Biomaterials最新文献_第10页

Alkalinity and LSPR effect-based cuproptosis sensitizer to reverse tumor microenvironment for melanoma therapy 碱度和LSPR效应为基础的铜增生增敏剂逆转肿瘤微环境用于黑色素瘤治疗

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-13 DOI: 10.1016/j.biomaterials.2025.123913

Lidan Liu , Mei Li , Panpan Huo , Shun Xing , Feng Peng , Haifeng Zhang , Haobo Pan , Yuehua Li , Xuanyong Liu

{"title":"Alkalinity and LSPR effect-based cuproptosis sensitizer to reverse tumor microenvironment for melanoma therapy","authors":"Lidan Liu , Mei Li , Panpan Huo , Shun Xing , Feng Peng , Haifeng Zhang , Haobo Pan , Yuehua Li , Xuanyong Liu","doi":"10.1016/j.biomaterials.2025.123913","DOIUrl":"10.1016/j.biomaterials.2025.123913","url":null,"abstract":"<div><div>Cuproptosis is a promising therapeutic strategy for tumor, but its therapeutic efficacy is limited by the weak acidity and high concentration of glutathione (GSH) in the tumor microenvironment (TME). In this study, a novel alkalinity and localized surface plasmon resonance (LSPR) effect-based nanoreactor (MgO/Cu@C) is constructed to sensitise cuproptosis. Firstly, the alkalinity produced by MgO could reverse the acidic tumor microenvironment. Additionally, near-infrared (NIR) induced photothermal property and LSPR effect synergistic alkalinity can enhance GSH depletion of MgO/Cu@C. Thus, MgO/Cu@C+NIR sensitizes melanoma cells to cuproptosis by reversing TME. Furthermore, RNA sequencing transcriptome analysis confirms that MgO/Cu@C+NIR induces cuproptosis through copper overload-triggered lipoylated protein aggregation, inhibition of tumor metabolic pathways by alkalinity, NIR-drived HSP hyperactivation that depletes ATP reserves, and phosphatidylinositol signaling-mediated hijacking of survival pathways, which synergistically enforces irreversible metabolic collapse for melanoma cells. Meanwhile, MgO/Cu@C+NIR could inhibit bacterial infection and promote wound healing, thus addressing dual clinical applications for melanoma treatment and wound healing. Particularly, this study firstly reveals the mechanisms by which alkalinity and LSPR effect potentiate GSH depletion, as well as that alkalinity could sensitise cuproptosis by reversing the acidic microenvironment of tumor. The study provides a promising perspective for potential melanoma treatment based on cuproptosis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123913"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838272","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

Peptide-conjugated biodegradable polyester scaffolds for bone regeneration 用于骨再生的肽共轭可生物降解聚酯支架。

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-18 DOI: 10.1016/j.biomaterials.2025.123919

Tongqing Zhou , Peter X. Ma

{"title":"Peptide-conjugated biodegradable polyester scaffolds for bone regeneration","authors":"Tongqing Zhou , Peter X. Ma","doi":"10.1016/j.biomaterials.2025.123919","DOIUrl":"10.1016/j.biomaterials.2025.123919","url":null,"abstract":"<div><div>Bone grafting remains one of the most common surgical procedures worldwide, with alloplastic grafts offering scalable and versatile alternatives to autografts. Biodegradable polyester-based scaffolds have emerged as a promising solution due to their tunable mechanical properties, biocompatibility, biodegradability, and recent advances in fabrication technologies. However, their lack of intrinsic bioactivity has driven increasing interest in bioactive functionalization. As a candidate for such functionalization, peptides offer several advantages, including ease of synthesis, specificity in biological interactions, and adaptability to chemical modification. This review provides a comprehensive overview of biodegradable polyester–peptide scaffold systems for bone tissue engineering. In particular, the review outlines essential design requirements for bone scaffolds, introduces widely used polyesters, and summarizes established techniques for scaffold fabrication and peptide conjugation. A range of examples demonstrating in vitro and in vivo efficacy is presented to depict the current progress in peptide-functionalized polyester scaffold systems. By summarizing current advances and outlining key challenges, this review inspires the rational design of next-generation scaffolds for bone regeneration.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123919"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825496","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

Metabolic microenvironment-forming porous hydrogels for the protection of phenylalanine ammonia-lyase in the intestine 代谢微环境形成多孔水凝胶保护肠内苯丙氨酸解氨酶。

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-22 DOI: 10.1016/j.biomaterials.2025.123942

Sofie Dhondt , Philippe Delbreil , Shihao Pei , Catherine Nadeau , Inès Kadi , Isabelle Masseau , Fatma Moawad , Xavier Banquy , Davide Brambilla

