Tendon adhesion

肌腱粘连
  • 文章类型: Journal Article
    肌腱损伤后粘连的形成是肌腱修复的主要障碍,目前临床上尚无有效的防粘连方法。氧化应激,炎症,肌腱损伤可发生纤维化,这些因素可导致肌腱粘连。抗氧化碳点和熊果酸(UA)都具有抗氧化和抗炎特性。在这个实验中,我们首次使用红色荧光碳点和UA共包裹的脂质体复合透明质酸甲基丙烯酰水凝胶创建了RCDs/UA@Lipo-HAMA。我们发现RCD/UA@Lipo-HAMA可以更好地减轻肌腱损伤中的粘连形成并增强肌腱愈合。
    制备并表征RCD/UA@Lipo-HAMA。进行了细胞氧化应激和纤维化的体外实验。活性氧(ROS),和I型胶原蛋白(COLI)的免疫荧光染色,胶原蛋白III型(COLIII),和α-平滑肌肌动蛋白(α-SMA)用于评估抗氧化和抗纤维化能力。建立跟腱损伤修复(ATI)和趾深屈肌腱损伤修复(FDPI)的体内模型。对大鼠的主要器官和血液生化指标进行检测,以确定RCD/UA@Lipo-HAMA的毒性。生物力学测试,运动功能分析,免疫荧光,并进行免疫组织化学染色以评估肌腱损伤后的肌腱粘连和修复。
    体外,RCD/UA@Lipo组清除了过量的ROS,稳定线粒体膜电位(ΔkW),并降低COLI的表达,COLIII,和α-SMA。在体内,评估结果表明,RCDs/UA@Lipo-HAMA组改善了胶原排列和生物力学特性,减少肌腱粘连,促进肌腱损伤后的运动功能。此外,RCDs/UA@Lipo-HAMA组核因子红细胞相关因子2(Nrf2)和血红素加氧酶1(HO-1)的表达增加;分化簇68(CD68)诱导型一氧化氮合酶(iNOS),COLIII,α-SMA,Vimentin,基质金属肽酶2(MMP2)降低。
    在这项研究中,RCD/UA@Lipo-HAMA通过减轻氧化应激减轻肌腱粘连形成并增强肌腱愈合,炎症,和纤维化。本研究为肌腱损伤的临床治疗提供了一种新的治疗方法。
    UNASSIGNED: The formation of adhesion after tendon injury represents a major obstacle to tendon repair, and currently there is no effective anti-adhesion method in clinical practice. Oxidative stress, inflammation, and fibrosis can occur in tendon injury and these factors can lead to tendon adhesion. Antioxidant carbon dots and ursolic acid (UA) both possess antioxidant and anti-inflammatory properties. In this experiment, we have for the first time created RCDs/UA@Lipo-HAMA using red fluorescent carbon dots and UA co-encapsulated liposomes composite hyaluronic acid methacryloyl hydrogel. We found that RCDs/UA@Lipo-HAMA could better attenuate adhesion formation and enhance tendon healing in tendon injury.
    UNASSIGNED: RCDs/UA@Lipo-HAMA were prepared and characterized. In vitro experiments on cellular oxidative stress and fibrosis were performed. Reactive oxygen species (ROS), and immunofluorescent staining of collagens type I (COL I), collagens type III (COL III), and α-smooth muscle actin (α-SMA) were used to evaluate anti-oxidative and anti-fibrotic abilities. In vivo models of Achilles tendon injury repair (ATI) and flexor digitorum profundus tendon injury repair (FDPI) were established. The major organs and blood biochemical indicators of rats were tested to determine the toxicity of RCDs/UA@Lipo-HAMA. Biomechanical testing, motor function analysis, immunofluorescence, and immunohistochemical staining were performed to assess the tendon adhesion and repair after tendon injury.
    UNASSIGNED: In vitro, the RCDs/UA@Lipo group scavenged excessive ROS, stabilized the mitochondrial membrane potential (ΔΨm), and reduced the expression of COL I, COL III, and α-SMA. In vivo, assessment results showed that the RCDs/UA@Lipo-HAMA group improved collagen arrangement and biomechanical properties, reduced tendon adhesion, and promoted motor function after tendon injury. Additionally, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the RCDs/UA@Lipo-HAMA group increased; the levels of cluster of differentiation 68 (CD68), inducible Nitric Oxide Synthase (iNOS), COL III, α-SMA, Vimentin, and matrix metallopeptidase 2 (MMP2) decreased.
