Regenerative Biomaterials
·
2024
·
IF 5.6
Han Qibin,Bai Lang,Qian Yinhua,Zhang Xiaoyu,Wang Juan,Zhou Jing,Cui Wenguo,Hao Yuefeng,Yang Xing
Tendinopathy is a common disorder that causes local dysfunction and reduces quality of life. Recent research has indicated that alterations in the inflammatory microenvironment play a vital role in the pathogenesis of tendinopathy. Herein, injectable methacrylate gelatin (GelMA) microspheres (GM) were fabricated and loaded with heparin-dopamine conjugate (HDC) and hepatocyte growth factor (HGF). GM@HDC@HGF were designed to balance the inflammatory microenvironment by inhibiting oxidative stress and inflammation, thereby regulating extracellular matrix (ECM) metabolism and halting tendon degeneration. Combining growth factors with heparin was expected to improve the encapsulation rate and maintain the long-term efficacy of HGF. In addition, the catechol groups on dopamine have adhesion and antioxidant properties, allowing potential attachment at the injured site, and better function synergized with HGF. GM@HDC@HGF injected in situ in rat Achilles tendinopathy (AT) models significantly down-regulated oxidative stress and inflammation, and ameliorated ECM degradation. In conclusion, the multifunctional platform developed presents a promising alternative for the treatment of tendinopathy.
研究领域:
生物医学工程
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药理学
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组织工程
·
炎症生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2021
·
IF 15.881
Anlong Liu,Qi Wang,Zinan Zhao,Rui Wu,Maochun Wang,Jiawei Li,Kuoyang Sun,Ziying Sun,Zhongyang Lv,Jia Xu,Huiming Jiang,Mimi Wan,Dongquan Shi,Chun Mao
The microneedle (MN) provides a promising strategy for transdermal delivery of exosomes (EXO), in which the therapeutic effects and clinical applications are greatly reduced by the fact that EXO can only partially reach the injury site by passive diffusion. Here, we designed a detachable MN array to deliver EXO modified by a nitric oxide nanomotor (EXO/MBA) for Achilles tendinopathy (AT) healing. With the releasing of EXO/MBA, l-arginine was converted to nitric oxide by NOS or ROS as the driving force. Benefiting from the motion ability and the property of MPC tending to lower pH, EXO could accumulate at the injury site more efficiently. This work demonstrated that EXO/MBA-loaded MN notably suppressed the inflammation of AT, facilitated the proliferation of tendon cells, increased the expression of Col1a, and prevented extracellular matrix degradation, indicating its potential value in enthesiopathy healing and other related biomedical fields.
研究领域:
生物医学工程
·
药学
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组织工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2024
·Vol. 10
·期 40
·
IF 11.7
Yijie Fang,Dantian Zhu,Jingyue Wei,Lei Qian,Rongmao Qiu,Taoyu Jia,Kui Huang,Suwen Zhao,Jun Ouyang,Man Li,Shaolin Li,Yang Li
Achilles tendinopathy is often attributed to overuse, but its pathophysiology remains poorly understood. Disruption to the molecular structure of collagen is fundamental for the onset and progression of tendinopathy but has mostly been investigated in vitro. Here, we interrogated the in vivo molecular structure changes of collagen in rat Achilles tendons following treadmill running. Unexpectedly, the tendons’ collagen molecules were not mechanically unfolded by running but denatured through proteolysis during physiological post-run remodeling. We further revealed that running induces inflammatory gene expressions in Achilles tendons and that long-term running causes prolonged, elevated collagen degradation, leading to the accumulation of denatured collagen and tendinopathy development. For applications, we demonstrated magnetic resonance imaging of collagenase-induced Achilles tendon injury in vivo using a denatured collagen targeting contrast agent. Our findings may help close the knowledge gaps in the mechanobiology and pathogenesis of Achilles tendinopathy and initiate new strategies for its imaging-based diagnosis.
