Molecular Medicine Reports
·
2016
·Vol. 13
·期 4
·3567-3573
·
IF 1.559
Ke Jiang,Guo Chun,Ziming Wang,Quanyin Du,Aimin Wang,Yan Xiong
Tendon adhesion is a common problem in the healing of injured tendons. The molecular mechanisms of the TGF-β/Smad signaling pathway have been determined, and the role of TGF-β has been well characterized in wound healing. However, the intracellular mechanism or downstream signals by which TGF-β3 modulates its effects on tendon healing have not been well elucidated. The aim of this study was to determine the effect of TGF‑β3 on the TGF-β/Smad signaling pathway in tenocytes. Quantitative polymerase chain reaction and western blot analysis were used to analyze the effect of TGF‑β3 on the regulation of the expression of Smad proteins in tenocytes. The results demonstrated that TGF‑β3 has no significant effect on the proliferation of tendon cells. The addition of TGF‑β3 to tenocytes can significantly downregulate the expression of Smad3 and upregulate the expression of Smad7 at the gene and protein levels. The results demonstrate that TGF‑β3 may regulate Smad3 and Smad7 proteins through the TGF-β/Smad signaling pathway to minimize extrinsic scarring. Thus, it may provide a novel approach to decrease tendon adhesion and promote tendon healing.
研究领域:
分子生物学
·
细胞生物学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Yu Wei,Xing Yun,Yanjun Guan,Shunze Cao,Xiangling Li,Yu Wang,Haoye Meng,Yujie Liu,Qi Quan,Min Wei
Inflammation is part of the natural healing response, but persistent inflammatory events tend to contribute to pathology changes of tendon or ligament. Phenotypic switching of macrophages within the inflammatory niche is crucial for tendon healing. One viable strategy to improve the functional and biomechanical properties of ruptured tendons is to modulate the transition from inflammatory to regenerative signals during tendon regeneration at the site of injury. Here, we developed a tendon repair scaffold made of biodegradable polycaprolactone by electrospinning, which was modified to deliver Wnt3a protein and served as an implant to improve tendon healing in a rat model of Achilles tendon defect. During the in vitro study, Wnt3a protein promoted the polarization of M2 macrophages. In the in vivo experiment, Wnt3a scaffold promoted the early recruitment and counting curve of macrophages and increased the proportion of M2 macrophages. Achilles function index and mechanical properties showed that the implantation effect of the Wnt3a group was better than that of the control group. We believe that this type of scaffold can be used to repair tendon defects. This work highlights the beneficial role of local delivery of biological factors in directing inflammatory responses toward regenerative strategies in tendon healing.
研究领域:
生物材料
·
组织工程
·
再生医学
·
炎症生物学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Qian Zhang,Yansha Qiao,Chaojing Li,Jing Lin,Hui Han,Xiaoli Li,Jifu Mao,Fujun Wang,Lu Wang
The inferior tendon healing after surgery is inextricably linked to the surgical suture. Poor load transfer along the suture often results in a high tendon re-tear rate. Besides, the severe inflammation and infection induced by sutures even cause a second surgery. Herein, to alleviate the above-mentioned issues, a multifunctional suture was fabricated by decorating chitosan/gelatin-tannic acid (CS/GE-TA) on the porous tape suture. The porous tape suture ensured the required mechanical properties and sufficient space for tissue integration. Compared to the pristine suture, the CS/GE-TA decorated suture (TA100) presented a 332% increase in pull-out force from the tendon, indicating potentially decreased re-tear rates. Meanwhile, TA100 showed superior anti-inflammatory and antibacterial performances. In vivo experiments further proved that TA100 could not only reduce inflammatory action but also facilitate collagen deposition and blood vessel formation . These results indicate that the multifunctional sutures are promising candidates for accelerating tendon healing.