    UNASSIGNED: In this study, the RCDs/UA@Lipo-HAMA alleviated tendon adhesion formation and enhanced tendon healing by attenuating oxidative stress, inflammation, and fibrosis. This study provided a novel therapeutic approach for the clinical treatment of tendon injury.
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  • 文章类型: Journal Article
    伸展肌腱粘连最近受到的关注较少。本研究旨在分析手部伸肌腱粘连患者粘连和工作损失天数延长的影响因素。
    我们对接受初次手术修复和早期康复的伸肌腱损伤患者进行了一项回顾性研究。我们观察了非肌腱粘连患者和手术修复后粘连患者之间的差异。并使用接收器工作特性曲线来区分它们。然后探讨了附着力的影响因素。此外,我们研究了失去的工作天数和影响因素。
    共纳入305例患者。24.6%的患者出现肌腱粘连,平均损失工作天数为12周。MHISS得分,VAS评分,职业和血甘油三酯水平是粘连的影响因素。粘连患者的MHISS评分增加(p<0.001),VAS评分(p<0.001),血甘油三酯水平(p<0.001)和失去工作天数(p<0.001)比非肌腱粘连。血甘油三酯水平区分非肌腱粘连和粘连的最佳临界值为1.625mml/L,MHISS评分为20.5。吸烟,MHISS得分,血甘油三酯水平是粘连患者损失工作天数的影响因素。工作损失天数与甘油三酯水平呈正相关(r=0.307,p=0.007),和MHISS评分(r=0.276,p=0.016)。
    为了最大程度地减少粘连的发生,医生应该注意MHISS和VAS评分较高的患者,血甘油三酯水平,尤其是蓝领和失业者。高甘油三酯水平可能是一个新的影响因素。
    UNASSIGNED: Extensor tendon adhesion receive less attention recently. This study aims to analyze influencing factors of adhesion and prolonged lost days of work in patients with extensor tendon adhesion of the hand.
    UNASSIGNED: We performed a retrospective study in patients with extensor tendon injuries who underwent primary surgical repair and early rehabilitation. We observed the differences between non-tendon adhesion and adhesion patients after surgical repair, and used the receiver operating characteristic curve to distinguish them. Then we explored the influencing factors of adhesion. In addition, we studied the lost days of work and the influencing factors.
    UNASSIGNED: A total of 305 patients were included. 24.6% patients appeared tendon adhesion and the mean lost days of work was 12 weeks. MHISS scores, VAS scores, occupation and blood triglyceride level were the influencing factors of adhesion. The adhesion patients have increased MHISS scores (p < 0.001), VAS scores (p < 0.001), blood triglyceride levels (p < 0.001) and lost days of work (p < 0.001) than non-tendon adhesion. The optimal cut-off value of blood triglyceride level to distinguish non-tendon adhesion from adhesion was 1.625 mml/L, and MHISS scores was 20.5. Smoking, MHISS scores, blood triglyceride levels were the influencing factors of lost days of work in adhesion patients. There was positive correlation between lost days of work and triglyceride level (r = 0.307, p = 0.007), and MHISS scores (r = 0.276, p = 0.016).
    UNASSIGNED: To minimize the occurrence of adhesion, doctors should pay attention to patients with higher MHISS and VAS scores, blood triglyceride levels, especial for the blue-collar and unemployed one. High triglyceride level may be a new influencing factor.
