Xiaohua Wang, Tingting Gao, Jingjing Wu, Xu Zhou, Yuanyuan Chu, Lei Zhang, Xi Cao
{"title":"A dual-targeted nano-system co-regulating macrophage ROS and fibroblast ferroptosis for rheumatoid arthritis treatment.","authors":"Xiaohua Wang, Tingting Gao, Jingjing Wu, Xu Zhou, Yuanyuan Chu, Lei Zhang, Xi Cao","doi":"10.1039/d5bm00618j","DOIUrl":"https://doi.org/10.1039/d5bm00618j","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a marked macrophage polarization imbalance and abnormal synovial fibroblast proliferation. Herein, we developed a multifunctional drug delivery platform utilizing a glycosaminoglycan heparin derivative. This derivative combines heparin (Hep), which targets macrophages and synovial fibroblasts, with phenylboronic acid (PBA), which exhibits ROS-responsive properties, to regulate macrophage polarization and inhibit synovial fibroblast proliferation. Celastrol (CLT) was encapsulated in multifunctional lipid vesicles (Hep-Lips/CLT) to ameliorate the inflammatory microenvironment. This platform specifically targeted macrophages and synovial fibroblasts, achieving a dual therapeutic effect. Hep-Lips/CLT could serve as an inflammation-targeted therapy, thereby regulating macrophage repolarization, inducing ferroptosis in synovial fibroblasts to inhibit proliferation, and achieving ROS-responsive release. Overall, Hep-Lips/CLT delivery supported by glycosaminoglycan derivatives could be used as a new therapy for RA. Notably, this study presents the first synthetic glycosaminoglycan derivative for preparing multifunctional lipid vesicles to simultaneously target macrophages and synovial fibroblasts, offering an effective RA therapeutic strategy.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A pH-responsive nanoplatform enhancing tumor therapy <i>via</i> calcium overload-induced oxidative stress to potentiate phototherapy and chemotherapy.","authors":"Shanshan Fan, Shengsheng Cui, Xinni Pan, Haisong Tan, Cheng Cao, Yueqi Zhu, Yanlei Liu","doi":"10.1039/d5bm00599j","DOIUrl":"https://doi.org/10.1039/d5bm00599j","url":null,"abstract":"<p><p>The specific tumor microenvironment (TME) and the ability of tumor cells to evade drug therapy pose challenges to the efficacy of single monotherapies. Herein, a multifunctional calcium carbonate-based nanoprobe (Fe<sub>3</sub>O<sub>4</sub>/CaCO<sub>3</sub>-CSL/ICG) was synthesized using a simple one-step method. This nanoprobe is designed to respond specifically to the acidic TME, where the calcium carbonate shell dissolves, releasing therapeutic agents. It combines three therapeutic modalities: phototherapy, chemotherapy, and ion interference therapy. In cell experiments, it was confirmed that after entering tumor cells, the acidic intracellular environment triggered the release of calcium ions from the nanoprobe, leading to mitochondrial calcium ion overload. The loaded indocyanine green (ICG) produced photothermal and photodynamic effects under near-infrared laser irradiation. The reactive oxygen species (ROS) generated by photodynamic therapy further amplify oxidative stress caused by mitochondrial calcium overload. Additionally, celastrol (CSL) enhanced calcium ion-induced mitochondrial calcium death. Differential gene expression analysis further supported the combined therapeutic effect of Fe<sub>3</sub>O<sub>4</sub>/CaCO<sub>3</sub>-CSL/ICG, indicating the regulation of genes related to calcium regulation, oxidative stress and apoptosis. In summary, we developed a responsive nanoplatform with pH-triggered degradation and controlled drug release, which enhances tumor suppression by inducing mitochondrial apoptosis through calcium overload and ROS accumulation, in combination with chemotherapy and phototherapy. This work presents a promising nanotherapeutic strategy for tumor treatment.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ugi-reaction-derived ionizable lipids with cyclic tertiary amine heads enable spleen-targeted mRNA delivery.","authors":"Yashuai Wang, Xiaoyin Liu, Haiyin Yang, Shuxiang Wang, Shutao Guo, Yuhua Weng, Jinchao Zhang, Luwei Li, Kun Ge, Xing-Jie Liang","doi":"10.1039/d5bm00738k","DOIUrl":"https://doi.org/10.1039/d5bm00738k","url":null,"abstract":"<p><p>Lipid nanoparticles (LNPs) have become an important platform for nucleic acid delivery. However, LNP-mediated delivery to non-hepatic organs and specific cell types remains a non-negligible challenge. As a key component of LNPs, ionizable lipids were rationally designed to adjust the LNPs properties to achieve organ-targeted delivery. The use of the Ugi four-component reaction (Ugi-4CR) as a one-pot multicomponent synthesis strategy to construct ionizable lipid molecules offers advantages, as it enables multidimensional structural diversity of ionizable lipids. We use isocyanides with cyclic tertiary amine substituents to construct ionizable lipids <i>via</i> an Ugi one-pot reaction. Twenty-five ionizable lipid molecules (W1-W25) containing different cyclic tertiary amine hydrophilic heads, linkers, and hydrophobic tails were synthesized. The W19 LNPs exhibited highly selective mRNA delivery to the spleen upon intravenous administration.