Bioactive Materials最新文献

{"title":"Unraveling osteogenesis mechanisms of the empowered VitaFlux adaptive regeneration biomaterials for bone tissue engineering: Insights into the role of BBGs/BSBGs","authors":"Xian Li ,&nbsp;Kun Su ,&nbsp;Limin Zhao ,&nbsp;Hao Zhang ,&nbsp;Qiang Yang ,&nbsp;Ping Du ,&nbsp;Xiaofeng Chen ,&nbsp;Haobo Pan","doi":"10.1016/j.bioactmat.2025.03.006","DOIUrl":"10.1016/j.bioactmat.2025.03.006","url":null,"abstract":"<div><div>Bone tissue engineering materials are crucial for bone repair, but existing repair materials still face many challenges, including poor biocompatibility and bioactivity, slow self-repair processes, limited adaptability, inability to promote angiogenesis and so on. To address these issues, the development of third-generation bone repair materials, which are being designed to stimulate specific cellular responses at the molecular level, such as borate and borosilicate bioactive glasses (BBGs/BSBGs) that activate cells and genes, offers new potential for promoting bone tissue self-renewing. Their unique characteristic lies in a flow of life-giving energy, releasing beneficial ions such as boron, calcium and silicon to stimulate cell proliferation and differentiation, accelerating the regeneration of bones. Through this dynamic repair mechanism, these VitaFlux glasses operate like a “living system” within the body, not only speeding up the healing of damaged tissues but also interacting seamlessly with surrounding tissues during the repair process. In this review, we provide a comprehensive analysis of the current understanding of the osteogenesis mechanisms of BBGs/BSBGs, emphasizing their interactions with cells, including ion release and exchange, protein adsorption, and cell adhesion. We also examine key osteogenic signaling pathways related to the alkaline and ionic microenvironments of BBGs/BSBGs, such as the cell cycle, Wnt, MAPK, and BMP signaling pathways, along with macrophage polarization and angiogenesis. Additionally, strategies and future prospects for advancing BBGs/BSBGs research are discussed. Special attention is given to the NaBC1 and GPCR-mediated signaling pathways, which require further investigation.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 271-290"},"PeriodicalIF":18.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A sequential drug delivery system based on silk fibroin scaffold for effective cartilage repair","authors":"Menglin Xiao ,&nbsp;Liangyan Sun ,&nbsp;Kang Wu ,&nbsp;Yuqi Ding ,&nbsp;Peipei Wang ,&nbsp;Chuangchuang Mu ,&nbsp;Jinrong Yao ,&nbsp;Zhengzhong Shao ,&nbsp;Bingjiao Zhao ,&nbsp;Xin Chen","doi":"10.1016/j.bioactmat.2025.03.005","DOIUrl":"10.1016/j.bioactmat.2025.03.005","url":null,"abstract":"<div><div>Endogenous repair of cartilage defects is a preferential strategy for cartilage repair, but always hindered by insufficient early-stage cells and incomplete cell differentiation at later stages. For <em>in-situ</em> cartilage regeneration, it is crucial to develop a sequential drug release system capable of recruiting endogenous bone marrow mesenchymal stem cells (BMSCs) and promoting their chondrogenic differentiation. Herein, based on our long-term and fruitful research on silk fibroin (SF) porous scaffolds, a cell-free sequential drug delivery SF scaffold was developed. BMSCs affinity peptide PFSSTKT (PFS) was coated on the surface of SF scaffold, in which chondrogenic inducer kartogenin (KGN) and anti-inflammatory factor dexamethasone (DEX) were loaded. PFS was rapidly released within the first 10 days while KGN and DEX could be released over 28 days. The scaffold promoted BMSCs migration and chondrogenic differentiation through the release of PFS and KGN <em>in vitro</em>. Finally, the sequential drug released by the implanted SF scaffolds in rats indeed recruited endogenous BMSCs and significantly promoted the <em>in-situ</em> regeneration of their knee cartilage defects. In summary, this study not only introduces a green and environmentally friendly all silk-based sequential drug delivery system, but also provides an effective tissue engineering functional scaffold for <em>in-situ</em> cartilage regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 255-270"},"PeriodicalIF":18.