The roles and mechanisms of the NF-κB signaling pathway in tendon disorders.

Both acute and chronic tendon injuries are the most frequently occurring musculoskeletal diseases in human and veterinary medicine, with a limited repertoire of successful and evidenced-based therapeutic strategies. Inflammation has been suggested as a key driver for the formation of scar and adhesion tissue following tendon acute injury, as well as pathological alternations of degenerative tendinopathy. However, prior efforts to completely block this inflammatory process have yet to be largely successful. Recent investigations have indicated that a more precise targeted approach for modulating inflammation is critical to improve outcomes. The nuclear factor-kappaB (NF-κB) is a typical proinflammatory signal transduction pathway identified as a key factor leading to tendon disorders. Therefore, a comprehensive understanding of the mechanism or regulation of NF-κB in tendon disorders will aid in developing targeted therapeutic strategies for human and veterinary tendon disorders. In this review, we discuss what is currently known about molecular components and structures of basal NF-κB proteins and two activation pathways: the canonical activation pathway and the non-canonical activation pathway. Furthermore, we summarize the underlying mechanisms of the NF-κB signaling pathway in fibrosis and adhesion after acute tendon injury, as well as pathological changes of degenerative tendinopathy in all species and highlight the effect of targeting this signaling pathway in tendon disorders. However, to gain a comprehensive understanding of its mechanisms underlying tendon disorders, further investigations are required. In the future, extensive scientific examinations are warranted to full characterize the NF-κB, the exact mechanisms of action, and translate findings into clinical human and veterinary practice.

Extensor tendon rupture and preoperative mri confirmations of suture anchor prolapse: a case report and literature review.

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. CASE PRESENTATION: 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.

Factors predicting the adhesion and prolonged lost days of work in patients with extensor tendon adhesion of the hand.

Objective: 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. Method: 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. Results: 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). Conclusion: 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.

Prevented Cell Clusters' Migration Via Microdot Biomaterials for Inhibiting Scar Adhesion.

Cluster-like collective cell migration of fibroblasts is one of the main factors of adhesion in injured tissues. In this research, a microdot biomaterial system is constructed using α-helical polypeptide nanoparticles and anti-inflammatory micelles, which are prepared by ring-opening polymerization of α-amino acids-N-carboxylic anhydrides (NCAs) and lactide, respectively. The microdot biomaterial system slowly releases functionalized polypeptides targeting mitochondria and promoting the influx of extracellular calcium ions under the inflammatory environment, thus inhibiting the expression of N-cadherin mediating cell-cell interaction, and promoting apoptosis of cluster fibroblasts, synergistically inhibiting the migration of fibroblast clusters at the site of tendon injury. Meanwhile, the anti-inflammatory micelles are celecoxib (Cex) solubilized by PEG/polyester, which can improve the inflammatory microenvironment at the injury site for a long time. In vitro, the microdot biomaterial system can effectively inhibit the migration of the cluster fibroblasts by inhibiting the expression of N-cadherin between cell-cell and promoting apoptosis. In vivo, the microdot biomaterial system can promote apoptosis while achieving long-acting anti-inflammation effects, and reduce the expression of vimentin and α-smooth muscle actin (α-SMA) in fibroblasts. Thus, this microdot biomaterial system provides new ideas for the prevention and treatment of tendon adhesion by inhibiting the cluster migration of fibroblasts.

Janus Membranes Patch Achieves High-Quality Tendon Repair: Inhibiting Exogenous Healing and Promoting Endogenous Healing.

The imbalance between endogenous and exogenous healing is the fundamental reason for the poor tendon healing. In this study, a Janus patch was developed to promote endogenous healing and inhibit exogenous healing, leading to improved tendon repair. The upper layer of the patch is a poly(dl-lactide-co-glycolide)/polycaprolactone (PLGA/PCL) nanomembrane (PMCP-NM) modified with poly(2-methylacryloxyethyl phosphocholine) (PMPC), which created a lubricated and antifouling surface, preventing cell invasion and mechanical activation. The lower layer is a PLGA/PCL fiber membrane loaded with fibrin (Fb) (Fb-NM), serving as a temporary chemotactic scaffold to regulate the regenerative microenvironment. In vitro, the Janus patch effectively reduced 92.41% cell adhesion and 79.89% motion friction. In vivo, the patch inhibited tendon adhesion through the TGF-ß/Smad signaling pathway and promoted tendon maturation. This Janus patch is expected to provide a practical basis and theoretical guidance for high-quality soft tissue repair.

