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An injectable hydrogel loaded with miRNA nanocarriers promotes vessel-associated osteoclast (VAO)-mediated angiogenesis and bone regeneration in osteonecrosis of the rat femoral head 携带miRNA纳米载体的可注射水凝胶可促进大鼠股骨头骨坏死中血管相关破骨细胞(VAO)介导的血管生成和骨再生
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-10 DOI: 10.1016/j.biomaterials.2025.123252
Hongyu Quan , Chencan Ren , Hongkun Xie , Zibo He , Haibin Ding , Jinbao Li , Taiyang Li , Fuyou Wang , Shiwu Dong , Hong Jiang
{"title":"An injectable hydrogel loaded with miRNA nanocarriers promotes vessel-associated osteoclast (VAO)-mediated angiogenesis and bone regeneration in osteonecrosis of the rat femoral head","authors":"Hongyu Quan ,&nbsp;Chencan Ren ,&nbsp;Hongkun Xie ,&nbsp;Zibo He ,&nbsp;Haibin Ding ,&nbsp;Jinbao Li ,&nbsp;Taiyang Li ,&nbsp;Fuyou Wang ,&nbsp;Shiwu Dong ,&nbsp;Hong Jiang","doi":"10.1016/j.biomaterials.2025.123252","DOIUrl":"10.1016/j.biomaterials.2025.123252","url":null,"abstract":"<div><div>Osteonecrosis of the femoral head (ONFH) remains a significant clinical challenge. Despite various strategies aimed at promoting bone repair and halting disease progression, an effective cure remains elusive. Recent studies have identified a non-bone-resorbing osteoclast subtype, vessel-associated osteoclasts (VAOs), distinct from classical bone-associated osteoclasts (BAOs), offering new therapeutic opportunities for ONFH. Notably, we observed alterations in the populations and distributions of VAOs and BAOs in the femoral head of ONFH patients, suggesting that the imbalance between these two osteoclast subtypes contributes to ONFH pathology. Here, we developed an injectable alginate/hydroxyapatite hydrogel (AHH) loaded with graphene oxide-based miR-7b nanocarriers (GPC@miR) for ONFH treatment. The controlled release of GPC@miR from AHH/GPC@miR inhibited BAO formation by suppressing dendritic cell-specific transmembrane protein (DC-STAMP), thereby reducing bone resorption. Meanwhile, mono-/bi-nucleated VAOs were preserved and increased in number, promoting angiogenesis of type H vessels and osteogenesis via platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor-A (VEGF-A) secretion. Intraosseous administration of AHH/GPC@miR rebalanced VAOs and BAOs, restored the femoral head microenvironment, and enhanced vascularization and bone regeneration in ONFH rat models. This study introduces a novel biomaterial-based strategy for ONFH repair by regulating osteoclast subtypes, providing insights into VAO-mediated angiogenesis and osteogenesis for bone regeneration.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123252"},"PeriodicalIF":12.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610273","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}
引用次数: 0
Acid and phosphatase-triggered release and trapping of a prodrug on cancer cell enhance its chemotherapy 酸和磷酸酶触发的前药在癌细胞上的释放和捕获增强了它的化疗
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-10 DOI: 10.1016/j.biomaterials.2025.123254
Liangxi Zhu , Zixiu Shen , Xiaoyang Liu , Runqun Tang , Ziyi Zhang , Furong Zhao , Jue Wang , Wenjun Zhan , Lei Zhou , Gaolin Liang , Rui Wang
{"title":"Acid and phosphatase-triggered release and trapping of a prodrug on cancer cell enhance its chemotherapy","authors":"Liangxi Zhu ,&nbsp;Zixiu Shen ,&nbsp;Xiaoyang Liu ,&nbsp;Runqun Tang ,&nbsp;Ziyi Zhang ,&nbsp;Furong Zhao ,&nbsp;Jue Wang ,&nbsp;Wenjun Zhan ,&nbsp;Lei Zhou ,&nbsp;Gaolin Liang ,&nbsp;Rui Wang","doi":"10.1016/j.biomaterials.2025.123254","DOIUrl":"10.1016/j.biomaterials.2025.123254","url":null,"abstract":"<div><div>Using anticancer drug-encapsulated nanocarriers to actively target tumors is a promising chemotherapy strategy. Nevertheless, premature release of the drugs in tumor microenvironment (TME) or low tumor targeting efficiency of the nanocarriers significantly reduces its therapeutic