Pub Date : 2025-11-12DOI: 10.1016/j.biomaterials.2025.123846
Xing Lu , Jiancheng Zhu , Bingyan Li , Sheng Pan , Yao He , Houyu Wang
Clinical antiresorptive drugs primarily target bone metabolism but often neglect the simultaneous oxidative stress and inflammation inherent in osteoporosis. Here we developed a novel triple-function nanoagent consisting of aptamer-silica-DNA nanopatch for reliable, targeted and synergistic osteoporosis treatment. We controlled the mineralization of DNA origami with silica via electrostatic interactions between silica precursors and DNA strands, achieving optimal mineralization at 23 %. This modification enhanced nuclease resistance—reducing degradation by 60.36 %—while preserving bone-targeting and reactive oxygen species-scavenging functions. Furthermore, functionalizing the nanopatch with FDA-approved sclerostin aptamers enabled specific binding to sclerostin, effectively reactivating Wnt signaling in osteoblasts to promote bone formation. In vivo studies demonstrated that the nanopatch reversed osteoporotic bone loss in ovariectomized mice, increasing bone density by approximately 30 % compared to bisphosphonate treatments. Overall, this triple-function nanopatch addresses structural instability, oxidative stress, and disrupted bone metabolism, offering a comprehensive therapeutic strategy for osteoporosis.
{"title":"Sclerostin-targeted silica-mineralized DNA origami enables reliable and synergistic osteoporosis therapy","authors":"Xing Lu , Jiancheng Zhu , Bingyan Li , Sheng Pan , Yao He , Houyu Wang","doi":"10.1016/j.biomaterials.2025.123846","DOIUrl":"10.1016/j.biomaterials.2025.123846","url":null,"abstract":"<div><div>Clinical antiresorptive drugs primarily target bone metabolism but often neglect the simultaneous oxidative stress and inflammation inherent in osteoporosis. Here we developed a novel triple-function nanoagent consisting of aptamer-silica-DNA nanopatch for reliable, targeted and synergistic osteoporosis treatment. We controlled the mineralization of DNA origami with silica via electrostatic interactions between silica precursors and DNA strands, achieving optimal mineralization at 23 %. This modification enhanced nuclease resistance—reducing degradation by 60.36 %—while preserving bone-targeting and reactive oxygen species-scavenging functions. Furthermore, functionalizing the nanopatch with FDA-approved sclerostin aptamers enabled specific binding to sclerostin, effectively reactivating Wnt signaling in osteoblasts to promote bone formation. In vivo studies demonstrated that the nanopatch reversed osteoporotic bone loss in ovariectomized mice, increasing bone density by approximately 30 % compared to bisphosphonate treatments. Overall, this triple-function nanopatch addresses structural instability, oxidative stress, and disrupted bone metabolism, offering a comprehensive therapeutic strategy for osteoporosis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123846"},"PeriodicalIF":12.9,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145526493","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 : 2025-11-12DOI: 10.1016/j.biomaterials.2025.123851
Rita Quinteira , Sara Gimondi , Maria Elena Melica , David Caballero , Ana Castanheira , Begoña Espiña , Laura Lasagni , Paola Romagnani , Rui L. Reis , Nuno M. Neves
Extracellular vesicles (EVs) are naturally occurring nanoparticles that mediate intercellular communication and hold great promise as a cell-free therapeutic strategy for kidney disease. However, their clinical translation remains limited by rapid clearance and inefficient tissue targeting. To overcome these challenges, we developed a decellularized kidney extracellular matrix (DKECM)-based bioink capable of sustained EV delivery. Unlike existing bioinks that combine extracellular matrix with other biomaterials, this formulation uses DKECM alone, preserving renal-specific bioactivity.
We report the first successful isolation and characterization of EVs from human renal progenitor cells (RPCs), confirmed by nanoparticle tracking analysis, cryo-electron microscopy, and enrichment of specific-EV markers. Functionally, RPC-derived EVs were readily internalized by tubular epithelial cells and modulated oxidative stress, proliferation, and injury responses under hypoxic conditions.
The DKECM based-bioink exhibited shear-thinning behavior, high shape fidelity, and efficient layer stacking, supporting precise bioprinting and gradual EV release over two weeks. This system recreates key features of the renal microenvironment, providing a platform for controlled, localized EV delivery.
In summary, this study introduces a fully extracellular matrix-derived bioink that enables sustained EV release and maintains renal bioactivity, offering a promising strategy for biofabrication approaches in kidney repair and regeneration.