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  • 文章类型: Case Reports
    背景:虽然缝合锚钉因其优点而被广泛用于医疗程序中,它们有时会导致并发症,包括锚脱垂。本文介绍了伸肌腱断裂重建手术后小指远端指骨底部缝合锚脱出的独特病例。
    方法:35岁男性,使用不可吸收的缝合锚钉进行伸肌腱断裂重建。七年后,病人去看了我们的门诊病人,抱怨僵硬,疼痛,手术部位突出。最初的X射线成像提示远端指骨骨折或肌腱粘连,但缺乏明确的诊断。随后的磁共振成像(MRI)显示,中部和远端指骨之间的骨连接具有不规则的信号阴影和不清晰的边界,同时保持规则的手指形状。MRI在诊断缝合锚脱出方面被证明是优越的,标志着首例此类病例的报告。手术干预证实了MRI发现。
    结论:缝合锚钉并发症,比如脱垂,是医疗实践中的一个问题。此病例强调了MRI对准确诊断的重要性以及针对这种罕见并发症进行量身定制的手术管理的重要性。
    BACKGROUND: While suture anchors are widely used in medical procedures for their advantages, they can sometimes lead to complications, including anchor prolapse. This article presents a unique case of suture anchor prolapse at the base of the distal phalanx of the little finger after extensor tendon rupture reconstruction surgery.
    METHODS: A 35-year-old male, underwent extensor tendon rupture reconstruction using a non-absorbable suture anchor. After seven years the patient visited our outpatients complaining of stiffness, pain, and protrusion at the surgical site. Initial X-ray imaging suggested suggesting either a fracture of the distal phalanx or tendon adhesion but lacked a definitive diagnosis. Subsequent magnetic resonance imaging (MRI) revealed bone connectivity between the middle and distal phalanges with irregular signal shadow and unclear boundaries while maintaining a regular finger shape. MRI proved superior in diagnosing prolapsed suture anchors, marking the first reported case of its kind. Surgical intervention confirmed MRI findings.
    CONCLUSIONS: Suture anchor complications, such as prolapse, are a concern in medical practice. This case underscores the significance of MRI for accurate diagnosis and the importance of tailored surgical management in addressing this uncommon complication.
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  • 文章类型: Journal Article
    目的:研究氨甲环酸局部应用在手肌腱松解术中的临床效果。
    方法:这是在根据赫尔辛基宣言指南获得当地伦理委员会批准后进行的一项随机对照试验。选取2021年1月至2022年12月在我院行手肌腱松解术的患者80例,随机分为2组。氨甲环酸组(40例)患者在肌腱松解术后接受术中局部应用2g氨甲环酸,常规组(40例)术中未局部应用氨甲环酸。操作时间,围手术期血红蛋白变化,总失血量,术后早期并发症的发生率,比较两组术前和术后6个月的总主动运动(TAM)。连续变量服从正态分布,以平均值±SD表示,组间比较采用t检验。同时,分类变量采用卡方检验,p<0.05表示差异有统计学意义。
    结果:两组均随访7~18个月,平均10.3个月。氨甲环酸组术后血红蛋白下降明显少于常规组(t=7.611,p<0.05)。氨甲环酸组总失血量(74.33±20.50)mL少于常规组(83.05±17.73)mL,差异有统计学意义(p<0.05)。两组患者术后拇指/手指屈伸活动度均有改善,与手术前相比,TAM有所改善,差异有统计学意义(p<0.05)。氨甲环酸组术后6个月TAM改善(87.68°±10.44°)较常规组(80.47°±10.93°)更显著,差异有统计学意义(t=3.013,p<0.05)。两组患者手术时间及术后早期并发症发生率差异无统计学意义(p>0.05)。
    结论:在手肌腱松解术中局部应用氨甲环酸可明显减少术后出血,提高手术疗效。值得推广。
    OBJECTIVE: To study the clinical effectiveness of the topical application of tranexamic acid in hand tendon release.
    METHODS: This was a randomized controlled trial conducted after receiving approval from the local ethics committee according to guidelines from the Helsinki Declaration. Eighty patients who underwent hand tendon release operation in our hospital from January 2021 to December 2022 were included and randomly divided into 2 groups. Patients in the tranexamic acid group (40 cases) received intraoperative topical application of 2 g of tranexamic acid after tendon release, while patients in the conventional group (40 cases) did not receive topical application of tranexamic acid during operation. The operation time, perioperative hemoglobin changes, total blood loss, incidence of early postoperative complications, and total active movement (TAM) before surgery and 6 months after surgery were compared between the 2 groups. The continuous variable which follows normal distribution expressed by mean ± SD and used t-test to compare between groups. Meanwhile, categorical variables were used by Chi-square test, and a p < 0.05 indicated that the differences were statistically significant.