efficiency. Herein, we propose a release-and-trapping strategy that significantly enhances the chemotherapeutic efficiency of an anticancer drug camptothecin. TME acid triggers the release of its prodrug from the nanocarrier and thereafter phosphatase instructs the prodrug to form hydrogel to trap the nanocarrier on cancer cell membrane. As trapped nanocarrier facilitates cell uptake of the prodrug and its intracellular carboxylesterase-mediated hydrolysis to release camptothecin. In vitro studies showed that the prodrug release from nanocarrier was maximized at pH 6.5. In tumor-bearing mice, our release-and-trapping strategy significantly prolonged the retention of the nanocarrier in tumor and significantly enhanced the anticancer efficacy of camptothecin. We propose that our release-and-trapping strategy be applied for more efficient cancer treatment in the future.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123254"},"PeriodicalIF":12.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620482","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}
引用次数: 0
SDF-1α/BMP-12 loaded biphasic sustained-release SIS hydrogel/SA microspheres composite for tendon regeneration 负载SDF-1α/BMP-12的双相缓释SIS水凝胶/SA微球复合材料用于肌腱再生
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-08 DOI: 10.1016/j.biomaterials.2025.123246
Bo-Quan Qin , Shi-Zhou Wu , Rong Nie , Qing-Yi Zhang , Jie Tan , Hui Zhang , Hui-Qi Xie
{"title":"SDF-1α/BMP-12 loaded biphasic sustained-release SIS hydrogel/SA microspheres composite for tendon regeneration","authors":"Bo-Quan Qin ,&nbsp;Shi-Zhou Wu ,&nbsp;Rong Nie ,&nbsp;Qing-Yi Zhang ,&nbsp;Jie Tan ,&nbsp;Hui Zhang ,&nbsp;Hui-Qi Xie","doi":"10.1016/j.biomaterials.2025.123246","DOIUrl":"10.1016/j.biomaterials.2025.123246","url":null,"abstract":"<div><div>Due to the inherent limited regenerative capacity of tendons, rendering countermeasures for tendon injury remains challenging. The pathophysiology of tendon healing is complex and contains three sequential phases including inflammation, proliferation and remodeling. Aiming at the treatment of different stages of tendon injury, in our work, an injectable small intestinal submucosa hydrogel/sodium alginate microspheres (SIS/SA) composite co-encapsulating stromal cell derived factor-1α (SDF-1α) and bone morphogenetic protein-12 (BMP-12) was developed for effective tendon regeneration. BMP-12 was initially embedded into SA microspheres by microfluid method, and then, microspheres were subsequently encapsulated into the SDF-1α loaded SIS hydrogel. The two bioactive molecules were released in a biphasic and controlled manner to facilitate cell recruitment in the early stage and tendon differentiation in the long-time stage, respectively. Meanwhile, with the degradation of hydrogel/microspheres composite, the regeneration process was accelerated through multiple pathways encompassing immune regulation, angiogenesis, and extracellular matrix (ECM) synthesis. The findings of this study present a compelling translational strategy with significant clinical potential for advancing tendon regeneration therapies.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123246"},"PeriodicalIF":12.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143591522","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}
引用次数: 0
Ultrasound-triggered lysosomal alkalinization to block autophagy in tumor therapy 超声触发溶酶体碱化阻断肿瘤自噬治疗
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-08 DOI: 10.1016/j.biomaterials.2025.123250
Yong Liu , Bowen Li , Run Yang , Chenxu Shang , Yang Bai , Bin Zheng , Liang Zhao
