A first data set refers to tissue inhibitor of matrix metalloprotease-1 (TIMP-1) protein inclusion into a DegraPol® fibres utilizing emulsion electrospinning and the characterization of the random fibre mesh. Specifically, the release kinetics of the protein from the mesh was studied over 7 days. Moreover, the static and the dynamic water contact angles were determined. Finally, we assessed Fourier-Transformed Infrared Spectra (FTIR spectra) for DegraPol® with and without TIMP-1. A second data set represents proliferation data obtained with the Alamar Blue Assay, applied on rabbit Achilles tenocytes and rabbit adipose-derived stem cells, when stimulated in vitro with 1, 10, and 100 ng/mL TIMP-1 supplementation compared to the corresponding cell culture without TIMP-1 (control). Furthermore, qPCR was performed and collagen I, ki67, tenomodulin and alkaline phosphatase gene expression data are presented for both cell types in vitro stimulated with 1, 10, and 100 ng/mL TIMP-1 supplementation, respectively, and data are presented as manifold induction compared to a TIMP-1-free cell culture medium (control).

Tendon-bone insertion trauma is prevalent in both rotator cuff and anterior cruciate ligament injuries, which are frequently encountered conditions in the field of sports medicine. The main treatment for such injuries is reconstructive surgery. The primary determinant impacting this process is the graft's capacity to integrate with the bone tunnel. In recent years, researchers have attempted to use a variety of methods to facilitate tendon-bone healing after reconstructive surgery. Such as the implantation of biological materials, cytokines and the local application of permanently differentiated cells from various sources. However, there are limitations to the efficacy of one therapy alone in facilitating tendon-bone healing. Therefore, researchers are trying to combine strategies to overcome this conundrum. At present, most studies are based on biomaterial combined with other therapeutic strategies for tissue repair and regeneration. Biomaterials mainly include the application of bioengineering scaffolds, hydrogels and bioabsorbable interference screws. By conducting a thorough review of relevant literature, this study provides a comprehensive overview of the present research progress in enhancing tendon-bone healing using biomaterials. Additionally, it explores the potential benefits of combining biomaterials with other approaches to promote tendon-bone healing. The ultimate goal is to offer insights for future basic research endeavors and establish a solid groundwork for advancing clinical applications in the near future.

Tendon injury is a common and frequent disease in the field of sports medicine, and tendon repair after injury is a common clinical difficulty. Repair strategy based on tendon stem cells (TDSCs) therapy is considered a promising therapeutic option for the treatment of tendon injuries. Icariin (ICA) has been shown to be an effective herbal monomer for the treatment of tendon-bone healing and may be effective in the repair of tendon injuries.

In vitro, TDSCs isolated from C57 mice were treated with ICA (0.01-100 µM) to assess proliferation (CCK-8 assay) and tendonogenic differentiation (qRT-PCR). In vivo, 42 C57 mice with surgically induced patellar tendon defects were randomized into three groups (n = 14/group): (1) 20 mg/kg ICA, (2) 40 mg/kg ICA, and (3) control group (DMSO), administered intraperitoneally for 14 days. Half of each group (n = 7) underwent histopathological (hematoxylin-eosin staining, Masson staining) and molecular (qRT-PCR) analyses at 2 and 4 weeks post-surgery.

In vitro, after 7 days of ICA intervention in TDSC, the expression of Mohawk (MKX), Scleraxis (SCX), fibromodulin (FMOD), and Tenomodulin (TNC) were higher in the ICA group than in the control group. In vivo, the expression of MKX, SCX, FMOD, and TNC was higher in the 20 mg/kg ICA group and 40 mg/kg ICA group than in the control group at 2 and 4 weeks after surgery. Histological evaluation revealed superior tendon repair in both ICA-treated groups compared to controls at both 2 and 4 weeks postoperative intervals. The 20 mg/kg ICA group demonstrated a significant enhancement in tissue continuity and collagen fiber organization, exhibiting greater defect filling, fewer interstitial gaps, and reduced vascular infiltration. In contrast, control specimens exhibited disorganized collagen architecture with prominent interstitial gaps. The 40 mg/kg ICA group showed intermediate repair outcomes between the 20 mg/kg ICA and control groups.

ICA can improve tendon injury repair by enhancing tendonogenic differentiation of TDSC.

To evaluate the effectiveness of a novel grid-based pie-crusting technique for soft tissue release at different locations of the medial collateral ligament (MCL) during total knee arthroplasty (TKA).

Twelve fresh-frozen cadaveric knee joints were dissected. A novel grid was designed to cover the entire surface of the MCL. The specimens were divided into two groups: Group A, where only the central portion of the ligament underwent pie-crusting release, and Group B, where selective release targeted the femoral and tibial attachment points of the MCL. Mechanical testing was conducted via a Shimadzu AG-X precision instrument. Each group underwent twelve punctures, and data were collected to calculate deformation and stiffness metrics. The mean elongation and stiffness values were analyzed, and regression analysis was performed to evaluate correlations between the number of punctures and changes in elongation and stiffness.

No significant differences in initial stiffness were observed between the two groups (P = 0.42). Following 12 punctures, the stiffness decreased by 6.47 ± 4.06 N/mm in Group A and 1.08 ± 1.32 N/mm in Group B (P = 0.006). Despite this disparity in stiffness reduction, no significant differences in MCL elongation were observed between the groups. Group A demonstrated an elongation of 0.171 ± 0.180 mm, whereas Group B exhibited an elongation of 0.164 ± 0.123 mm (P = 0.47). A linear relationship was identified between stiffness reduction and the number of punctures (R 2 = 0.61 ± 0.29), as well as between ligament elongation and the number of punctures (R 2 = 0.89 ± 0.09).

The grid-assisted pie-crusting technique, which uniformly covers the MCL, enables precise and controlled soft tissue release. This approach provides valuable insights for clinicians performing MCL release during TKA, facilitating improved soft tissue balance and potentially enhancing surgical outcomes.

Excessive expression of proinflammatory cytokines after rotator cuff (RC) surgery impairs the quality of tendon-bone interface (TBI) healing. There is evidence that the asthma drug montelukast (MS) inhibits the expression of proinflammatory cytokines. This study was conducted to verify the effect of MS administration on TBI healing after RC repair.