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering a stem cell-embedded bilayer hydrogel with biomimetic collagen mineralization for tendon-bone interface healing","authors":"Tingyun Lei ,&nbsp;Tao Zhang ,&nbsp;Tianshun Fang ,&nbsp;Jie Han ,&nbsp;Chunyi Gu ,&nbsp;Youguo Liao ,&nbsp;Yang Fei ,&nbsp;Junchao Luo ,&nbsp;Huanhuan Liu ,&nbsp;Yan Wu ,&nbsp;Weiliang Shen ,&nbsp;Xiao Chen ,&nbsp;Zi Yin ,&nbsp;Junjuan Wang","doi":"10.1016/j.bioactmat.2025.03.001","DOIUrl":"10.1016/j.bioactmat.2025.03.001","url":null,"abstract":"<div><div>The tendon-bone interface effectively transfers mechanical stress for movement, yet its regeneration presents significant clinical challenges due to its hierarchical structure and composition. Biomimetic strategies that replicate the distinctive characteristics have demonstrated potential for enhancing the healing process. However, there remains a challenge in developing a composite that replicates the nanostructure of the tendon-bone interface and embeds living cells. Here, we engineered a nanoscale biomimetic bilayer hydrogel embedded with tendon stem cells for tendon-bone interface healing. Specifically, the biomimetic hydrogel incorporates intra- and extrafibrillar mineralized collagen fibrils as well as non-mineralized collagen fibrils resembling the tendon-bone interface at the nanoscale. Furthermore, biomimetic mineralization with the presence of cells realizes living tendon-bone-like tissue constructs. In the <em>in vivo</em> patella-patellar tendon-interface injury model, the tendon stem cell-laden biomimetic hydrogel promoted tendon-bone interface regeneration, demonstrated by increased fibrocartilage formation, improved motor function, and enhanced biomechanical outcomes. This study highlights the potential of the stem cell-laden biomimetic hydrogel as an effective strategy for tendon-bone interface regeneration, offering a novel approach to engineering complex tissue interfaces.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 207-217"},"PeriodicalIF":18.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in locally administered nucleic acid therapeutics","authors":"Jie Shen ,&nbsp;Xusheng Duan ,&nbsp;Ting Xie ,&nbsp;Xinrui Zhang ,&nbsp;Yue Cai ,&nbsp;Junhao Pan ,&nbsp;Xin Zhang ,&nbsp;Xuanrong Sun","doi":"10.1016/j.bioactmat.2025.02.043","DOIUrl":"10.1016/j.bioactmat.2025.02.043","url":null,"abstract":"<div><div>Nucleic acid drugs represent the latest generation of precision therapeutics, holding significant promise for the treatment of a wide range of intractable diseases. Delivery technology is crucial for the clinical application of nucleic acid drugs. However, extrahepatic delivery of nucleic acid drugs remains a significant challenge. Systemic administration often fails to achieve sufficient drug enrichment in target tissues. Localized administration has emerged as the predominant approach to facilitate extrahepatic delivery. While localized administration can significantly enhance drug accumulation at the injection sites, nucleic acid drugs still face biological barriers in reaching the target lesions. This review focuses on non-viral nucleic acid drug delivery techniques utilized in local administration for the treatment of extrahepatic diseases. First, the classification of nucleic acid drugs is described. Second, the current major non-viral delivery technologies for nucleic acid drugs are discussed. Third, the bio-barriers, administration approaches, and recent research advances in the local delivery of nucleic acid drugs for treating lung, brain, eye, skin, joint, and heart-related diseases are highlighted. Finally, the challenges associated with the localized therapeutic application of nucleic acid drugs are addressed.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 218-254"},"PeriodicalIF":18.