EUROPEAN JOURNAL OF PHARMACOLOGY
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2023
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IF 5
Sujuan Guan,Tingting Hu,Liushan Chen,Zheng Li,Zhenming Lin,Jinping Lei,Juan Shen
Background Diabetes ulcer is one of the leading causes of disability and death in diabetics. Y8 [(2-(2-fluoro-4-((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy) phenoxy)acetic acid)], a dual agonist of peroxisome proliferation activated receptorβ (PPARβ) and free fatty acid receptor 1 (FFA1/FFAR1/GPR40), a new compound molecule with the potential for diabetes ulcer treatment. Objective To research the effect of the dual target agonist Y8 and its mechanism of action in the treatment of diabetic ulcers. Methods We have established a wound model in diabetic mice. After treatment with Y8, wound healing was evaluated by tissue pathology, reactive oxygen species (ROS) levels, and gene expression testing. Under high sugar conditions, the mechanism of Y8 affecting fibroblasts' proliferation and keratinocytes' migration is further studied. Results We found that Y8 accelerated wound healing and shortened healing time in diabetic mice. Granulation tissue generation and extracellular matrix (ECM) deposition were significantly increased in Y8-treated mice. Mechanistically, Y8 promotes keratinocyte proliferation by activating PPARβ and migration of keratinocytes by triggering FFA1 in vitro. In addition, Y8 also decreased ROS levels in fibroblasts in vitro and in vivo by activating PPARβ, reducing their release of superoxide anions. Conclusion Our results suggest that PPARβ/FFA1 dual agonist Y8 has the effect of promoting the healing of diabetic ulcer wounds in vivo and in vitro, and its therapeutic effect is better than that of single-target agonists.
研究领域:
药理学
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糖尿病研究
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伤口愈合
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细胞生物学
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DOI
PubMed
高影响因子
Bioengineering-Basel
·
2024
·Vol. 11
·期 8
·772
·
IF 3.8
Zhiqiang Tai,Jiashang Liu,Bixue Wang,Shu Chen,Changsheng Liu,Xi Chen
The impact of traumatic spinal cord injury (SCI) can be extremely devastating, as it often results in the disruption of neural tissues, impeding the regenerative capacity of the central nervous system. However, recent research has demonstrated that mesenchymal stem cells (MSCs) possess the capacity for multi-differentiation and have a proven track record of safety in clinical applications, thus rendering them effective in facilitating the repair of spinal cord injuries. It is urgent to develop an aligned scaffold that can effectively load MSCs for promoting cell aligned proliferation and differentiation. In this study, we prepared an aligned nanofiber scaffold using the porcine decellularized spinal cord matrix (DSC) to induce MSCs differentiation for spinal cord injury. The decellularization method removed 87% of the immune components while retaining crucial proteins in DSC. The electrospinning technique was employed to fabricate an aligned nanofiber scaffold possessing biocompatibility and a diameter of 720 nm. In in vitro and in vivo experiments, the aligned nanofiber scaffold induces the aligned growth of MSCs and promotes their differentiation into neurons, leading to tissue regeneration and nerve repair after spinal cord injury. The approach exhibits promising potential for the future development of nerve regeneration scaffolds for spinal cord injury treatment.
研究领域:
神经科学
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组织工程
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再生医学
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DOI
PubMed
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2026
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IF 3.5
Li Tong,Li Ning,Li Yi,Liu Jinwen,Hao Dajie
Oxidative stress and inflammasome-driven inflammation are key contributors to atherosclerotic disease progression. Here, we report a ROS-responsive hyaluronic acid-PEGDA hydrogel designed for the sustained delivery of palmitoleic acid. In the study, catechol-functionalized hyaluronic acid was cross-linked with polyethylene glycol diacrylate to create an extracellular matrix mimic that possessed tunable mechanical strength and redox-sensitive degradability. It showed controlled release of palmitoleic acid under normal physiological conditions and a faster rate of release under oxidative conditions. In vitro studies using vascular endothelial cells and macrophages demonstrated good cytocompatibility and a marked reduction in intracellular reactive oxygen species, lipid peroxidation, and pro-inflammatory cytokine secretion. At the molecular level, treatment with the palmitoleic acid-loaded hydrogel resulted in activation of AMP-activated protein kinase, inhibition of NF-κB nuclear translocation, and suppression of NLRP3 inflammasome activation, as evidenced by decreased caspase-1 cleavage and IL-1β maturation. These findings indicate that ROS-responsive hydrogel-mediated delivery of palmitoleic acid effectively modulates oxidative and inflammatory signalling pathways relevant to atherosclerosis. Graphical
