ACS Nano
·
2022
·
IF 18.027
Kun Liu,Lin Li,Jingsheng Chen,Yizhi Li,Wei Wen,Lu Lu,Lihua Li,Hong Li,Mingxian Liu,Changren Zhou,Binghong Luo
Implanting a 3D printing scaffold is an effective therapeutic strategy for personalized bone repair. As the key factor for the success of bone tissue engineering, the scaffold should provide an appropriate bone regeneration microenvironment and excellent mechanical properties. In fact, the most ideal osteogenic microenvironment is undoubtedly provided by natural bone extracellular matrix (ECM), which exhibits liquid crystalline and viscoelastic characteristics. However, mimicking a bone ECM-like microenvironment in a 3D structure with outstanding mechanical properties is a huge challenge. Herein, we develop a facile approach to fabricate a bionic scaffold perfectly combining bone ECM-like microenvironment and robust mechanical properties. Creatively, 3D printing a poly(l-lactide) (PLLA) scaffold was effectively strengthened via layer-by-layer electrostatic self-assembly of chitin whiskers. More importantly, a kind of chitin whisker/chitosan composite hydrogel with bone ECM-like liquid crystalline state and viscoelasticity was infused into the robust PLLA scaffold to build the bone ECM-like microenvironment in 3D structure, thus highly promoting bone regeneration. Moreover, deferoxamine, an angiogenic factor, was encapsulated in the composite hydrogel and sustainably released, playing a long-term role in angiogenesis and thereby further promoting osteogenesis. This scaffold with bone ECM-like microenvironment and excellent mechanical properties can be considered as an effective implantation for bone repair.
研究领域:
生物医学工程
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组织工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2025
·
IF 7.3
Yiyun Liu,Yan-Ling Liao,Jin-Xia Wang,Bao-Fu Zhang,Qi-Ping Tang,Yuan Ding,Si-Jia Zuo,Qin-Hong Zhou,De-Sheng Pei
The widespread application of nano-cerium dioxide (Nano-CeO 2 ) in agriculture, industry, and other fields has led to an increasing amount of it being released into the environment and becoming a pollutant with potential biological hazards. However, studies on the effects of ceria on cardiovascular development were limited. This study aims to detect the cardiovascular toxicity of Nano-CeO 2 , focusing on its impact on zebrafish hematopoietic function and cardiac development, and to explore its potential molecular mechanisms. We found that exposing zebrafish embryos to different concentrations of Nano-CeO 2 after 6 hpf of fertilization does not hinder the growth and development of zebrafish embryos during their early life stages. However, RNA-Seq analysis indicates that the hematopoietic system of zebrafish is suppressed, the ECM-receptor interaction pathway is disrupted, and the expression of related genes is significantly downregulated. The results of o-dianisidine staining, neutral red staining, and Sudan black staining showed that the hemoglobin, macrophages, and neutrophils of zebrafish were reduced, and the vascular dysplasia of zebrafish was observed. Meanwhile, Reactive oxygen species (ROS) accumulated in the heart of zebrafish larvae treated with Nano-CeO 2 , and heart development-related genes ( nppa , hand2 , nppb , nkx2.5 , and myh7 ) were significantly down-regulated, while gata4 was up-regulated. The addition of the integrin agonist manganese ions restored the expression of genes related to ECM-receptor interaction pathways, alleviating cardiovascular abnormalities caused by Nano-CeO 2 . Besides, significant changes in cardiac histopathology were observed with long-term exposure (120 d post-fertilization), indicating that Nano-CeO 2 exposure affected the development of the cardiovascular system in zebrafish. In summary, acute and chronic exposure to Nano-CeO 2 exhibits cardiovascular toxicity in zebrafish, affecting hematopoietic function and cardiac development, and the mechanism may be related to the ECM-receptor interaction pathway. This study provides useful information for a comprehensive understanding of the toxicity mechanisms and environmental risks of Nano-CeO 2 .