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A self-accelerating ‘copper bomb’ strategy activated innate and adaptive immune response against triple-negative breast cancer","authors":"Xinzhi Xu ,&nbsp;Hang Zhou ,&nbsp;Ruixia Hong ,&nbsp;Jiaqi Gong ,&nbsp;Yujie Wan ,&nbsp;Qihuan Fu ,&nbsp;Kaifeng Huang ,&nbsp;Ying Li ,&nbsp;Na Wang ,&nbsp;Peng Zhao ,&nbsp;Kaiyong Cai ,&nbsp;Fang Li","doi":"10.1016/j.bioactmat.2025.02.019","DOIUrl":"10.1016/j.bioactmat.2025.02.019","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) presents therapeutic challenges due to its aggressive, drug-resistance, and low immunological reactivity. Cuproptosis, an emerging therapeutic modality, is a promising strategic intervention for treating TNBC. Nonetheless, the effectiveness of cuproptosis is compromised by tumor adaptations, including the Warburg effect, increased intracellular glutathione (GSH), and copper efflux, thus breaking the barrier of cuproptosis is the basis for developing cuproptosis-based clinical therapies. Herein, a self-accelerating strategy utilizing a pH-responsive copper framework encapsulating glucose oxidase (GOx), modified with polyethylene glycol (PEG) and tumor-penetrating peptide (tLyp1) has been developed. Upon reaching the acidic tumor microenvironment, the released GOx increases intracellular acidity and hydrogen peroxide (H₂O₂). The elevated intracellular GSH and H₂O₂ serve as “fuel” to amplify the copper-based catalytic within tumor cells. Concurrently, the reduction of copper efflux proteins (ATP7B) and the depletion of GSH lead to copper overload in tumor cells, leading to cuproptosis via copper overload, mitochondrial disruption, and Fe-S protein instability. This constellation of interrelated events constitutes a potent “Copper Bomb,” which concurrently triggers the immune system and effectively kills the tumor. It robustly engages innate and adaptive immunity via the release of mitochondrial DNA, facilitating the cGAS-STING pathway and precipitating immunogenic cell death. This process reverses the immunosuppressive tumor microenvironment, eliminates tumor cells, and suppresses metastasis, thus offering a novel therapeutic modality for the comprehensive treatment of triple-negative breast cancer (TNBC).</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 193-206"},"PeriodicalIF":18.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering functional electroconductive hydrogels for targeted therapy in myocardial infarction repair","authors":"Qianqian Lv ,&nbsp;Dandan Zhou ,&nbsp;Yutong He ,&nbsp;Tao Xu ,&nbsp;Xiaozhong Qiu ,&nbsp;Junwei Zeng","doi":"10.1016/j.bioactmat.2025.01.013","DOIUrl":"10.1016/j.bioactmat.2025.01.013","url":null,"abstract":"<div><div>Myocardial infarction (MI) is characterized by a paucity of cardiomyocyte regeneration, leading to significant morbidity and mortality. Contemporary therapeutic modalities, while mitigating ischemic effects, fail to reconstitute the impaired electromechanical coupling within the infracted myocardium. Emerging evidence supports the utility of electroconductive hydrogels (ECHs) in facilitating post-MI cardiac function recovery by restoring the conductive microenvironment of the infarcted tissue. This comprehensive review delineates the taxonomy of ECHs predicated on their constituent conductive materials. It also encapsulates prevailing research trends in ECH-mediated MI repair, encompassing innovative design paradigms and microenvironment-sensitive strategies. The review also provides a critical appraisal of various implantation techniques, underscored by a thorough examination of the attendant considerations. It elucidates the mechanistic underpinnings by which hydrogels exert salutary effects on myocardial repair, namely by augmenting mechanical and electrical integrity, exerting anti-inflammatory actions, fostering angiogenesis, and curtailing adverse remodeling processes. Furthermore, the review engages with the pressing challenge of optimizing ECH functionality to achieve superior reparative outcomes post-MI. The discourse concludes with an anticipatory perspective on the evolution of ECH scaffolds, advocating for a tailored approach that integrates multifaceted physicochemical properties to cater to the nuances of personalized medicine.