研究领域:
生物医学工程
·
组织工程
·
手术材料
✓ 已验证
DOI
PubMed
高影响因子
Advanced Materials Interfaces
·
2023
·
IF 5.4
Weixing Wang,Yifeng Yu,Hao Zhang,Zhiwei Wang,Honglian Dai,Aixi Yu
To solve the problem of tendon adhesion after an operation, an anti-adhesion membrane is designed, which can inhibit the exogenous healing of tendons and promote endogenous healing. Here, poly[3(S)-methyl-morpholine-2,5-dione- co -lactic acid] P(MMD- co -LA) containing alanine units is obtained by melt ring-opening polymerization (ROP). It can effectively reduce the production of acidic degradation products that cause aseptic inflammation. Then a kind of oriented P(MMD- co -LA)/deferoxamine (DFO) anti-adhesion membrane with good mechanical properties, cell adhesion properties, and induced macrophage polarization properties is constructed by electrospinning. In vitro and in vivo studies have shown that oriented fibrous membranes can down-regulate the expression of inflammatory cytokines. In addition, the fibrous membrane can up-regulate the expression of angiogenesis-related genes, namely HIF1-α, SDF-1α, and VEGF, by releasing DFO in situ, thus promoting the revascularization of tendon defects and providing nutritional support for endogenous tendon healing. This method provides a new barrier strategy to reduce tendon adhesion through anti-inflammation combined with vascularization to inhibit exogenous tendon healing while promoting tendon endogenous healing. The results provide essential insights into the corresponding regulation of the tendon healing microenvironment.
研究领域:
生物医学工程
·
组织工程
·
材料科学
·
再生医学
✓ 已验证
DOI
高影响因子
Science Advances
·
2023
·Vol. 9
·期 6
·
IF 13.6
Lei Xiang,Jing Liang,Zhen Wang,Feng Lin,Yaping Zhuang,Qimanguli Saiding,Fei Wang,Lianfu Deng,Wenguo Cui
Mechanical activation of fibroblasts, caused by friction and transforming growth factor–β1 recognition, is one of the main causes of tissue adhesions. In this study, we developed a lubricated gene-hydrogel patch, which provides both a motion lubrication microenvironment and gene therapy. The patch’s outer layer is composed of polyethylene glycol polyester hydrogel. The hydrogel forms hydrogen bonds with water molecules to create the motion lubrication layer, and it also serves as a gene delivery library for long-term gene silencing. Under the motion lubricated microenvironment, extracellular signal–regulated kinase–small interfering RNA can silence fibroblasts and enhance the blocking effect against fibroblast activation. In vitro, the proposed patch effectively inhibits fibroblast activation and reduces the coefficient of friction. In vivo, this patch reduces the expression of vimentin and α–smooth muscle actin in fibroblasts. Therefore, the lubricated gene-hydrogel patch can inhibit the mechanical activation of fibroblasts to promote tendon healing.