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PubMed
高影响因子
BIOMATERIALS
·
2026
·
IF 13.6
Chao Xie,Zhongshi Wu,Qiying Wu,Zeguo Chen,Sicheng Chen,Liang Yi,Chao Deng,Haoyong Yuan,Ting Lu,Yuhong Liu,Can Huang
Despite advancements in small-diameter vascular grafts (SDVGs), they continue to face significant clinical challenges, including thrombosis, insufficient endothelialization, and incompatible mechanical properties. To address these limitations, this study developed a heparin-incorporated vascular adventitia extracellular matrix (vaECM)/PCL fiber-co-hydrogel vascular scaffold using electrospinning-co-electrospray technology combined with vaECM self-assembly gelation. This scaffold combines the mechanical strength of PCL fibers with the bioactivity of vaECM hydrogel, while the incorporated heparin enhances its antithrombotic properties. Material characterization reveals that the fiber-co-hydrogel scaffold possesses a biomimetic layered structure, tunable mechanical properties, self-healing ability, low swelling ratio, and hierarchical degradation. Co-culture experiments with endothelial cells and smooth muscle cells demonstrate that this scaffold significantly promotes endothelial cell adhesion, proliferation, and migration, as well as the maturation of smooth muscle cells. Blood compatibility tests confirm its superior anticoagulant and antiplatelet properties. In a rat abdominal aorta replacement model, the scaffold showed significantly enhanced endothelial coverage by week 4, and by week 16, it supported the regeneration of mature vascular smooth muscle and orderly remodeling of the extracellular matrix. These results highlight the remarkable vascular regenerative potential of this fiber-co-hydrogel scaffold, driven by its bioactive vaECM hydrogel and bio-matched material stiffness, offering a promising avenue for the clinical application of small-diameter vascular grafts.
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DOI
PubMed
高影响因子
Applied Materials Today
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2024
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IF 7.2
Yi Wu,Xuan Li,Shaopeng Liu,Ruichen Ma,Peng Liu,Kaiyong Cai
Bone repair in elderly patients is significantly weaker compared to normal bone repair, and one of the main reasons for this is the senescence of bone marrow mesenchymal stem cells (MSCs), which play a key role in the bone repair process. Therefore, we considered the corresponding surface modification of orthopedic implants to cope with the practical problem of bone defects in elderly patients. In this thesis, we prepared TiO 2 nanotubes loaded with metformin (Glucophage) on Ti substrates, followed by self-assembly layer by layer using chitosan-catechol and gelatin on the surface, to delay MSCs senescence by eliminating excessive reactive oxygen species (ROS) and reconstructing extracellular matrix (ECM), thereby achieving osteogenesis. The results showed a significant reduction in senescence-associated secretory phenotype (SASP) generation, an enhancement of PINK1/Parkin-mediated mitochondrial autophagy, and a decrease in intracellular and extracellular ROS levels in MSCs under the dual effects of antioxidants and ECM reconstruction, suggesting that the degree of senescence in MSCs was significantly reduced. Osteogenesis was also demonstrated by expression of osteogenesis-related genes and staining of animal sections. In conclusion, our material can indeed promote the proliferation and osteogenic differentiation of MSCs by delaying cellular senescence, which is expected to provide a novel approach for clinical solutions to tissue repair problems in elderly patients with bone defects.
研究领域:
骨科
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生物材料
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组织工程
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干细胞生物学
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老年医学
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DOI
高影响因子
Science of Advanced Materials
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2015
·Vol. 7
·期 11
·2380-2387
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IF 2.598
Liu Yuangang,Sun Qingqing,Wang Shibin,Fan Jingqian,Chen Aizheng,Wu Wenguo
Normally a useful tissue engineering scaffold should provide suitable micropores and fibrous structure to mimic the natural extracellular matrix (ECM), which can induce desired cellular activities and guide tissue regeneration. In this work, a microporous and micro/nanofibrous silk
fibroin-poly(lactic-co-glycolic acid) (SF-PLGA) scaffold prepared by thermal induced phase separation (TIPS) was described. Minitab statistical software was used to analyze the TIPS parameters effect on the pore size, porosity and fibre diameter. Results showed that the ECM-like architecture
could be achieved by TIPS with the mean porosity 81 ± 16% and the pore size among 0.0–66.7 μm. Besides, cell viability tests revealed that the cells could proliferate on the SF/PLGA scaffolds. These results reveal that the SF-PLGA scaffolds prepared by TIPS are suitable
for the future tissue engineering applications.