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 172-192"},"PeriodicalIF":18.0,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailoring hyaluronic acid hydrogels: Impact of cross-linker length and density on skin rejuvenation as injectable dermal fillers and their potential effects on the MAPK signaling pathway suppression","authors":"Mohanapriya Murugesan ,&nbsp;Ramya Mathiyalagan ,&nbsp;Zelika Mega Ramadhania ,&nbsp;Jinnatun Nahar ,&nbsp;Cuong Hung Luu ,&nbsp;V.H. Giang Phan ,&nbsp;Deok Chun Yang ,&nbsp;Qihui Zhou ,&nbsp;Se Chan Kang ,&nbsp;Thavasyappan Thambi","doi":"10.1016/j.bioactmat.2025.03.002","DOIUrl":"10.1016/j.bioactmat.2025.03.002","url":null,"abstract":"<div><div>Hyaluronic acid (HA) hydrogels, obtained through cross-linking, provide a stable 3D environment that is important for controlled delivery and tissue engineering applications. Cross-linking density has a significant impact on the physicochemical properties of hydrogels, including their shape stability, mechanical stiffness and macromolecular diffusivity. However, often cross-linking chemistries require photoinitiator and catalyst that may be toxic and cause unwanted tissue response. Here, we prepared a series of HA hydrogel with varying cross-linker length and cross-linking density, which can be obtained by altering the feed ratio of three different cross-linkers from small molecules to macromolecules (e.g., 1,4-butanediol diglycidyl ether (BDDE), ferulic acid (FA), pluronic (PLU)), to ameliorate skin wrinkles in mice models. HA cross-linked with FA and PLU exhibited enzyme and temperature-dependent sol-to-gel phase transition, respectively, and the gels possess good injectability. In vitro test confirmed that HA hydrogels co-cultured with RAW 264.7 and HDF cells showed good biocompatibility. In particular, HA cross-linked with PLU stimulated the growth of HDF cells and HaCaT cells. HA cross-linked with PLU suppressed the expression levels of proteins involved in collagen degradation including mitogen-activated protein kinases (ERK, JNK, p38) and matrix metalloproteases (MMP-1, MMP-3, and MMP-9) resulting in increased deposition of Collagen I. The free-flowing sols of HA hydrogel precursors are subcutaneously injected into the back of BALB/c mice and form stable gels at the dermis layer and found to be non-toxic. More importantly, HA hydrogel cross-linked with PLU showed an enhanced anti-wrinkling effect in the wrinkled mice model. Thus, properties of HA hydrogels such as injectability, biocompatibility, and good anti-wrinkling effect altered through varying cross-linking density must be considered in the context of soft tissue engineering applications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 154-171"},"PeriodicalIF":18.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing PD-1 blockade in NSCLC: Reprogramming tumor immune microenvironment with albumin-bound statins targeting lipid rafts and mitochondrial respiration","authors":"Na Chen ,&nbsp;Zhanfeng Li ,&nbsp;Heyuan Liu ,&nbsp;Aimin Jiang ,&nbsp;Liqiang Zhang ,&nbsp;Siqi Yan ,&nbsp;Wangxiao He ,&nbsp;Jingyue Yang ,&nbsp;Tianya Liu","doi":"10.1016/j.bioactmat.2025.03.003","DOIUrl":"10.1016/j.bioactmat.2025.03.003","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) has shown limited response to immunotherapy, primarily due to an immunosuppressive tumor microenvironment characterized by hypoxia and lipid raft formation, which together inhibit T-cell infiltration and function, impeding effective immune responses. To address these challenges, we developed Abstatin, an albumin-bound fluvastatin formulation that targets lipid raft disruption and mitochondrial respiration inhibition, aiming to reduce hypoxia and destabilize lipid rafts to enhance T-cell activity within the tumor. Using bioinformatics analysis, <em>in vitro</em> assays, and <em>in vivo</em> studies in both murine and humanized PDX models, we demonstrated that Abstatin reprograms the NSCLC microenvironment by concurrently lowering hypoxia levels and lipid raft integrity, thereby restoring T-cell infiltration, enhancing cytotoxic T-cell function, and ultimately improving response to Anti-PD-1 therapy. Results showed that Abstatin significantly amplifies Anti-PD-1 efficacy with minimal toxicity, indicating a favorable safety profile for clinical use. This study highlights Abstatin as a promising immunotherapy adjuvant that addresses critical barriers in NSCLC by modulating metabolic pathways linked to immune resistance. Abstatin's approach, which combines modulation of cellular metabolism with immune sensitization, broadens the potential of immunotherapy and provides a practical, scalable strategy to enhance treatment outcomes in NSCLC and potentially other tumors, offering insights into combinatory cancer therapies.