Biomaterials Science
·
2025
·
IF 5.7
Min Sun,Jinke Cao,Yang Zou,Haiyan Ju,Yonggang Lv
During tendon injury repair, deficiency of basic fibroblast growth factor (bFGF) is a critical factor leading to unsatisfactory repair results. This study aims to prepare bFGF-loaded zeolite imidazole framework-8 (ZIF-8) nanocrystals using one-pot synthesis method. Subsequently, a bilayer nanofibrous membrane incorporating these drug-loaded nanocrystals was fabricated through electrospinning technology. The potential of this composite nanofibrous membrane to facilitate the continuous release of bFGF at the site of tendon injury was evaluated, with the aim of enhancing the quality of tendon repair. The efficacy of the nanofibrous membrane in promoting tendon differentiation, preventing tendon adhesion, and facilitating tendon repair was assessed through both in vitro and in vivo experiments. At the site of tendon injury, the degradation of ZIF-8 in an acidic microenvironment resulted in the release of bFGF and Zn2+, which contribute to the enhancement of tendon repair. ZIF-8 nanocrystals, achieving an encapsulation efficiency of 50.13% ± 1.42%. Following a continuous release period exceeding 40 days, the cumulative in vitro release rate was determined to be 35.02% ± 4.27%. The incorporation of ZIF-8 nanocrystals into a nanofibrous membrane demonstrated the ability to effectively preserve the bioactivity of bFGF while enabling sustained sustained release at the site of tendon injury, thereby facilitating tendon repair. The findings offer novel insights into the treatment of tendon injuries and provide significant theoretical guidance for the tendon repair process.
研究领域:
生物医学工程
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组织工程
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Huamin Li,Ying Zhang,Haidi Wu,Zhanqi Liu,Cheng Guan,Jin Zhang,Jingyi Chen,Shaohua He,Xuewu Huang,Wancheng Gu,Yiu Wing Mai,Jiefeng Gao
It is highly desirable but still remains challenging to develop high-performance hydrogels with satisfactory mechanical properties for tissue engineering. Here, anisotropic yet transparent hydrogels (AHs) are prepared for tendon repair via a facile “poor solvent evaporation assisted hot-stretching” strategy. AHs have great mechanical properties with tensile strength, toughness, and fracture energy as high as 33.14 ± 2.05 MPa, 44.1 ± 3.5 MJ m −3 , and 106.18 ± 7.2 kJ m −2 , respectively. Especially, AHs show unique flaw-insensitive characteristics, and cracks can only deflect along the fiber alignment direction rather than propagate transverse to this direction, showing an interesting self-protection function. The high strength, toughness, and fatigue resistance originate from the hierarchal structure of AHs, i.e., the densified polymeric network comprising fiber bundles and nanofibrils with aligned macromolecular chains, crystalline domains, and intermolecular hydrogen bonds. AHs with superior biocompatibility and swelling resistance can be used to repair rat tendons, and implantation of AHs can promote collagen regeneration for the tendon repair. This study provides a new method to fabricate strong and anti-fatigue hydrogels as a new class of promising materials for soft tissues.
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
Advanced Science
·
2025
·
IF 14.1
Chenguang Ouyang,Tian Tu,Haojie Yu,Li Wang,Zhipeng Ni,Jian Yang,Yanzhao Dong,Xiaodi Zou,Weijie Zhou,Jinyi Liu,Dingning Chen,Yu Wang,Xudong Wu,Hong Yi,Xunchun Yuan,Zhenfeng Liu,Hui Lu
Janus hydrogels have promising applications in tendon healing and anti-peritendinous adhesions. However, their complicated preparation methods, weak mechanical properties, and unstable adhesion interfaces have severely limited their application in suture-free and high-quality tendon healing. In this work, by controlling the interfacial distribution of free -COOH groups and cationic-π structures on both sides of the hydrogels, a series of PZBA-EGCG-ALC Janus hydrogels with varying degrees of asymmetric properties are successfully prepared using a simple and efficient one-step synthesis method. The tensile strength and elongation at the break of the Janus hydrogel are as high as 0.51 ± 0.04 MPa and 922.89 ± 28.59%. In addition, the Janus hydrogel can achieve a high difference in adhesion strength (nearly 20-fold) while maintaining a strong adhesion strength on their bottom sides (up to 524.8 ± 33.1 J m −2 ). In the spatial dimension, its excellent mechanical compliance and one-sided adhesion behavior can provide effective mechanical support and physical barriers for the injured Achilles tendons. More importantly, the Janus hydrogel can also minimize early inflammation generation in the time dimension via its ROS-responsive PZBA-EGCG prodrug macromolecules. This study provided a more effective and convenient suture-free strategy for constructing Janus hydrogels to promote high-quality tendon healing.
