrity and mineral homeostasis. At the nano-scale, the osteocytes orchestrate mechanosensing, signaling, and nutrient transport across the mineralized matrix utilizing their extensive network of cell dendrites. The lacunar-canalicular network (OLCN) houses the cellular components within the matrix. How this network integrates across bone regions formed during different remodeling cycles remains unresolved. How the cellular network is connected across interfaces between different remodeling regions or cement lines is the focus of this exploration: is the network integration merely stochastical occurrences or result of a cued, directed formation process?</div><div>Using synchrotron-based nano computed tomography (nano-CT), we analyze human bone samples of 35 different patients with sub-micron resolution to characterize canalicular structures around cement lines. The results show the network's ability and affinity to integrate, and the strong influence of local tissue conditions on the degree of integration. We novelly include the structural analysis of canalicular network architecture to interpret underlying formation processes. Besides 'cross-generational' canalicular connections, we identify previously overlooked canalicular loops in newly formed bone near cement lines and interpret these as morphological indicators of a directed, adaptive search for reconnection. The study suggests a mechanism combining random outgrowth and directed progression influenced by local cues.</div><div>We propose a 'cross-generational' OLCN: a deliberately integrated network that enhances tissue connectivity, functional resilience, and osteocyte survival across temporal remodeling stages. These findings advance the understanding of bone network complexity and introduce canalicular looping as a nano-structural signature of directed formation in bone network architecture.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102813"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024480","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 : 2026-04-01Epub Date: 2026-01-12DOI: 10.1016/j.mtbio.2026.102794
Junyu Qian , Yukun Zhou , Zhenhai Xie , Jinjing Liu , Ping Li , Wenjie Tao , Yuanhao Wang , Fei Gao , Hui Zeng , Deli Wang , Haotian Qin , Yingqi Chen , Guojiang Wan
Bone fracture repair, particularly assisted by load-bearing implants, faces tough clinical challenges, necessitating novel biomaterials that are mechanically strong, biocompatible and biodegradable to achieve effective healing. Metallic molybdenum (Mo) has shown promise in this regard, whereas little has been done with considering its alloys that are more advantageous on many aspects over its pure counterpart. Herein, we demonstrate that the TZM Mo alloy (namely Titanium-Zirconium-Molybdenum, also Mo-Ti-Zr) performed superb efficacy in the repair of rat femoral fractures with its intramedullary nails (IMNs) prototype product even as compared with pure Mo. The TZM alloy had superior mechanical strength and more uniform degradation than Mo, meeting the requirements for next-generation biodegradable IMNs. Moreover, the in vitro assays verified the TZM promoted adhesion, migration and proliferation of endothelial cells and bone marrow mesenchymal stem cells and elicited no toxicity. Molecular expression results revealed the TZM may enhance angiogenesis by activating Wnt/β-catenin signaling and facilitated bone formation by up-regulating osteogenic genes via PI3K–Akt, MAPK–ERK, and cAMP–PKA pathways. More important, TZM-based IMNs achieved nearly complete fracture healing at 12 weeks in a rat femoral fracture model. Thus, the TZM Mo alloy holds super potential for clinical translation.
骨折修复，特别是在承重植入物的辅助下，面临着严峻的临床挑战，需要机械强度高、生物相容性好、可生物降解的新型生物材料来实现有效的愈合。金属钼（Mo）在这方面显示出了希望，而很少有人考虑它的合金在许多方面比纯钼更有优势。本研究证明，与纯Mo相比，TZM Mo合金（即钛锆钼，Mo- ti - zr）的髓内钉（IMNs）原型产品在大鼠股骨骨折的修复中表现出极好的效果。TZM合金具有比Mo更好的机械强度和更均匀的降解，满足下一代可生物降解IMNs的要求。此外，体外实验证实了TZM对内皮细胞和骨髓间充质干细胞的粘附、迁移和增殖有促进作用，且无毒性。分子表达结果显示，TZM可能通过激活Wnt/β-catenin信号通路促进血管生成，并通过PI3K-Akt、MAPK-ERK和cAMP-PKA通路上调成骨基因促进骨形成。更重要的是，在大鼠股骨骨折模型中，基于tzm的IMNs在12周时实现了几乎完全的骨折愈合。因此，TZM钼合金具有超强的临床转化潜力。