Repurposing of Angiotensin-converting-enzyme Inhibitor on Prevention of Post-surgical Tendon Adhesion.

BACKGROUND: Formation of adhesion bands is a frequent clinical complication after tendon injury or surgery with limited treatment options. This study investigates the repurposing of Angiotensin-Converting-Enzyme Inhibitor (ACEI) in attenuating post-operative tendon-sheath adhesion bands in an Achilles tendon rat model. METHODS: Structural, mechanical, histological, and biochemical characteristics of the Achilles tendons were compared in the presence and absence of oral ACEI (enalapril) using the Achilles tendon adhesion (TA) model in rats. Inflammation and total fibrosis of tendon tissues were compared between groups using molecular investigations along with macroscopic and histological scoring methods. RESULTS: ACEI significantly alleviated the severity, length, and density of Achilles TAs. Moreover, histopathological changes, recruitment of inflammatory cells, and inflammation were significantly decreased in post-operative tissue samples as quantified with the Moran scoring model. We showed that ACEI treatment elicits a potent anti-fibrotic effect on tendon tissue samples, as illustrated by decreasing the severity and extent of the formed fibrotic tissue and collagen accumulation at the site of surgery when scored either by Tang or Ishiyama grading systems. The H&E staining showed no histopathological changes or damage to the principal organs. CONCLUSION: Our results showed that ACEI is a safe and effective therapeutic candidate with potent immunomodulatory and anti-fibrotic features to alleviate surgery-induced development of fibrotic adhesive tissue. However, its efficacy needs to be further validated in clinical studies.

Clinical efficacy of the topical application of tranexamic acid in tendon release in the hand: A randomized controlled trial.

PURPOSE: 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). CONCLUSION: The topical application of tranexamic acid during hand tendon release can significantly reduce postoperative bleeding and improve surgical efficacy, which is worth promoting.

Multilayer amnion-PCL nanofibrous membrane loaded with celecoxib exerts a therapeutic effect against tendon adhesion by improving the inflammatory microenvironment.

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-1ß, 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.

Encircling tendon repair site with collagen sheet in flexor zone 2: retrospective study.

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.

Flexor Tendon Adhesion Formation: Current Concepts.

Over the years, various physical and chemical/biological methods of inhibiting adhesion formation have been developed, focusing on how to suppress healing around the tendon and not inhibit healing within the tendon. Unfortunately, however, these methods are accompanied by drawbacks, both large and small, and no absolute antiadhesion method capable of maintaining tendon repair strength has yet been developed. Recent innovations in biomaterials science and tissue engineering have produced new antiadhesion technologies, such as barriers combined with cytokines and cells, which have improved outcomes in animal models, and which may find clinical relevance in the future.

Hyaluronic acid/platelet rich plasma-infused core-shell nanofiber membrane to prevent postoperative tendon adhesion and promote tendon healing.

An anti-adhesive barrier membrane incorporating hyaluronic acid (HA) can reduce fibroblasts attachment and impart lubrication effect for smooth tendon gliding during management of post-surgical tendon adhesion. On the other hand, as numerous growth factors are required during tendon recovery, growth factors released by platelets in platelet-rich plasma (PRP) can provide beneficial therapeutic effects to facilitate tendon recovery post tendon injury. Furthermore, PRP is reported to be associated with anti-inflammatory properties for suppressing postoperative adhesion. Toward this end, we fabricate core-shell nanofiber membranes (NFM) with HA/PRP-infused core and polycaprolactone shell in this study. Different NFM with 100 % (H-P), 75 % (HP31-P), 50 % (HP11-P) and 25 % (H31-P) HA in the core was fabricated through coaxial electrospinning and analyzed through microscopic, pore size, mechanical, as well as HA and growth factor release studies. In vitro study with fibroblasts indicates the NFM can act as a barrier to prevent cell penetration and reduce cell attachment/focal adhesion, in addition to promoting tenocyte migration in tendon healing. In vivo studies in a rabbit flexor tendon rupture model indicates the HP11-P NFM shows improved efficacy over H-P NFM and control in reducing tendon adhesion formation and inflammation, while promoting tendon healing, from functional assays and histological analysis.