研究领域:
生物材料学
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再生医学
·
创伤修复
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
Jingwen Liu,Liang Chen,Zhenyu Sun,Zaijin Tao,Volotovski Pavel,Yusheng Li,Fei Wang,Wenguo Cui,Shen Liu
Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases. However, unidirectional targeting gene therapy is always desired at the tissue interface. In this study, inspired by the principle that like charges repulse each other, a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers, thus realizing unidirectional gene therapy at the tendon-paratenon interface. Under the charge repulsion of positively charged layer, more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue, which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation, but also avoided adverse effects on the fragile endogenous healing of tendon itself. In summary, this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.
研究领域:
生物医学工程
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组织工程
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基因治疗
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DOI
PubMed
高影响因子
Biomed Research International
·
2019
·
IF 2.197
Xuancheng Zhang,Zhaoyi Fang,Eunshinae Cho,Kai Huang,Jinzhong Zhao,Jia Jiang,Xiaoqiao Huangfu
Background. Repairs of large to massive rotator cuff tears have a high failure rate. We investigated the efficacy of a novel, reinforced, low immunogenic, porcine small intestine submucosa (SIS) patch to repair a supraspinatus tendon defect in a rabbit model. We hypothesized that the histological and biomechanical results of SIS patch repair would be comparable with those of autologous fascia lata (FL) repair. Methods. The study mainly comprised two parts. First, the characteristics of the SIS patch were evaluated, including its micromorphology, mechanical properties, and immunogenic properties. Second, a supraspinatus tendon defect model was created in 36 rabbits (72 shoulders). The bilateral shoulders were randomly chosen to undergo repair using either a SIS patch (SIS group) or autologous FL (FL group). At 4, 8, and 12 weeks, histological analysis was performed using four shoulders from each group, and biomechanical tests were performed using eight shoulders from each group. Results. The SIS patch was a three-dimensional construct mainly composed of collagen fibers. The mean single and double suture retention loads of the SIS patch were 48.6 ± 5.8 N and 117.9 ± 2.7 N, respectively. The DNA content in the SIS patch was 53.9 ± 10.9 ng/mg dry weight. Both the histological score and ultimate load to failure increased in a time-dependent manner in both groups, with no significant differences between the SIS and FL groups at 12 weeks. Conclusion. Repair of a large supraspinatus tendon defect using a reinforced, low immunogenic, SIS patch achieves similar effects as autologous FL in a rabbit model. This novel patch might be useful to be employed as a structural tissue replacement in medical activities.
研究领域:
运动医学
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组织工程
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生物材料学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
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2022
·
IF 0
Daisy M. Ramos,Sama Abdulmalik,Michael R. Arul,Naseem Sardashti,Yeshavanth Kumar Banasavadi-Siddegowda,Syam P. Nukavarapu,Hicham Drissi,Sangamesh G. Kumbar
Approximately half of annual musculoskeletal injuries in the US involve tendon tears. The naturally hypocellular and hypovascular tendon environment makes tendons injury-prone and heal slowly. Tendon tissue engineering strategies often use biomimetic scaffolds combined with bioactive factors and/or cells to enhance healing. FDA-approved growth factors to promote tendon healing are lacking, which highlights the need for safe and effective bioactive factors. Our previous work evaluated insulin as a bioactive factor and identified an optimal dose to promote in vitro mesenchymal stem cell survival, division, and tenogenesis. The present work evaluates the ability of insulin-functionalized electrospun nanofiber matrices with or without mesenchymal stem cells to enhance tendon repair in a rat Achilles injury model. Electrospun nanofiber matrices were functionalized with insulin, cultured with or without mesenchymal stem cells, and sutured to transected Achilles tendons in rats. We analyzed rat tendons 4 and 8 weeks after surgery for the tendon morphology, collagen production, and mechanical properties. Bioactive insulin-functionalized fiber matrices with mesenchymal stem cells resulted in significantly increased collagen I and III at 4 and 8 weeks postsurgery. Additionally, these matrices supported highly aligned collagen fibrils in the regenerated tendon tissue at 8 weeks. However, treatment- and control-regenerated tissues had similar tensile properties at 8 weeks, which were less than that of the native Achilles tendon. Our preliminary results establish the benefits of insulin-functionalized fiber matrices in promoting higher levels of collagen synthesis and alignment needed for functional recovery of tendon repair.
