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Aging-US · 2021 · IF 5.682

Hsa-circ-0007292 promotes the osteogenic differentiation of posterior longitudinal ligament cells via regulating SATB2 by sponging miR-508-3p

Anlong Jiang,Nanxiang Wang,Xinxing Yan,Yunheng Jiang,Chengchao Song,Hui Chi,Guanghua Chen,Feng Wu,Ye Ji,Jinglong Yan

Ossification of the posterior longitudinal ligament (OPLL) is a disorder with multiple pathogenic mechanisms and leads to different degrees of neurological symptoms. Recent studies have revealed that non-coding RNA (ncRNA), including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), could influence the development of OPLL. Nevertheless, the molecular mechanisms linking circular RNAs (circRNAs) and the progression of OPLL is still unknown. The current research explored the expression profiles of OPLL-related circRNAs by microarray analysis, and applied qRT-PCR to validate the results. Subsequently, we confirmed the upregulation of hsa_circ_0007292 in OPLL cells by qRT-PCR and validated the circular characteristic of hsa_circ_0007292 by Sanger sequencing. Fluorescence in situ hybridization (FISH) unveiled that hsa_circ_0007292 was predominantly located in the cytoplasm. Functionally, gain-of-function and loss-of-function experiments showed that hsa_circ_0007292 promoted the osteogenic differentiation of OPLL cells. Mechanistically, the interaction of hsa_circ_0007292 and miR-508-3p was predicted and validated by bioinformatics analysis, dual-luciferase reporter assays, and Ago2 RNA immunoprecipitation (RIP). Similarly, we validated the correlation between miR-508-3p and SATB2. Furthermore, rescue experiments were performed to prove that hsa_circ_0007292 acted as a sponge for miR-508-3p, and SATB2 was revealed to be the target gene of miR-508-3p. In conclusion, our research shows that hsa_circ_0007292 regulates OPLL progression by the miR-508-3p/SATB2 pathway. Our results indicate that hsa_circ_0007292 can be used as a promising therapeutic target for patients with OPLL.

CAS / MDL: 50-81-7 50-02-2
研究领域: 分子生物学 · 遗传学 · 骨科
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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

Trans-Tissue Photothermal Stimulation Accelerates In Situ Repair after ACL Reconstruction: Calcium/Copper Reservoir Scaffold-Mediated Strategy

Shibo Liu,Hao Wang,Xiaohan Mei,Zehao Yu,Dapeng Zeng,Xiangjun Pan,Boda Ying,Xinyu Xu,Chuanyao Dong,Si Pu,Xiaoming Dong,Ruiyan Li,Yanguo Qin

Rapid rehabilitation of the ligament-bone interface following anterior cruciate ligament (ACL) reconstruction remains challenging due to poor vascularization and inadequate integration between graft, bone tunnel, and scaffold. Conventional rehabilitation stimuli are limited by their shallow tissue penetration, which fails to effectively target the bone tunnel. This study proposes a synergistic strategy using a dual calcium/copper reservoir-functionalized scaffold with trans-tissue mild photothermal therapy (mPTT, 40–42 °C) to promote phase-specific healing.​ A 3D-printed polyetherimide (PEI) scaffold incorporating Calcium carbonate (CaCO 3 ) serves as a calcium reservoir, while it is modified with a Cupric oxide-polydopamine (CuO-PDA) coating, serving both as a copper reservoir and a photothermal agent. Upon implantation, the rapid release of Cu 2+ accelerates early-stage vascularization, while sustained release of Ca 2+ creates a calcium-enriched osteogenic microenvironment, promoting osteogenic differentiation and bone regeneration. Crucially, near-infrared light-triggered activation of the CuO-PDA coating enables trans-tissue mPTT. This upregulates heat shock protein expression, which synergistically enhances reservoir-driven osteogenesis and collagen remodeling. This study marks the first application of mPTT in ligament-bone healing. This synergistic platform facilitates direct thermal stimulation and in situ repair at the ACL reconstruction site, offering a novel therapeutic strategy to enhance post-surgical recovery following ligament reconstruction with bone–interface fixation scaffolds.