{"title":"3D bioprinting meets nanotherapeutics: a vehicle for sustained extracellular vesicle delivery","authors":"Rita Quinteira , Sara Gimondi , Maria Elena Melica , David Caballero , Ana Castanheira , Begoña Espiña , Laura Lasagni , Paola Romagnani , Rui L. Reis , Nuno M. Neves","doi":"10.1016/j.biomaterials.2025.123851","DOIUrl":"10.1016/j.biomaterials.2025.123851","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are naturally occurring nanoparticles that mediate intercellular communication and hold great promise as a cell-free therapeutic strategy for kidney disease. However, their clinical translation remains limited by rapid clearance and inefficient tissue targeting. To overcome these challenges, we developed a decellularized kidney extracellular matrix (DKECM)-based bioink capable of sustained EV delivery. Unlike existing bioinks that combine extracellular matrix with other biomaterials, this formulation uses DKECM alone, preserving renal-specific bioactivity.</div><div>We report the first successful isolation and characterization of EVs from human renal progenitor cells (RPCs), confirmed by nanoparticle tracking analysis, cryo-electron microscopy, and enrichment of specific-EV markers. Functionally, RPC-derived EVs were readily internalized by tubular epithelial cells and modulated oxidative stress, proliferation, and injury responses under hypoxic conditions.</div><div>The DKECM based-bioink exhibited shear-thinning behavior, high shape fidelity, and efficient layer stacking, supporting precise bioprinting and gradual EV release over two weeks. This system recreates key features of the renal microenvironment, providing a platform for controlled, localized EV delivery.</div><div>In summary, this study introduces a fully extracellular matrix-derived bioink that enables sustained EV release and maintains renal bioactivity, offering a promising strategy for biofabrication approaches in kidney repair and regeneration.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123851"},"PeriodicalIF":12.9,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145547510","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 : 2025-11-11DOI: 10.1016/j.biomaterials.2025.123853
Kongqi Chen , Qiong Liu , Mengjie Wang , Chuen Kam , Mingmin Zhang , Zhiming Wang , Sijie Chen
Migrasomes, recently identified as extracellular vesicles formed along the retraction fibers (RFs) in migrating cells, are evident in damaged mitochondria clearance, intercellular signaling, embryonic development, and pathological progression of diseases. During migrasome biogenesis, signaling cues and membrane dynamics interplay with each other in the maturation, expansion, and detachment of migrasomes from RFs. Membrane tension plays a crucial role in migrasome dynamics, and tools for monitoring the dynamic mechanical properties of migrasomes are highly desired. In this study, we developed and characterized a novel mechanosensitive but viscosity-insensitive fluorescent probe, named OT2SQ, for real-time investigation of migrasome dynamics in living cells. OT2SQ is a twisted small molecule with multiple rotatable units, exhibiting longer fluorescence lifetimes in response to increased membrane tension but showing no response to altered viscosity. Using time-lapse fluorescence lifetime imaging, we identified distinct modes of migrasome biogenesis and detachment from retraction fibers, each associated with unique membrane tension dynamics. Furthermore, phasor-FLIM analysis revealed alterations in migrasome membrane tension during content release and internalization processes. This study introduces a versatile fluorescent tool for real-time monitoring of migrasome morphology, spatiotemporal distribution, and membrane tension dynamics.