研究领域:
再生医学
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组织工程
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生物材料科学
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DOI
PubMed
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2024
·Vol. 72
·期 7
·669-675
·
IF 1.5
Xiongwei Deng,Qiang Li,Haitao Yuan,Hejun Hu,Shaoyong Fan
Tendon injury is a prevalent orthopedic disease that currently lacks effective treatment. Galangin (GLN) is a vital flavonoid found abundantly in galangal and is known for its natural activity. This study aimed to investigate the GLN-mediated molecular mechanism of tendon-derived stem cells (TDSCs) in tendon repair. The TDSCs were characterized using alkaline phosphatase staining, alizarin red S staining, oil red O staining, and flow cytometry. The effect of GLN treatment on collagen deposition was evaluated using Sirius red staining and quantitative (q)PCR, while a Western bot was used to assess protein levels and analyze pathways. Results showed that GLN treatment not only increased the collagen deposition but also elevated the mRNA expression and protein levels of multiple tendon markers like collagen type I alpha 1 (COL1A1), decorin (DCN) and tenomodulin (TNMD) in TDSCs. Moreover, GLN was also found to upregulate the protein levels of transforming growth factor β1 (TGF-β1) and p-Smad3 to activate the TGF-β1/Smad3 signaling pathway, while GLN mediated collagen deposition in TDSCs was reversed by LY3200882, a TGF-β receptor inhibitor. The study concluded that GLN-mediated TDSCs enhanced tendon repair by activating the TGF-β1/Smad3 signaling pathway, suggesting a novel therapeutic option in treating tendon repair.
研究领域:
骨科
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干细胞研究
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Genbin Wu,Binbin Sun,Chunfeng Zhao,Zhuoying Wang,Songsong Teng,Mengkai Yang,Zhi Cui,Guoliang Zhu,Yinxian Yu
Tendon adhesion formation is associated with the aberrant expression of many genes, and interfering with the expression of these genes can prevent adhesion and promote tendon repair. Recent studies have found that silencing the transforming growth factor β-1 (TGF-β1) gene can reduce the occurrence of tendon adhesions. The development of tissue engineering and three-dimensional (3D) printing technology have provided new solutions for tendon repair. In this study, TGF-β1 gene silencing microRNA (miRNA) based RNAi plasmid was loaded on a 3D tendon scaffold using 3D printing technology. In vitro experiments confirmed the sustained release of plasmid and the good biocompatibility of the printed tendon scaffold. Subsequently, the TGF-β1 gene silencing plasmid loaded tendon scaffold was implanted in a chicken tendon defect model to evaluate the effect of the scaffold in vivo. The results from biomechanical tests and histological examinations showed that the scaffold not only promoted tendon regeneration but also prevented tendon adhesion, which was conducive to the recovery of biofunction. Evaluation of protein expression showed that the loaded plasmids prevented tendon adhesion and promoted tendon functional repair via silencing of the TGF-β1 gene.
研究领域:
组织工程
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再生医学
·
分子生物学
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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
EXPERIMENTAL ANIMALS
·
2022
·
IF 1.798
Kai KANG,Lukuan CUI,Qian ZHANG,Shijun GAO
Although many surgical or non-operative therapies have been developed to treat Achilles tendon injuries, the prognosis of which is often unsatisfactory. Recently, biologic approaches using multipotent stem cells like tendon-derived stem cells (TDSCs) pose a possible treatment option. To evaluate whether the Leucine rich repeat containing 32 (Lrrc32) affects the tenogenic differentiation of TDSCs and thus promotes Achilles tendon healing. TDSCs were infected with the recombinant Lrrc32-overexpressing lentivirus (LV-Lrrc32) and then locally injected into the injured site of rat. Four weeks after surgery, the Achilles tendon tissue (~0.5 cm) around the injured area was harvested for analysis. Pathological results showed that Lrrc32-overexpressing TDSCs significantly improved the morphological changes of the injured tendons. Specifically, the increased collagen-I expression and hydroxyproline content in extracellular matrix, and more orderly arrangement of the regenerated collagen fibers were observed in the Lrrc32 overexpression group. Moreover, 4 weeks after injection of Lrrc32-overexpressing TDSCs, the expression of tenocyte-related genes such as tenomodulin (Tnmd), scleraxis (Scx) and decorin (Dcn) were upregulated in the area of the healing tendon. These findings indicated that Lrrc32 promoted the tenogenic differentiation of TDSCs in vivo. Additionally, Lrrc32 overexpression also increased the expression of TGF-β1 and p-SMAD2/3, suggesting that the beneficial effects of Lrrc32 on tendon repair might be associated with the expression of TGF-β1 and p-SMAD2/3. Our findings collectively revealed that Lrrc32-overexpressed TDSCs promoted tendon healing more effectively than TDSCs alone.