Thirteen rats in the MS group were intraperitoneally administered 10 mg/kg of the drug daily for 2 weeks after RC surgery, and 13 rats in the control group were administered only 0.9% saline. The healing effect of the TBI was assessed through histologic and biomechanical analysis 4 weeks after tendon repair.

In the MS group, the expression of interleukin-1 beta (IL-1β; P<.01) and interleukin 6 (IL-6; P<.01) was significantly reduced compared with the control group. In the evaluation of supraspinatus fatty infiltration, the MS group showed significant inhibition of fatty infiltration compared with the control group (P<.001). Histologic analysis showed that the MS group had significant improvements in collagen density (P=.035) and alignment (P=.011). Biomechanical analysis after systemic administration of MS showed an increase in the cross-sectional area (P<.001) and elongation (P<.01) of the TBI.

The use of MS improved tendon elasticity through suppressing fatty infiltration and improving TBI collagen density and arrangement. The mechanism is down-regulation of IL-1β and IL-6. These results strongly support the use of MS as an anti-inflammatory agent that does not impair tendon healing. [Orthopedics. 2025;48(2):e105-e112.].

The tendon-bone interface, known as the tenosynovial union or attachment, can be easily damaged by excessive exercise or trauma. Tendon-bone healing is a significant research topic in orthopedics, encompassing various aspects of sports injuries and postoperative recovery. Surgery is the most common treatment; however, it has limited efficacy in promoting tendon-bone healing and carries a risk of postoperative recurrence, necessitating the search for more effective treatments. Recently, plant-active ingredients such as tanshinone IIA, astragaloside, ginsenoside Rb1, and resveratrol have garnered significant attention due to their unique advantages in promoting tendon-bone healing. This review outlines the various mechanisms and research progress of these four plant-active ingredients, as well as compound ingredients, in promoting tendon-bone healing. For instance, tanshinone IIA significantly accelerates the healing rate and improves healing quality through anti-inflammatory, antioxidant, and cell proliferation-promoting mechanisms. Astragaloside expedites tendon-bone healing and enhances the mechanical strength of healing tissues primarily through anti-inflammatory, antioxidant, and immunoregulatory effects. Ginsenoside Rb1 enhances local blood supply and facilitates tendon-bone tissue repair through angiogenesis, anti-inflammatory, and antioxidant pathways. Resveratrol protects cellular function and accelerates tissue healing due to its potent antioxidant and anti-inflammatory effects. Additionally, the mechanisms and progress of certain Chinese herbal compound components in tendon-bone healing are outlined. This review concludes that these four plant-active ingredients and herbal compound components promote tendon-bone healing through various mechanisms. The efficacy mechanisms and research progress of these plant-active ingredients are summarized to provide references for clinical treatment and related research.

The purpose of this study was to analyse the influence of coronal lower limb alignment on collateral ligament strain.

Twelve fresh-frozen human cadaveric knees were used. Long-leg standing radiographs were obtained to assess lower limb alignment. Specimens were axially loaded in a custom-made kinematics rig with 200 and 400 N, and dynamic varus/valgus angulation was simulated in 0°, 30°, and 60° of knee flexion. The changes in varus/valgus angulation and strain within different fibre regions of the collateral ligaments were captured using a three-dimensional optical measuring system to examine the axis-dependent strain behaviour of the superficial medial collateral ligament (sMCL) and lateral collateral ligament (LCL) at intervals of 2°.

The LCL and sMCL were exposed to the highest strain values at full extension (p < 0.001). Regardless of flexion angle and extent of axial loading, the ligament strain showed a strong and linear association with varus (all Pearson's r ≥ 0.98; p < 0.001) and valgus angulation (all Pearson's r ≥ -0.97; p < 0.01). At full extension and 400 N of axial loading, the anterior and posterior LCL fibres exceeded 4% ligament strain at 3.9° and 4.0° of varus, while the sMCL showed corresponding strain values of more than 4% at a valgus angle of 6.8°, 5.4° and 4.9° for its anterior, middle and posterior fibres, respectively.

The strain within the native LCL and sMCL was linearly related to coronal lower limb alignment. Strain levels associated with potential ultrastructural damages to the ligaments of more than 4% were observed at 4° of varus and about 5° of valgus malalignment, respectively. When reconstructing the collateral ligaments, an additional realigning osteotomy should be considered in cases of chronic instability with a coronal malalignment exceeding 4°-5° to protect the graft and potentially reduce failures.

There is no level of evidence as this study was an experimental laboratory study.

The electrospinning technique is a commonly employed approach to fabricate fibers intended for various tissue engineering applications. The aim of this study is to develop a novel strategy for tendon repair through the use of aligned poly(ε-caprolactone) (PCL) and poly(glycerol sebacate) (PGS) fibers fabricated in benign solvents, and further explore the potential application of PGS in tendon tissue engineering (TTE). The fibers were characterized for their morphological and physicochemical properties; amniotic epithelial stem cells (AECs) were used to assess the fibers teno-inductive and immunomodulatory potential due to their ability to teno-differentiate undergoing first a stepwise epithelial to mesenchymal transition, and due to their documented therapeutic role in tendon regeneration. The addition of PGS to PCL improved the spinnability of the polymer solution, as well as the uniformity and directionality of the so-obtained fibers. The mechanical properties were in the range of most TTE applications, specifically in the case of PCL/PGS 4:1 and 2:1 ratios. Compared to PCL alone, the same ratios also allowed a better AECs infiltration and growth over 7 days of culture, and triggered the activation of tendon-related genes (SCX, COL1, TNMD) and the expression of tenomodulin (TNMD) at the protein level. Concerning the immunomodulatory properties, both PCL and PCL/PGS fibers negatively affected the immunomodulatory profile of AECs, up-regulating both anti-inflammatory (IL-10) and pro-inflammatory (IL-12) cytokines over 7 days of culture. Overall, PCL/PGS 2:1 fibers fabricated with benign solvents proved to be the most suitable composition for TTE application based on their topographical cues, mechanical properties, biocompatibility, and teno-inductive properties.