{"title":"A mechanosensitive fluorescent probe for visualizing migrasome mechano-spatiotemporal dynamics","authors":"Kongqi Chen , Qiong Liu , Mengjie Wang , Chuen Kam , Mingmin Zhang , Zhiming Wang , Sijie Chen","doi":"10.1016/j.biomaterials.2025.123853","DOIUrl":"10.1016/j.biomaterials.2025.123853","url":null,"abstract":"<div><div>Migrasomes, recently identified as extracellular vesicles formed along the retraction fibers (RFs) in migrating cells, are evident in damaged mitochondria clearance, intercellular signaling, embryonic development, and pathological progression of diseases. During migrasome biogenesis, signaling cues and membrane dynamics interplay with each other in the maturation, expansion, and detachment of migrasomes from RFs. Membrane tension plays a crucial role in migrasome dynamics, and tools for monitoring the dynamic mechanical properties of migrasomes are highly desired. In this study, we developed and characterized a novel mechanosensitive but viscosity-insensitive fluorescent probe, named OT2SQ, for real-time investigation of migrasome dynamics in living cells. OT2SQ is a twisted small molecule with multiple rotatable units, exhibiting longer fluorescence lifetimes in response to increased membrane tension but showing no response to altered viscosity. Using time-lapse fluorescence lifetime imaging, we identified distinct modes of migrasome biogenesis and detachment from retraction fibers, each associated with unique membrane tension dynamics. Furthermore, phasor-FLIM analysis revealed alterations in migrasome membrane tension during content release and internalization processes. This study introduces a versatile fluorescent tool for real-time monitoring of migrasome morphology, spatiotemporal distribution, and membrane tension dynamics.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123853"},"PeriodicalIF":12.9,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145526494","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 : 2025-11-11DOI: 10.1016/j.biomaterials.2025.123850
Shengji Gu , Jian Zhou , Qiang Liu , Paul K. Chu , Zheyi Meng , Yongfeng Shao , Kelvin W.K. Yeung , Guomin Wang
Anastomosis is essential in cardiovascular surgery. However, traditional hand-sewn techniques are technically demanding, and existing sutureless methods often result in complications such as thrombosis and delayed healing due to poor mechanical compliance and insufficient endothelialization. Herein, we propose a cannula connection strategy that combines mechanical and biochemical support via a vascular-shaped polyetheretherketone (PEEK) connector. The PEEK substrate is coated with polydopamine (PDA) and chemically grafted with S-nitroso-N-acetylpenicillamine (SNAP) to enable sustained nitric oxide (NO) release. This approach significantly enhances anastomotic mechanical performance by improving tensile strength and burst pressure, thereby holding promise for reducing operation time and minimizing blood leakage. Compared to non-grafted SNAP coatings (PP–S), the chemically grafted version (PP@S) maintains elevated NO release for over 30 days, effectively modulating the local microenvironment, inhibiting platelet adhesion, and promoting the proliferation and spreading of human umbilical vein endothelial cells (HUVECs). In vivo studies show that the cannula device shortens surgical time by approximately 50 % and significantly decreases intraoperative bleeding. The mechanical structure offers resistance to pressure fluctuations, provides spatial reinforcement, and prevents anastomotic leakage. Concurrently, the biochemical modulation minimizes inflammatory responses and systemic toxicity, facilitating collagen fiber formation and further enhancing structural support. This positive feedback loop results in a 99.04 % anastomotic patency rate two months post-surgery. Overall, this integrated cannula strategy provides an alternative to traditional anastomosis techniques by combining mechanical and biochemical support to enhance anastomotic integrity and facilitate healing.
{"title":"A cannula connecting strategy fostering vascular anastomosis based on mechanical support and biochemical modulation","authors":"Shengji Gu , Jian Zhou , Qiang Liu , Paul K. Chu , Zheyi Meng , Yongfeng Shao , Kelvin W.K. Yeung , Guomin Wang","doi":"10.1016/j.biomaterials.2025.123850","DOIUrl":"10.1016/j.biomaterials.2025.123850","url":null,"abstract":"<div><div>Anastomosis is essential in cardiovascular surgery. However, traditional hand-sewn techniques are technically demanding, and existing sutureless methods often result in complications such as thrombosis and delayed healing due to poor mechanical compliance and insufficient endothelialization. Herein, we propose a cannula connection strategy that combines mechanical and biochemical support via a vascular-shaped polyetheretherketone (PEEK) connector. The PEEK substrate is coated with polydopamine (PDA) and chemically grafted with S-nitroso-N-acetylpenicillamine (SNAP) to enable sustained nitric oxide (NO) release. This approach significantly enhances anastomotic mechanical performance by improving tensile strength and burst pressure, thereby holding promise for reducing operation time and minimizing blood leakage. Compared to non-grafted SNAP coatings (PP–S), the chemically grafted version (PP@S) maintains elevated NO release for over 30 days, effectively modulating the local microenvironment, inhibiting platelet adhesion, and promoting the proliferation and spreading of human umbilical vein endothelial cells (HUVECs). <em>In vivo</em> studies show that the cannula device shortens surgical time by approximately 50 % and significantly decreases intraoperative bleeding. The mechanical structure offers resistance to pressure fluctuations, provides spatial reinforcement, and prevents anastomotic leakage. Concurrently, the biochemical modulation minimizes inflammatory responses and systemic toxicity, facilitating collagen fiber formation and further enhancing structural support. This positive feedback loop results in a 99.04 % anastomotic patency rate two months post-surgery. Overall, this integrated cannula strategy provides an alternative to traditional anastomosis techniques by combining mechanical and biochemical support to enhance anastomotic integrity and facilitate healing.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123850"},"PeriodicalIF":12.9,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577083","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 : 2025-11-11DOI: 10.1016/j.biomaterials.2025.123823