研究领域:
干细胞生物学
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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
PubMed
高影响因子
Science China-Chemistry
·
2015
·Vol. 58
·期 7
·1159-1168
·
IF 1.695
Song Zhiming,Shi Bo,Ding Jianxun,Zhuang Xiuli,Zhang Xiaonan,Fu Changfeng,Chen Xuesi
Complications arising from tendon injury include tendon sheath infection and peritendinous adhesion, in which tendon adhesion often leads to serious motor dysfunction. In this work, the electrospun membranes of poly( L -lactide) (PLA) and poly(ε-caprolactone) (PCL) with different degradation kinetics were used to investigate their efficacy for anti-adhesion toward Achilles tendon repair. Compared with the PCL membrane, the PLA sample showed a faster rate of degradation in 42 d, and all the degradation media (i.e., phosphate-buffered saline) maintained at a constant pH of around 7.4. Meanwhile, the superior biocompatibility of both the PLA and PCL membranes were proved by the in vitro cellular adhesion tests and in vivo histopathological assays. Simultaneously, the PLA membrane was more effective than the PCL sample in decreasing adhesion and promoting functional recovery. Furthermore, the experiment result was further confirmed by hematoxylin-eosin and Masson’s trichrome staining, and type I collagen immunohistochemical analysis. All results revealed that the model treated with the electrospun PLA membrane was obviously better with regard to both anti-adhesion and tendon repair than that in the PCL membrane group. Considering the results of degradation and adhesion prevention efficacy, the electrospun polyester membranes, especially the PLA one, would be applied with fascinating potential in clinical prevention of postoperative tendon adhesion.
研究领域:
生物材料
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组织工程
·
骨科手术
·
生物医学工程
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产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Zhencheng Xiong,Bingqing Lin,Cheng Huang,Ao Duan,Chaoyi Zhang,Guangliang Qiang,Wenzheng Liu,Renliang Zhao,Xiangtian Deng,Dong Wang,Zilu Ge,Guanglin Wang,Xiaoran Hu,Wei Lin
Achilles tendon rupture is a common and serious condition that remains a challenge in the restoration of tendon structure and function. The design and use of high-performance piezoelectric materials serve as an effective solution to enhance repair outcomes, shorten recovery times, and reduce the risk of recurrence. In this study, we prepared a chitosan piezoelectric gel (CSPG) as an organic polymer with excellent biocompatibility, stretchability, and piezoelectric properties as well as excellent antibacterial properties. In vitro experiments showed that CSPG, which induces a piezoelectric effect, can inhibit bacterial growth, promote cell proliferation and migration, upregulate the expression of tendon-related genes, and inhibit the expression of inflammation-related genes. In vivo experiments showed improved outcomes for Achilles tendon repair following CSPG intervention, as evidenced by enhanced animal mobility and improved mechanical test results. In addition, the CSPG exhibited sensory functions capable of monitoring temperature and motion, providing timely feedback on repair efficacy. In summary, this study not only successfully prepared a multifunctional piezoelectric material that can effectively promote Achilles tendon rupture repair and regeneration and control inflammatory response, it also possesses antibacterial and sensing functions, thus offering a new strategy for Achilles tendon rupture repair.
研究领域:
生物材料
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组织工程
·
生物医学工程
·
骨科
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材料科学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2022
·
IF 9.417
Qiang Zhang,Kui Ma,Chun-Hei Lam,Ho-Pan Bei,Yu Liu,Xing Yang,Xin Zhao
Despite promise in preventing peritendinous adhesion, electrospun membranes face many challenges related to their complex fabrication process, untargeted/uncontrolled drug delivery and consequently low therapeutical effect. Here, a micro-and nano-environment dual-modulated barrier membrane (MNBM) with on-demand gene delivery capability is presented. Our MNBM is developed by first preparing extracellular signal-regulated kinase-2 (ERK2) siRNA-loaded gelatin methacryloyl (GelMA) nanogels via facile nano-emulsification technique, then incorporating these nanogels into poly-L-lactic acid (PLLA) fibers via simple blending electrospinning. The GelMA nanogels offer a nano-niche for ERK2-siRNA encapsulation and allow for a nano-environment controlled siRNA release by readily tuning the GelMA concentrations during nano-emulsification, while the resultant MNBM can mediate a micro-environment controlled siRNA delivery in response to the matrix metalloproteinase-2 (MMP-2) enriched micro-environment at the tendon repair site. Such MNBM can not only biologically orchestrate fibroblast behaviors by silencing the target gene expression, but also physically shield the tendon from extrinsic cell/tissue invasion. This study provides a proof-of-concept of anti-adhesion barrier membrane as an intelligent gene delivery system to offer a spatiotemporal and biophysical dual control over tendon recovery according to disease state and ensure long-term therapeutic efficacy. We envision such MNBM represents a promising therapeutic platform with great efficacy to achieve adhesion-free tendon repair.
研究领域:
生物医学工程
·
组织工程
·
基因治疗
·
材料科学
✓ 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）