    RESULTS: Both groups were followed up for 7 - 18 months, with a mean of 10.3 months. Postoperative decrease in hemoglobin was significantly less in the tranexamic acid group than in the conventional group (t = 7.611, p < 0.001). The total blood loss in the tranexamic acid group (74.33 ± 20.50) mL was less than that in the conventional group (83.05 ± 17.73) mL, and the difference was statistically significant (p < 0.05). Both groups showed improvement in thumb/finger flexion and extension range of motion after surgery, and the TAM improved compared with those before surgery, and the difference was statistically significant (p < 0.001). The TAM improved more significantly in the tranexamic acid group (87.68° ± 10.44°) than in the conventional group (80.47° ± 10.93°) at 6 months after surgery, with a statistically significant difference (t = 3.013, p < 0.001). There was no significant difference in operation time and incidence of early postoperative complications between the 2 groups (p = 0.798, 0.499, respectively).
    CONCLUSIONS: The topical application of tranexamic acid during hand tendon release can significantly reduce postoperative bleeding and improve surgical efficacy, which is worth promoting.
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  • 文章类型: Journal Article
    肌腱粘连是肌腱手术后常见的并发症。肌腱愈合的炎症阶段的特点是大量炎症因子的释放,其介导的过度炎症反响是肌腱粘连构成的重要缘由。非甾体抗炎药(NSAIDs)用于通过减少炎症反应来预防肌腱粘连。然而,最近的研究表明,NSAIDs部分损害肌腱愈合。因此,优化加载NSAIDs的抗粘连膜以减轻对肌腱愈合的影响需要进一步深入研究.羊膜(AM)是来自富含基质的生物体的天然聚合物半透膜,生长因子,和其他活性成分。在这项研究中,我们采用静电纺丝技术构建了负载塞来昔布和AM的PCL膜的多功能纳米纤维膜。体外细胞测定显示,随着塞来昔布浓度的增加,负载塞来昔布的PCL膜显着抑制成纤维细胞的粘附和增殖。在兔肌腱修复模型中,生物力学测试进一步证实,负载塞来昔布的PCL膜具有更好的抗粘连效果。进一步的实验研究表明,PCL/AM膜通过下调COX-2、IL-1β等促炎因子的表达,改善炎症微环境,和TNF-α蛋白;并抑制COLⅠ和COLⅢ的合成。PCL/AM膜可持续释放塞来昔布以减轻炎症反应,并将生长因子传递到受损区域,为肌腱修复建立合适的微环境,为提高肌腱的修复效率提供了新的方向。
    Tendon adhesion is a common complication after tendon surgery. The inflammatory phase of tendon healing is characterized by the release of a large number of inflammatory factors, whose mediated excessive inflammatory response is an important cause of tendon adhesion formation. Nonsteroidal anti-inflammatory drugs(NSAIDs) were used to prevent tendon adhesions by reducing the inflammatory response. However, recent studies have shown that the NSAIDs partially impairs tendon healing. Therefore, optimizing the anti-adhesive membrane loaded with NSAIDs to mitigate the effects on tendon healing requires further in-depth study. Amniotic membranes(AM) are natural polymeric semi-permeable membranes from living organisms that are rich in matrix, growth factors, and other active ingredients. In this study, we used electrostatic spinning technology to construct multifunctional nanofiber membranes of the PCL membrane loaded with celecoxib and AM. In vitro cellular assays revealed that celecoxib-loaded PCL membranes significantly inhibited the adhesion and proliferation of fibroblasts with increasing concentrations of celecoxib. In a rabbit tendon repair model, biomechanical tests further confirmed that the PCL membrane loaded with celecoxib had better anti-adhesion effects. Further experimental studies revealed that the PCL/AM membrane improved the inflammatory microenvironment by downregulating the expression of pro-inflammatory factors such as COX-2, IL-1β, and TNF-α proteins; and inhibiting the synthesis of COL I and COL Ⅲ. The PCL/AM membrane can continuously release celecoxib to reduce the inflammatory response and deliver growth factors to the damaged area to build a suitable microenvironment for tendon repair, which provides a new direction to improve the repair efficiency of tendon.