研究领域:
运动医学
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生物力学
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分子生物学
·
医学影像学
✓ 已验证
DOI
PubMed
高影响因子
BMC MUSCULOSKELETAL DISORDERS
·
2024
·Vol. 25
·期 1
·1-13
·
IF 2.2
Xu Kuishuai,Zhang Liang,Wang Tianrui,Yu Tengbo,Zhao Xia,Yu Ning,Zhang Yingze
Objective To assess the mechanism of supraspinatus tendinopathy induced by type 2 diabetes mellitus (T2DM) in rats using untargeted metabolomics analysis. Methods The liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics approach was used to screen tendon biomarkers of supraspinatus tendinopathy in rats with T2DM. Seventy-eight Sprague-Dawley rats were divided into normal group (NG) and T2DM groups. Rats in T2DM groups were divided into 12-week (T2DM-12w), and 24-week (T2DM-24w) subgroups according to the time point of the establishment of the T2DM rat model. Histological evaluation (modified Bonar score) and biomechanical testing were used to analyze the adverse effects of type 2 diabetes on the tendon of the supraspinatus muscle in rats.Three comparable groups were set up, including T2DM-12w group vs. NG, T2DM-24w group vs. NG, and T2DM-24w group vs. T2DM-12w group. Differentially expressed metabolites (DEMs) in the supraspinatus tendons in the three groups of rats were analyzed using LC-MS, and data were analyzed using multivariate statistical methods to screen potential biomarkers. The DEMs included in the intersection of the three groups were identified as those associated with the development of diabetic supraspinatus tendinopathy, and trend analysis and pathway topology analysis were performed. Results With the progression of diabetes, the tendinopathy of the supracinatus muscle of diabetic rats gradually intensified, mainly manifested as inflammatory reactions, disordered collagen fibers, fat infiltration, and increased modified Bonar score. The intersection of DEMs among the three comparable groups was resulted in the identification of 10 key DEMs, in which melezitose and raffinose showed a continuous increasing trend with the prolongation of disease course. By pathway topology analysis, 10 DEMs ( P < 0.01) were mainly associated with the pathways of galactose metabolism, which could be involved in the development of diabetes-induced supraspinatus tendinopathy. Conclusion T2DM causes tendinopathy of the supraspinatus muscle in rats. 10 key DEMs obtained by untargeted metabolomics assay suggested that the development of diabetes-induced supraspinatus tendinopathy was associated with changes in metabolic pathways, such as galactose metabolism. melezitose and raffinose hold promise as a biomarker for disease discrimination and/or disease indication in diabetic supraspinatus tendinopathy.
研究领域:
代谢组学
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糖尿病研究
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肌肉骨骼疾病
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动物模型
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2024
·Vol. 113
·期 1
·e37844
·
IF 3.9
Qibin Han,Yinhua Qian,Lang Bai,Jing Zhou,Yuefeng Hao,Dan Hu,Zhouzhou Zhang,Xing Yang
Tendinopathy is a disorder characterized by pain and reduced function due to a series of changes in injured or diseased tendons. Inflammation and collagen degeneration are key contributors to the onset and chronic nature of tendinopathy. Acetyl-11-keto-β-boswellic acid (AKBA) is an effective anti-inflammatory agent widely used in chronic inflammatory disorders and holds potential for tendinopathy treatment; however, its therapeutic efficacy is limited by poor aqueous solubility. Here, we fabricated AKBA-encapsulated cationic liposome-gelatin methacrylamide (GelMA) microspheres (GM-Lipo-AKBA) using thin-film hydration and microfluidic technology for drug delivery therapy. GM-Lipo-AKBA exhibited high encapsulation efficiency, extended AKBA release for over 4 weeks, and prolonged degradation. In vitro and in vivo experiments demonstrated its effectiveness in improving inflammation and ECM remodeling in tendinopathy. In summary, the injectable nano-micron drug delivery platform provides a promising strategy for the sustained and localized delivery of AKBA for tendinopathy treatment.
研究领域:
药学
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生物医学工程
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骨科
·
药物递送系统
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炎症研究
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2024
·Vol. 28
·期 20
·e70127
·
IF 4.3
Ming Zhang,Guan-Chun Dai,Yuan-Wei Zhang,Pan-Pan Lu,Hao Wang,Ying-Juan Li,Yun-Feng Rui
Diabetic calcific tendinopathy is the leading cause of chronic pain, mobility restriction, and tendon rupture in patients with diabetes. Tendon stem/progenitor cells (TSPCs) have been implicated in the development of diabetic calcified tendinopathy, but the molecular mechanisms remain unclear. This study found that diabetic tendons have a hyperoxic environment, characterized by increased oxygen delivery channels and carriers. In hyperoxic environment, TSPCs showed enhanced osteogenic differentiation and increased levels of reactive oxygen species (ROS). Additionally, hypoxia-inducible factor-1a (HIF-1a), a protein involved in regulating cellular responses to hyperoxia, was decreased in TSPCs by the ubiquitin-proteasome system. By intervening with antioxidant N-acetyl-L-cysteine (NAC) and overexpressing HIF-1a, we discovered that blocking the ROS/HIF-1a signalling axis significantly inhibited the osteogenic differentiation ability of TSPCs. Animal experiments further confirmed that hyperoxic environment could cause calcification in the Achilles tendon tissue of rats, while NAC intervention prevented calcification. These findings demonstrate that hyperoxia in diabetic tendons promotes osteogenic differentiation of TSPCs through the ROS/HIF-1a signalling axis. This study provides a new theoretical basis and research target for preventing and treating diabetic calcified tendinopathy.