Pyrrolidine Dithiocarbamate-loaded Electrospun Membranes for Peritendinous Anti-adhesion through Inhibition of the Nuclear Factor-κB Pathway.

Peritendinous adhesion is a major cause of limb dysfunction and disability in clinical practice. Numerous studies suggest that activation of nuclear factor-κB (NF-κB) pathway in macrophages could be the pivotal figure in excessive collagen synthesis and thus peritendinous adhesion formation. In this study, we assumed this pathological process could be suppressed by inhibiting NF-κB phosphorylation and nuclear translocation using pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor with the ability to penetrate cell membranes, in macrophages. Then, we conducted electrospinning process to incorporate PDTC into poly(L-lactic) acid (PLA) electrospinning membranes, that is, the PDTC-PLA membranes. Further, with integral film quality and stable drug release property, the PDTC-PLA membranes were subsequently analyzed in the capability and mechanism of preventing adhesion formation both in vitro and in vivo. Our results showed inhibition of macrophage proliferation as well as NF-κB pathway activation from in vitro assays and outstanding promotion in inhibiting NF-κB p65 phosphorylation and reducing adhesion formation from in vivo assays of PDTC-PLA compared to PLA membranes. In conclusion, our findings suggested that PDTC-PLA as an alternative therapeutic approach alleviated inflammation and peritendinous adhesion formation through NF-κB signaling pathway. STATEMENT OF SIGNIFICANCE: Pyrrolidine dithiocarbamate (PDTC) can be blended into poly-L-lactic acid (PLA) fibrous membranes by electrospinning process. This incorporation of PDTC into PLA is an effective way to inhibit proinflammatory activation of macrophages and to achieve advanced anti-adhesion outcome after tendon repair.

Enhancement of Tendon Repair Using Tendon-Derived Stem Cells in Small Intestinal Submucosa via M2 Macrophage Polarization.

(1) Background: Reconstruction of Achilles tendon defects and prevention of postoperative tendon adhesions were two serious clinical problems. In the treatment of Achilles tendon defects, decellularized matrix materials and mesenchymal stem cells (MSCs) were thought to address both problems. (2) Methods: In vitro, cell adhesion, proliferation, and tenogenic differentiation of tendon-derived stem cells (TDSCs) on small intestinal submucosa (SIS) were evaluated. RAW264.7 was induced by culture medium of TDSCs and TDSCs-SIS scaffold groups. A rat Achilles tendon defect model was used to assess effects on tendon regeneration and antiadhesion in vivo. (3) Results: SIS scaffold facilitated cell adhesion and tenogenic differentiation of TDSCs, while SIS hydrogel coating promoted proliferation of TDSCs. The expression of TGF-ß and ARG-1 in the TDSCs-SIS scaffold group were higher than that in the TDSCs group on day 3 and 7. In vivo, the tendon regeneration and antiadhesion capacity of the implanted TDSCs-SIS scaffold was significantly enhanced. The expression of CD163 was significantly highest in the TDSCs-SIS scaffold group; meanwhile, the expression of CD68 decreased more significantly in the TDSCs-SIS scaffold group than the other two groups. (4) Conclusion: This study showed that biologically prepared SIS scaffolds synergistically promote tendon regeneration with TDSCs and achieve antiadhesion through M2 polarization of macrophages.

Effects of 6-Hydroxykaempferol: A Potential Natural Product for Amelioration of Tendon Impairment.

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.

A Simplified Murine Model to Imitate Flexor Tendon Adhesion Formation without Suture.

Peritendinous adhesion (PA) around tendons are daunting challenges for hand surgeons. Tenotomy with various sutures are considered classical tendon repair models (TRM) of tendon adhesion as well as tendon healing. However, potential biomimetic therapies such as anti-adhesion barriers and artificial tendon sheaths to avoid recurrence of PA are sometimes tested in these models without considering tendon healing. Thus, our aim is to create a simplified model without sutures in this study by using three 6 mm longitudinal and parallel incisions called the longitudinal incision model (LCM) in the murine flexor tendon. We found that the adhesion score of LCM has no significant difference to that in TRM. The range of motion (ROM) reveals similar adhesion formation in both TRM and LCM groups. Moreover, mRNA expression levels of collagen I and III in LCM shows no significant difference to that in TRM. The breaking force and stiffness of LCM were significantly higher than that of TRM. Therefore, LCM can imitate flexor tendon adhesion formation without sutures compared to TRM, without significant side effects on biomechanics with an easy operation.