{"title":"Metabolic microenvironment-forming porous hydrogels for the protection of phenylalanine ammonia-lyase in the intestine","authors":"Sofie Dhondt , Philippe Delbreil , Shihao Pei , Catherine Nadeau , Inès Kadi , Isabelle Masseau , Fatma Moawad , Xavier Banquy , Davide Brambilla","doi":"10.1016/j.biomaterials.2025.123942","DOIUrl":"10.1016/j.biomaterials.2025.123942","url":null,"abstract":"<div><div>Biological therapeutics drive biomedical innovation, yet their oral delivery is hindered by gastrointestinal instability. Phenylalanine ammonia-lyase (PAL), a promising enzyme for phenylketonuria management, exemplifies this challenge. Here, we present ultraporous template-based hydrogels (TGels) that protect and deliver PAL in the small intestine. PAL-TGels are obtained via UV crosslinking of poly(ethylene glycol) diacrylamide in the presence of sacrificial CaCO<sub>3</sub> templates, followed by absorption-based loading of PAL and a protease inhibitor. The interconnected porous matrix retains PAL while allowing phenylalanine and <em>trans</em>-cinnamic acid diffusion for continuous catalysis. In vitro studies confirmed robust protein retention and preserved enzymatic activity in simulated intestinal fluid, without impairing global trypsin function, while large animal tests validated matrix properties and transit. This fabrication-efficient platform enables localized intestinal enzyme protection, offering a promising route toward safe and accessible oral PAL therapy for phenylketonuria.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123942"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831704","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

Engineering bioactive fibrous constructs: Bioprinting stem cell-laden collagen-derived hydrogels with short collagen microfibers 工程生物活性纤维结构：具有短胶原微纤维的生物打印满载干细胞的胶原衍生水凝胶。

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-29 DOI: 10.1016/j.biomaterials.2025.123965

Hongjuan Weng , Monize C. Decarli , Wen Chen , Katrien V. Bernaerts , Lorenzo Moroni

{"title":"Engineering bioactive fibrous constructs: Bioprinting stem cell-laden collagen-derived hydrogels with short collagen microfibers","authors":"Hongjuan Weng , Monize C. Decarli , Wen Chen , Katrien V. Bernaerts , Lorenzo Moroni","doi":"10.1016/j.biomaterials.2025.123965","DOIUrl":"10.1016/j.biomaterials.2025.123965","url":null,"abstract":"<div><div>Natural hydrogels (e.g., collagen hydrogels) show good potential in understanding cell-matrix interaction and find application in tissue engineering. However, it remains challenging to bioprint cell-laden natural hydrogels with good printability, shape retention and stability. In this study, non-water-soluble short collagen type I microfibers (COL-I μFiber) were blended with water-soluble methacrylated collagen peptide (COPMA) and xanthan gum (XG), forming an interpenetrated network, and bioprinted into stable natural-derived COPMA-μFiber-XG constructs, followed by <em>in situ</em> stem cell proliferation and differentiation. First, to enhance the printability and the mechanical properties of COPMA, a COPMA-μFiber-XG bioink was developed, featuring rapid UV-curing and self-healing properties. The encapsulated human mesenchymal stem cells (hMSCs) spread along the COL-I μFibers in the bioprinted constructs, with increased metabolic activity and production of extracellular matrix and bioactive proteins (COL-I and scleraxis) in 28 days. The internal biophysical and biochemical signals provided by COL-I μFibers and the fibrous COPMA matrix synergistically interacted with exogenous biochemical signals (e.g., transforming growth factor-beta 3) to further promote stem cell differentiation. Overall, bioprinted fibrous COPMA-μFiber-XG constructs are biocompatible and bioactive matrices to support hMSCs proliferation and differentiation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123965"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964872","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

Biomimetic antimicrobial peptides against gram-positive bacteria 抗革兰氏阳性细菌的仿生抗菌肽

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-12 DOI: 10.1016/j.biomaterials.2025.123916

Yu-Ting Li , Tian-Ci Wei , Jun-Xiao Yuan , Jia-Qi Feng , Pei-Pei Yang , Shu-Sheng Tang , Lei Wang , Hao Wang