CAS / MDL: 1317-38-0 62-31-7
研究领域: 骨科生物材料 · 组织工程 · 再生医学 · 运动医学 · 生物医学工程 · 分子骨科学
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Bioactive Materials · 2023 · IF 18.9

Multiphasic bone-ligament-bone integrated scaffold enhances ligamentization and graft-bone integration after anterior cruciate ligament reconstruction

Xianrui Xie,Jiangyu Cai,Dan Li,Yujie Chen,Chunhua Wang,Guige Hou,Thorsten Steinberg,Bernd Rolauffs,Mohamed EL-Newehy,Hany EL-Hamshary,Jia Jiang,Xiumei Mo,Jinzhong Zhao,Jinglei Wu

The escalating prevalence of anterior cruciate ligament (ACL) injuries in sports necessitates innovative strategies for ACL reconstruction. In this study, we propose a multiphasic bone-ligament-bone (BLB) integrated scaffold as a potential solution. The BLB scaffold comprised two polylactic acid (PLA)/deferoxamine (DFO)@mesoporous hydroxyapatite (MHA) thermally induced phase separation (TIPS) scaffolds bridged by silk fibroin (SF)/connective tissue growth factor (CTGF)@Poly( l -lactide-co-ε-caprolactone) (PLCL) nanofiber yarn braided scaffold. This combination mimics the native architecture of the ACL tissue. The mechanical properties of the BLB scaffolds were determined to be compatible with the human ACL. In vitro experiments demonstrated that CTGF induced the expression of ligament-related genes, while TIPS scaffolds loaded with MHA and DFO enhanced the osteogenic-related gene expression of bone marrow stem cells (BMSCs) and promoted the migration and tubular formation of human umbilical vein endothelial cells (HUVECs). In rabbit models, the BLB scaffold efficiently facilitated ligamentization and graft-bone integration processes by providing bioactive substances. The double delivery of DFO and calcium ions by the BLB scaffold synergistically promoted bone regeneration, while CTGF improved collagen formation and ligament healing. Collectively, the findings indicate that the BLB scaffold exhibits substantial promise for ACL reconstruction. Additional investigation and advancement of this scaffold may yield enhanced results in the management of ACL injuries.

CAS / MDL: 57-09-0 371-90-4
研究领域: 生物医学工程 · 运动医学 · 组织工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMISTRY OF MATERIALS · 2025 · IF 7

Bioinspired Structure with Hierarchical Hydrogen Bonding and Metal Coordination for Enhanced Properties of Biobased Polyurethane Applied in Artificial Ligaments

Junjie Wang,Xiaoyu Dong,Haojie Qiu,Zhixiu Liu,Yufeng Kang,Jinghua Du,Xuefeng Yang,Xue-liang Li,Yunsheng Ding

The utilization of biobased polyurethanes in medical engineering is constrained by their inferior mechanical properties. A variety of strategies that aim to improve the mechanical properties of these materials have been developed to meet the specific requirements of biomedical applications. Inspired by the chemical structure of the jawbone of a marine worm called Nereis, the polymer chain can be coordinated with zinc ions to improve biobased polyurethane mechanical properties. In this study, a series of biobased polyurethanes were synthesized via a prepolymerization process involving the usage of biobased polycarbonate diol in conjunction with lysine diisocyanate and isophorone diisocyanate, followed by the addition of isophorone diamine and 2-amino-5-(2-hydroxyethyl)-6-methylpyrimidin-4-ol to complete the chain expansion along with the addition of Zn2+ for coordination. The mechanical properties (including tensile, cycling, and fatigue resistance) and biocompatibility of the biobased polyurethanes were evaluated through a series of tests. The resulting biobased polyurethane, comprising a bioinspired syngeneic structure, exhibited remarkable properties, including a tensile strength of 40.6 MPa, a toughness of 147.6 MPa/m3, and an energy recovery of 91.6%, which represents a 167% improvement in toughness compared to the biobased polyurethane without metal coordination. Furthermore, the biobased polyurethane with the syngenetic effect of hierarchical hydrogen bonding and metal coordination retains 80.2% of its strength after 300 cycles without any crack propagation. In addition, the good biocompatibility of biobased polyurethanes indicates the possibility of in vivo bioapplication, so they should have potential application in artificial ligaments.