Xinting Liang , Lei Yang , Xiuli Chen , Yusheng Gong , Rengui Xu , Qi Zeng , Jiarong Xu , Jiajing Liu , Yuan Liu , Guanyue Li , Linxi He , Wenhao Jiao , Hui Liu , Wei Chen
Dexmedetomidine, known as an exceptionally potent and highly selective α2-adrenergic receptor agonist, is widely used as a safe and effective intravenous sedative agent in both surgical and nonsurgical settings. As the need for an optimized sedative delivery system grows—one that is not only easy to apply but also demonstrates superior efficacy, particularly among pediatric patients and other groups with lower levels of cooperation—innovative delivery methods are increasingly sought. To address this need, we developed a caramelized amorphous sucrose-based lunging microneedle array (CALM), incorporating an advanced Kelvin cell lattice framework. This lattice improves the microneedle array's surface contact with tissues, accelerating and enhancing the drug release process. Additionally, unlike conventional sucrose-based microneedles, which often crystallize and lose mechanical strength, the caramelization process reduces crystallinity, increasing both the stability and structural integrity of the system. These combined features make CALM a highly effective and patient-friendly option for administering dexmedetomidine. Preliminary trials in clinical simulations showed a rapid onset of sedation with minimal discomfort, highlighting its potential as a promising solution for vulnerable populations needing fast and secure sedation.
{"title":"Swift-acting structured lattice-enhanced caramelized sucrose system for painless sedative delivery","authors":"Xinting Liang , Lei Yang , Xiuli Chen , Yusheng Gong , Rengui Xu , Qi Zeng , Jiarong Xu , Jiajing Liu , Yuan Liu , Guanyue Li , Linxi He , Wenhao Jiao , Hui Liu , Wei Chen","doi":"10.1016/j.biomaterials.2025.123823","DOIUrl":"10.1016/j.biomaterials.2025.123823","url":null,"abstract":"<div><div>Dexmedetomidine, known as an exceptionally potent and highly selective α2-adrenergic receptor agonist, is widely used as a safe and effective intravenous sedative agent in both surgical and nonsurgical settings. As the need for an optimized sedative delivery system grows—one that is not only easy to apply but also demonstrates superior efficacy, particularly among pediatric patients and other groups with lower levels of cooperation—innovative delivery methods are increasingly sought. To address this need, we developed a caramelized amorphous sucrose-based lunging microneedle array (CALM), incorporating an advanced Kelvin cell lattice framework. This lattice improves the microneedle array's surface contact with tissues, accelerating and enhancing the drug release process. Additionally, unlike conventional sucrose-based microneedles, which often crystallize and lose mechanical strength, the caramelization process reduces crystallinity, increasing both the stability and structural integrity of the system. These combined features make CALM a highly effective and patient-friendly option for administering dexmedetomidine. Preliminary trials in clinical simulations showed a rapid onset of sedation with minimal discomfort, highlighting its potential as a promising solution for vulnerable populations needing fast and secure sedation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123823"},"PeriodicalIF":12.9,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145526492","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 : 2025-11-10DOI: 10.1016/j.biomaterials.2025.123848
Zhaonan Liu , Qing Guan , Jianfeng Xin , Wei Tang , Yu Chen , Jiaying Zhang , Junjie Chen , Shijie Bi , Peng Wang , Jun Liu
Bacteriotherapy holds great promise for cancer treatment, yet few bacterial agents have progressed to clinical application. Inspired by the acidic growth conditions of Lactobacillus rhamnosus GG (LGG), which resemble the tumor microenvironment, we systematically investigated its intrinsic anti-tumor potential. LGG demonstrated acid-environment tropism, strong adhesion to tumor cells, and active penetration into deep tumor tissues. Both LGG and its secretions exhibited potent cytotoxicity against various tumor cell lines, associated with mitochondrial dysfunction and apoptosis, likely due to acidification of the surrounding environment. Furthermore, LGG competitively inhibited tumor-promoting bacteria and activated immune responses by promoting M1-type macrophage polarization and dendritic cell maturation. To enhance its therapeutic efficacy, we further developed a biohybrid system by conjugating paclitaxel-loaded poly (lactic-co-glycolic acid) nanoparticles to LGG (PTX-NPs-LGG), enabling both targeted chemotherapy and bacteriotherapy. Additionally, a thermo-sensitive hydrogel was employed for peritumoral delivery, ensuring sustained release and localized activity. In the 4T1 breast tumor lung metastasis model and the B16F10 tumor postoperative recurrence model, PTX-NPs-LGG@gel exhibited superior anti-tumor efficacy with favorable safety profiles. These findings highlight the potential of LGG-based biohybrids as a safe and effective platform for chemo-immunotherapy in cancer treatment.