{"title":"TZM Mo alloy behaves superb as biodegradable metal for bone-fracture healing intramedullary nail implant","authors":"Junyu Qian , Yukun Zhou , Zhenhai Xie , Jinjing Liu , Ping Li , Wenjie Tao , Yuanhao Wang , Fei Gao , Hui Zeng , Deli Wang , Haotian Qin , Yingqi Chen , Guojiang Wan","doi":"10.1016/j.mtbio.2026.102794","DOIUrl":"10.1016/j.mtbio.2026.102794","url":null,"abstract":"<div><div>Bone fracture repair, particularly assisted by load-bearing implants, faces tough clinical challenges, necessitating novel biomaterials that are mechanically strong, biocompatible and biodegradable to achieve effective healing. Metallic molybdenum (Mo) has shown promise in this regard, whereas little has been done with considering its alloys that are more advantageous on many aspects over its pure counterpart. Herein, we demonstrate that the TZM Mo alloy (namely Titanium-Zirconium-Molybdenum, also Mo-Ti-Zr) performed superb efficacy in the repair of rat femoral fractures with its intramedullary nails (IMNs) prototype product even as compared with pure Mo. The TZM alloy had superior mechanical strength and more uniform degradation than Mo, meeting the requirements for next-generation biodegradable IMNs. Moreover, the <em>in vitro</em> assays verified the TZM promoted adhesion, migration and proliferation of endothelial cells and bone marrow mesenchymal stem cells and elicited no toxicity. Molecular expression results revealed the TZM may enhance angiogenesis by activating Wnt/β-catenin signaling and facilitated bone formation by up-regulating osteogenic genes via PI3K–Akt, MAPK–ERK, and cAMP–PKA pathways. More important, TZM-based IMNs achieved nearly complete fracture healing at 12 weeks in a rat femoral fracture model. Thus, the TZM Mo alloy holds super potential for clinical translation.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102794"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024394","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 : 2026-04-01Epub Date: 2026-01-30DOI: 10.1016/j.mtbio.2026.102848
Jiachen Li , Yaping Zhuang , Huijie Han , Yuewen Zhu , Chao Lin , Rui Wang , Ana Catarina Rodrigues da Silva , Marc C.A. Stuart , Guimei Jiang , Siyu Fan , Romana Schirhagl , Mohammad-Ali Shahbazi , Lígia Raquel Marona Rodrigues , Wenguo Cui , Hélder A. Santos
Triple-negative breast cancer (TNBC) exhibits high local-recurrence risk despite modern systemic therapy assisted with surgery or irradiation therapy. Here, we report an injectable nano-in-micro microsphere depot (cPAG) that integrates conductivity enhancement, photothermal conversion, O2 and reactive oxygen species (ROS) generation, and innate immune agonist co-delivery to support staged, local multimodal therapy. Monodispersed Au@GelMA microspheres prepared via microfluidics and photocrosslinking reduced high electrostatic resistance of GelMA hydrogels and provided stable 808 nm laser-responsive heating. The porous surface possessed abundant electrostatic adsorption sites for loading MnOx nanoflowers and anionic stimulator of interferon genes (STING) agonist. MnOx nanoflowers catalyzed H2O2 to generate O2, produced free radical signals and increased pro-inflammatory cytokines secretion in vitro. Co-delivery of agonist and MnOx nanoparticles further increased interferon-β secretion, consistent with induction of type I interferon response. In a 4T1 residual-tumor model established by partial tumor resection, a staged regimen consisting of cPAG-assisted irreversible electroporation followed by cPAG-mediated photothermal therapy showed the strongest suppression of local tumor regrowth among tested groups, with maintained body weight during the study window. Overall, cPAG provides a modular nano-in-micro depot strategy to integrate multiple local treatments for postoperative control of TNBC tumor.