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  • 文章类型: Journal Article
    背景:肌腱周围粘连是手部肌腱修复的最常见并发症,通常需要手术干预,导致劳动力损失增加,治疗成本增加。在动物模型中用于减少肌腱粘连的许多药物,然而,这些药物尚未进入临床应用。这项研究是有史以来的第一项临床研究,该研究评估了以胶原片作为抗粘连屏障的环绕肌腱修复部位。
    方法:2014年12月至2020年1月,本研究纳入156名患者,在屈肌腱区2处切割干净的孤立指屈肌腱(FDP)肌腱损伤。所有肌腱都用改良的双凯斯勒技术修复。在76名患者中,肌腱修复部位周围有胶原片。从我们的临床记录中随机选择80例患者,并将功能结果与Strickland的总主动运动分级系统进行比较。
    结果:对照组的平均总运动范围为79%,胶原片组为81%,两组间差异无统计学意义(Z:-1.393,p=0.164)。在对照组中,根据Strikland分类,非常好和良好的修复为65/80(81%)。在胶原片组中,是62/76(82%),分别。胶原片与对照组的5个FDPTAM测量值之间存在统计学差异(t(35)=0.29,p=0.016,p<0.05)。胶原片组5个FDP肌腱的平均TAM:83.8(SD:8.2),对照组76.1(SD:9.5)。
    结论:在文献中第一次,报告了清洁切断肌腱损伤患者使用胶原片修复2区屈肌腱的功能结果。然而,对照组和胶原片组的总主动运动无统计学差异,第5例胶原片环绕的FDS肌腱修复效果较好。建议在具有高粘连风险的患者组中进行前瞻性研究。
    BACKGROUND: Peritendinous adhesion is the most common complication of tendon repairs in the hand and often requires surgical intervention, resulting in increased labor loss and increased treatment costs. Many agents used to reduce tendon adhesion in animal models, however these agents have not entered clinical use. This study is the first-ever clinical study that evaluates encircling tendon repair site with collagen sheet as an anti-adhesion barrier.
    METHODS: Between December 2014 and January 2020, 156 patients included in this study, with clean cut isolated flexor digitorum profundus (FDP) tendon injury in flexor tendon zone 2. All tendons repaired with modified double Kessler technique. In 76 patients, tendon repair site encircled with collagen sheet. 80 patients were randomly selected from our clinical records and functional results are compared with Strickland\'s total active motion grading system.
    RESULTS: The mean total range of motion was 79% in the control group and 81% in the collagen sheet group, and there was no statistically significant difference between the two groups (Z: - 1.393, p = 0.164). In the control group, very good and good repair according to Strikland classification was 65/80 (81%). In the collagen sheet group, it was 62/76 (82%), respectively. There was statistically significant difference between 5 FDP TAM measurements between collagen sheet and control group (t(35) = 0.29, p = 0.016, p < 0.05). The mean TAM of the 5 FDP tendons in the collagen sheet group: 83.8 (SD: 8.2) in the and 76.1 (SD: 9.5) in the control group.
    CONCLUSIONS: For the first time in the literature, functional results of Zone 2 flexor tendon repair using collagen sheets in patients with clean cut tendon injuries reported. However, there were no statistical difference about total active motion between control and collagen sheet group, 5th FDS tendon repairs encircled with collagen sheets had better outcomes. Prospective studies in patient groups with high adhesion risk are recommended.