{"title":"Chemo-immunotherapeutic potential of Lactobacillus rhamnosus GG and its bioengineering for cancer therapy","authors":"Zhaonan Liu , Qing Guan , Jianfeng Xin , Wei Tang , Yu Chen , Jiaying Zhang , Junjie Chen , Shijie Bi , Peng Wang , Jun Liu","doi":"10.1016/j.biomaterials.2025.123848","DOIUrl":"10.1016/j.biomaterials.2025.123848","url":null,"abstract":"<div><div>Bacteriotherapy holds great promise for cancer treatment, yet few bacterial agents have progressed to clinical application. Inspired by the acidic growth conditions of <em>Lactobacillus rhamnosus</em> GG (LGG), which resemble the tumor microenvironment, we systematically investigated its intrinsic anti-tumor potential. LGG demonstrated acid-environment tropism, strong adhesion to tumor cells, and active penetration into deep tumor tissues. Both LGG and its secretions exhibited potent cytotoxicity against various tumor cell lines, associated with mitochondrial dysfunction and apoptosis, likely due to acidification of the surrounding environment. Furthermore, LGG competitively inhibited tumor-promoting bacteria and activated immune responses by promoting M1-type macrophage polarization and dendritic cell maturation. To enhance its therapeutic efficacy, we further developed a biohybrid system by conjugating paclitaxel-loaded poly (lactic-co-glycolic acid) nanoparticles to LGG (PTX-NPs-LGG), enabling both targeted chemotherapy and bacteriotherapy. Additionally, a thermo-sensitive hydrogel was employed for peritumoral delivery, ensuring sustained release and localized activity. In the 4T1 breast tumor lung metastasis model and the B16F10 tumor postoperative recurrence model, PTX-NPs-LGG@gel exhibited superior anti-tumor efficacy with favorable safety profiles. These findings highlight the potential of LGG-based biohybrids as a safe and effective platform for chemo-immunotherapy in cancer treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123848"},"PeriodicalIF":12.9,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522525","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 : 2025-11-08DOI: 10.1016/j.biomaterials.2025.123845
Wei Wei , Yuyi Zhu , Xiaoqin Shui , Caihong Liu , Yongxiu Huang , Jinglei Ren , Chang Liu , Letian Yang , Liang Ma , Meng Gong , Ping Fu , Dingkun Zhang , Yuliang Zhao
Acute kidney injury (AKI), characterized by rapid renal dysfunction, lacks effective therapies due to its complex pathophysiology involving oxidative stress and mitochondrial damage. Molybdenum carbide (Mo2C) nanozymes show promise through their tunable catalytic properties and reactive oxygen species (ROS)-scavenging capacity. To elucidate the metabolic basis of their therapeutic effects, we employed metabolomics analysis for molecular-level metabolic profiling, combined with evaluation in lipopolysaccharide (LPS)-, cisplatin (CP)-, and ischemia-reperfusion injury (IRI)-induced AKI models and TCMK-1 cell validation. Key findings demonstrated that Mo2C restored renal function, reduced oxidative damage/apoptosis, and preserved mitochondrial integrity. Metabolomic mechanistic investigation revealed normalization of dysregulated pathways including glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. Consistently, in LPS-challenged TCMK-1 cells, Mo2C suppressed ROS, attenuated apoptosis, reduced inflammation, and specifically stabilized TCA cycle function. Most importantly, inhibition of citrate synthase causally demonstrated that Mo2C's renoprotection depends on TCA cycle modulation. These integrated findings establish Mo2C nanozymes as a novel AKI treatment paradigm through TCA cycle homeostasis restoration, with significant translational potential. To realize this potential, future studies focusing on comprehensive safety profiling and clinical validation may facilitate the translation of Mo2C nanozymes into therapeutic applications for AKI and related renal disorders.