{"title":"Nano-in-Micro GelMA depots assist electro-thermal-immuno orchestral treatment for solid triple negative breast tumor","authors":"Jiachen Li , Yaping Zhuang , Huijie Han , Yuewen Zhu , Chao Lin , Rui Wang , Ana Catarina Rodrigues da Silva , Marc C.A. Stuart , Guimei Jiang , Siyu Fan , Romana Schirhagl , Mohammad-Ali Shahbazi , Lígia Raquel Marona Rodrigues , Wenguo Cui , Hélder A. Santos","doi":"10.1016/j.mtbio.2026.102848","DOIUrl":"10.1016/j.mtbio.2026.102848","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) exhibits high local-recurrence risk despite modern systemic therapy assisted with surgery or irradiation therapy. Here, we report an injectable nano-in-micro microsphere depot (cPAG) that integrates conductivity enhancement, photothermal conversion, O<sub>2</sub> and reactive oxygen species (ROS) generation, and innate immune agonist co-delivery to support staged, local multimodal therapy. Monodispersed Au@GelMA microspheres prepared <em>via</em> microfluidics and photocrosslinking reduced high electrostatic resistance of GelMA hydrogels and provided stable 808 nm laser-responsive heating. The porous surface possessed abundant electrostatic adsorption sites for loading MnO<sub>x</sub> nanoflowers and anionic stimulator of interferon genes (STING) agonist. MnO<sub>x</sub> nanoflowers catalyzed H<sub>2</sub>O<sub>2</sub> to generate O<sub>2,</sub> produced free radical signals and increased pro-inflammatory cytokines secretion <em>in vitro</em>. Co-delivery of agonist and MnO<sub>x</sub> nanoparticles further increased interferon-β secretion, consistent with induction of type I interferon response. In a 4T1 residual-tumor model established by partial tumor resection, a staged regimen consisting of cPAG-assisted irreversible electroporation followed by cPAG-mediated photothermal therapy showed the strongest suppression of local tumor regrowth among tested groups, with maintained body weight during the study window. Overall, cPAG provides a modular nano-in-micro depot strategy to integrate multiple local treatments for postoperative control of TNBC tumor.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102848"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146169947","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 : 2026-04-01Epub Date: 2026-01-29DOI: 10.1016/j.mtbio.2026.102875
Jilai Tian , Zhen Yang , Shixiao Wan , Chenyi Shou , Lijun Zhang , Ying Zhao , Shi Chen , Kaili Huang , Huanhuan Zhao , Xianrui Song , Yichen Guo , Jun Guo
The heterogeneity of cancer stem cells and the immunosuppressive hypoxic microenvironment are key challenges in the development of therapeutic vaccines for solid tumors. In this study, oxygen was attempted as an adjuvant to investigate the enhancing immunotherapeutic efficacy of cancer nanovaccines. Lipid-encapsulated oxygen nanobubbles (Lipo-NBs-O2) that co-modified with anti-CD3 and anti-epidermal growth factor receptor antibodies (2P@Lipo-NBs-O2) was developed enabling T cell–tumor cell bridging. BMS 202, a programmed cell death 1/programmed cell death 1 Ligand 1 (PD-L1) inhibitor, was loaded yielding 2P@Lipo-BMS-NBs-O2, which was found to reduce the expression levels hypoxia-inducible factor-1α and PD-L1, synergistically enhanced the pharmacodynamics of BMS 202, meanwhile, enhanced cytotoxic T-cell infiltration. Combined technology of oxygen delivery and T cell redirection effectively enhances cancer immunotherapy. Further incorporation of a fused cytomembrane (FM) from dendritic and B16F10 cells produced FM-2P@Lipo-BMS-NBs-O2, which exhibited superior heterogeneous tumor growth suppression, reduced stemness gene expression, increased CD8+ T-cell infiltration, and elevated IFN-γ levels in serum. Oxygen-carrying nanovaccine possess the features of oxygen delivery, T cell redirection and FM coating, represents full activation of T-cell function and a potent reduction of tumor stemness, offering a promising strategy for the treatment of highly heterogeneous solid tumors.
{"title":"Oxygen-carrying nanovaccine potentiates cancer immunotherapy for heterogeneous solid tumors","authors":"Jilai Tian , Zhen Yang , Shixiao Wan , Chenyi Shou , Lijun Zhang , Ying Zhao , Shi Chen , Kaili Huang , Huanhuan Zhao , Xianrui Song , Yichen Guo , Jun Guo","doi":"10.1016/j.mtbio.2026.102875","DOIUrl":"10.1016/j.mtbio.2026.102875","url":null,"abstract":"<div><div>The heterogeneity of cancer stem cells and the immunosuppressive hypoxic microenvironment are key challenges in the development of therapeutic vaccines for solid tumors. In this study, oxygen was attempted as an adjuvant to investigate the enhancing immunotherapeutic efficacy of cancer nanovaccines. Lipid-encapsulated oxygen nanobubbles (Lipo-NBs-O<sub>2</sub>) that co-modified with anti-CD3 and anti-epidermal growth factor receptor antibodies (2P@Lipo-NBs-O<sub>2</sub>) was developed enabling T cell–tumor cell bridging. BMS 202, a programmed cell death 1/programmed cell death 1 Ligand 1 (PD-L1) inhibitor, was loaded yielding 2P@Lipo-BMS-NBs-O<sub>2</sub>, which was found to reduce the expression levels hypoxia-inducible factor-1α and PD-L1, synergistically enhanced the pharmacodynamics of BMS 202, meanwhile, enhanced cytotoxic T-cell infiltration. Combined technology of oxygen delivery and T cell redirection effectively enhances cancer immunotherapy. Further incorporation of a fused cytomembrane (FM) from dendritic and B16F10 cells produced FM-2P@Lipo-BMS-NBs-O<sub>2</sub>, which exhibited superior heterogeneous tumor growth suppression, reduced stemness gene expression, increased CD8<sup>+</sup> T-cell infiltration, and elevated IFN-γ levels in serum. Oxygen-carrying nanovaccine possess the features of oxygen delivery, T cell redirection and FM coating, represents full activation of T-cell function and a potent reduction of tumor stemness, offering a promising strategy for the treatment of highly heterogeneous solid tumors.