{"title":"Ultrasound-triggered lysosomal alkalinization to block autophagy in tumor therapy","authors":"Yong Liu ,&nbsp;Bowen Li ,&nbsp;Run Yang ,&nbsp;Chenxu Shang ,&nbsp;Yang Bai ,&nbsp;Bin Zheng ,&nbsp;Liang Zhao","doi":"10.1016/j.biomaterials.2025.123250","DOIUrl":"10.1016/j.biomaterials.2025.123250","url":null,"abstract":"<div><div>Lysosomes play a crucial role in regulating cancer progression and drug resistance. However, there is a pressing need for the development of drugs that can safely and effectively modulate the pH of cancerous lysosomes in a controlled manner. In this study, we propose a novel strategy for lysosomal alkalinization triggered by piezoelectricity. Our findings indicate that the electrons generated by (BaTiO<sub>3</sub>/Zr/Ca) BCZT under sonication effectively alkalinize the lysosomes. Molecular dynamics simulations further demonstrate that alterations in lysosomal pH lead to modifications in the conformation of V-ATPase (proton pump), enhancing its interaction with sodium ions while partially excluding hydrogen ions from entering the lysosomes. This mechanism helps maintain lysosomal alkalization, resulting in reduced hydrolase activity and preventing the degradation of proteins and damaged organelles. The accumulation of nanoparticles within the lysosomes causes swelling and gradual destruction of the lysosomal membrane. Consequently, this lysosomal dysfunction hampers the fusion with autophagosomes, inhibiting autophagy in tumor cells and promoting apoptosis in various tumor types. Our strategy significantly inhibited tumor volume growth in mice during animal studies. In conclusion, our piezoelectric-triggered lysosomal alkalinization strategy holds promise for innovative breakthroughs in the treatment of multiple cancers.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123250"},"PeriodicalIF":12.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600509","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}
引用次数: 0
Investigation of the protein corona and biodistribution profile of polymeric nanoparticles for intra-amniotic delivery 用于羊膜内分娩的聚合纳米颗粒蛋白冠和生物分布谱的研究
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-06 DOI: 10.1016/j.biomaterials.2025.123238
Anna Y. Lynn , Kwangsoo Shin , David A. Eaton , Micky Rose , Xianzhi Zhang , Madalina Ene , Julian Grundler , Emily Deschenes , Rachel Rivero , Laura G. Bracaglia , Peter M. Glazer , David H. Stitelman , W. Mark Saltzman
{"title":"Investigation of the protein corona and biodistribution profile of polymeric nanoparticles for intra-amniotic delivery","authors":"Anna Y. Lynn ,&nbsp;Kwangsoo Shin ,&nbsp;David A. Eaton ,&nbsp;Micky Rose ,&nbsp;Xianzhi Zhang ,&nbsp;Madalina Ene ,&nbsp;Julian Grundler ,&nbsp;Emily Deschenes ,&nbsp;Rachel Rivero ,&nbsp;Laura G. Bracaglia ,&nbsp;Peter M. Glazer ,&nbsp;David H. Stitelman ,&nbsp;W. Mark Saltzman","doi":"10.1016/j.biomaterials.2025.123238","DOIUrl":"10.1016/j.biomaterials.2025.123238","url":null,"abstract":"<div><div>When exposed to the biological environment, nanoparticles (NPs) form a protein corona that influences delivery profile. We present a study of protein corona formation and NP biodistribution in amniotic fluid (AF) for poly(lactic-co-glycolic acid) (PLGA) and poly(lactic-acid) (PLA) NPs, with and without polyethylene glycol (PEG), as well as poly(amine-co-ester)-PEG (PACE-PEG) NPs. The presence of surface PEG and polyvinyl alcohol (PVA) were characterized to investigate surfactant role in determining protein corona formation. The surface density of PEG groups demonstrated an inverse correlation with the total amount of protein surface adsorption. All PEGylated NPs exhibited a dense brush conformation and demonstrated higher levels of stability in AF than non-PEGylated NPs. The protein corona composition varied by core polymer, while the amount of protein adsorption varied by PEGylation status. In A549 cells, <em>in vitro</em> cellular association of each NP type correlated with the amount of albumin that was found in the protein corona. <em>In vivo</em>, only PEGylated NPs were able successfully distribute to fetal organs, likely due to the enhanced stability imparted by PEG. PLGA-PEG and PACE-PEG NPs had both high levels of albumin in the protein corona and high biodistribution to the fetal lung, consistent with the association with lung cells <em>in vitro</em>. PLA-PEG NPs distributed exclusively to the fetal bowel, which we propose is associated with known gastrointestinal targeting keratin proteins. By furthering our understanding of polymeric NP behavior in AF, this novel study provides a basis for optimization of intra-amniotic NP delivery systems targeting congenital pulmonary and gastrointestinal diseases.