{"title":"Mo2C nanozyme targets citrate synthase to treat acute kidney injury through alleviating oxidative stress and dysfunction of energy metabolism","authors":"Wei Wei , Yuyi Zhu , Xiaoqin Shui , Caihong Liu , Yongxiu Huang , Jinglei Ren , Chang Liu , Letian Yang , Liang Ma , Meng Gong , Ping Fu , Dingkun Zhang , Yuliang Zhao","doi":"10.1016/j.biomaterials.2025.123845","DOIUrl":"10.1016/j.biomaterials.2025.123845","url":null,"abstract":"<div><div>Acute kidney injury (AKI), characterized by rapid renal dysfunction, lacks effective therapies due to its complex pathophysiology involving oxidative stress and mitochondrial damage. Molybdenum carbide (Mo<sub>2</sub>C) nanozymes show promise through their tunable catalytic properties and reactive oxygen species (ROS)-scavenging capacity. To elucidate the metabolic basis of their therapeutic effects, we employed metabolomics analysis for molecular-level metabolic profiling, combined with evaluation in lipopolysaccharide (LPS)-, cisplatin (CP)-, and ischemia-reperfusion injury (IRI)-induced AKI models and TCMK-1 cell validation. Key findings demonstrated that Mo<sub>2</sub>C restored renal function, reduced oxidative damage/apoptosis, and preserved mitochondrial integrity. Metabolomic mechanistic investigation revealed normalization of dysregulated pathways including glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. Consistently, in LPS-challenged TCMK-1 cells, Mo<sub>2</sub>C suppressed ROS, attenuated apoptosis, reduced inflammation, and specifically stabilized TCA cycle function. Most importantly, inhibition of citrate synthase causally demonstrated that Mo<sub>2</sub>C's renoprotection depends on TCA cycle modulation. These integrated findings establish Mo<sub>2</sub>C nanozymes as a novel AKI treatment paradigm through TCA cycle homeostasis restoration, with significant translational potential. To realize this potential, future studies focusing on comprehensive safety profiling and clinical validation may facilitate the translation of Mo<sub>2</sub>C nanozymes into therapeutic applications for AKI and related renal disorders.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123845"},"PeriodicalIF":12.9,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494073","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 : 2025-11-07DOI: 10.1016/j.biomaterials.2025.123843
Peirong Zhou , Xuemin Ma , Yajuan Hu , Yongcen Chen , Huiyue Wang , Tao Wang , Junliang Chen , Rui Cai , Yun He , Gang Tao
Periodontitis, a chronic inflammatory disease marked by oxidative stress, dysregulated inflammation, and alveolar bone resorption, remains a major oral health challenge due to conventional therapy's limited spatiotemporal control over tissue repair. To address this, we developed a sericin-based dual-module microsphere system (SeHA@EC): an inner pro-angiogenic/osteogenic module (ZnSr–Se-HA nanoparticles) and an outer anti-oxidant/anti-inflammatory module (EGCG-Ce Metal–phenolic networks, MPNs). The outer EGCG-Ce MPNs mitigate acute inflammation by scavenging ROS and modulating macrophage polarization toward M2, while the inner ZnSr–Se-HA module sequentially drives angiogenesis and osteogenesis during tissue repair. In vitro investigations demonstrated that SeHA@EC attenuated intracellular ROS levels, stabilized mitochondrial membrane potential, directed macrophage polarization toward the M2 phenotype via activating the SIRT1/FOXO3a/SOD-CAT axis and inhibiting NF-κB signaling, while additionally promoting angiogenesis and osteogenic differentiation of hPDLSCs. In vivo experiments further validated SeHA@EC's therapeutic efficacy in a rat periodontitis model: it significantly reduced intracellular ROS levels, suppressed pro-inflammatory cytokine expression (TNF-α, iNOS), upregulated anti-inflammatory marker expression (arginase, CD206), enhanced angiogenic and osteogenic activity, suppressed osteoclast activity, and accelerated alveolar bone regeneration. By overcoming the single-modal limitations of conventional biomaterials, this dual-module system establishes a microenvironment remodeling strategy for periodontal regeneration through spatiotemporal regulation of the pathological cascade.