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  • 文章类型: Journal Article
    肌腱损伤是与活动范围和疼痛的损害相关的常见损伤。目前,有证据证实,天然草药有助于骨科,并在肌腱损伤的临床治疗中显示出优异的效果。舒筋活血片(SHT)及其复方常用于肌腱断裂治疗,效果良好。本研究旨在发现促进肌腱愈合的潜在分子。中药系统药理学数据库分析平台(TCMSP)是主要资源。以中医综合数据库和中医百科全书数据库为二级数据库。GeneCards数据库用于按关键词搜索报告的肌腱病相关基因。使用基因本体论富集分析和京都基因和基因组百科全书分析靶向基因的功能。从STRING数据库中提取蛋白质-蛋白质相互作用信息。对接研究,MTT测定,实时定量PCR,根据细胞功能,进行迁移试验以更好地了解草药,以测试其体外基本药理作用。总共104个疾病节点,496个靶基因节点,35个成分节点,并提取了一个药物节点。根据TCMSP数据库,6-羟基山奈酚,据报道,这促进了微血管内皮细胞的增殖,是在SHT中发现的分子。我们发现它促进了肌腱成纤维细胞的增殖和迁移,并升高了肌腱修复相关基因的表达。纯化的6-羟基山奈酚促进肌腱成纤维细胞的增殖和迁移,并增加其在肌腱增殖中的mRNA表达。
    Tendon impairment is a common injury associated with impairment of range of motion and pain. Currently, evidence has confirmed that natural herbs contribute to orthopedics and have shown excellent results in the clinical management of tendon impairment. Shujin Huoxue tablet (SHT) and its complex prescriptions are regularly used in tendon rupture therapy with positive results. This study aimed to discover the potential molecules that promote tendon healing. The Chinese traditional medicine system pharmacological database analysis platform (TCMSP) is the primary resource. The Traditional Chinese Medicine Integrated Database and Encyclopedia of Traditional Chinese Medicine database were used as secondary databases. The GeneCards database was used to search for reported tendinopathy-related genes by keywords. Functions of the targeted genes were analyzed using Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes. Protein-protein interaction information was extracted from the STRING database. Docking study, MTT assay, quantitative real-time PCR, and migration assays were performed to obtain a better understanding of the herbs according to cell function to test the basic pharmacological action in vitro. A total of 104 disease nodes, 496 target gene nodes, 35 ingredient nodes, and one drug node were extracted. According to the TCMSP database, 6-hydroxykaempferol, which reportedly promotes the proliferation of microvascular endothelial cells, is a molecule found in SHT. We found that it promoted the proliferation and migration of tendon fibroblasts and elevated tendon repair-related gene expression. Purified 6-hydroxykaempferol promoted the proliferation and migration of tendon fibroblasts and increased their mRNA expression in tendon proliferation.
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  • 文章类型: Journal Article
    在受伤的屈肌腱愈合过程中,肌腱组织容易与周围组织形成极其致密的粘连,严重影响手功能恢复。钩藤在临床上应用广泛,其主要成分,钩藤碱(Rhy),据报道其良好的治疗效果,能有效抑制腹腔粘连的形成。然而,Rhy对肌腱愈合和粘连形成的治疗作用尚不清楚。由于Rhy的半衰期短,构建了用于Rhy递送的透明质酸(HA)缓释系统,它还可以避免药物在运输过程中不期望的损失。在受伤的肌腱周围应用了Rhy输送系统后,粘连形成,评估了肌腱的滑行功能和愈合强度。我们的结果表明,修复肌腱的滑行偏移和愈合强度均显着增加,以及附着力被抑制。从体内实验来看,Rhy能够增加ColⅠ/ColⅢ的表达,并帮助成纤维细胞有序组织肌腱组织。但是对于粘连组织,Rhy促进细胞凋亡,加速细胞外基质的降解。体外研究表明,Rhy可以帮助TGF-β1刺激的肌腱细胞恢复到正常的细胞功能,涉及细胞增殖和凋亡水平。通过高通量测序,我们发现Rhy参与了细胞外基质(ECM)信号通路的调节。我们得出结论,Rhy通过抑制Smad2的磷酸化来增强肌腱的愈合并防止粘连形成。一句话,这种Rhy的缓释系统可能是治疗肌腱损伤的有希望的策略。
    During the injured flexor tendon healing process, tendon tissue is easy to form extremely dense adhesion with the surrounding tissue, which causes the serious influence of hand function recovery. Uncaria is widely used in clinic and its main composition, Rhynchophylline (Rhy), has been reported on its good therapeutic effect, which could effectively inhibit the intra-abdominal adhesion formation. However, the therapeutic effect of Rhy on tendon healing and adhesion formation is still unclear. Due to the short half-life of Rhy, hyaluronic acid (HA) sustained-release system for Rhy delivery was constructed and it could also avoid drug from the undesired loss during the transit. After Rhy delivery system was applied around the injured tendons, adhesion formation, gliding function and healing strength of tendons were evaluated. Our results showed that the gliding excursion and healing strength of repaired tendons were both significantly increased, as well as the adhesion was inhibited. From in vivo experiments, Rhy could be able to increase the expression of Col Ⅰ/Col Ⅲ and helped fibroblasts to ordered organization for tendon tissues. But for adhesion tissues, Rhy promoted the apoptosis and accelerated the degradation of extracellular matrix. In vitro study showed Rhy could help tenocytes stimulated with TGF-β1 to recover to normal cell functions involving cell proliferation and apoptosis level. Through high-throughput sequencing, we found that Rhy was involved in the regulation of Extracellular Matrix (ECM) signaling pathway. We draw a conclusion that Rhy enhanced the tendon healing and prevented adhesion formation through inhibiting the phosphorylation of Smad2. In a word, this sustained release system of Rhy may be a promising strategy for the treatment of injured tendons.
