Injured Tendons Research Articles

Injectable bioactive glass/sodium alginate hydrogel with immunomodulatory and angiogenic properties for enhanced tendon healing.

Tendon healing is a complex process involving inflammation, proliferation, and remodeling, eventually achieving a state of hypocellularity and hypovascularity. Currently, few treatments can satisfactorily restore the structure and function of native tendon. Bioactive glass (BG) has been shown to possess immunomodulatory and angiogenic properties. In this study, we investigated whether an injectable hydrogel fabricated of BG and sodium alginate (SA) could be applied to enhance tenogenesis following suture repair of injured tendon. We demonstrated that BG/SA hydrogel significantly accelerated tenogenesis without inducing heterotopic ossification based on histological analysis. The therapeutic effect could attribute to increased angiogenesis and M1 to M2 phenotypic switch of macrophages within 7 days post-surgery. Morphological characterization demonstrated that BG/SA hydrogel partially reverted the pathological changes of Achilles tendon, including increased length and cross-sectional area (CSA). Finally, biomechanical test showed that BG/SA hydrogel significantly improved ultimate load, failure stress, and tensile modulus of the repaired tendon. In conclusion, administration of an injectable BG/SA hydrogel can be a novel and promising therapeutic approach to augment Achilles tendon healing in conjunction with surgical intervention.

Graphene-MoS2 polyfunctional hybrid hydrogels for the healing of transected Achilles tendon.

Healing of injured tendon is a major clinical challenge in orthopaedic medicine, due to the poor regenerative potential of this tissue. Two-dimensional nanomaterials, as versatile scaffolds, have shown a great potential to support, trigger and accelerate the tendon regeneration. However, weak mechanical properties, poor functionality and low biocompatibility of these scaffolds as well as post-surgery infections are main drawbacks that limit their development in the higher clinical phases. In this work, a series of hydrogels consisting polyglycerol functionalized reduced graphene oxide (PG), polyglycerol-functionalized molybdenum disulfide (PMoS2) and PG/PMoS2 hybrid within the gelatin matrix are formulated in new scaffolds and their ability for the healing of injured Achilles tendon, due to their high mechanical properties, low toxicity, cell proliferation enhancement, and antibacterial activities is investigated. While scaffolds containing PG and PMoS2 showed a moderate tendon regeneration and anti-inflammatory effect, respectively, their hybridization into PG/PMoS2 demonstrated a synergistic healing efficiency. Along the same line, an accelerated return of tendon function with low peritendinous adhesion and low cross-sectional area in animal group treated with scaffold containing PG/PMoS2 was observed. Taking advantage of the high biocompatibility, high strength, straightforward construction and fast tendon regeneration, PG/PMoS2 can be used as a new scaffold for the future tissue engineering.

Increased stiffness and reoperation rate in partial rotator cuff repairs treated with a bovine patch: a propensity-matched trial

Treating high-grade (grade 2 and 3) partial-thickness rotator cuff tears after failed conservative care remains challenging. Arthroscopic repair techniques are often considered with or without subacromial decompression and biological injections. More recently, a bioinductive bovine collagen patch (Regeneten; Smith & Nephew, Memphis, TN, USA) has been proposed to create a healing response and thicken the injured tendon. Although promising early results have been shown, previous studies lacked control subjects or comparison to other surgical treatments. The purpose of this study was to compare the reoperation rates of arthroscopic débridement and repair without a bioinductive collagen patch vs. arthroscopic débridement and repair with a bioinductive collagen patch in patients with high-grade partial-thickness rotator cuff tears in whom a minimum of 6 months of nonoperative treatment failed. Thirty-two patients with high-grade partial-thickness supraspinatus tears were treated with surgical repair with a bioinductive patch. A control group of 32 patients with high-grade partial-thickness supraspinatus tears treated with débridement or tear completion and repair without a bioinductive patch was selected and matched for age, sex, and tear size. Patients were followed up at regular intervals of 6 weeks, 12 weeks, and 6 months postoperatively, and range of motion was assessed at respective clinic visits. Stiffness and reoperations were compared between groups. Postoperative stiffness was observed in the first 12 weeks in 8 of 32 patients in the patch group compared with 1 of 32 patients in the control group. Six patients in the patch group underwent reoperations compared with no patients in the control group (P<.001). All 6 reoperations in the patch group were performed to address stiffness. There were no differences in race, smoking status, or diabetes between groups (P>.05). Patients in the patch group had a significantly higher rate of postoperative stiffness. In the majority of patients in whom shoulder stiffness developed, reoperation was required.