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123238"},"PeriodicalIF":12.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579547","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}
引用次数: 0
Ultrasound-activated piezoelectric heterojunction drives nanozyme catalysis to induce bacterial cuproptosis-like death and promote bone vascularization and osseointegration 超声激活压电异质结驱动纳米酶催化诱导细菌铜裂样死亡,促进骨血管形成和骨整合
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-05 DOI: 10.1016/j.biomaterials.2025.123249
Longhai Qiu , Sushuang Ma , Ren Yang , Dengwen Zheng , Yuliang Huang , Zhengwei Zhu , Sijun Peng , Mei Li , Hua Zhong , Feng Peng
{"title":"Ultrasound-activated piezoelectric heterojunction drives nanozyme catalysis to induce bacterial cuproptosis-like death and promote bone vascularization and osseointegration","authors":"Longhai Qiu ,&nbsp;Sushuang Ma ,&nbsp;Ren Yang ,&nbsp;Dengwen Zheng ,&nbsp;Yuliang Huang ,&nbsp;Zhengwei Zhu ,&nbsp;Sijun Peng ,&nbsp;Mei Li ,&nbsp;Hua Zhong ,&nbsp;Feng Peng","doi":"10.1016/j.biomaterials.2025.123249","DOIUrl":"10.1016/j.biomaterials.2025.123249","url":null,"abstract":"<div><div>Osteomyelitis is a severe and persistent bone infection that poses significant challenges to clinical treatment, often requiring prolonged antibiotic therapy and invasive procedures. Nanomaterial-based non-antibiotic therapies have emerged as promising alternatives in combating bacterial infections. However, effectively treating osteomyelitis while simultaneously promoting bone repair remains a challenge. Herein, we developed a nanoheterojunction catalytic reactor composed of copper ferrite (CuFe<sub>2</sub>O<sub>4</sub>) and molybdenum disulfide (MoS<sub>2</sub>) quantum dots (CFO@MoS<sub>2</sub>), leveraging ultrasound catalysis in combination with copper ions to induce bacterial cuproptosis-like death. Theoretical calculations indicate that the establishment of a heterojunction interface can accelerate oxygen adsorption, inducing electron flow toward oxygen atoms at the interface, thereby enhancing the separation of interface electron-hole pairs. Furthermore, copper ions released from CFO@MoS<sub>2</sub> undergo valence state changes under ultrasound, activating the Fenton reaction and releasing reactive oxygen species to kill bacteria. Gene sequencing shows that CFO@MoS<sub>2</sub>, when activated by ultrasound, disrupts bacterial energy synthesis, interferes with bacterial metabolism, and induces copper-related bacterial death. More importantly, the microcurrents generated by ultrasound synergistic with the released copper and iron ions stimulate the expression of angiogenic and osteogenic genes, promoting bone regeneration. The ultrasound-triggered catalytic reaction by CFO@MoS<sub>2</sub> disrupts bacterial homeostasis, accelerates bacterial death, and offers a novel therapeutic strategy for osteomyelitis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123249"},"PeriodicalIF":12.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579544","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}
引用次数: 0
Reprogrammed glycolysis-induced augmentation of NIR-II excited photodynamic/photothermal therapy 重编程糖酵解诱导的NIR-II增强激发光动力/光热疗法
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-04 DOI: 10.1016/j.biomaterials.2025.123235
Chunbai Xiang , Qihang Ding , Ting Jiang , Yu Liu , Chao Li , Xing Yang , Jia Jia , Jingjing Xiang , Yue Wang , Hui Zhou , Zhiyun Lu , Ping Gong , Jong Seung Kim