研究领域:
环境毒理学
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分子生物学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2026
·
IF 19.9
Xinming Wang,Weichang Xie,Zichen Wang,Haonan Zhang,Jia Li,Xingjian Gao,Dingjie Zhou,Huaiyu Jiang,Shixing Huang,Qiang Zhao,Xiaofeng Ye
Repairing anisotropic tissues such as the myocardium requires implanted cells to organize into highly ordered structures. However, achieving controlled cell alignment remains a major challenge for current cell delivery patches. Here, we develop a magnetically aligned, fiber-reinforced extracellular matrix (ECM) patch that directs anisotropic cell organization and supports stem cell implantation. Poly-lactic acid fibers containing Fe 3 O 4 are fabricated via electrospinning and controlled hydrolysis, and are aligned uniaxially within ECM hydrogels using an external magnetic field prior to gelation. The resulting ECM–fiber patches exhibit enhanced mechanical strength and reliably guide the alignment of cardiomyocytes, fibroblasts, and endothelial cells. A beating patch is also created by seeding human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). In a nude mouse myocardial infarction (MI) model, implantation of iPSC-CMs@ECM–fiber patches preserves cardiac function, reduces apoptosis, limits fibrosis, and enhances vascularization. Implanted iPSC-CMs demonstrate high viability and low immunogenicity. Molecular profiling reveals transient modulation of early inflammatory responses post-MI, probably mediated through IL-17, IL-3, and IL-1β pathways. Overall, the ECM–fiber patch provides a versatile platform for delivering highly organized cells for in vivo tissue repair.
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DOI
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Xiyue Duan,Kepeng Hu,Jiawei Wang,Xiaozhao Wang,Xiaojun Long,Weiming Lin,Chengwei Wu,Wenjian Weng,Zhangfa Song,Kui Cheng
The imbalance of macrophage polarization between M1 and M2 phenotypes in rheumatoid arthritis (RA) results in a persistent inflammatory cascade. Activating M2 anti-inflammatory polarization, which remove excess extracellular matrix (ECM) via phagocytosis, represents a potential therapeutic target for RA. This study introduces Col/Cs@ECM microspheres, a novel drug delivery system designed for macrophage recognition via a tailored ECM surface, enhancing phagocytic efficiency and accumulation. Moreover, the Col/Cs@ECM microspheres are composed of biocompatible and fully degradable materials, ensuring their safety profile within the physiological environment. Following cell phagocytosis, the collagen/chitosan (Col/Cs) core release the drug (Dexamethasone, Dex) intracellularly to inhibit M1 polarization by inhibiting the NF-κB signaling pathway and to facilitate M2 polarization. This macrophage targeted and intracellular release approach offers a significant advantage over traditional medications by reducing systemic side effects and improving the therapeutic index. The strategy prompts macrophages to express anti-inflammatory cytokines like IL-10 while suppressing pro-inflammatory cytokines such as TNF-α, thereby remodeling the immune microenvironment. Additionally, the specially engineered ECM shell of the microspheres extends the anti-inflammatory response by prolonging macrophage lifespan, a feature that is not present in conventional treatments. This results in improved treatment outcomes in an in vivo RA animal model. This research presents a possible intracellular anti-inflammatory treatment approach for rheumatoid arthritis injection therapy with the potential to outperform existing treatments in terms of efficacy and safety.
研究领域:
生物医学工程
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免疫治疗
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药物递送系统
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风湿病学
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细胞生物学
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生物材料
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Yizhi Li,Shengyue Tang,Ziang Luo,Kun Liu,Yiting Luo,Wei Wen,Shan Ding,Lihua Li,Mingxian Liu,Changren Zhou,Binghong Luo
Natural bone exhibits a complex anisotropic and micro-nano hierarchical structure, more importantly, bone extracellular matrix (ECM) presents liquid crystal (LC) phase and viscoelastic characteristics, providing a unique microenvironment for guiding cell behavior and regulating osteogenesis. However, in bone tissue engineering scaffolds, the construction of bone-like ECM microenvironment with exquisite microstructure is still a great challenge. Here, we developed a novel polysaccharide LC hydrogel supported 3D printed poly( l -lactide) (PLLA) scaffold with bone-like ECM microenvironment and micro-nano aligned structure. First, we prepared a chitin whisker/chitosan polysaccharide LC precursor, and then infuse it into the pores of 3D printed PLLA scaffold, which was previously surface modified with a polydopamine layer. Next, the LC precursor was chemical cross-linked by genipin to form a hydrogel network with bone-like ECM viscoelasticity and LC phase in the scaffold. Subsequently, we performed directional freeze-casting on the composite scaffold to create oriented channels in the LC hydrogel. Finally, we soaked the composite scaffold in phytic acid to further physical cross-link the LC hydrogel through electrostatic interactions and impart antibacterial effects to the scaffold. The resultant biomimetic scaffold displays osteogenic activity, vascularization ability and antibacterial effect, and is expected to be a promising candidate for bone repair.