Bioactive hydrogels have emerged as promising artificial niches for enhancing stem cell-mediated tendon repair. However, a substantial knowledge gap remains regarding the optimal combination of niche features for targeted cellular responses, which often leads to lengthy development cycles and uncontrolled healing outcomes. To address this critical gap, an innovative, data-driven materiomics strategy is developed. This approach is based on in-house RNA-seq data that integrates bioinformatics and mathematical modeling, which is a significant departure from traditional trial-and-error methods. It aims to provide both mechanistic insights and quantitative assessments and predictions of the tenogenic effects of adipose-derived stem cells induced by systematically modulated features of a tendon-mimetic hydrogel (TenoGel). The knowledge generated has enabled a rational approach for TenoGel design, addressing key considerations, such as tendon extracellular matrix concentration, uniaxial tensile loading, and in vitro pre-conditioning duration. Remarkably, our optimized TenoGel demonstrated robust tenogenesis in vitro and facilitated tendon regeneration while preventing undesired ectopic ossification in a rat tendon injury model. These findings shed light on the importance of tailoring hydrogel features for efficient tendon repair. They also highlight the tremendous potential of the innovative materiomics strategy as a powerful predictive and assessment tool in biomaterial development for regenerative medicine.

Tendinopathy is very common in clinical practice, which is highly prevalent in athletes, sports enthusiasts and other people involved in high-load weight-bearing activities. Common types of tendinopathy include rotator cuff injury, Achilles tendinitis, tennis elbow and so on. Macrophages (Macs) are key immune cells in the pathogenesis of tendinopathy. In this study, CCL4L2+ M1-related signaling pathways were screened by combining single-cell RNA sequencing (scRNA-seq) to explore their significance in tendinopathy treatment.

Immune cell populations were screened by Uniform Manifold Approximation and Projection (UMAP) downscaling, and Mac cell subsets were annotated using cell marker genes. The cellular communication mechanism between different cellular subsets such as Macs and tendon stem/progenitor cells (TSPCs) was demonstrated by cellular communication analysis. Based on cell marker genes of CCL4L2 + M1, Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed to compare the expression differences in M1 and M2 between the Disease and Healthy groups. Associations between CCL4L2+ M1 and TSPCs were inferred by cell-cell communication analysis. The effects of CCL4L2 on Mac polarization and TSPCs were verified by enzyme-linked immunosorbent assay (ELISA) and real-time fluorescence quantitative PCR (qPCR).

The proportions of TSPCs, endothelial cells (ECs), smooth muscle cells (SMCs), and immune cells were significantly elevated in the Disease group. The proportion of M1 cells in the Disease group was higher than that in the Healthy group, while the proportion of M2 cells was lower than that in the Healthy group. M1 differentially expressed genes (DEGs) were mainly enriched to disease-related and immunoinflammation-related signaling pathways. Signaling intensities between M1 and TSPCs in pathways related to immunoinflammation and ischemic injury were significantly increased in the Disease group. The proportion of CCL4L2 + M1 in the Disease group was significantly higher than in the Healthy group, and communications between CCL4L2 + M1 and TSPCs varied significantly. Compared with the Control group, the expression levels of inflammatory cytokines were higher in the CCL4L2 group, and the expression levels of tendon differentiation markers (Egr1, Mkx, Scx, Type 1 collagen, Tnmd) were significantly down-regulated.

The present study analyzed the heterogeneous alterations in the Healthy and Disease groups by scRNA-seq data and found that there was a significant inflammatory infiltrate in the Disease group with markedly increased Mac activity, which was associated with activation of the CCL4L2 + M1-associated signaling pathways. CCL4L2 promotes M1 polarization and inhibits TSPC differentiation through activating M1-related inflammatory signaling pathways. These findings contribute to a more comprehensive understanding of tendon injury progression and provide potential targets for tendinopathy treatment.

Tendon injuries represent an ongoing challenge in clinical practice due to poor regenerative capacity, structure, and biomechanical function recovery of ruptured tendons. This study is focused on the assessment of a novel strategy to repair ruptured Achilles tendons in a Nude rat model using stem cell-seeded biomaterial.

Specifically, we have used induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) overexpressing the early tendon marker Scleraxis (SCX, iMSCSCX+, iTenocytes) in combination with an elastic collagen scaffold. Achilles tendon defects in Nude rat models were created by isolating the tendon and excising 3 mm of the midsection. The Achilles tendon defects were then repaired with iTenocyte-seeded scaffolds, unseeded scaffolds, or suture only and compared to native Nude rat tendon tissue using gait analyses, biomechanical testing, histology, and immunohistochemistry.

The results show faster functional recovery of gait in iTenocyte-seeded scaffold group comparing to scaffold only and suture only groups. Both iTenocyte-seeded scaffold and scaffold only treatment groups had improved biomechanical properties when compared to suture only treatment group, however no statistically significant difference was found in comparing the cell seeding scaffold an scaffold only group in terms of biomechanical properties. Immunohistochemistry staining further demonstrated that iTenocytes successfully populated the collagen scaffolds and survived 9 weeks after implantation in vivo. Additionally, the repaired tissue of iTenocyte-treated injuries exhibited a more organized structure when compared to tendon defects that were repaired only with suturing or unseeded scaffolds.

We suggest that iTenocyte-seeded DuRepair™ collagen scaffold can be used as potential treatment to regenerate the tendon tissue biomechanically and functionally.

Tendons are fibroblastic structures that link muscle and bone. There are two kinds of tendon injuries, including acute and chronic. Each form of injury or deterioration can result in significant pain and loss of tendon function. The recovery of tendon damage is a complex and time-consuming recovery process. Depending on the anatomical location of the tendon tissue, the clinical outcomes are not the same. The healing of the wound process is divided into three stages that overlap: inflammation, proliferation, and tissue remodeling. Furthermore, the curing tendon has a high re-tear rate. Faced with the challenges, tendon injury management is still a clinical issue that must be resolved as soon as possible. Several newer directions and breakthroughs in tendon recovery have emerged in recent years. This article describes tendon injury and summarizes recent advances in tendon recovery, along with stem cell therapy, gene therapy, Platelet-rich plasma remedy, growth factors, drug treatment, and tissue engineering. Despite the recent fast-growing research in tendon recovery treatment, still, none of them translated to the clinical setting. This review provides a detailed overview of tendon injuries and potential preclinical approaches for treating tendon injuries.