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  • 文章类型: Journal Article
    肌腱愈合过程中的粘连形成在临床实践中仍然是一个严重的问题。多种因素导致术后粘连形成,巨噬细胞驱动的炎症被认为与这一过程密切相关。我们假设,通过调节M1至M2巨噬细胞极化来减少受损肌腱中巨噬细胞介导的炎症可能有效地抑制粘附形成。这里,我们开发了一种无细胞免疫调节生物材料,该材料由电纺丝聚己内酯/丝素蛋白(PCL/SF)复合纤维支架与间充质干细胞(MSC)衍生的细胞外基质(ECM)功能化。为了增强MSCs的免疫调节潜能,我们用IFN-γ进行了炎症许可,以获得免疫调节性ECM(iECM).来自不同培养条件的MSC及其分泌的ECM组分的蛋白质组学分析揭示了MSC-ECM分子特征和ECM免疫调节的潜在机制。然后,在体外和体内评估了iECM修饰的支架的免疫调节潜力。相对于PCL/SF纤维支架,iECM功能化的支架促进M2巨噬细胞极化并抑制多种细胞因子(IL-1β,IL-6,CXCL11,IL-10,IL-1R2和TGF-β1)体外,强烈提示来自炎性许可MSC的iECM的免疫抑制能力。与体外研究结果一致,大鼠皮下植入结果表明,PCL/SF-iECM组的异物反应(FBR)明显低于其他组,如较薄的纤维化包膜形成所证明的那样,I型胶原蛋白产生较少,M2型巨噬细胞极化较多。在大鼠跟腱损伤模型中,PCL/SF-iECM支架极大地减轻了肌腱粘连,在肌腱和支架之间形成了清晰的鞘间隙。这些数据突出了iECM功能化的纤维支架通过调节M2巨噬细胞极化来减弱FBR的免疫调节潜力,从而防止肌腱粘连。重要声明:开发了由炎症因子IFN-γ刺激的MSC分泌的ECM功能化的电纺PCL/SF纤维支架,其结合了物理屏障和免疫调节功能以防止肌腱粘连形成。通过乳液静电纺丝制备的PCL/SF微纳米尺度双峰纤维支架具有高孔隙率和大孔径,有利于养分运输以促进内在愈合;此外,用免疫调节ECM(iECM)进行表面修饰减轻纤维支架的FBR以防止肌腱粘连。iECM功能化的电纺支架在体外和体内表现出强大的免疫调节能力。此外,iECM修饰的支架,作为具有免疫调节能力的抗粘连物理屏障,在大鼠跟腱粘连模型中具有优异的表现。基于MSC分泌组的疗法,作为一种无细胞再生医学策略,由于其强大的免疫调节潜力,有望应用于其他炎症性疾病。
    Adhesion formation during tendon healing remains a severe problem in clinical practice. Multiple factors contribute to postoperative adhesion formation, and macrophage-driven inflammation is thought to be greatly involved in this process. We hypothesize that reducing macrophage-mediated inflammation in the injured tendon by regulating M1 to M2 macrophage polarization may effectively inhibit adhesion formation. Here, we developed an acellular immunomodulatory biomaterial consisting of an electrospun polycaprolactone/silk fibroin (PCL/SF) composite fibrous scaffold functionalized with mesenchymal stem cell (MSC)-derived extracellular matrix (ECM). To enhance the immunoregulatory potential of MSCs, we performed inflammatory licensing with IFN-γ to obtain immunomodulatory ECM (iECM). Proteomic analyses of MSCs and their secreted ECM components from different culture conditions revealed the MSC-ECM molecular signatures and the potential mechanism of ECM immunoregulation. Then, the immunoregulatory potential of the iECM-modified scaffold was evaluated in vitro and in vivo. Relative to the PCL/SF fibrous scaffold, the iECM-functionalized scaffold facilitated M2 macrophage polarization and inhibited the expression of multiple cytokines (IL-1β, IL-6, CXCL11, IL-10, IL-1R2, and TGF-β1) in vitro, strongly suggesting the immunosuppressive ability of iECM derived from inflammatory licensed MSCs. Consistent with the in vitro findings, the results of rat subcutaneous implantation indicated that a markedly lower foreign-body reaction (FBR) was obtained in the PCL/SF-iECM group than in the other groups, as evidenced by thinner fibrotic capsule formation, less type I collagen production and more M2-type macrophage polarization. In the rat Achilles tendon injury model, the PCL/SF-iECM scaffold greatly mitigated tendon adhesion with clear sheath space formation between the tendon and the scaffold. These data highlight the immunomodulatory potential of iECM-functionalized fibrous