研究领域: 材料科学 · 生物医学工程 · 组织工程
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CELLULAR AND MOLECULAR LIFE SCIENCES · 2024 ·Vol. 81 ·期 1 ·1-16 · IF 6.2

N6-methyladenosine-modified circCDK14 promotes ossification of the ligamentum flavum via epigenetic modulation by targeting AFF4

Zhao Yongzhao,Chen Longting,Xiang Qian,Lin Jialiang,Jiang Shuai,Li Weishi

Background The ligamentum flavum (LF) is an important anatomical structure of the spine. Ossification of the LF (OLF) has become the leading cause of thoracic spinal stenosis. Circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification are reported to be associated with several human diseases. However, the role of circRNAs and m6A modification in the pathogenesis of OLF has not been fully investigated. Here, we aimed to explore the vital function of circRNAs and m6A modification in OLF. Materials and methods We analysed the circRNA expression of 4 OLF tissues and 4 normal LF tissues using bioinformatic analysis and identified circCDK14 for further analysis. We investigated the effects of circCDK14 on the osteogenic differentiation of LF cells. We observed that circCDK14 regulated its target genes by binding to miRNAs as a miRNA sponge. Moreover, the circRNA pull-down assay indicated that RNA-binding proteins might regulate the expression of circCDK14 via m6A modification. Results CircCDK14 was significantly upregulated in OLF tissues compared to normal LF tissues. Overexpression of circCDK14 promoted the osteogenic differentiation of LF cells. Mechanistically, CircCDK14 promoted the expression of ALF transcription elongation Factor 4 (AFF4) by serving as a sponge for miR-93-5p. Moreover, Wilms tumour 1-associated protein (WTAP) increased the stability of circCDK14 via N6-methyladenosine modification. Conclusion The m6A-modified CircCDK14 binding to miR-93-5p played an important role in the osteogenesis of LF cells by targeting AFF4, providing a promising therapeutic target for OLF.

CAS / MDL: 1122-62-9
研究领域: 分子生物学 · 表观遗传学 · 骨科 · 生物信息学
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Amelogenin-Derived Peptide-Modified Poly(amidoamine) Dendrimers for Root Caries Prevention

Xue Cai,Yuxing Chen,Jilin Wu,Aijing Wang,Xiaoyan Wang

Root caries present a significant challenge in dentistry. The unsatisfactory prognosis of restorative treatments requires novel, noninvasive preventive strategies. Here, we developed an amelogenin-derived peptide-modified poly(amidoamine), PAMAM-C11, to prevent demineralization in caries lesions and control periodontal destruction. PAMAM can induce dentin remineralization, whereas the C11 peptide strongly binds hydroxyapatite. When C11 is modified on the surface groups of PAMAM, it anchors the entire molecule on demineralized dentin surfaces, thereby resisting washout and enhancing the mineralization efficiency, especially in the presence of collagenase in the cariogenic environment. PAMAM-C11 also inhibits matrix metalloproteinases in dentin and periodontal tissues, protecting the necessary mineralization templates and controlling periodontal destruction. Furthermore, PAMAM-C11 can promote the proliferation and osteogenic differentiation of periodontal ligament stem cells, indicating its potential use in periodontal regeneration. These findings were ultimately validated in an in vivo rat caries model. It can be concluded that PAMAM-C11 has great potential for clinical applications on root caries prevention.

研究领域: 牙科学 · 生物材料学 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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COMPOSITES PART B-ENGINEERING · 2024 · IF 12.7

Directional anneal-casting strategy enables mechanically enhanced biomimetic hydrogel for ligament reconstruction

He Zhu,Cheng Wang,Chen Xin,Ziyi Dai,Yican Yang,Yan Li,Mingrui Wang,Yang Zhang,Shouwei Yue,Rong Cai,Kai Qian

Artificial ligaments play a crucial role in replacing injured natural ligaments and facilitating rehabilitation. However, existing artificial ligaments lack real-time strain monitoring capability, which limits personalized rehabilitation guidance. Here, we develop a highly biomimetic and intelligent electronic hydrogel ligament (IEHL) based on polyvinyl alcohol/sodium alginate through a universal directional anneal-casting (DAC) strategy. This innovative approach creates aligned microstructures that overcome conventional hydrogels' limitations of poor structural integrity and inadequate mechanical properties. The IEHL exhibits integrated bionics of microstructure, mechanical parameters and water content closely matching natural ligaments. The efficacy of the IEHL in stabilizing knee joint and monitoring movements is validated through in vivo models, and a wireless monitoring system is developed to detect and analyze ligament strain characteristics in real-time. This IEHL provides a superior intraoperative replacement strategy and quantitative guidance for post-surgical rehabilitation.