研究领域:
生物材料学
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组织工程学
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再生医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Hao Liu,Xin Tian,Chenyang Jin,Yangfeng Li,Xuesong Zhu,Ming Pei,Tao Liu,Huilin Yang,Yong Xu,Fan He
Nucleus pulposus (NP) discectomy is a clinical procedure for the treatment of late-stage intervertebral disc (IVD) degeneration; however, it is associated with the potential for serious complications. The reconstruction of the NP tissue presents challenges due to its avascular structure and prolonged compression within the IVD. In this study, we have developed a novel biomimetic hydrogel microsphere composed of gelatin methacryloyl (GelMA) and fucoidan, a polysaccharide derived from marine brown seaweed, to mimic the extracellular matrix (ECM) of the native NP. The GelMA and fucoidan (GelMA@FD) hydrogel microspheres demonstrate favorable cytocompatibility and significantly enhance the synthesis of matrix components in nucleus pulposus cells (NPCs), including aggrecan and type II collagen. Transcriptome sequencing analysis demonstrates a correlation between the augmentation of matrix synthesis and the enrichment of genes and pathways related to mitochondrial function. Subsequent molecular investigations provide evidence that NPCs cultured on GelMA@FD exhibit enhanced mitochondrial functions, including elevated adenosine triphosphate production and respiratory chain factor expression, alongside a reduction in mitochondrial reactive oxygen species. When implantated into rat lumbar IVDs that have undergone discectomy, the incorporation of NPCs within GelMA@FD hydrogel microspheres facilitates the regeneration of the NP and reinstates its structural and biomechanical properties. This is substantiated by the observed augmentation in IVD disc height and water content within the NP compartment. Collectively, these results demonstrate the potential of employing cell-laden GelMA@FD hydrogel microspheres as a promising strategy for NP regeneration in degenerated IVDs.
研究领域:
生物材料
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组织工程
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再生医学
·
骨科
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产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·Vol. 24
·期 1
·167
·
IF 12.6
Jin Jingyu,Zhu Chengjie,Wang Nuoya,Jin Mingji,Jin Yanxin,Jin Heying,Zhang Shuang,Zhou Yanhong,Zhao Lei,Luo Yinli,Gao Zhonggao,Jin Zhehu,Wang Shuangqing
Keloids are refractory fibroproliferative disorders. Their treatment faces multiple clinical challenges, including the coexistence of multiple pathological mechanisms, low drug bioavailability, and keloid-related pruritus. This study developed an UV-responsive cross-linked hydrogel (FZRL) using lipoic acid-grafted chitosan (LACS) as the matrix. The hydrogel encapsulates ZIF-8 nanoparticles loaded with 5-fluorouracil (5Fu, denoted as 5Fu@ZIF-8) and the local anesthetic ropivacaine. Before injection, the hydrogel exists as a liquid precursor. It can be precisely delivered to the area around keloids. Under mild UV irradiation, it rapidly cross-links into a stable hydrogel. This enables long-term local retention of 5Fu and ropivacaine, preventing premature drug leakage. In the weakly acidic microenvironment of keloids, FZRL hydrogel degrades specifically and releases 5Fu and ropivacaine on demand. A nude mouse keloid model with subcutaneous inoculation of human keloid fibroblasts (KFs) showed that FZRL hydrogel regulates the TGF-β/Smad pathway. It inhibits KFs proliferation and abnormal angiogenesis, modifies the extracellular matrix structure, and remodels the keloid microenvironment. After treatment, the average keloid volume was reduced by 54.7 ± 12.1%. At the same time, it significantly relieved itching-related scratching and irritable behaviors. In conclusion, FZRL hydrogel has dual delivery properties, including UV-responsive gelation and acid-responsive drug release. It synergistically achieves multi-target anti-keloid effects, as well as pruritus relief and analgesia. It provides a new minimally invasive treatment strategy for refractory keloids and has potential clinical translation value. Graphical
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DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2020
·
IF 0
Anqi Chen,Wen Huang,Liang Wu,Ying An,Tengxiao Xuan,Huacheng He,Mengqi Ye,Lamei Qi,Jiang Wu