研究领域:
糖尿病
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干细胞生物学
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细胞信号传导
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骨科
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Richun Liu,Bo Zhou,Hong Zhang,Yangwu Chen,Chunmei Fan,Tao Zhang,Tian Qin,Jie Han,Shichen Zhang,Xiao Chen,Weiliang Shen,Jiang Chang,Zi Yin
In the inflammatory environment of tendinopathy, tendon stem/progenitor cells (TSPCs) have been demonstrated to aberrantly differentiate into osteochondral lineage causing late-stage heterotopic ossification (HO) of the tendon, which severely damages tissue function and worsens patients’ activities. However, no effective treatment for tendinopathy currently exist because the mechanism underlying the TSPCs abnormal differentiation is unclear. In this article, high levels of reactive oxygen species (ROS) were found in tendinopathy samples. In vitro results revealed that proanthocyanidins (PC) can potentially regulate the differentiation of TSPCs by scavenging excess ROS, which would promote tenogenesis instead of chondrogenesis or osteogenesis. Moreover, in vivo results demonstrated that PC-loaded mesoporous silica nanocomposite (MSNs-PC) hinders the recurrence of HO in repaired tendons owing to the inhibition of oxidative stress, showing anti-inflammatory effects. Our findings indicate a high level of ROS in tendinopathy, which is probably the cause of aberrant differentiation of TSPCs. MSNs-PCs can effectively ameliorate HO of the tendon by scavenging excess ROS, providing a promising avenue to for other ROS-related diseases.
研究领域:
生物医学工程
·
组织工程
·
纳米技术
·
骨科
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
BMC Medical Genomics
·
2024
·Vol. 17
·期 1
·1-10
·
IF 2.1
Xu Kuishuai,Zhang Liang,Wang Tianrui,Yu Tengbo,Zhao Xia,Zhang Yingze
Objective There is increasing evidence that type 2 diabetes mellitus (T2DM) is an independent risk factor for the occur of tendinopathy. Therefore, this study is the first to explore the dynamic changes of the “gene profile” of supraspinatus tendon in rats at different time points after T2DM induction through transcriptomics, providing potential molecular markers for exploring the pathogenesis of diabetic tendinopathy. Methods A total of 40 Sprague-Dawley rats were randomly divided into normal (NG, n = 10) and T2DM groups (T2DM, n = 30) and subdivided into three groups according to the duration of diabetes: T2DM-4w, T2DM-8w, and T2DM-12w groups; the duration was calculated from the time point of T2DM rat model establishment. The three comparison groups were set up in this study, T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG. Differentially expressed genes (DEGs) in 3 comparison groups were screened. The intersection of the three comparison groups’ DEGs was defined as key genes that changed consistently in the supraspinatus tendon after diabetes induction. Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto encyclopedia of genes and genomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. Results T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG detected 519 (251 up-regulated and 268 down-regulated), 459 (342 up-regulated and 117 down-regulated) and 328 (255 up-regulated and 73 down-regulated) DEGs, respectively. 103 key genes of sustained changes in the supraspinatus tendon following induction of diabetes, which are the first identified biomarkers of the supraspinatus tendon as it progresses through the course of diabetes.The GO analysis results showed that the most significant enrichment in biological processes was calcium ion transmembrane import into cytosol (3 DEGs). The most significant enrichment in cellular component was extracellular matrix (9 DEGs). The most significant enrichment in molecular function was glutamate-gated calcium ion channel activity (3 DEGs). The results of KEGG pathway enrichment analysis showed that there were 17 major pathways ( p < 0.05) that diabetes affected supratinusculus tendinopathy, including cAMP signaling pathway and Calcium signaling pathway. Conclusions Transcriptomics reveals dynamic changes in the“gene profiles”of rat supraspinatus tendon at three different time points after diabetes induction. The 103 DEGs identified in this study may provide potential molecular markers for exploring the pathogenesis of diabetic tendinopathy, and the 17 major pathways enriched in KEGG may provide new ideas for exploring the pathogenesis of diabetic tendinopathy.
研究领域:
分子生物学
·
基因组学
·
糖尿病研究
·
肌肉骨骼疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Fiber Materials
·
2025
·
IF 21.3
Li Chao,Li Wentao,Deng Ronghui,Huang Lingan,Song Yifan,Wei Xianjie,Xu Bingbing,Cui Guoqing,Chen Zehao,Yu Jiakuo
Excessive interface friction and advanced glycation end products (AGEs) disrupt collagen ordered deposition, promoting scar formation in tendinopathies. Inspired by tendon sheath anatomy, we developed a bionic bilayer nano-membrane via electrospinning and photocrosslinking to initiate the directional and orderly regeneration process of tendon tissue. The lubricating layer (PP), containing phosphatidylserine (PS), reduces frictional stress, while the regenerative layer (GM/GV), composed of gelatin methacrylate (GM) and vanillin-modified gelatin (GV), scavenges ROS and mitigates AGEs-induced collagen disorder deposition. This parallel bilayer structure guides tendon cell alignment and promotes ordered collagen deposition. Additionally, vanillin suppresses the AGEs/TGF-β/Smad pathway, reducing scar formation and tissue adhesion. In vitro/in vivo tests showed a fivefold decrease in coefficient of friction (COF) and a tenfold increase in Achilles tendon function index (AFI) compared to the PCL and normal groups, respectively. The PP@GM/GV membrane, regulated by mechano-biochemical coupling factors, offers a promising strategy for tendinopathy repair, and holds significant potential for clinical translation in guiding functional tendon regeneration and improving patient outcomes. Graphical
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
生物材料
·
骨科
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）