研究领域:
生物材料
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组织工程
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生物医学工程
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DOI
高影响因子
BIOMATERIALS
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2020
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IF 10.317
Pingli Wu,Lina Wang,Wen Li,Yu Zhang,Yifan Wu,Dengke Zhi,Hongjun Wang,Lianyong Wang,Deling Kong,Meifeng Zhu
Design and fabrication of scaffolds with three-dimensional (3D) topological cues inducing regeneration of the neo-tissue comparable to native one remains a major challenge in both scientific and clinical fields. Here, we developed a well-designed vascular graft with 3D highly interconnected and circumferentially oriented microchannels by using the sacrificial sugar microfiber leaching method. The microchannels structure was capable of promoting the migration, oriented arrangement, elongation, and the contractile phenotype expression of vascular smooth muscle cells (VSMCs) in vitro . After implantation into the rat aorta defect model, the microchannels in vascular grafts simultaneously improved the infiltration and aligned arrangement of VSMCs and the oriented deposition of extracellular matrix (ECM), as well as the recruitment and polarization of macrophages. These positive results also provided protection and support for ECs growth, and ultimately accelerated the endothelialization . Our research provides a new strategy for the fabrication of grafts with the capability of inducing arterial regeneration, which could be further extended to apply in preparing other kinds of oriented scaffolds aiming to guide oriented tissue in situ regeneration.
研究领域:
组织工程
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生物医学工程
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再生医学
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2018
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IF 5.08
Yiqun Wang,Yi Lu,Jinkang Gong,Yuan Yao
Intermediate filaments, together with actin microfilaments and microtubules constituent the cytoskeleton of mammalian cells, involving in various cellular activities. The roles of intermediate filaments in cell skeleton reorganization when responding with extracellular matrix (ECM) nanostructure are poorly understood yet. To unveil the effects of fibrous composition and orientation on cells, we developed electrospun nanofibers of varying topology and components, and the effects on assembly of intermediate filaments as keratin and vimentin were investigated in detail. We found that aligned nanofibers enhanced expression of E-cadherin and promoted assembly of keratin intermediate filaments. Meanwhile, the compositional variation show different preference on up-regulation of the two intermediate filaments. Compared to keratin, the assembly of vimentin intermediate filaments were promoted by incorporating bovine serum albumin (BSA) functionalized graphene oxide (BSA-GO) into polycaprolactone (PCL) nanofibers. Thus, our findings elucidate how the different physical factors of fibrous extracellular matrix affect the reorganization of cytoskeleton by assembly of keratin and vimentin intermediate filaments.
研究领域:
材料科学
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细胞生物学
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癌症研究
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纳米技术
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Jia-Nan Song,Kun Liu,Jie Mei,Luozixian Wang,Jiao Lin,Ping Du,Yung-Chiang Liu,Yafan Wan,Raymond C. B. Wong,Ji-Ye Yin,Peng-Yuan Wang
Biophysical and biochemical cues modulate mammalian cell behavior and phenotype simultaneously. Macrophages, indispensable cells in the innate immune system, respond to external threats such as bacterial infections and implanted devices, undergoing the classical M1 polarization to become a pro-inflammatory phenotype. In the study, lipopolysaccharide (LPS)-induced M1 polarization was examined using RAW264.7, THP-1, and primary human PBMCs on a family of artificial extracellular matrix (ECM), named colloidal self-assembled patterns (cSAPs). The results showed that cSAPs were biocompatible, which cannot induce M1 or M2 polarization. Interestingly, specific cSAPs (e.g., cSAP3) suppress the level of M1 polarization (i.e., reduced nitric oxide production, down-regulated gene expression of iNOS, IL-6, TNF-α, IL-1β, and TLR4, and reduced proportion of CD11b+CD86+ cells). Transcriptome analysis showed that cell adhesion and cell-ECM interaction participated in the M1 polarization, and the mechano-sensitive genes such as PIEZO1 were down-regulated on the cSAP3. More interestingly, these genes were also down-regulated under LPS stimulation, indicating that cells became insensitive to the LPS. The abovementioned results indicate that the defined physicochemical cues can govern macrophage polarization. This study illustrates a potential surface design at biointerface, which is critical in tissue engineering and materiobiology. The outcome is also inspiring in ECM-mediated immune responses.