{"title":"Sericin-based dual-module microspheres promote periodontal regeneration through four-dimensional microenvironment remodeling","authors":"Peirong Zhou , Xuemin Ma , Yajuan Hu , Yongcen Chen , Huiyue Wang , Tao Wang , Junliang Chen , Rui Cai , Yun He , Gang Tao","doi":"10.1016/j.biomaterials.2025.123843","DOIUrl":"10.1016/j.biomaterials.2025.123843","url":null,"abstract":"<div><div>Periodontitis, a chronic inflammatory disease marked by oxidative stress, dysregulated inflammation, and alveolar bone resorption, remains a major oral health challenge due to conventional therapy's limited spatiotemporal control over tissue repair. To address this, we developed a sericin-based dual-module microsphere system (SeHA@EC): an inner pro-angiogenic/osteogenic module (ZnSr–Se-HA nanoparticles) and an outer anti-oxidant/anti-inflammatory module (EGCG-Ce Metal–phenolic networks, MPNs). The outer EGCG-Ce MPNs mitigate acute inflammation by scavenging ROS and modulating macrophage polarization toward M2, while the inner ZnSr–Se-HA module sequentially drives angiogenesis and osteogenesis during tissue repair. <em>In vitro</em> investigations demonstrated that SeHA@EC attenuated intracellular ROS levels, stabilized mitochondrial membrane potential, directed macrophage polarization toward the M2 phenotype <em>via</em> activating the SIRT1/FOXO3a/SOD-CAT axis and inhibiting NF-κB signaling, while additionally promoting angiogenesis and osteogenic differentiation of hPDLSCs. <em>In vivo</em> experiments further validated SeHA@EC's therapeutic efficacy in a rat periodontitis model: it significantly reduced intracellular ROS levels, suppressed pro-inflammatory cytokine expression (TNF-α, iNOS), upregulated anti-inflammatory marker expression (arginase, CD206), enhanced angiogenic and osteogenic activity, suppressed osteoclast activity, and accelerated alveolar bone regeneration. By overcoming the single-modal limitations of conventional biomaterials, this dual-module system establishes a microenvironment remodeling strategy for periodontal regeneration through spatiotemporal regulation of the pathological cascade.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123843"},"PeriodicalIF":12.9,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145501328","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 : 2025-11-07DOI: 10.1016/j.biomaterials.2025.123844
Gomathi Sankar , Arka Roy Choudhury , Rashmita Luha , Akshay Kumar , Ketan Kulkarni , Mingxi Yao , Rudra Pratap , Aravind Kapali , Ajay Tijore
Recent studies show that stretch/ultrasound (US)-generated mechanical forces cause selective apoptosis in several cancer cells, tumor organoids and animal models without damaging normal cells. Cancer-associated fibroblasts (CAFs) are an integral tumor microenvironment (TME) constituent. They display altered biomechanical properties similar to cancer cells, such as matrix secretion and its remodelling, chemokine secretion, and high contractile force generation. We thus test the effect of US-mediated mechanical forces on patient-derived CAF survival. Surprisingly, US treatment causes CAF apoptosis (mechanoptosis) through a calcium-activated apoptotic pathway but not in normal fibroblasts. MicroRNA-21 (miR-21) secreted by primary cancer cells suppresses the mechanosensory cytoskeletal protein tropomyosin 2.1 (Tpm2.1) in CAFs. This Tpm2.1 depletion in CAFs is responsible for mechanoptosis. Interestingly, normal fibroblasts behave similarly when Tpm2.1 was depleted. Further, 3D gel contractility and migration assay confirm that a prolonged US treatment disrupts myosin IIA-mediated contractility, which CAFs primarily use to support cancer invasion. Since US treatment causes mechanoptosis and reduces contractility, this approach could be used to develop ultrasound-based CAF-targeting therapy to augment cancer treatment.