{"title":"Reprogrammed glycolysis-induced augmentation of NIR-II excited photodynamic/photothermal therapy","authors":"Chunbai Xiang ,&nbsp;Qihang Ding ,&nbsp;Ting Jiang ,&nbsp;Yu Liu ,&nbsp;Chao Li ,&nbsp;Xing Yang ,&nbsp;Jia Jia ,&nbsp;Jingjing Xiang ,&nbsp;Yue Wang ,&nbsp;Hui Zhou ,&nbsp;Zhiyun Lu ,&nbsp;Ping Gong ,&nbsp;Jong Seung Kim","doi":"10.1016/j.biomaterials.2025.123235","DOIUrl":"10.1016/j.biomaterials.2025.123235","url":null,"abstract":"<div><div>Small molecule-based multifunctional optical diagnostic materials have garnered considerable interest due to their highly customizable structures, tunable excited-state properties, and remarkable biocompatibility. We herein report the synthesis of a multifaceted photosensitizer, PPQ-CTPA, which exhibits exceptional efficacy in generating Type I reactive oxygen species (ROS) and thermal energy under near-infrared-II (NIR-II, &gt;1000 nm) laser excitation at 1064 nm, thereby combining photodynamic therapy (PDT) and photothermal therapy (PTT) functionalities. To enhance therapeutic efficacy, we engineered lonidamine (LND) by conjugating it with triphenylphosphonium (TPP) cations, producing LND-TPP. This compound inhibits mitochondrial glycolysis and downregulates heat shock protein 90 (HSP 90) levels in a breast cancer mouse model, potentiating both PDT and PTT. For <em>in vivo</em> applications, PPQ-CTPA and LND-TPP are encapsulated within the amphiphilic polymer DSPE–SS–PEG to obtain <strong>PPQ-CTPAL NPs</strong>. In breast cancer cell lines, <strong>PPQ-CTPAL NPs</strong> are decomposed by cellular GSH, simultaneously releasing the dual-functioning photosensitizer PPQ-CTPL and the mitochondria-disrupting agent LND-TPP. Upon 1064 nm laser irradiation, we found that tumor growth in breast cancer mice is effectively restrained by <strong>PPQ-CTPAL NPs</strong>. This work highlights the synergistic integration of PDT, PTT, and chemotherapy facilitated by NIR-II fluorescence, photoacoustic, and photothermal imaging under 1064 nm irradiation, underscoring the clinical potential of multifunctional phototherapeutic agents.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123235"},"PeriodicalIF":12.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579548","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}
引用次数: 0
Enhanced stem cell-mediated therapeutic immune modulation with zinc oxide nanoparticles in liver regenerative therapy 氧化锌纳米颗粒在肝脏再生治疗中增强干细胞介导的治疗性免疫调节
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-04 DOI: 10.1016/j.biomaterials.2025.123232
Naeun Park , Kyoung Sub Kim , Sanghee Lee , Jang Ho Choi , Kun Na
{"title":"Enhanced stem cell-mediated therapeutic immune modulation with zinc oxide nanoparticles in liver regenerative therapy","authors":"Naeun Park ,&nbsp;Kyoung Sub Kim ,&nbsp;Sanghee Lee ,&nbsp;Jang Ho Choi ,&nbsp;Kun Na","doi":"10.1016/j.biomaterials.2025.123232","DOIUrl":"10.1016/j.biomaterials.2025.123232","url":null,"abstract":"<div><div>Liver regenerative therapy is critical for severe liver damage, including acute liver failure, fibrosis, post-cancer resection recovery, and autoimmune liver diseases, where restoration of liver tissues is essential. Stem cell-based therapies hold significant promise in liver regeneration by modulating immune responses to create a favorable healing microenvironment. However, their clinical efficacy has been limited by challenges such as poor cell engraftment and survival within the hostile injury site. To address these limitations, we developed a zinc oxide-derived nanoparticle (PZnONP) that enhances stem cell proliferation and activation by releasing bioactive Zn<sup>2+</sup> and reactive oxygen species (ROS). Functionalized PZnONP exhibits pH-responsive behavior and improved dispersibility, enabling a lysosome-specific and sustained release of