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heng Yin, Zhuo Zhang, Yi Wang, Weiyong Song, Chaoyu Pu, Yong Wang, Ke Jiang
{"title":"Nano-enzymatic functionalized dual network hydrogel promotes tendon repair by modulating the inflammatory cycle and cellular behavior.","authors":"Heng Yin, Zhuo Zhang, Yi Wang, Weiyong Song, Chaoyu Pu, Yong Wang, Ke Jiang","doi":"10.1039/d5bm00441a","DOIUrl":"https://doi.org/10.1039/d5bm00441a","url":null,"abstract":"<p><p>Tendon injuries are prone to adhesions after repair, which in turn lead to limb dysfunction, which remains a major challenge in clinical treatment. Current research suggests that tendon injuries are affected by the accumulation of reactive oxygen species (ROS), inflammatory responses, and type III collagen deposition. These factors lead to an imbalance between extrinsic and intrinsic tendon healing and are the main reasons for the occurrence of peritendinous adhesions. In this study, we constructed a carrier using a polyvinyl alcohol/polyethylene glycol (PVA/PEG) dual network hydrogel and loaded it with zeolite imidazolium ester framework-8@CeO<sub>2</sub> nano-enzymes (ZIF-8@CeO<sub>2</sub>) to form a nano-enzyme-functionalized hydrogel (PVA/PEG/ZIF-8@CeO<sub>2</sub>) therapeutic system. The surface of PVA/PEG/ZIF-8@CeO<sub>2</sub> is rich in hydrophilic hydroxyl groups that form hydrogen bonds with water molecules, creating a hydrated layer that inhibits fibrin adsorption and fibroblast adhesion, reduces the impact of exogenous healing, and reduces the formation of adhesions. Similarly, the loaded ZIF-8@CeO<sub>2</sub> has catalase (CAT) and superoxide dismutase (SOD) activities, which can effectively remove the excessive ROS in the injured tendon, down-regulate the inflammatory response, enhance the tendon differentiation of tendon stem cells, promote intrinsic healing, and ultimately promote the repair of injured tendons. Furthermore, the system can accelerate the transition from inflammation to repair and remodeling in the tendon healing process. The PVA/PEG/ZIF-8@CeO<sub>2</sub> treatment system is a novel approach for reducing peritendinous adhesions and effectively promoting the repair of injured tendons.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Scaffold stiffness affects oligodendrocyte proliferation <i>via</i> cell traction forces.","authors":"Haruki Watanabe, Akiko Uyeda, Lili Quan, Shogo Iwai, Ze Zhang, Shinjiro Umezu, Tatsunori Suzuki, Rieko Muramatsu","doi":"10.1039/d5bm00689a","DOIUrl":"https://doi.org/10.1039/d5bm00689a","url":null,"abstract":"<p><p>Drugs that promote the regeneration of the central nervous system (CNS) have motivated the development of a method to assess the functions of CNS cells, such as oligodendrocytes, which sustain the homeostasis of neuronal networks. In this study, we evaluated the effects of scaffold stiffness on the phenotypic and transcriptomic levels of MO3.13 cells, a human oligodendrocyte lineage cell line. Cells cultured on gels of varying stiffness exhibited different growth potentials. RNA sequencing detected differences in the expression of genes associated with cell proliferation and actin cytoskeleton polymerization. Treatment with actin polymerization inhibitor prevented changes in the growth potential, which were mediated by cell traction forces. These results suggest that scaffold stiffness-transduced biological signaling is an important factor to consider when assessing CNS cell function.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiyu Jessica Tian, Hamid Ebrahimi Orimi, Natalie Fekete, Nicolas Drolet, Katie Campbell, Michel L Tremblay, Linda Peltier, Pierre Laneuville, Pierre-Luc Girard-Lauriault, Corinne A Hoesli