{"title":"Biomimetic antimicrobial peptides against gram-positive bacteria","authors":"Yu-Ting Li , Tian-Ci Wei , Jun-Xiao Yuan , Jia-Qi Feng , Pei-Pei Yang , Shu-Sheng Tang , Lei Wang , Hao Wang","doi":"10.1016/j.biomaterials.2025.123916","DOIUrl":"10.1016/j.biomaterials.2025.123916","url":null,"abstract":"<div><div>Anti-Gram-positive bacteria, including multidrug-resistant strains such as methicillin-resistant <em>S</em><em>taphylococcus aureus</em> (MRSA), face significant challenges due to their robust cell wall structures, biofilm formation, and resistance mechanisms. Natural antimicrobial peptides (NAMPs) with a long history of development and wide use in clinical applications demonstrate broad-spectrum antibacterial activities through multi-target mechanisms, including disrupting bacterial cell walls and membranes. Owing to methodological limitations, conventional approaches for discovering NAMPs are becoming less effective in identifying new candidates. Therefore, biomimetic antimicrobial peptides (BAMPs) have been developed through structural modifications to enhance stability, safety, and antimicrobial efficacy. This review systematically summarizes recent advances in NAMPs and BAMPs against Gram-positive bacteria, and describes their mechanisms of action, including targeting peptidoglycan precursors in bacterial cell walls, disrupting membrane integrity, and interfering with DNA/RNA to inhibit bacterial growth. This review emphasizes the bacterial trapping mechanism via in situ self-assembly. We also highlight molecular modifications to optimize BAMPs that improve their antimicrobial potential and expand their application in clinic. Finally, we discuss the current limitations and future perspectives of NAMPs and BAMPs, provide valuable guidance for designing next-generation antimicrobial agents.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123916"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760544","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

Long-acting multiple programmed cell death nanoinducers based on polyunsaturated fatty acid supplemented liposomal photosensitizers for enhanced photodynamic immunotherapy 基于多不饱和脂肪酸补充脂质体光敏剂增强光动力免疫治疗的长效多重程序性细胞死亡纳米诱导剂

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-24 DOI: 10.1016/j.biomaterials.2025.123948

Yu Hao , Minming Chen , Yunyun Zhang , Hongchao Yang , Sisi Ling , Chunjie Wang , Yujie Zhu , Ziliang Dong , Chunyan Li , Zhuang Liu , Liangzhu Feng

{"title":"Long-acting multiple programmed cell death nanoinducers based on polyunsaturated fatty acid supplemented liposomal photosensitizers for enhanced photodynamic immunotherapy","authors":"Yu Hao , Minming Chen , Yunyun Zhang , Hongchao Yang , Sisi Ling , Chunjie Wang , Yujie Zhu , Ziliang Dong , Chunyan Li , Zhuang Liu , Liangzhu Feng","doi":"10.1016/j.biomaterials.2025.123948","DOIUrl":"10.1016/j.biomaterials.2025.123948","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) has been investigated for minimal invasive treatment of superficial tumors, but its clinical efficacy is constrained by its immediate light-dependent cytotoxicity, low immunogenicity, and other reasons. Building on the capacity of polyunsaturated fatty acids (PUFAs) to convert short-lived reactive oxygen species into longer-lived, highly cytotoxic lipid radicals, we develop a long-acting liposomal photosensitizer by co-encapsulating chlorin e6 (Ce6) and linoleic acid (LA) with commercial lipids. The resulting LA-Ce6@liposome converts short-lived singlet oxygens to persistent lipid radicals during light exposure, sustaining free LA peroxidation even post-irradiation. Mechanistic studies demonstrate that LA-Ce6@liposome-mediated PDT drives immunogenic ferroptosis and PANoptosis in cancer cells via amplified lipid peroxidation. In preclinical models, this strategy not only inhibits the growth of light-irradiated primary tumors but also activates systemic antitumor immunity, delaying progression of distal metastatic and rechallenged tumors, particularly when synergized with immune checkpoint blockade therapy. This study highlights a streamlined strategy to augment conventional PDT by integrating photosensitizers with PUFAs, offering prolonged tumoradical activity and immune activation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123948"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838262","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

Solvent-free melt-electrowriting of polycaprolactone-bioceramic composites 聚己内酯-生物陶瓷复合材料的无溶剂熔融电解。

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-24 DOI: 10.1016/j.biomaterials.2025.123943

M.L. Eames , A. Weekes , T. Ayyachi , R.A. Pepper , E. Pickering , S. Bell , C. Wu , M.A. Woodruff , T.J. Klein