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 140-153"},"PeriodicalIF":18.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zn-DHM nanozymes regulate metabolic and immune homeostasis for early diabetic wound therapy","authors":"Shuo Zhang ,&nbsp;Xinyu Zhao ,&nbsp;Wei Zhang ,&nbsp;Xiaolong Wei ,&nbsp;Xu-Lin Chen ,&nbsp;Xianwen Wang","doi":"10.1016/j.bioactmat.2025.02.041","DOIUrl":"10.1016/j.bioactmat.2025.02.041","url":null,"abstract":"<div><div>Diabetic wounds heal slowly or incompletely because of the microenvironment of hyperglycemia, high levels of reactive oxygen species (ROS), excessive inflammation, metabolic disorders and immune dysregulation, and the therapeutic effect is limited only by disruption of the reactive oxygen species (ROS)-inflammation cascade cycle. Here, a novel metal-polyphenolic nanozyme (Zn-DHM NPs) synthesized by the coordination of Zn²⁺ with dihydromyricetin (DHM) was designed, which not only has a superior ability to scavenge ROS and promote cell proliferation and migration but also functions in the regulation of metabolism and immune homeostasis. <em>In vitro</em> and <em>in vivo</em> experiments and RNA sequencing analyses revealed that Zn-DHM NPs could increase the levels of intracellular SOD and CAT enzymes to scavenge ROS and maintain the level of the mitochondrial membrane potential to reduce apoptosis. In terms of glucose metabolism, Zn-DHM NPs downregulated excessive levels of intracellular glucose and HK2, inhibited excessive glycolysis and downregulated the AGE-RAGE pathway to restore cellular function. In terms of immune regulation, Zn-DHM NPs not only downregulate M1/M2 levels to promote tissue repair but also maintain Th17/Treg homeostasis, downregulate the IL-17 signaling pathway to reduce inflammation, and upregulate FOXP3 to maintain immune homeostasis, thereby promoting early wound healing in diabetic mice. The development of Zn-DHM NPs provides a new therapeutic target to promote early healing of diabetic wounds.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 63-84"},"PeriodicalIF":18.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stromal/stem cell spheroid-derived extracellular vesicles advance the therapeutic efficacy of 3D-printed vascularized artificial liver lobules in liver failure treatment","authors":"Jiabin Zhang ,&nbsp;Xiaodie Chen ,&nbsp;Yurong Chai ,&nbsp;Yuanyuan Jin ,&nbsp;Fenfang Li ,&nbsp;Chenya Zhuo ,&nbsp;Yanteng Xu ,&nbsp;Haixia Wang ,&nbsp;Enguo Ju ,&nbsp;Yeh-Hsing Lao ,&nbsp;Xi Xie ,&nbsp;Mingqiang Li ,&nbsp;Yu Tao","doi":"10.1016/j.bioactmat.2025.02.042","DOIUrl":"10.1016/j.bioactmat.2025.02.042","url":null,"abstract":"<div><div>Acute liver failure (ALF) is a highly lethal condition characterized by massive tissue necrosis, excessive oxidative stress, and serious inflammatory storms, necessitating prompt medical intervention. Although hepatocyte-like cells (HLCs) derived from mesenchymal stromal/stem cells (MSCs) offer a promising alternative cell source for hepatocyte therapy, their low <em>in-vivo</em> integration and differentiation efficiency may compromise the eventual therapeutic efficacy. To this end, MSCs are bioengineered into multicellular spheroids in the present study. The proteomic analyses and experimental results reveal that extracellular vesicles (EVs) derived from these MSC spheroids (SpEV) contain abundant highly expressed bioactive proteins and can be efficiently endocytosed by recipient cells, resulting in enhanced pro-angiogenic and antioxidative effects. In addition, MSC spheroids exhibit superior hepatic cell differentiation compared to an equivalent number of dissociated single MSCs, particularly when being co-cultured with hexagonally patterned endothelial cells in a liver lobule-like arrangement. Following orthotopic implantation in the mouse model, the enhanced paracrine effects of SpEV, combined with an immunoregulatory decellularized extracellular matrix hydrogel carrier and functional artificial liver lobules (ALL), synergically contribute to the effective amelioration of ALF, highlighting the substantial potential for clinical translation.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 121-139"},"PeriodicalIF":18.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}