{"title":"Impact of culture vessel materials on biomanufacturing of dendritic cell-based immunotherapies in closed systems.","authors":"Jiyu Jessica Tian, Hamid Ebrahimi Orimi, Natalie Fekete, Nicolas Drolet, Katie Campbell, Michel L Tremblay, Linda Peltier, Pierre Laneuville, Pierre-Luc Girard-Lauriault, Corinne A Hoesli","doi":"10.1039/d5bm00245a","DOIUrl":"https://doi.org/10.1039/d5bm00245a","url":null,"abstract":"<p><p>Dendritic cell-based immunotherapy is a promising strategy to treat malignant diseases. <i>In vitro</i> manufacturing of dendritic cells conventionally relies on culturing primary monocytes in dishes or vessels made from tissue culture treated polystyrene. For clinical applications, the implementation of closed culture vessels such as cell culture bags is highly desirable to minimize the risks of contamination and allow automated fluid handling. However, this transition typically represents a significant change in substrate surface properties which can impact cell-surface interactions. This review provides an overview of closed culture systems for dendritic cell therapy product biomanufacturing and describes how material selection can impact cell-surface interactions and thereby the resulting cell fate decisions. Gaining a fundamental understanding of cell culture vessel material surface properties, how proteins adsorb to these materials, and how monocyte-derived dendritic cells may adhere or interact with these surfaces can help guide closed cell culture vessel selection.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent progress in multifunctional theranostic hydrogels: the cornerstone of next-generation wound care technologies.","authors":"Laxmanan Karthikeyan, Hyun Wook Kang","doi":"10.1039/d5bm00781j","DOIUrl":"https://doi.org/10.1039/d5bm00781j","url":null,"abstract":"<p><p>Theranostic hydrogels represent a groundbreaking approach by integrating therapeutic and diagnostic capabilities within a single platform, enabling real-time monitoring of wounds and precise treatment applications. These advanced materials are engineered to maintain a moist, antimicrobial environment while promoting tissue regeneration through enhanced conductivity and bioactivity. Theranostic hydrogels, which incorporate electro-responsive and stimuli-sensitive polymers, enable the continuous monitoring of important biomarkers like pH and glucose levels, ensuring accurate, timely therapeutic interventions. Bioelectronic components, including flexible biosensors, wearable electronic patches, and implantable microdevices, significantly enhance the functionality of wound care technology. Recent advancements in materials science have further improved the adaptability of these hydrogels, allowing for the integration of nanomaterials to accelerate healing and optimize therapeutic outcomes. Additionally, these hydrogels can be combined with cutting-edge technologies such as 3D bioprinting and artificial intelligence, paving the way for personalized wound care solutions tailored to individual patient needs. This review highlights recent progress in theranostic hydrogels and their transformative potential in managing complex wounds. By integrating both diagnostics and therapeutic capabilities into a multifunctional platform, theranostic hydrogels represent a promising frontier for next-generation wound care technologies.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Macrophage-targeted emodin nanomaterials for effective acute pancreatitis treatment <i>via</i> modulation of the JNK pathway.","authors":"Liying Wang, Mengxiang Tian, Bingzhi Dong, Weiqi Li, Liang Shi, Yifan Tong, Wei Chen, Xin Yu, Hongxia Xu, Bo Shen, Hong Yu","doi":"10.1039/d5bm00018a","DOIUrl":"https://doi.org/10.1039/d5bm00018a","url":null,"abstract":"<p><p>Acute pancreatitis (AP) is a common abdominal inflammatory disease, characterized by pancreatic autodigestion, acinar cell necrosis, and systemic inflammation. Currently, there is a lack of specific drugs in the treatment of AP. Traditional Chinese medicine (TCM) is an effective approach in the prevention and treatment of AP, with rheum being one of the key components in commonly used TCM formulas for treating AP. We screened emodin as the core active ingredient of rheum and developed a heparin-modified emodin carrier, EMO@ZIF-8/Heparin (HEZ), which specifically delivers emodin to the inflamed pancreatic tissue <i>via</i> CD44-targeted macrophage activation. The HEZ exhibited higher macrophage uptake efficiency in the inflammatory microenvironment, restored the mitochondrial membrane potential, alleviated oxidative stress, and effectively reduced the levels of cytokines in the AP cell model. Moreover, the formulation exhibited targeted enrichment and retention in the pancreas under AP conditions, blocking the systemic inflammatory amplification cascade, reducing approximately 50% of pathological damage in both pancreatic and lung tissues, decreasing the proportion of apoptotic pancreatic cells, and increasing the 15-day survival rate of AP mice from 15% to around 50%. Mechanistically, the formulation restored impaired macrophage mitochondrial function to a healthy state by inhibiting the JNK pathway. In summary, the multifunctional HEZ provides an upstream therapeutic strategy by targeting macrophages in AP, offering a novel and effective approach to potentially enhance AP treatment in the future.