Zn<sup>2+</sup> and ROS. Stem cells labeled with PZnONP (ZnBA) demonstrated anti-inflammatory properties, with paracrine effects influencing macrophages and damaged hepatocytes. In murine models of acute and fibrotic liver injury, it effectively migrated to the liver through stem cell homing effects and promoted anti-inflammatory responses by modulating Treg and Th17 cell polarization, as well as M2 and M1 macrophage balance, while reducing collagen synthesis. This study underscores the potential of integrating stem cell-based therapy with nanomedicine to improve regenerative outcomes in liver disease treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123232"},"PeriodicalIF":12.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579546","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}
引用次数: 0
Hydrogen generators-protected mesenchymal stem cells reverse articular redox imbalance-induced immune dysfunction for osteoarthritis treatment 氢发生器保护的间充质干细胞逆转关节氧化还原失衡引起的骨关节炎治疗免疫功能障碍
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-04 DOI: 10.1016/j.biomaterials.2025.123239
Zhou Xu , Ruilong Song , Zhiling Chen , Yu Sun , Yinhe Xia , Haixiang Miao , Weijie Wang , Yuankai Zhang , Xinyi Jiang , Gang Chen
{"title":"Hydrogen generators-protected mesenchymal stem cells reverse articular redox imbalance-induced immune dysfunction for osteoarthritis treatment","authors":"Zhou Xu ,&nbsp;Ruilong Song ,&nbsp;Zhiling Chen ,&nbsp;Yu Sun ,&nbsp;Yinhe Xia ,&nbsp;Haixiang Miao ,&nbsp;Weijie Wang ,&nbsp;Yuankai Zhang ,&nbsp;Xinyi Jiang ,&nbsp;Gang Chen","doi":"10.1016/j.biomaterials.2025.123239","DOIUrl":"10.1016/j.biomaterials.2025.123239","url":null,"abstract":"<div><div>Stem cell therapy has revolutionized the management of osteoarthritis (OA), but the articular dysregulated redox status diminishes cell engraftment efficiency and disrupts immune homeostasis, therefore compromising the overall therapeutic efficacy. Here, we present hydrogen (H<sub>2</sub>) generators-backpacked mesenchymal stem cells (MSCs) which preserve the biological functions and survival of transplanted cells and reverse articular immune dysfunction, mitigating OA. Specifically, post systemic transplantation, H<sub>2</sub> generators-laden MSCs home to OA joints, and upon stimulation in acidic OA environment, H<sub>2</sub> produced from the generators remodels articular redox balance, thereby relieving the loss of mitochondrial membrane potential, decreasing cell apoptosis rate, and maintaining pluripotent and paracrine functions of MSCs. Furthermore, the reactive oxygen species scavenging by H<sub>2</sub> in combination with paracrine effects of the MSCs promote macrophage polarization towards the anti-inflammatory M2 phenotype, which contributes to reversing synovial immune disorder. In severe OA model, the backpacked MSCs reduce osteoarthritic degeneration, osteophyte formation and joint inflammation, and promote cartilage regeneration. In sum, our work demonstrates that arming with H<sub>2</sub> generators effectively boosts the therapeutic efficacy of MSCs, which hold great potential for alleviating redox imbalance-related tissue lesions, including but not limited to OA.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123239"},"PeriodicalIF":12.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562901","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}
引用次数: 0
MXene-loaded multifunctional nanoparticles with on-demand controlled antimicrobial and antioxidant capacity for multi-modal treating bacterial prostatitis 负载mxene的多功能纳米颗粒具有按需控制的抗菌和抗氧化能力,用于多模式治疗细菌性前列腺炎
IF 12.8 1区 医学
Biomaterials Pub Date : 2025-03-04 DOI: 10.1016/j.biomaterials.2025.123234
Kailai Liu , Yanyao Gao , Yuchen Zhang , Yunhe Zheng , Jiangchuan He , Yu Huang , Xi Chen , Ruixiao Li , Qiang Fu , Bin Song , He Wang , Lei Wang , Geng Zhang , Ke Wang
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