Diabetes is one of the most common metabolic diseases worldwide, leading to complications, mortality, and significant healthcare expenditures, which impose a substantial social and financial burden globally. A diabetic environment can induce metabolic changes, negatively affecting tendon homeostasis, leading to alterations in biomechanical properties and histopathology. Numerous studies have investigated the mechanisms through which diabetes exerts pathological effects on tendons, including increased free radical production, oxidative stress, inflammatory responses, deposition of advanced glycation end products (AGEs), and microvascular changes. These metabolic changes damages tendon structure, biomechanics, and tendon repair processes. The proliferation of tendon stem cells decreases, apoptosis increases, and abnormal differentiation, along with abnormal expression of myofibroblasts, ultimately lead to insufficient tendon repair, fibrosis, and remodeling. Although researches unveiling the effects of diabetes on tendinopathy, fibrosis or contracture, and tendon injury healing are growing, systematic understanding is still lacking. Therefore, this review summarizes the current research status and provides a comprehensive overview, offering theoretical guidance for future in-depth exploration of the impact of diabetes on tendons and the development of treatments for diabetes-related tendon diseases.

Adult tendon tissue has limited and slow regenerative capacity. Sambucus nigra plant possesses antioxidant and anti-inflammatory attributes.

This study aimed to evaluate the effect of hydroalcoholic extract of this plant's fruit on superficial digital flexor tendon repair in rabbits (SDFT).

Twenty-five male New Zealand white rabbits weighing 1.5-2 kg were selected, quarantined and randomly divided into four groups of six. By performing a partial left posterior limb tenotomy, differentiating the SDFT and creating multiple scrapes were performed. During 3 consecutive days post-surgery, the positive control group was injected with 0.5 mg/kg dexamethasone, whereas the treatment groups received extract doses of 200 and 400 mg/kg, respectively. The negative control group did not receive any medication. Evaluation of sonographic and histopathological parameters was conducted on days 0, 7 and 28 post-surgeries. Findings were analysed and compared using SPSS22.

Both treatment groups showed significant differences in echogenicity, and collagen fibre alignment compared to the control and positive control groups, in sonographic evaluation. Histopathological examination revealed fewer inflammatory cells and increased collagen fibre formation in the treatment groups compared to the other two groups. No significant difference in angiogenesis was observed among the groups on days 7 and 28 (p value <0.05).

The results indicate that the S. nigra fruit extract, by stimulating collagen synthesis and reducing inflammation, effectively accelerates the healing process of injured tendons.

Tendinopathy refers to conditions characterized by collagen degeneration within tendon tissue, accompanied by the proliferation of capillaries and arteries, resulting in reduced mechanical function, pain, and swelling. While inflammation in tendinopathy can play a role in preventing infection, uncontrolled inflammation can hinder tissue regeneration and lead to fibrosis and impaired movement.

The inability to regulate inflammation poses a significant limitation in tendinopathy treatment. Therefore, an ideal treatment strategy should involve modulation of the inflammatory process while promoting tissue regeneration.

The current review article was prepared by searching PubMed, Scopus, Web of Science, and Google Scholar databases. Several treatment approaches based on biomaterials have been developed.

This review examines various treatment methods utilizing small molecules, biological compounds, herbal medicine-inspired approaches, immunotherapy, gene therapy, cell-based therapy, tissue engineering, nanotechnology, and phototherapy.

These treatments work through mechanisms of action involving signaling pathways such as transforming growth factor-beta (TGF-β), mitogen-activated protein kinases (MAPKs), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), all of which contribute to the repair of injured tendons.

Postoperative tissue adhesion and poor tendon healing are major clinical problems associated with tendon surgery. To avoid postoperative adhesion and promote tendon healing, we developed and synthesized a membrane to wrap the surgical site after tendon suturing. The bilayer-structured porous membrane comprised an outer layer [1,4-butanediol diglycidyl ether cross-linked with carboxymethyl cellulose (CX)] and an inner layer [1,4-butanediol diglycidyl ether cross-linked with Bletilla striata polysaccharides and carboxymethyl cellulose (CXB)]. The morphology, chemical functional groups, and membrane structure were determined. In vitro experiments revealed that the CX/CXB membrane demonstrated good biosafety and biodegradability, promoted tenocyte proliferation and migration, and exhibited low cell attachment and anti-inflammatory effects. Furthermore, in in vivo animal study, the CX/CXB membrane effectively reduced postoperative tendon-peripheral tissue adhesion and improved tendon repair, downregulating inflammatory cytokines in the tendon tissue at the surgical site, which ultimately increased tendon strength by 54% after 4 weeks.

Proximal peroneal tendinopathy is a relatively rare condition and can cause severe pain, discomfort, and often disability, especially if it coexists with other pathologies of the lower limbs. This case report discusses a 32-year-old male surgeon with the condition of chronic lateral ankle pain due to proximal peroneal tendinopathy, complicated by an anterior cruciate ligament sprain, a posterior cruciate ligament ganglion cyst, and early medial meniscus degeneration. His ability to perform surgeries has been compromised due to the need to stand for prolonged periods. A multi-factorial rehabilitation approach was designed to address the tendon pathology and the knee dysfunctions associated with it. The treatment program included patient education, therapeutic exercise, and pain management. There were considerable improvements in terms of pain, range of motion, muscle strength, and function from the previous stage of six weeks. This case indicates the clinical necessity of kinetic-chain-oriented, very individualized approaches to rehabilitation for complex musculoskeletal conditions such as this, especially in active professionals. The success of the rehabilitation lies in the potential for recovery even with some tough conditions if the treatment modality is appropriately designed to address the interactive aspects of the patient's condition. This case highlights the importance of an integrated approach in managing complex peroneal tendonitis, especially when associated with upstream joint pathology. The positive outcome underscores the value of early recognition and individualized management to restore function and avoid permanent complications. Additionally, the report serves as a guide for future research into the potential long-term benefits of holistic, patient-specific approaches for similar cases.

Hand tendinopathies represent a pathological condition associated with significant disability. However, due to this high heterogeneity of the treatments and their efficacy, there is still a lack of consensus on the infiltrative therapy of the hand. This systematic review aimed to investigate the efficacy of injection techniques in the treatment of pain related to the main hand tendinopathies. We searched online medical databases (PubMed, Pedro, Cochrane Library, Scopus, and WoS). Only RCTs published in the last 10 years (up to 5 August 2024), written in English, and related to infiltrative treatment in wrist and hand tendinopathies were evaluated. The risk of bias in RCTs was assessed with Version 2 of the Cochrane Risk of Bias tool for randomized trials (RoB 2). Out of 641 articles identified, 23 were included in the final synthesis: 14 RCTs on trigger finger, and 9 RCTs on de Quervain's tenosynovitis. The present systematic review showed that infiltrative therapy of trigger finger and de Quervain's tenosynovitis constitutes a fundamental element in the treatment of these pathological conditions, in terms of pain reduction and improvement in the functionality of the hand.