Successful dermal wound regeneration requires the coordination of repair cells and cellular signals with the extracellular matrix (ECM), which serves as an indispensable mechanical and biological supporter for cell functions and communications with varied cytokines during healing processes. Here, we developed an injectable bioactive wound dressing, methacrylated hyaluronic acid (Me-HA)-based hydrogel loading with basic fibroblast growth factor (bFGF), endowing the dressing with the pleiotropic bioactivity to mimic natural ECM. This bFGF@Me-HA dressing was applied to a mouse with full-thickness excisional wounds to investigate its positive roles in wound repair owing to the complementary functions of HA with sustained release of bioactive bFGF. Compared with the single Me-HA and bFGF group, bFGF@Me-HA hydrogel dressings significantly enhanced wound healing with accelerated re-epithelialization, granulation formation, collagen, deposition and skin appendage regeneration. Further investigations showed significantly promoted cell proliferation and vascularization in the bFGF@Me-HA group, which was mediated by the upregulation of transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) expressions. In conclusion, this bFGF@Me-HA hydrogel realized the optimization of simple ECM mimic dressing via introducing the bioactive effector, bFGF, and has the potential to be widely used as an effective bioactive ECM-based wound dressing in future wound care.
研究领域:
生物材料学
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再生医学
·
皮肤修复
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产品关联
DOI
PubMed
Antioxidants
·
2023
·Vol. 12
·期 3
·679
·
IF 7
Tong Zhu,Jingjing Song,Bin Gao,Junjie Zhang,Yabei Li,Zhaoyang Ye,Yuxiang Zhao,Xiaogang Guo,Feng Xu,Fei Li
Myocardial fibrosis progression and imbalanced redox state are closely associated with increased extracellular matrix (ECM) stiffness. Candesartan (CAN), an angiotensin II (Ang II) receptor inhibitor, has shown promising anti-fibrosis and antioxidant efficacy in previous cardiovascular disease studies. However, the effect of ECM stiffness on CAN efficacy remains elusive. In this study, we constructed rat models with three different degrees of myocardial fibrosis and treated them with CAN, and then characterized the stiffness, cardiac function, and NADPH oxidase-2 (NOX2) expression of the myocardial tissues. Based on the obtained stiffness of myocardial tissues, we used polyacrylamide (PA) gels with three different stiffness to mimic the ECM stiffness of cardiac fibroblasts (CFs) at the early, middle, and late stages of myocardial fibrosis as the cell culture substrates and then constructed CFs mechanical microenvironment models. We studied the effects of PA gel stiffness on the migration, proliferation, and activation of CFs without and with CAN treatment, and characterized the reactive oxygen species (ROS) and glutathione (GSH) levels of CFs using fluorometry and scanning electrochemical microscopy (SECM). We found that CAN has the best amelioration efficacy in the cardiac function and NOX2 levels in rats with medium-stiffness myocardial tissue, and the most obvious anti-fibrosis and antioxidant efficacy in CFs on the medium-stiffness PA gels. Our work proves the effect of ECM stiffness on CAN efficacy in myocardial anti-fibrosis and antioxidants for the first time, and the results demonstrate that the effect of ECM stiffness on drug efficacy should also be considered in the treatment of cardiovascular diseases.Keywords:myocardial fibrosis;candesartan (CAN);extracellular matrix (ECM);oxidative stress;scanning electrochemical microscopy (SECM)
研究领域:
心脏病学
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药理学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2025
·
IF 3.6
Lijun Wang,Miao Lei,Jie Hao,Xiaojun Zhang,Wei Jiang,Zhenming Hu
The therapeutic efficacy of chemotherapy in solid tumors such as osteosarcoma is hindered by the dense, collagen-rich extracellular matrix (ECM). In this work, we report an acid-responsive nanogel that co-encapsulates bromelain (BL), a proteolytic enzyme, and doxorubicin (DOX) with spatially distinct localization and independent pH-responsive release mechanisms. BL is encapsulated within the nanogel network, whereas DOX is covalently grafted onto the nanogel surface via an acid-labile linker, enabling the nanocarrier (ng(BL–DOX)) to remain stable under physiological conditions while promoting controlled release in the mildly acidic tumor microenvironment. The released BL degrades collagenous ECM components and reduces matrix density, thereby improving the penetration and intratumoral distribution of the concurrently released DOX. In a murine osteosarcoma model, the PEG-rich nanogels showed prolonged circulation and increased tumor accumulation via the enhanced permeability and retention (EPR) effect, accompanied by collagen I degradation and effective tumor growth inhibition, with final tumor volumes reduced to approximately one-tenth of those in the control group and without observable systemic toxicity. This microencapsulation approach provides an enzyme–drug co- encapsulation system that combines ECM degradation with chemotherapy in a single nanogel platform and may be adapted to other proteolytic enzymes and cytotoxic agents for the treatment of stroma-rich solid tumors.