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ann-Cathrin Schmitt, Maximilian Braun, Stefanie Wedepohl, Mathias Dimde, Philip Nickl, Kai Ludwig, Tatyana L Povolotsky, Rainer Haag
{"title":"Multivalent 2D- and 3D-nanogels as carbohydrate-lectin binders.","authors":"Ann-Cathrin Schmitt, Maximilian Braun, Stefanie Wedepohl, Mathias Dimde, Philip Nickl, Kai Ludwig, Tatyana L Povolotsky, Rainer Haag","doi":"10.1039/d5bm00286a","DOIUrl":"10.1039/d5bm00286a","url":null,"abstract":"<p><p>The development of synthetic glycoarchitectures for targeted bacterial adhesion represents a promising strategy in anti-adhesion therapy. This study presents the synthesis and characterization of two distinct mannosylated nanogel architectures. First, a spherical 3D-nanogel was prepared <i>via</i> nanoprecipitation and functionalized with α-D-mannose units. This system demonstrated enhanced precipitation kinetics in turbidity measurements with Concanavalin A and exhibited single-site binding behavior comparable to monovalent reference compounds when tested with intact <i>E. coli</i> strain ORN 178 (FimH<sup>+</sup>) <i>via</i> microscale thermophoresis. Cryo-TEM imaging revealed clear co-localization with bacterial pili, confirming specific bacterial interactions. The complementary sheet-like 2D-nanogel, synthesized using a removable graphene template and functionalized with α-D-mannose units, showed distinct dual binding characteristics with significantly different affinities in FimH binding studies. Notably, the high-affinity site of the 2D-nanogel maintained superior binding compared to the 3D architecture. Both architectures were extensively characterized using multiple analytical techniques, confirming their defined structures, sizes, and surface modifications. These findings provide fundamental insights into the influence of spatial ligand presentation on multivalent binding interactions, contributing to the rational design of glycoarchitectures for bacterial targeting.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hee Gyeong Ko, Yun-A Kim, Jun Kwon, So Won Jeon, Jong Sang Yoon, Min-Ho Kang, Ju-Ro Lee, Han Young Kim
{"title":"Metabolic click-labeling of interleukin-10 enhances the immunomodulatory potential and wound healing properties of mesenchymal stem cell-derived extracellular nanovesicles.","authors":"Hee Gyeong Ko, Yun-A Kim, Jun Kwon, So Won Jeon, Jong Sang Yoon, Min-Ho Kang, Ju-Ro Lee, Han Young Kim","doi":"10.1039/d4bm01601g","DOIUrl":"https://doi.org/10.1039/d4bm01601g","url":null,"abstract":"<p><p>Mesenchymal stem cell-derived extracellular nanovesicles (MSC-NVs) exhibit unique biological properties and tissue-regenerative effects comparable to their parent MSCs. However, despite the robust angiogenic and anti-apoptotic effects of MSC-NVs, their immunomodulatory effect is limited due to insufficient translation of anti-inflammatory cytokines from parent MSCs to isolated NVs. Hence, in this study we suggest the incorporation of interleukin (IL)-10, a key anti-inflammatory mediator in the body's immune system, on the surface of MSC-NVs <i>via</i> bio-orthogonal click chemistry. Metabolically engineered MSCs were serially extruded to generate azido-displaying MSC-NV-N<sub>3</sub>, followed by click chemistry-based conjugation of IL-10. Synthesized MSC-NV/IL-10 exhibited superior abilities for cell proliferation and migration of fibroblast and endothelial cells. MSC-NV/IL-10 markedly attenuated the activity of the pro-inflammatory M1 macrophage and promoted the expression of the anti-inflammatory M2 marker. We also demonstrated that MSC-NV/IL-10 induces the phenotypic transition of dendritic cells (DCs) from mature DCs to immune-tolerogenic DCs. Moreover, RNA sequencing revealed that metabolic engineering does not alter the regenerative potential or immunomodulatory functions of MSCs. In animal studies, MSC-NV/IL-10 treated mice exhibited significantly accelerated wound healing, accompanied by resolution of inflammatory responses in injured skin.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}