Quercetin (QC), a naturally occurring bioflavonoid found in various fruits and vegetables, possesses many potential health benefits, primarily attributed to its robust antioxidant properties. The generation of oxidative stress in bone cells is a key modulator of their physiological behavior. Moreover, oxidative stress status influences the pathophysiology of mineralized tissues. Increasing scientific evidence demonstrates that manipulating the redox balance in bone cells might be an effective technique for developing bone disease therapies. The QC antioxidant abilities in skeletal muscle significantly enhance muscle regeneration and reduce muscle atrophy. In addition, QC has been shown to have protective effects against oxidative stress, inflammation, apoptosis, and matrix degradation in tendons, helping to maintain the structural integrity and functionality of tendons. Thus, the antioxidant properties of QC might be crucial for addressing age-related musculoskeletal disorders like osteoporosis, sarcopenia, and tendon-related inflammatory conditions. Understanding how QC influences redox signaling pathways involved in musculoskeletal disorders, including their effect on bone, muscle, and tendon differentiation, might provide insights into the diverse advantages of QC in promoting tissue regeneration and preventing cellular damage. Therefore, this study reviewed the intricate relationship among oxidative stress, inflammation, and tissue repair, affected by the antioxidative abilities of QC, in age-related musculoskeletal tissues to improve the overall health of bones, muscles, and tendons of the skeletal system. Also, reviewing the ongoing clinical trials of QC for musculoskeletal systems is encouraging. Given the positive effect of QC on musculoskeletal health, further scientific investigations and controlled human intervention studies are necessary to explore the therapeutic potential to its optimum strength.

Tendons serve as important weight-bearing structures that smoothly transfer forces from muscles to skeletal parts, allowing contracted muscle movements to be translated into corresponding joint movements. For body mechanics, tendon tissue plays an important role. If the tendons are damaged to varying degrees, it can lead to disability or pain in patients. That is to say, tendon injuries havea significant impact on quality of life and deserve our high attention. Compared to other musculoskeletal tissues, tendons are hypovascular and hypo-cellular, and therefore have a greater ability to heal, this will lead to a longer recovery period after injury or even disability, which will significantly affect the quality of life. There are many causes of tendon injury, including trauma, genetic factors, inflammation, aging, and long-term overuse, and the study of related mechanisms is of great significance. Currently, tendon there are different treatment modalities, like injection therapy and surgical interventions. However, they have a high failure rate due to different reasons, among which the formation of adhesions severely weakens the tissue strength, affecting the functional recovery and the patient's quality of life. A large amount of data has shown that non coding RNAs can play a huge role in this field, thus attracting widespread attention from researchers from various countries. This review summarizes the relevant research progress on non-coding RNAs in tendon injuries, providing new ideas for a deeper understanding of tendon injuries and exploring new diagnostic and therapeutic approaches.

The aim of this study was to assess the effectiveness of combining sericin with swimming exercise as a treatment for type-I collagenase-induced Achilles tendinopathy (AT) in rats, with a focus on inflammatory cytokines. An experimental AT model was established using type-I collagenase in male Sprague-Dawley rats, categorized into five groups: Group 1 (Control + Saline), Group 2 (AT), Group 3 (AT + exercise), Group 4 (AT + sericin), and Group 5 (AT + sericin + exercise). Intratendinous sericin administration (0.8 g/kg/mL) took place from days 3 to 6, coupled with 30 min daily swimming exercise sessions (5 days/week, 4 weeks). Serum samples were analyzed using ELISA for tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), and total antioxidant-oxidant status (TAS-TOS), alongside histopathological and immunohistochemical assessments of Achilles tendon samples. Elevated TNF-α and IL-1β and decreased IL-10 levels were evident in Group 2; Of these, TNF-α and IL-1β were effectively reduced and IL-10 increased across all treatment groups, particularly groups 4 and 5. Serum TAS was notably lower in Group 2 and significantly increased in Group 5 compared to Group 2. Histopathologically, Group 2 displayed severe degeneration, irregular fibers, and round cell nuclei, while Group 5 exhibited decreased degeneration and spindle-shaped fibers. The Bonar score increased in Group 2 and decreased in groups 4 and 5. Collagen type-I alpha-1 (Col1A1) expression was notably lower in Group 2 (P = 0.001) and significantly increased in groups 4 and 5 compared to Group 2 (P = 0.011 and 0.028, respectively). This study underscores the potential of sericin and swimming exercises in mitigating inflammation and oxidative stress linked to AT pathogenesis, presenting a promising combined therapeutic strategy.

To investigate the forces on a medial collateral ligament (MCL) reconstruction (MCLR) relative to the valgus alignment of the knee.

Eight fresh-frozen human cadaveric knees were subjected to dynamic valgus loading at 400 N using a custom-made kinematics rig. After resection of the superficial medial collateral ligament, a single-bundle MCLR with a hamstring tendon autograft was performed. A medial opening wedge distal femoral osteotomy was performed and fixed with an external fixator to gradually adjust the alignment in 5° increments from 0° to 10° valgus. For each degree of valgus deformity, the resulting forces acting on the MCLR were measured through a force sensor and captured in 15° increments from 0° to 60° of knee flexion.

Irrespective of the degree of knee flexion, increasing valgus malalignment resulted in significantly increased forces acting on the MCLR compared to neutral alignment (p < 0.05). Dynamic loading at 5° valgus resulted in increased forces on the MCLR at all flexion angles ranging between 16.2 N and 18.5 N (p < 0.05 from 0° to 30°; p < 0.01 from 45° to 60°). A 10° valgus malalignment further increased the forces on the MCLR at all flexion angles ranging between 29.4 N and 40.0 N (p < 0.01 from 0° to 45°, p < 0.05 at 60°).

Valgus malalignment of the knee caused increased forces acting on the reconstructed MCL. In cases of chronic medial instabilities accompanied by a valgus deformity ≥ 5°, a realigning osteotomy should be considered concomitantly to the MCLR to protect the graft and potentially reduce graft failures.