Interosseous wiring for fragmented proximal phalangeal fractures.

Fragmented proximal phalangeal fractures are difficult to treat. Fixation with plate and screws often lead to contractures and extensor tendon adhesions. Interosseous wiring could prevent those complications by repairing the periosteum and avoiding direct contact between implants and extensor tendon, while a good total active motion can be achieved.

Nanofibrous polycaprolactone/chitosan membranes for preventing postsurgical tendon adhesion.

Peritendinous adhesion is considered a major postsurgical tendon complication in hand surgery. This complication could be mitigated partially through early tendon mobilization. However, development of new treatment modalities to guide tissue regeneration and to reduce postsurgical tendon adhesion has recently gained attentions. In this article, synthesis and characterization of electrospun nanofibrous membranes (NFMs) of polycaprolactone (PCL) and chitosan to form a physical barrier against cellular migration leading to tendon adhesion is presented. The mechanical properties of the NFMs are modulated to maintain high integrity during postsurgical tendon mobilization. The tensile strength of the NFMs is examined in wet and dry conditions after 1000 cyclic pull loadings. In addition, the mechanical strength of the NFMs is evaluated after a degradation period of 30 days. To obtain NFM with desired properties, concentrations of polymer solutions, operation parameters of electrospinning and the thickness of NFMs were optimized. Based on the biodegradation and mechanical evaluations, the optimum NFM was obtained for specified amounts of PCL (5 wt %) + chitosan (2 wt %) at an electrospinning drum speed of 400 rpm. The engineered NFM could withstand forces of 33 and 19 N before and after 1000 pull cycles that are sufficient during tendon healing process. The bonding of chitosan fibers over PCL nanofibers allowed for production of NFMs with appropriate mechanical integrity and degradation rate. In vitro cell culture tests demonstrated that PCL/chitosan could only have minor impact on decreasing fibroblast attachment over the membranes probably due to protonation of amine groups.

LncRNA XIST Prevents Tendon Adhesion and Promotes Tendon Repair Through the miR-26a-5p/COX2 Pathway.

Tendon adhesion is the biggest obstacle to repair of tendon injury. Long-chain non-coding RNA X-inactive specific transcript (lncRNA XIST) is highly expressed in populations at high risk of tendon injury. However, whether XIST participates in tendon injury and the specific mechanism remain unknown. Here, we aimed to explore the effects and underlying mechanism of XIST in tendon injury. A mouse model of tendon injury was constructed by the transection method in vivo. XIST and COX2 were highly expressed in tendon tissues of mice with tendon injury, while miR-26a-5p was lowly expressed. Fibroblasts were isolated from tendon injury mice. Overexpression of XIST promoted fibroblast proliferation and upregulated α-SMA and Collagen I protein expression, while silencing XIST indicated the opposite effects. Further dual-luciferase reporter gene assay and RIP assay verified a targeting relationship between XIST and miR-26a-5p, as well as miR-26a-5p and COX2, and XIST targeted miR-26a-5p to act on COX2 expression. miR-26a-5p inhibition and COX2 overexpression reversed the decrease in fibroblast proliferation and the downregulation of α-SMA and Collagen I expression caused by XIST silencing, while interference with si-COX2 eliminated the effects of miR-26a-5p inhibitor. This study revealed that XIST promoted fibroblast proliferation and the formation of tendon adhesion through miR-26a-5p/COX2 pathway, suggesting that XIST/miR-26a-5p/COX2 may be a potential target for the treatment of tendon injury.

Three-Dimensional Tendon Scaffold Loaded with TGF-ß1 Gene Silencing Plasmid Prevents Tendon Adhesion and Promotes Tendon Repair.

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 ß-1 (TGF-ß1) 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-ß1 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-ß1 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-ß1 gene.

Sustained-Release Hydrogel-Based Rhynchophylline Delivery System Improved Injured Tendon Repair.

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-ß1 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.