研究领域:
生物医学工程
·
组织工程
·
基因治疗
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Wei Chen,Yi Chen,Yiming Ren,Cangjian Gao,Chao Ning,Haotian Deng,Peiqi Li,Yang Ma,Hao Li,Liwei Fu,Guangzhao Tian,Zhen Yang,Xiang Sui,Zhiguo Yuan,Quanyi Guo,Shuyun Liu
Inferior healing and peritendinous adhesions are the major clinical problems following Achilles tendon injury, leading to impaired motor function and an increased risk of re-rupture. These complications are presumed to be inextricably linked to inflammation and fibroscar formation. Here, microRNA29a is identified as a promising therapeutic target for tendon injury through the cross-regulation of the immune response and matrix remodeling. MiR29a-LNPs were successfully prepared by microfluidic technology. They are then loaded into the core-shell nanofibers to achieve local delivery in the injured tendon , where the shell layer is composed of PELA for anti-adhesion. Our studies reveal that miR29a regulates collagen synthesis and NF-κB activation in tenocytes , and promotes macrophage polarization by inhibiting the inflammasome pathway. In vivo studies of the Achilles tendon-rupture model indicate the best repair in the miR29a group, as evidenced by superior collagen composition and alignment, higher mechanical strength , and better functional recovery. In conclusion, a functionalized anti-adhesive membrane that promotes nascent tendon matrix remodeling and improves the regenerative immune microenvironment is developed for the treatment of tendon injury.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Zuofa Yan,Xiangjun Meng,Yun Su,Yiqing Chen,Lidong Zhang,Jialu Xiao
Electrospun membranes and hydrogels are widely used to prevent tendon adhesion. Hydrophobic anti-inflammatory drugs could be fully loaded on the electrospinning membrane through the electrospinning process, which can better prevent tendon adhesion. Basic fibroblast growth factor (bFGF) could promote tendon healing. However, the bioactivity of free bFGF is easily inactivated, therefore, a suitable carrier is needed. As a carrier, hydrogel has little effect on the bioactivity of the protein drugs. In this work, a poly(lactic- co -glycolic) acid (PLGA) electrospun membrane loaded with ibuprofen (IBU) was prepared and named EMI. Additionally, Methoxy poly(ethylene glycol)- block -poly(L-valine) (PEG-PLV) was synthesized. bFGF was added to the PEG-PLV solution, a hydrogel containing bFGF (PLVB) was obtained after gelling. PLVB was applied to the surface of EMI, a double-layer composite membrane named EMI-PLVB was obtained. This membrane was used to prevent Achilles tendon adhesion and promote healing. IBU and bFGF in EMI-PLVB were continuously released in vitro. The inflammatory factors at the tendon healing site were significantly reduced, and the production of type I collagen (Col- I) and type III Collagen (Col-III) at the tendon healing site was also increased in vivo. In conclusion, this double-layer composite membrane drug release system can effectively prevent tendon adhesion and promote tendon healing.
研究领域:
生物医学工程
·
组织工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Jixia Deng,Zhixiao Yao,Shikun Wang,Xinyu Zhang,Lei Zhan,Tongyu Wang,Wenhua Yu,Jiamei Zeng,Jinglei Wu,Shaoju Fu,Shihao Wu,Yuanming Ouyang,Chen Huang
Drug-loaded porous membranes have been deemed to be effective physicochemical barriers to separate postoperative adhesion-prone tissues in tendon healing. However, cell viability and subsequent tissue regeneration might be severely interfered with the unrestricted release and the locally excessive concentration of anti-inflammatory drugs. Herein, we report a double-layered membrane with sustained and uni-directional drug delivery features to prevent peritendinous adhesion without hampering the healing outcome. A vortex-assisted electrospinning system in combination with ibuprofen (IBU)-in-water emulsion was utilized to fabricate IBU-loaded poly-ʟ-lactic-acid (PLLA) fiber bundle membrane (PFB-IBU) as the anti-adhesion layer. The resultant highly porous structure, oleophilic and hydrophobic nature of PLLA fibers enabled in situ loading of IBU with a concentration gradient across the membrane thickness. Aligned collagen nanofibers were further deposited at the low IBU concentration side of the membrane for regulating cell growth and achieving uni-directional release of IBU. Drug release kinetics showed that the release amount of IBU from the high concentration side reached 79.32% at 14 d, while it was only 0.35% at the collagen side. Therefore, fibroblast proliferation at the high concentration side was successfully inhibited without affecting the oriented growth of tendon-derived stem cells at the other side. In vivo evaluation of the rat Achilles adhesion model confirmed the successful peritendinous anti-adhesion of our double-layered membrane, in that the macrophage recruitment, the inflammatory factor secretion and the deposition of pathological adhesion markers such as α-SMA and COL-III were all inhibited, which greatly improved the peritendinous fibrosis and restored the motor function of tendon.
研究领域:
生物医学工程
·
药剂学
·
组织工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）