Level III.

Shoulder pain and disabilities are prevalent issues among the elderly population, with rotator cuff tear (RCT) being one of the leading causes. Although surgical treatment has shown some success, high postoperative retear rates remain a great challenge, particularly in elderly patients. Aging-related degeneration of muscle, tendon, tendon-to-bone enthesis, and bone plays a critical role in the development and prognosis of RCT. Studies have demonstrated that aging worsens muscle atrophy and fatty infiltration, alters tendon structure and biomechanical properties, exacerbates enthesis degeneration, and reduces bone density. Although recent researches have contributed to understanding the pathophysiological mechanisms of aging-related RCT, a comprehensive systematic review of this topic is still lacking. Therefore, this article aims to present a review of the pathophysiological changes and their clinical significance, as well as the molecular mechanisms underlying aging-related RCT, with the goal of shedding light on new therapeutic approaches to reduce the occurrence of aging-related RCT and improve postoperative prognosis in elderly patients.

We conducted this study aimed to examine the impact of evidence-based nursing interventions on postoperative wound pain and complications after surgery for finger tendon injury. A total of 86 patients treated for finger tendon injuries at our hospital from January 2021 to October 2023 were selected and randomly divided into an experimental group and a control group. The control group received conventional nursing care, while the experimental group received evidence-based nursing interventions. The study compared the postoperative wound pain intensity, incidence of complications and patient satisfaction with nursing care between the two groups. The analysis revealed that compared with conventional care, evidence-based nursing interventions significantly reduced the level of wound pain (p = 0.034) and the incidence of complications (4.65% vs. 18.60%, p = 0.043). It also increased patient satisfaction with the nursing care (97.67% vs. 83.72%, p = 0.026). The study indicates that the application of evidence-based nursing interventions for patients with finger tendon injuries can reduce postoperative wound pain, decrease the incidence of complications and enhance patient satisfaction with nursing care.

Tendon injury and healing involve intricate changes to tissue metabolism, biology, and inflammation. Current techniques often require animal euthanasia or tissue destruction, limiting assessment of dynamic changes in tendon, including treatment response, disease development, rupture risk, and healing progression. Microdialysis, a minimally invasive technique, offers potential for longitudinal assessment, yet it has not been applied to rat tendon models. Therefore, the objective of this study is to adapt a novel application of an in vivo assay, microdialysis, using acute injury as a model for extreme disruption of the tendon homeostasis. We hypothesize that microdialysis will be able to detect measurable differences in the healing responses of acute injury with high specificity and sensitivity. Overall results suggest that microdialysis is a promising in vivo technique for longitudinal assessment for this system with strong correlations between extracellular fluid (ECF) and dialysate concentrations and reasonable recovery rates considering the limitations of this model. Strong positive correlations were found between dialysate and extracellular fluid (ECF) concentration for each target molecule of interest including metabolites, inflammatory mediators, and collagen synthesis and degradation byproducts. These results suggest that microdialysis is capable of detecting changes in tendon healing following acute tendon injury with high specificity and sensitivity. In summary, this is the first study to apply microdialysis to a rat tendon model and assess its efficacy as a direct measurement of tendon metabolism, biology, and inflammation.NEW & NOTEWORTHY This study adapts a novel application of microdialysis to rat tendon models, offering a minimally invasive avenue for longitudinal tendon assessment. Successfully detecting changes in tendon healing after acute injury, it showcases strong correlations between extracellular fluid and dialysate concentrations. The results highlight the potential of microdialysis as a direct measure of tendon metabolism, biology, and inflammation, bypassing the need for animal euthanasia and tissue destruction.

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.

We assessed damaged anterior capsulolabral motion during axial shoulder rotation in patients with anterior shoulder instability.

Twenty-nine shoulders of 28 patients with anterior shoulder instability who underwent cine-magnetic resonance imaging during axial rotation of the adducted arm were included. The motion was captured after an intra-articular injection of saline solution (10-20 mL). During imaging, the shoulder was rotated passively from maximum internal rotation to maximum external rotation in the first 10 s and then back to maximum internal rotation in the subsequent 10 s. We assessed the rotational angles of the damaged labrum during compressing and pulling the humeral head against the glenoid. Evaluation of the rotational angles was performed on a series of axial images through the humeral head center.

The mean angles that damaged labrum compressed and pulled off against the glenoid were 12.0 ± 19.1° and 2.8 ± 21.2°, respectively. Additionally, seven of the 29 shoulders showed that the damaged labrum compressed on the glenoid rim before the rotational angle exceeded 0° during external rotation. In 13 shoulders, the damaged labrum could remain repositioned on the glenoid rim over the neutral position during internal rotation. In two shoulders, the damaged labrum was not compressed against the glenoid at the maximum external rotation. The injected saline moved from the posterior to the anterior side of the glenohumeral joint during internal rotation in each shoulder.

The damaged labrum could be positioned on the glenoid when the arm was in a traditional internal immobilization.

Current tissue-engineered tendons are mostly limited to the replication of fibrous organizations of native tendons, which lack the biomimicry of a densely packed cell arrangement. In this study, composite tendon constructs (CTCs) with fibrous arrangement, high cell density, and enhanced cell alignment were developed by integrating the electrohydrodynamic jet 3D printing (e-jetting) technique and the fabrication of tissue strands (TSs). A tubular polycaprolactone (PCL) scaffold was created using e-jetting, followed by coating a thin layer of alginate. Human mesenchymal stem cells were then microinjected into the PCL scaffolds, aggregated into TSs, and formed CTCs with a core-shell structure. Owing to the presence of TSs, CTCs demonstrated the anatomically relevant cell density and morphology, and cells migrated from the TSs onto e-jetted scaffolds. Also, the mechanical strength of CTCs approached that of native tendons due to the existence of e-jetted scaffolds (Young's modulus: ∼21 MPa, ultimate strength: ∼5 MPa). During the entire culture period, CTCs maintained high survival rates and good structural integrity without the observation of necrotic cores and disintegration of two portions. In addition, CTCs that were cultured with uniaxial cyclic stretching revealed not only the increased expression of tendon-related proteins but also the enhanced cellular orientation. The promising results demonstrated the potential of this novel biofabrication strategy for building tissue-engineered tendon constructs with the proper biological, mechanical, and histological relevance..