scaffolds to attenuate FBR by modulating M2 macrophage polarization, thereby preventing tendon adhesion. STATEMENT OF SIGNIFICANCE: Electrospun PCL/SF fibrous scaffolds functionalized with ECM secreted by MSCs stimulated by inflammatory factor IFN-γ was developed that combined physical barrier and immunomodulatory functions to prevent tendon adhesion formation. PCL/SF micro-nanoscale bimodal fibrous scaffolds prepared by emulsion electrospinning possess high porosity and a large pore size beneficial for nutrient transport to promote intrinsic healing; moreover, surface modification with immunomodulatory ECM (iECM) mitigates the FBR of fibrous scaffolds to prevent tendon adhesion. The iECM-functionalized electrospun scaffolds exhibit powerful immunomodulatory potency in vitro and in vivo. Moreover, the iECM-modified scaffolds, as an anti-adhesion physical barrier with immunomodulatory ability, have an excellent performance in a rat Achilles tendon adhesion model. MSC secretome-based therapeutics, as an acellular regenerative medicine strategy, are expected to be applied to other inflammatory diseases due to its strong immunoregulatory potential.
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  • 文章类型: Journal Article
    Titanium is one of the most commonly used materials for implants in trauma applications due to its low density, high corrosion resistance and biocompatibility. Nevertheless, there is still a need for improved surface modifications of Titanium, in order to change surface properties such as wettability, antibacterial properties or tissue attachment. In this study, different novel plasma electrolytic oxidation (PEO) modifications have been investigated for tendon adhesion to implants commonly used in hand surgery. Titanium samples with four different PEO modifications were prepared by varying the electrolyte composition and analyzed with regards to their surface properties. Unmodified titanium blanks and Dotize® coating served as controls. Samples were examined using scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), contact angle measuring system and analyzed for their biocompatibility and hemocompatibility (according to DIN ISO 10993-5 and 10,993-4). Finally, tendon adhesion of these specific surfaces were investigated by pull-off tests. Our findings show that surface thickness of PEO modifications was about 12-20 μm and had porous morphology. One modification demonstrated hydrophilic behavior accompanied by good biocompatibility without showing cytotoxic properties. Furthermore, no hemolytic effect and no significant influence on hemocompatibility were observed. Pull-off tests revealed a significant reduction of tendon adhesion by 64.3% (35.7% residual adhesion), compared to unmodified titanium (100%). In summary, the novel PEO-based ceramic-like porous modification for titanium surfaces might be considered a good candidate for orthopedic applications supporting a more efficient recovery.
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