{"title":"Solvent-free melt-electrowriting of polycaprolactone-bioceramic composites","authors":"M.L. Eames , A. Weekes , T. Ayyachi , R.A. Pepper , E. Pickering , S. Bell , C. Wu , M.A. Woodruff , T.J. Klein","doi":"10.1016/j.biomaterials.2025.123943","DOIUrl":"10.1016/j.biomaterials.2025.123943","url":null,"abstract":"<div><div>With increasing surgical cases for bone reconstruction, there is a rising need for advanced synthetic graft materials. In this paper, a novel pipeline for fabricating polycaprolactone (PCL)/bioceramic scaffolds was used to produce micron-fibre composite scaffolds comprising either 25 wt% 45S5 bioglass/45K PCL or 25 wt% molybdenum-doped bioglass/45K PCL (MoBG/PCL). Cryomixing was shown to be an effective method for evenly dispersing high concentrations of finely milled bioceramic particles into PCL without the need for chloroform solvents. The resulting composites had sufficiently low viscosity at 120 °C to be printed using melt electrowriting (MEW). The addition of bioceramic particles into PCL increased the elastic modulus and dramatically reduced the elongation at break. MEW scaffolds printed from a MoBG/PCL composite were shown to effectively support osteoblast cell growth. The cells on MoBG/PCL constructs displayed greater metabolic activity and DNA concentration after 7 days in culture relative to constructs made from unmodified PCL. Concentrated MoBG/PCL composite scaffolds may be a promising pathway for advanced bone tissue scaffolds.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123943"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145852798","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

A shear-responsive nanosystem engineered from fucoidan targets endothelial for atherosclerosis therapy 由岩藻糖聚糖设计的剪切反应纳米系统用于动脉粥样硬化治疗。

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-16 DOI: 10.1016/j.biomaterials.2025.123931

Ruyue Liu , Xuli Ruan , Mengran Guo , Zhongshan He , Yupei Zhang , Tingting Song , Haixing Shi , Xi He , Yaoyao Luo , Yuntao Gao , Min Sun , Chuansheng Huang , Liping Wang , Yunli Zhao , Yong Yuan , Xiangrong Song , Xinchun Wang

{"title":"A shear-responsive nanosystem engineered from fucoidan targets endothelial for atherosclerosis therapy","authors":"Ruyue Liu , Xuli Ruan , Mengran Guo , Zhongshan He , Yupei Zhang , Tingting Song , Haixing Shi , Xi He , Yaoyao Luo , Yuntao Gao , Min Sun , Chuansheng Huang , Liping Wang , Yunli Zhao , Yong Yuan , Xiangrong Song , Xinchun Wang","doi":"10.1016/j.biomaterials.2025.123931","DOIUrl":"10.1016/j.biomaterials.2025.123931","url":null,"abstract":"<div><div>Hemodynamic abnormalities within atherosclerotic plaque regions, particularly localized high shear stress and endothelial dysfunction, present novel targets for intervention by drug delivery systems. In this study, we designed a polysaccharide-based carrier (HF-AF) from fucoidan, featuring a dynamic supramolecular structure. A dynamic supramolecular network was established within this carrier via dynamic supramolecular interactions between hydroxypropyl-β-cyclodextrin and adamantane-methylamine. The anti-inflammatory compound tilianin, formulated into nanocrystals (Til NCs), was then encapsulated to create a shear-responsive nanosystem (HF-AF@Til NCs). The system's primary therapeutic strategy is its response to pathological hemodynamic forces: upon encountering high shear stress at a stenosis, the supramolecular network undergoes dissociation, triggering a mechanically-gated release of the encapsulated Til NCs. This shear-triggered function is complemented by the natural P-selectin affinity of the fucoidan backbone, which facilitates the anchoring of the nanocarrier at the inflamed lesion site. This sophisticated “anchor-and-release” mechanism enables superior drug accumulation precisely at plaque sites. In <em>ApoE</em><sup>−/−</sup> atherosclerotic mice, HF-AF@Til NCs significantly reduced aortic lipid deposition and exerted potent anti-atherosclerotic effects by modulating macrophage polarization, inhibiting the NF-κ-B signaling pathway, and improving lipid profiles. In conclusion, this shear-responsive nanodelivery system, which leverages a targeting polysaccharide, effectively enhances drug accumulation and therapeutic efficacy at atherosclerotic lesions, demonstrating significant potential for the targeted therapy of atherosclerosis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123931"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825572","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

Single H2S molecule mediates three-stage antibacterial and immunomodulatory effects in dendritic mesoporous organosilica (DMOS-4MPBA) nanoplatform 枝状介孔有机二氧化硅（DMOS-4MPBA）纳米平台中单个H2S分子介导三期抗菌和免疫调节作用。

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-22 DOI: 10.1016/j.biomaterials.2025.123941

Zulpya Mahmut , Bingshuai Zhou , Jiao Sun , Wenxin Zheng , Yifan Chen , Jiawei Li , Xinyao Zhang , Yumin Han , Haipeng Liu , Biao Dong