Tendon injuries are common disorders that can significantly impact people's lives. Unfortunately, the limited regenerative ability of tendons results in tissue healing in a scar-mediated manner. The current therapeutic strategies fail to fully recover the functions of the injured tendons, and as such, the conception of 'scarless healing' has gained prominent attention in the field of regenerative medicine. Interestingly, injured fetal tendons possess the capability to heal through regeneration, which builds an ideal blueprint for adult tendon regeneration. Studies have shown that fetal biochemical cues have the potential to improve adult tendon healing. Here we review the biological factors that contribute to fetal tendon regeneration and how manipulation of these biochemical cues in the adult tendon healing process could achieve regeneration.

Achilles tendon (AT) injury is one of the most common tendon injuries, especially in athletes, the elderly, and working-age people. In AT injury, the biomechanical properties of the tendon are severely affected, leading to abnormal function. In recent years, many efforts have been underway to develop effective treatments for AT injuries to enable patients to return to sports faster. For instance, several new techniques for tissue-engineered biological augmentation for tendon healing, growth factors (GFs), gene therapy, and mesenchymal stem cells were introduced. Increasing evidence has suggested that GFs can reduce inflammation, promote extracellular matrix production, and accelerate AT repair. In this review, we highlighted some recent investigations regarding the role of GFs, such as transforming GF-β(TGF-β), bone morphogenetic proteins (BMP), fibroblast GF (FGF), vascular endothelial GF (VEGF), platelet-derived GF (PDGF), and insulin-like GF (IGF), in tendon healing. In addition, we summarized the clinical trials and animal experiments on the efficacy of GFs in AT repair. We also highlighted the advantages and disadvantages of the different isoforms of TGF-β and BMPs, including GFs combined with stem cells, scaffolds, or other GFs. The strategies discussed in this review are currently in the early stages of development. It is noteworthy that although these emerging technologies may potentially develop into substantial clinical treatment options for AT injury, definitive conclusions on the use of these techniques for routine management of tendon ailments could not be drawn due to the lack of data.

Tendon injuries range from acute-related trauma to chronic-related injuries are prevalent and bring substantial pain, functional loss, and even disability to the patients. The management of tendon injuries is tricky due to the innate limited regenerative capability of the tendon. Currently, surgical intervention of tendon injuries with artificial tendons remains the standard of care. However, most of artificial tendons are manufactured with synthetic materials, which possess relatively poor biomimetic characteristics and inadequate inherent biodegradability, hence rendering limited cell proliferation and migration for tendon healing. To address these limitations, this work develops a mussel-derived artificial tendon based on double-cross-linked chitosan modification. In this design, decellularized artificial tendon serves as a natural biomimetic scaffold to facilitate the migration and adhesion of tendon repair cells. Additionally, as the cells proliferate, the artificial tendon can be degraded to facilitate tendon regeneration. Moreover, the chitosan cross-linking further enhances the mechanical strength of artificial tendon and offers a controllable degradation. The in vitro and in vivo experimental results demonstrate that mussel-derived artificial tendon not only accelerate the tendon functional reconstruction but also enable harmless clearance at postimplantation. The finding provides a promising alternative to conventional artificial tendons and spurs a new frontier to explore nature-derived artificial tendons.

Tendon injuries are the most common soft tissue injuries, caused by tissue overuse and age-related degeneration. However, the tendon repair process is slow and inefficient due to the lack of cellular structure and blood vessels in the tendon. Low-intensity pulsed ultrasound (LIPUS) has received increasing attention as a non-invasive, simple, and safe way to promote tendon healing. This review summarizes the effects and underlying mechanisms of LIPUS on tendon injury by comprehensively examining the published literature, including in vitro, in vivo, and clinical studies. This review reviewed 24 studies, with 87.5% showing improvement. The application of LIPUS in tendon diseases is a promising field worthy of further study.

Momordica charantia (MC) is a traditional plant widely used since ancient times for wound healing. This study evaluated its potential effects on tendon healing. Adult male Wistar albino rats (n = 32, 8 rats in each group) were anesthetized, and their Achilles tendons were prepared for surgical procedures. Group 1 (Cont = control group) was not subjected to any surgery and was used as a control group for baseline values. Group 2 (PR = primary repair group) underwent primary repair (PR) with a monofilament suture after a full-thickness incision of the Achilles tendon. A full-thickness incision was also made to the Achilles tendon of group 3 (CT = collagen tube-administered group), followed by PR and collagen tube insertion. In group 4 (MC = M. charantia-administered group), 1 mL of MC extract was applied locally on the collagen tube in addition to the surgical procedure applied to group 3. The Achilles tendons were excised on the postoperative 40th day and examined stereologically, histologically, and bioinformatically. Data showed that the total volume of the collagen fibers was higher in MC and CT groups than in the PR group. The total volume of the tendon was decreased in MC and CT groups than in the Cont group. The ratios between the volumes of the collagen fibers and total tendon in the MC and CT groups were significantly different from PR, but not different from the Cont group. Additionally, MC improved tenoblastic activity, collagen production, and neovascularization. Bioinformatic interactions showed that the proteases of MC could trigger the signals playing a role on vasculogenesis, reducing inflammation, and contributing to tenoblast activation and collagen remodeling. MC extract ameliorates the healing of injured tendon and can provide satisfactory tendon repair. Further works are recommended to explore the healing capacity of MC.

The growth of the skeleton depends on the transmission of contractile muscle forces from tendon to bone across the extracellular matrix-rich enthesis. Loss of muscle loading leads to significant impairments in enthesis development. However, little is known about how the enthesis responds to increased loading during postnatal growth. To study the cellular and matrix adaptations of the enthesis in response to increased muscle loading, we used optogenetics to induce skeletal muscle contraction and unilaterally load the Achilles tendon and enthesis in young (i.e., during growth) and adult (i.e., mature) mice. In young mice, daily bouts of unilateral optogenetic loading led to expansion of the calcaneal apophysis and growth plate, as well as increased vascularization of the normally avascular enthesis. Daily loading bouts, delivered for 3 weeks, also led to a mechanically weaker enthesis with increased molecular-level accumulation of collagen damage in young mice. However, adult mice did not exhibit impaired mechanical properties or noticeable structural adaptations to the enthesis. We then focused on the transcriptional response of the young tendon and bone following optogenetic-induced loading. After 1 or 2 weeks of loading, we identified, in tendon, transcriptional activation of canonical pathways related to glucose metabolism (glycolysis) and inhibited pathways associated with cytoskeletal remodeling (e.g., RHOA and CREB signaling). In bone, we identified activation of inflammatory signaling (e.g., NFkB and STAT3 signaling) and inhibition of ERK/MAPK and PTEN signaling. Thus, we have demonstrated the utility of optogenetic-induced skeletal muscle contraction to elicit structural, functional, and molecular adaptation of the enthesis in vivo especially during growth.