研究领域:
免疫学
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组织工程
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生物材料
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细胞生物学
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DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2024
·
IF 4.4
Yingjie Zhou,Yongbiao Xu,Rui Zhang,Haiyang Wang,Fangfang Wang,Zonghuan Wang,Chi Zhang,Zhihan Zhang,Jin Mei,Shengxiang Tao
The skin barrier is essential to prevent pathogenic invasion. When injury occurs, multiple biological pathways are promptly activated and wound repair processes are triggered. The effective healing of wounds is essential for survival, and dysfunction could result from aberrant wound repair. Preparation of many hydrogels, which involve the addition of growth/cell factors or mimic extracellular matrix (ECM) components, has not resulted in significant advances in tissue recovery. ECM contains a large number of biologically active molecules that activate a variety of cellular transduction pathways, which are essential for wound repair. Here, this work prepares hyaluronic acid-dopamine-thiourea (HA-DA-NCSN) hydrogels exhibiting ultrafast gelation in situ, following the methods of Xu et al., and subsequently designs a hydrogel containing ECM particles. In addition, the loaded ECM material, specifically decellularized ECM material, not only enhances the strength of the hydrogel network, but also delivers bioactive substances that make it a suitable platform for skin wound repair. The ECM hydrogel has great potential as an efficient bioactive wound dressing. This research suggests that this strategy is likely to improve skin wound closure in rat skin wound models.
研究领域:
生物医学工程
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组织工程
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伤口护理
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材料科学
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DOI
PubMed
高影响因子
ACS Nano
·
2025
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IF 16
Chunliang Zhang,Chunyuan Wang,Ruitao Cha,Qinghua Meng,Zhan Hu,Yang Sun,Zulan Li,Min Xiao,Yan Zhang,Xingyu Jiang
Extracellular matrix (ECM)-based small-diameter vascular grafts (SDVGs, inner diameter (ID) < 6 mm) hold great promise for clinical applications. However, existing ECM-based SDVGs suffer from limited donor availability, complex purification, high cost, and insufficient mechanical properties. SDVGs with ECM-like structure and function, and good mechanical properties were rapidly prepared by optimizing common materials and preparation, which can improve their clinical prospects. Here, we rapidly prepared an electrospinning film-collagen/red blood cell membrane-genipin hydrogel tube (ES-C/Rm-G-ht, ID = 2 mm) by the combination of the cross-linking of genipin, plastic compression, electrospinning, and rolling without a biological adhesive, which had a shorter preparation time of less than 17 h compared to the existing ECM-based SDVGs (preparation time of 4–18 weeks). ES-C/Rm-G-ht exhibited a layered honeycomb-like structure and demonstrated the ECM-like functions to promote the proliferation and migration of endothelial cells, and prevent thrombus and inflammation. Furthermore, ES-C/Rm-G-ht, possessing sufficient mechanical strength, showed high patency, rapid endothelialization (95%), good regeneration of smooth muscle cell layers and ECM, and effective antistenosis capability after implantation in the rabbit’s carotid artery for 31 days. This work provides a straightforward, cost-effective, and promising strategy to prepare SDVGs with ECM-like structure and function, which is an ideal alternative for vascular grafts and autologous vessels in the current clinic.
研究领域:
组织工程
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生物材料
·
血管生物学
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再生医学
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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
Biomaterials Science
·
2020
·Vol. 8
·期 17
·4779-4791
·
IF 6.183
Chuanchuan Lin,Kun Xu,Ye He,Bailong Tao,Zhang Yuan,Ke Li,Xuemin Li,Zengzilu Xia,Kaiyong Cai
The paracrine function of mesenchymal stromal cells (MSCs) contributes a lot to tissue development, and it is regulated by various physical factors. Moreover, the extracellular matrix (ECM) of MSCs is dynamic, and its remodeling is always occurring. In particular, stiffness changes are prevalent. Accordingly, ECM stiffness changes may affect the paracrine function of MSCs, which has not been investigated much. In this study, for the first time, alginate hydrogels with different stiffening times were used to assess the influence of dynamic ECM stiffness changes on the paracrine function of MSCs. It was found that a stiffer matrix (14.72 ± 1.44 kPa) under static conditions without any additional treatment could significantly potentiate the paracrine function of MSCs compared to a soft matrix (2.44 ± 0.23 kPa). Furthermore, this promotion was regulated by the activation of Yes-associated protein (YAP), which was caused by the polymerization of F-actin. Intriguingly, in a dynamic system, the MSC-encapsulating matrix that stiffened on the third day had stronger YAP activation than the Static-Stiff matrix. However, this activation was weakened when MSCs were cultured in a matrix that stiffened on the fifth day. The results show that an increase in ECM mechanical dosing levels would promote the paracrine function of MSCs. Moreover, an effective mechanical dose that can influence the paracrine function of MSCs indeed exists.
研究领域:
细胞生物学
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组织工程
·
生物力学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）