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102875"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170457","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 : 2026-04-01Epub Date: 2026-01-14DOI: 10.1016/j.mtbio.2026.102807
Haohua Lai , Li Dong , Dongdong Jiang , Chen Shi , Wenbo Zhong , Chengxiang Sha , Junwei Yan , Xiao Wang , Jing Zhang , Ziyi Yu , Zhaowei Yin , Bin Liang
Osteochondral defects (OCDs) remain challenging to repair due to the complex structural and biological heterogeneity of the cartilage–bone interface. Here, we developed a bilayer microsphere–scaffolds composite by integrating melt electrowriting (MEW) scaffolds with two types of functionalized hydrogel microspheres (HMPs). The upper layer consisted of disulfide-containing poly ethylene glycol diacrylate (HB-PBHE)/thiolated hyaluronic acid (SH-HA) microspheres encapsulating kartogenin (KGN) liposomes (HM@PHK) to promote chondrogenesis, while the lower layer was formed by GelMA/nano-hydroxyapatite (nHAP) microspheres loaded with curcumin (Cur) liposomes (HM@GMAC) to provide osteoinductive, antioxidative, and anti-inflammatory cues. This bilayer construct exhibited uniform architecture, favorable mechanics, and controlled drug release. In vitro, the system promoted bone marrow–derived mesenchymal stem cells (BMSCs) migration, chondrogenic and osteogenic differentiation, and attenuated oxidative stress–induced apoptosis while modulating macrophage polarization. Transcriptomic analysis revealed that both layers activated the PI3K-AKT pathway, with the upper phase regulating the PI3K-AKT-SOX9 axis for chondrogenesis and the lower phase promoting osteogenesis and cytoprotection via PI3K-AKT-RUNX2/BAX signaling. In vivo implantation in rat femoral condyle defects demonstrated superior cartilage–bone reconstruction. Collectively, this multifunctional bilayer microsphere–scaffolds system provides stratified regulation of osteochondral repair through coordinated structural support, bioactive delivery, and immunomodulation, offering a clinically translatable approach to osteochondral defect regeneration.
{"title":"Multifunctional bilayer scaffolds integrating melt electrowriting fibers and drug-loaded microspheres promote posteochondral regeneration through PI3K–AKT–mediated chondro-osteogenic signaling","authors":"Haohua Lai , Li Dong , Dongdong Jiang , Chen Shi , Wenbo Zhong , Chengxiang Sha , Junwei Yan , Xiao Wang , Jing Zhang , Ziyi Yu , Zhaowei Yin , Bin Liang","doi":"10.1016/j.mtbio.2026.102807","DOIUrl":"10.1016/j.mtbio.2026.102807","url":null,"abstract":"<div><div>Osteochondral defects (OCDs) remain challenging to repair due to the complex structural and biological heterogeneity of the cartilage–bone interface. Here, we developed a bilayer microsphere–scaffolds composite by integrating melt electrowriting (MEW) scaffolds with two types of functionalized hydrogel microspheres (HMPs). The upper layer consisted of disulfide-containing poly ethylene glycol diacrylate (HB-PBHE)/thiolated hyaluronic acid (SH-HA) microspheres encapsulating kartogenin (KGN) liposomes (HM@PHK) to promote chondrogenesis, while the lower layer was formed by GelMA/nano-hydroxyapatite (nHAP) microspheres loaded with curcumin (Cur) liposomes (HM@GMAC) to provide osteoinductive, antioxidative, and anti-inflammatory cues. This bilayer construct exhibited uniform architecture, favorable mechanics, and controlled drug release. In vitro, the system promoted bone marrow–derived mesenchymal stem cells (BMSCs) migration, chondrogenic and osteogenic differentiation, and attenuated oxidative stress–induced apoptosis while modulating macrophage polarization. Transcriptomic analysis revealed that both layers activated the PI3K-AKT pathway, with the upper phase regulating the PI3K-AKT-SOX9 axis for chondrogenesis and the lower phase promoting osteogenesis and cytoprotection via PI3K-AKT-RUNX2/BAX signaling. In vivo implantation in rat femoral condyle defects demonstrated superior cartilage–bone reconstruction. Collectively, this multifunctional bilayer microsphere–scaffolds system provides stratified regulation of osteochondral repair through coordinated structural support, bioactive delivery, and immunomodulation, offering a clinically translatable approach to osteochondral defect regeneration.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102807"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024399","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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