CAS / MDL: 9002-89-5
研究领域: 生物材料学 · 再生医学 · 运动医学
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APPLIED SURFACE SCIENCE · 2011 · IF 1.795

Composite coating of 58S bioglass and hydroxyapatite on a poly (ethylene terepthalate) artificial ligament graft for the graft osseointegration in a bone tunnel

Hong Li,Yang Wu,Yunsheng Ge,Jia Jiang,Kai Gao,Pengyun Zhang,Lingxiang Wu,Shiyi Chen

The purpose of this study was to determine the effect of the combination of hydroxyapatite (HA) and bioglass (BG) on polyethylene terephthalate (PET) artificial ligament graft osseointegration within the bone tunnel. The results of in vitro culturing of MC3T3-E1 mouse osteoblastic cells proved that this HA/BG composite coating can promote the cell compatibility of grafts. A rabbit extraarticular tendon-to-bone healing model was used to evaluate the effect of this composite coating on PET artificial ligaments in vivo. The final results demonstrated that HA/BG coating improved new bone formation at the graft-bone interface and increased the load-to-failure property of graft in bone tunnel compared to the control group at early time. The study has shown that HA/BG composite coating on the PET artificial ligament surface has a positive effect in the induction of artificial ligament osseointegration within the bone tunnel.

研究领域: 生物材料学 · 骨科医学
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ACS Nano · 2022 · IF 18.027

Ultrastretchable Organogel/Silicone Fiber-Helical Sensors for Self-Powered Implantable Ligament Strain Monitoring

Feifan Sheng,Bo Zhang,Yihan Zhang,Yanyan Li,Renwei Cheng,Chuanhui Wei,Chuan Ning,Kai Dong,Zhong Lin Wang

Implantable sensors with the abilities of real-time healthcare monitoring and auxiliary training are important for exercise-induced or disease-induced muscle and ligament injuries. However, some of these implantable sensors have some shortcomings, such as requiring an external power supply or poor flexibility and stability. Herein, an organogel/silicone fiber-helical sensor based on a triboelectric nanogenerator (OFS-TENG) is developed for power-free and sutureable implantation ligament strain monitoring. The OFS-TENG with high stability and ultrastretchability is composed of an organogel fiber and a silicone fiber intertwined with a double helix structure. The organogel fiber possesses the merits of rapid preparation (15 s), good transparency (>95%), high stretchability (600%), and favorable stability (over 6 months). The OFS-TENG is successfully implanted on the patellar ligament of the rabbit knee for the real-time monitoring of knee ligament stretch and muscle stress, which is expected to provide a solution for real-time diagnosis of muscle and ligament injuries. The prepared self-powered OFS-TENG can monitor data on human muscles and ligaments in real-time.

研究领域: 生物医学工程 · 材料科学 · 运动医学
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Stem Cells Translational Medicine · 2019 ·Vol. 8 ·期 9 ·971-982 · IF 5.962

Anterior Cruciate Ligament Reconstruction in a Rabbit Model Using a Decellularized Allogenic Semitendinous Tendon Combined with Autologous Bone Marrow-Derived Mesenchymal Stem Cells

Lu Wei,Xu Jian,Dong Shikui,Xie Guoming,Yang Shuanghui,Huangfu Xiaoqiao,Li Xiaoxi,Zhang Yang,Shen Peng,Yan Zhaowen,Liu Haifeng,Deng Zhenhan,Zhao Jinzhong