{"title":"Selective killing of cancer-associated fibroblasts by ultrasound-mediated mechanical forces","authors":"Gomathi Sankar , Arka Roy Choudhury , Rashmita Luha , Akshay Kumar , Ketan Kulkarni , Mingxi Yao , Rudra Pratap , Aravind Kapali , Ajay Tijore","doi":"10.1016/j.biomaterials.2025.123844","DOIUrl":"10.1016/j.biomaterials.2025.123844","url":null,"abstract":"<div><div>Recent studies show that stretch/ultrasound (US)-generated mechanical forces cause selective apoptosis in several cancer cells, tumor organoids and animal models without damaging normal cells. Cancer-associated fibroblasts (CAFs) are an integral tumor microenvironment (TME) constituent. They display altered biomechanical properties similar to cancer cells, such as matrix secretion and its remodelling, chemokine secretion, and high contractile force generation. We thus test the effect of US-mediated mechanical forces on patient-derived CAF survival. Surprisingly, US treatment causes CAF apoptosis (mechanoptosis) through a calcium-activated apoptotic pathway but not in normal fibroblasts. MicroRNA-21 (miR-21) secreted by primary cancer cells suppresses the mechanosensory cytoskeletal protein tropomyosin 2.1 (Tpm2.1) in CAFs. This Tpm2.1 depletion in CAFs is responsible for mechanoptosis. Interestingly, normal fibroblasts behave similarly when Tpm2.1 was depleted. Further, 3D gel contractility and migration assay confirm that a prolonged US treatment disrupts myosin IIA-mediated contractility, which CAFs primarily use to support cancer invasion. Since US treatment causes mechanoptosis and reduces contractility, this approach could be used to develop ultrasound-based CAF-targeting therapy to augment cancer treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123844"},"PeriodicalIF":12.9,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480504","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 : 2025-11-07DOI: 10.1016/j.biomaterials.2025.123841
Yangbo Xu , Congrui Zhao , Jingyao Gong, Yanqi Chen, Hui Wang, Han Zhu, Antian Xu, Fuming He
Metallic implants have been widely utilized in orthopedics surgery. Osseointegration is a local tradeoff between the inflammatory microenvironment and repair processes surrounding implants, driven by innate and adaptive immune cells. B cells contribute to bone metabolism during fracture healing and in several bone-destructive diseases, such as rheumatoid arthritis and periodontitis. However, the participation of B cells in implantable biomaterials-mediated osseointegration has not been extensively studied, even though they occupy a significant proportion at the injury site. Here, we characterized the heterogeneity of immune cells surrounding bone implants and identified the crucial role of infiltrating B cells based on the implantation model in murine tibias via single-cell RNA sequencing (scRNA-seq). Excessive B cell maturation was observed around implants with poor bone formation, compared with pro-osteogenic implants. Additionally, targeting mature B cells via anti-CD20 depletion antibody restored the damaged osseointegration. Differential expression genes analysis and the application of neutralizing antibodies demonstrated that up-regulated Tnfa and Il1b in B cell maturation attenuated the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs). In terms of potential mechanisms, we discovered that pro-osteogenic implants indirectly suppressed local B cell maturation through neutrophils-derived CD52-SiglecG axis, inhibiting downstream ERK1/2 and NF-κB signaling pathways. In summary, our study underscores the pivotal role of B cells in osseointegration and offers novel insights into a promising therapeutic avenue for developing bone biomaterials with immunomodulatory properties and promoting peri-implant bone regeneration.
{"title":"Pro-osteogenic implants inhibit local excessive B cell maturation via neutrophils-derived CD52 signaling to enhance osseointegration","authors":"Yangbo Xu , Congrui Zhao , Jingyao Gong, Yanqi Chen, Hui Wang, Han Zhu, Antian Xu, Fuming He","doi":"10.1016/j.biomaterials.2025.123841","DOIUrl":"10.1016/j.biomaterials.2025.123841","url":null,"abstract":"<div><div>Metallic implants have been widely utilized in orthopedics surgery. Osseointegration is a local tradeoff between the inflammatory microenvironment and repair processes surrounding implants, driven by innate and adaptive immune cells. B cells contribute to bone metabolism during fracture healing and in several bone-destructive diseases, such as rheumatoid arthritis and periodontitis. However, the participation of B cells in implantable biomaterials-mediated osseointegration has not been extensively studied, even though they occupy a significant proportion at the injury site. Here, we characterized the heterogeneity of immune cells surrounding bone implants and identified the crucial role of infiltrating B cells based on the implantation model in murine tibias via single-cell RNA sequencing (scRNA-seq). Excessive B cell maturation was observed around implants with poor bone formation, compared with pro-osteogenic implants. Additionally, targeting mature B cells via anti-CD20 depletion antibody restored the damaged osseointegration. Differential expression genes analysis and the application of neutralizing antibodies demonstrated that up-regulated <em>Tnfa</em> and <em>Il1b</em> in B cell maturation attenuated the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs). In terms of potential mechanisms, we discovered that pro-osteogenic implants indirectly suppressed local B cell maturation through neutrophils-derived CD52-SiglecG axis, inhibiting downstream ERK1/2 and NF-κB signaling pathways. In summary, our study underscores the pivotal role of B cells in osseointegration and offers novel insights into a promising therapeutic avenue for developing bone biomaterials with immunomodulatory properties and promoting peri-implant bone regeneration.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123841"},"PeriodicalIF":12.9,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511500","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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