{"title":"Single H2S molecule mediates three-stage antibacterial and immunomodulatory effects in dendritic mesoporous organosilica (DMOS-4MPBA) nanoplatform","authors":"Zulpya Mahmut , Bingshuai Zhou , Jiao Sun , Wenxin Zheng , Yifan Chen , Jiawei Li , Xinyao Zhang , Yumin Han , Haipeng Liu , Biao Dong","doi":"10.1016/j.biomaterials.2025.123941","DOIUrl":"10.1016/j.biomaterials.2025.123941","url":null,"abstract":"<div><div>Bacterial infections and inflammatory diseases pose a severe global health threat, driven by antibiotic resistance and dysregulated immune responses. To overcome these challenges, we designed redox-responsive dendritic mesoporous organosilica nanoparticles (DMOS-4MPBA) that utilize a single gaseous molecule - hydrogen sulfide (H<sub>2</sub>S) - as a multifunctional therapeutic agent. DMOS-4MPBA releases H<sub>2</sub>S selectively within infected microenvironments through glutathione-responsive cleavage of polysulfide bonds. The released H<sub>2</sub>S concurrently executes three therapeutic mechanisms: disrupting bacterial energy metabolism and membrane integrity, suppressing quorum sensing to inhibit biofilm formation, and promoting immune regulation via macrophage polarization toward the pro-repair M2 phenotype. Both in vitro and in vivo experiments demonstrate strong antibacterial effects, efficient biofilm disruption, and accelerated wound healing, without compromising biosafety. By integrating antibacterial, anti-biofilm, and immunomodulatory capacities into a single H<sub>2</sub>S-releasing platform, we provide a innovative and potent strategy for treating drug-resistant infections and inflammatory diseases.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123941"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831770","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

Osteosarcoma-on-a-chip model mimicking intra-tumoral heterogeneity to interrogate tumor-associated macrophage reprogramming for immunotherapeutics 骨肉瘤芯片模型模拟肿瘤内异质性，询问肿瘤相关巨噬细胞重编程的免疫治疗。

IF 12.9 1区医学

Biomaterials Pub Date : 2026-06-01 Epub Date: 2025-12-12 DOI: 10.1016/j.biomaterials.2025.123917

Chitra Jaiswal , Saki Sugihara , Souradeep Dey , Ajay Kumar , Arpita Sharma , Raghvendra Gupta , Biman B. Mandal

{"title":"Osteosarcoma-on-a-chip model mimicking intra-tumoral heterogeneity to interrogate tumor-associated macrophage reprogramming for immunotherapeutics","authors":"Chitra Jaiswal , Saki Sugihara , Souradeep Dey , Ajay Kumar , Arpita Sharma , Raghvendra Gupta , Biman B. Mandal","doi":"10.1016/j.biomaterials.2025.123917","DOIUrl":"10.1016/j.biomaterials.2025.123917","url":null,"abstract":"<div><div>The osteosarcoma tumor microenvironment (OS-TME) exhibits pronounced cellular and biophysical heterogeneity, arising from infiltrating immune cells, primarily tumor-associated macrophages (TAMs) and mechanical stress gradients, respectively. TAMs significantly contribute to OS progression through various mechanisms; hence, targeting TAMs could improve treatment outcome in OS patients. This study presents a novel immunocompetent tri-culture osteosarcoma (iTC-OS) model developed using a porous 3D silk fibroin blend-hydroxyapatite (SF-HA) scaffold seeded with human OS cells, human blood derived TAMs, and human umbilical vein endothelial cells (HUVECs). The physiological relevance of the iTC-OS model is further enhanced by integrating into a physiomimetic microfluidic bioreactor (iTC-OS-on-a-chip), featuring dynamic perfusion to simulate intra-tumoral mechanical stress gradient, validated through computational fluid dynamic (CFD). Additionally, we employed pexidartinib and tenalisib to evaluate TAMs reversal in the iTC-OS-on-a-chip model by selectively inhibiting CSF1R and PI3Kγ, respectively. TAMs reprogramming from tumor promoting M2 to tumor suppressing M1 phenotype is confirmed through gene expression analysis of M1 (CCR7, IL-1β, IL-6) and M2 (CD206, CD163, IL-10) macrophage markers, alongside quantification of secreted cytokines via ELISA assay. This advanced iTC-OS-on-a-chip model offers a robust platform for investigating OS-immune cell interactions, enabling pre-clinical evaluation of chemo/immunotherapeutics and improving the translational relevance in OS research.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123917"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145814847","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