As a regular adoptable material for anterior cruciate ligament (ACL) reconstruction, free tendon allograft exhibits unsatisfactory outcomes, such as retarded ligamentization and tendon–bone integration. The application of bone marrow-derived mesenchymal stem cells (BMSCs), as well as a decellularized free tendon allograft developed by our group, was proven to be effective in improving ACL reconstruction results. This study aimed to investigate the efficacy and feasibility of decellularized allogenic semitendinous tendon (ST) combined with autologous BMSCs used as a substitute to free tendon allograft in a rabbit model. This study finally shows that the decellularized allogenic ST combined with autologous BMSCs could significantly improve ACL reconstruction results compared with allograft. Stem Cells Translational Medicine  2019;8:971–982Significance StatementFree tendon allograft exhibits unsatisfactory outcomes, such as retarded ligamentization and tendon–bone integration. The application of bone marrow-derived mesenchymal stem cells, as well as a decellularized free tendon allograft developed by the authors, was proven to be effective in improving anterior cruciate ligament reconstruction results.

CAS / MDL: 9003-01-4 9003-04-7
研究领域: 运动医学 · 再生医学 · 组织工程
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A · 2022 ·Vol. 111 ·期 2 ·170-184 · IF 4.854

Feasibility study of oxidized naringin as a novel crosslinking agent for crosslinking decellularized porcine Achilles tendon and its potential application for anterior cruciate ligament repair

Can Cheng,Xu Peng,Linjie Xi,Yihao Luo,Yuhang Wang,Yufan Zhou,Xixun Yu

Naringin (Nar), a natural flavanone glycoside, has been shown to possess a variety of biological activities, including anti-inflammatory, anti-apoptotic, bone formation, and so forth. In this study, Nar was oxidized by sodium periodate and the oxidized naringin (ONar) was used as a novel biological crosslinking agent. In addition, ONar-fixed porcine decellularized Achilles tendon (DAT) was developed to substitute anterior cruciate ligament (ACL) for researching a novel ACL replacement material. The ONar with a 24 h oxidation time had appropriate aldehyde group content, almost no cytotoxicity, and a good crosslinking effect. The critical characteristics and cytocompatibility of ONar-fixed DAT were also investigated. The results demonstrated that 1% ONar-fixed DAT exhibited good resistance to enzymatic degradation and thermal stability as well as suitable mechanical strength. Moreover, 1% ONar-fixed specimens exhibited excellent L929 fibroblasts-cytocompatibility and MC3T3-E1-cytocompatibility. They also promoted the secretion of hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) from fibroblasts and bone morphogenetic protein-2 (BMP-2) from osteoblasts. And they also showed the good anti-inflammatory properties in vivo experiments. Our data provided an experimental basis for ONar as a new cross-linking reagent in chemical modification of DAT and ONar-fixed DAT for ACL repair.

CAS / MDL: 9003-98-9 9001-99-4
研究领域: 生物医学工程 · 组织工程 · 材料科学
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INTERNATIONAL ORTHOPAEDICS · 2010 ·Vol. 35 ·期 10 ·1561-1567 · IF 1.825

Hydroxyapatite coating enhances polyethylene terephthalate artificial ligament graft osseointegration in the bone tunnel

Li Hong,Ge Yunsheng,Wu Yang,Jiang Jia,Gao Kai,Zhang Pengyun,Wu Lingxiang,Chen Shiyi

The purpose of this study was to investigate whether hydroxyapatite (HAp) coating could induce polyethylene terephthalate (PET) artificial ligament graft osseointegration in the bone tunnel. Twenty-four New Zealand white rabbits underwent artificial ligament graft transplantation in bilateral proximal tibia tunnels. One limb was implanted with HAp-coated PET graft, and the contralateral limb was implanted with non-HAp-coated PET graft as control. The rabbits were randomly sacrificed at four and eight weeks after surgery. The loads to failure of the experimental group at eight weeks were significantly higher than those of the control group ( p  = 0.0057). Histologically, application of HAp coating induced new bone formation between graft and bone at eight weeks compared with the controls. Real-time polymerase chain reaction examination revealed significantly elevated messenger ribonucleic acid expression levels of osteopontin and collagen I in the grafts of the HAp group compared with the controls at four weeks ( p  < 0.05). The study has shown that HAp coating on the PET artificial ligament surface has a positive effect in the induction of artificial ligament osseointegration within the bone tunnel.

研究领域: 骨科 · 生物材料 · 组织工程
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