研究领域:
纳米医学
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癌症治疗
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药物递送系统
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生物材料
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肿瘤微环境
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Qingge Ma,Chenghao Song,Zhengmin Zhang,Feifei Li,Peng Yu,Ling Ye
The osteogenic differentiation of mesenchymal stem cells (MSCs) requires dynamic remodeling of the extracellular matrix (ECM) microenvironment. Biomimetic mineralization (BM) can recapitulate key features of the native bone microenvironment and thereby promote MSC osteogenesis. However, the development of artificial scaffolds capable of providing dynamically evolving mineralized niches for MSCs remains challenging, and the underlying osteogenic mechanisms are still poorly understood. In this study, a hierarchical graphene-doped polymethyl methacrylate (PMMA) scaffold was fabricated via vapor-induced phase separation. An organic-inorganic framework with continuous self-mineralization capability—composed of ovalbumin (OVA), tannins (TA), Ca 2+ , and PO 4 3- —was engineered on the graphene surface through a simple two-step immersion process. This bone tissue mimetic architecture, combined with sustained in situ mineralization, establishes an optimal dynamic niche that supports MSC adhesion and drives robust osteogenic differentiation. Furthermore, the self-mineralized calcium nodules synergize with MSC-mediated calcium deposition during osteogenesis, leading to accelerated scaffold remodeling and a significantly shortened bone repair timeline. Collectively, the hierarchical scaffold featuring a self-mineralizing MSC niche exhibits strong potential for the regeneration of critical-sized bone defects.
研究领域:
组织工程
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再生医学
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生物医学材料
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干细胞生物学
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骨生物学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2020
·
IF 8.724
Mingxue Chen,YangYang Li,Shuyun Liu,Zhaoxuan Feng,Hao Wang,Dejin Yang,Weimin Guo,Zhiguo Yuan,Shuang Gao,Yu Zhang,Kangkang Zha,Bo Huang,Fu Wei,Xinyu Sang,Qinyu Tian,Xuan Yang,Xiang sui,Yixin Zhou,Yufeng Zheng,Quanyi Guo
Tissue engineering provides a promising avenue for treating cartilage defects. However, great challenges remain in the development of structurally and functionally optimized scaffolds for cartilage repair and regeneration. In this study, decellularized cartilage extracellular matrix (ECM) and waterborne polyurethane (WPU) were employed to construct WPU and WPU-ECM scaffolds by water-based 3D printing using low-temperature deposition manufacturing (LDM) system, which combines rapid deposition manufacturing with phase separation techniques. The scaffolds successfully achieved hierarchical macro‐microporous structures. After adding ECM, WPU scaffolds were markedly optimized in terms of porosity, hydrophilia and bioactive components. Moreover, the optimized WPU-ECM scaffolds were found to be more suitable for cell distribution, adhesion, and proliferation than the WPU scaffolds. Most importantly, the WPU-ECM scaffold could facilitate the production of glycosaminoglycan (GAG) and collagen and the upregulation of cartilage-specific genes. These results indicated that the WPU-ECM scaffold with hierarchical macro‐microporous structures could recreate a favorable microenvironment for cell adhesion, proliferation, differentiation, and ECM production. In vivo studies further revealed that the hierarchical macro‐microporous WPU-ECM scaffold combined with the microfracture procedure successfully regenerated hyaline cartilage in a rabbit model. Six months after implantation, the repaired cartilage showed a similar histological structure and mechanical performance to that of normal cartilage. In conclusion, the hierarchical macro‐microporous WPU-ECM scaffold may be a promising candidate for cartilage tissue engineering applications in the future.
研究领域:
组织工程学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
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