The current literature has mainly focused on the biology of tendons and on the characterization of the biological properties of tenocytes and tenoblasts. It is still not understood how these cells can work together in homeostatic equilibrium. We put forward the concept of the "tendon unit" as a morpho-functional unit that can be influenced by a variety of external stimuli such as mechanical stimuli, hormonal influence, or pathological states. We describe how this unit can modify itself to respond to such stimuli. We evidence the capability of the tendon unit of healing itself through the production of collagen following different mechanical stimuli and hypothesize that restoration of the homeostatic balance of the tendon unit should be a therapeutic target.

Tendon is a collagen-enriched, tough, and intricately arranged connective tissue that connects muscle to the bone and transmits forces, resulting in joint movement. High mechanical demands can affect normal tissues and may lead to severe disorders, which usually require replacement of the damaged tendon. In recent decades, various decellularization methods have been studied for tissue engineering applications. One of the major challenges in tendon decellularization is preservation of the tendon extracellular matrix (ECM) architecture to maintain natural tissue characteristics. The aim of the present study was to create a decellularized bovine Achilles tendon scaffold to investigate its cytocompatibility with seeded hAd-MSCs (human adipose derived-mesenchymal stem cells) and blastema tissue in vitro. Here, we describe a reliable procedure to decellularize bovine Achilles tendon using a combination of physical and chemical treatments including repetitive freeze-thaw cycles and the ionic detergent SDS, respectively. The decellularization effectiveness and cytocompatibility of the tendon scaffolds were verified by histological studies and scanning electron microscopy for up to 30 days after culture. Histological studies revealed hAd-MSC attachment and penetration into the scaffolds at 5, 10, 15 and 20 days of culture. However, a decrease in cell number was observed on days 25 and 30 after culture in vitro. Moreover, migration of the blastema tissue cells into the scaffold were shown at 10 to 25 days post culture, however, destruction of the scaffolds and reduction in cell number were observed on 30th day after culture. Our results suggest that this decellularization protocol is an effective and biocompatible procedure which supports the maintenance and growth of both hAd-MSCs and blastema cells, and thus might be promising for tendon tissue engineering.

Despite all the efforts made in tissue engineering for tendon repair, the management of tendon injuries still poses a challenge, as current treatments are unable to restore the function of tendons following injuries. Hydrogels, due to their exceptional biocompatibility and plasticity, have been extensively applied and regarded as promising candidate biomaterials in tissue regeneration. Varieties of approaches have designed functionally-adapted hydrogels and combined hydrogels with other factors (e.g., bioactive molecules or drugs) or materials for the enhancement of tendon repair. This review first summarized the current state of knowledge on the mechanisms underlying the process of tendon healing. Afterward, we discussed novel strategies in fabricating hydrogels to overcome the issues frequently encountered during the applications in tendon repair, including poor mechanical properties and undesirable degradation. In addition, we comprehensively summarized the rational design of hydrogels for promoting stem-cell-based tendon tissue engineering via altering biophysical and biochemical factors. Finally, the role of macrophages in tendon repair and how they respond to immunomodulatory hydrogels were highlighted.

Tendon injuries are some of the most commonly diagnosed musculoskeletal diseases. Tendon regeneration is sensitive to the topology of the substitute as it affects the cellular microenvironment and homeostasis. To bionic in vivo three-dimensional (3D) aligned microenvironment, an ordered 3D sandwich model was used to investigate the cell response in the tendon. First, high-resolution 3D printing provided parallel-grooved topographical cues on the hydrogel surface. Then the cells were seeded on its surface to acquire a 2D model. Afterward, an additional hydrogel coating layer was applied to the cells to create the 3D model. The interaction between cells and order structures in three-dimensions is yet to be explored. The study found that the tendon stem/progenitor cells (TSPCs) still maintain their ordering growth in the 3D model as in the 2D model. The study also found that the 3D-aligned TSPCs exhibited enhanced tenogenic differentiation through the PI3K-AKT signaling pathway and presented a less inflammatory phenotype than those in the 2D model. The in vivo implantation of such a 3D-aligned TSPC composite promoted tendon regeneration and mitigated heterotopic ossification in an Achilles defect model. These findings demonstrated that 3D-aligned TSPCs within a biomimetic topology environment are promising for functional tendon regeneration.

Tendinopathies encompass a highly prevalent, multi-faceted spectrum of disorders, characterized by activity-related pain, compromised function, and propensity for an extended absence from sport and the workplace. The pathophysiology of tendinopathy continues to evolve. For decades, it has been related primarily to repetitive overload trauma but more recently, the onset of tendinopathy has been attributed to the tissue's failed attempt to heal after subclinical inflammatory and immune challenges (failed healing model). Conventional tendinopathy management produces only short-term symptomatic relief and often results in incomplete repair or healing leading to compromised tendon function. For this reason, there has been increased effort to develop therapeutics to overcome the tissue's failed healing response by targeting the cellular metaplasia and pro-inflammatory extra-cellular environment. On this basis, stem cell-based therapies have been proposed as an alternative therapeutic approach designed to modify the course of the various tendon pathologies. Mesenchymal stem/stromal cells (MSCs) are multipotent stem cells often referred to as "medicinal signaling cells" due to their immunomodulatory and anti-inflammatory properties that can produce a pro-regenerative microenvironment in pathological tendons. However, the adoption of MSCs into clinical practice has been limited by FDA regulations and perceived risk of adverse events upon infusion in vivo. The introduction of cell-free approaches, such as the extracellular vesicles of MSCs, has encouraged new perspectives for the treatment of tendinopathies, showing promising short-term results. In this article, we review the most recent advances in MSC-based and MSC-derived therapies for tendinopathies. Preclinical and clinical studies are included with comment on future directions of this rapidly developing therapeutic modality, including the importance of understanding tissue loading and its relationship to any treatment regimen.