Operative versus conservative treatment of acute Achilles tendon ruptures: preliminary results of clinical outcome, kinematic MRI and contrast-enhanced ultrasound

IntroductionThere is no uniform consensus on the gold standard therapy for acute Achilles tendon rupture. The aim of this pilot study was to compare operative and conservative treatment regarding imaging findings and clinical outcome.Materials and methodsSurgically or conservatively treated patients with acute Achilles tendon rupture were retrospectively evaluated. Differences in tendon length and diameter with and without load were analysed using kinematic MRI, tendon perfusion, structural alterations, movement and scar tissue by means of grey-scale and contrast-enhanced ultrasound (CEUS). Intra- and interobserver agreement were recorded.ResultsNo significant difference was detected regarding clinical outcome, B mode ultrasonography, contrast-enhanced sonography or MRI findings, although alterations in MRI-based measurements of tendon elasticity were found for both groups. Considerable elongation and thickening of the injured tendon were detected in both groups.ConclusionBoth, conservative and surgical treatment showed comparable outcomes in our preliminary results and may suggest non-inferiority of a conservative approach.

Fibrosis and Adipogenesis in Injured or Diseased Tendon

Fibrosis and Adipogenesis in Injured or Diseased Tendon

P281 In vitro evaluation of the response of human tendon-derived stromal cells to a novel electrospun suture

Abstract Background/Aims Recurrent tears after surgical tendon repair remain common, with 40% of rotator cuff repairs failing within one year. Repair failures can be partly attributed to the use of sutures not designed for the tendon cellular niche nor designed for the promotion of repair processes. Clinically-used sutures have high tensile strength to mechanically support injured tendon. However, these sutures do not support cell integration into the material, but instead can stimulate a chronic inflammatory response. Synthetic electrospun materials can mechanically support the tendon while providing topographical cues that modulate the immune response to promote wound healing. Electrospun material has an increased surface area and porosity which can mimic that of tendon tissue, thus promoting tendon cell infiltration and proliferation. Here, a novel electrospun suture made from twisted polydioxanone (PDO) polymer filaments is compared to PDS II, a clinically used PDO suture currently utilised in tendon repair. Methods We evaluated the ability of electrospun suture and PDS II to support the attachment and proliferation of human tendon-derived stromal cells using PrestoBlue cell viability assays and scanning electron microscopy. Suture surface chemistry was analysed using X-ray photoelectron spectroscopy. Bulk RNA-Seq interrogated the transcriptional response of primary tendon-derived stromal cells to sutures after 14 days. Results The electrospun suture showed increased initial cell attachment compared to PDS II. X-ray photoelectron spectroscopy revealed that the local surface chemistry of electrospun suture and PDS II is similar, indicating that the tendon-like architecture of electrospun suture was responsible for the greater cell attachment. Furthermore, electrospun suture elicited a stronger transcriptional response compared with PDS II, with relative enrichment of pathways including mTorc1 signalling and depletion of epithelial-to-mesenchymal transition and extracellular matrix gene sets. When compared to baseline, neither suture induced transcriptional upregulation of inflammatory pathways such as IL6-JAK-STAT3 signalling and TNF-α signalling via NF-κB. Conclusion Twisted electrospun sutures demonstrated a tendon-derived stromal cell response indicative of cell proliferation and wound healing, without significant fibrosis, when compared to clinically-used and safe PDS II suture. Twisted electrospun sutures therefore show promise in improving outcomes in surgical tendon repair by allowing increased cell attachment while maintaining an appropriate tissue response. Disclosure A. Nezhentsev: None. R.E. Abhari: None. M.J. Baldwin: None. J.Y. Mimpen: None. E. Augustyniak: None. M. Isaacs: None. P. Mouthuy: None. A.J. Carr: None. S.J.B. Snelling: None.

Functional biomaterials for tendon/ligament repair and regeneration.

With an increase in life expectancy and the popularity of high-intensity exercise, the frequency of tendon and ligament injuries has also increased. Owing to the specificity of its tissue, the rapid restoration of injured tendons and ligaments is challenging for treatment. This review summarizes the latest progress in cells, biomaterials, active molecules and construction technology in treating tendon/ligament injuries. The characteristics of supports made of different materials and the development and application of different manufacturing methods are discussed. The development of natural polymers, synthetic polymers and composite materials has boosted the use of scaffolds. In addition, the development of electrospinning and hydrogel technology has diversified the production and treatment of materials. First, this article briefly introduces the structure, function and biological characteristics of tendons/ligaments. Then, it summarizes the advantages and disadvantages of different materials, such as natural polymer scaffolds, synthetic polymer scaffolds, composite scaffolds and extracellular matrix (ECM)-derived biological scaffolds, in the application of tendon/ligament regeneration. We then discuss the latest applications of electrospun fiber scaffolds and hydrogels in regeneration engineering. Finally, we discuss the current problems and future directions in the development of biomaterials for restoring damaged tendons and ligaments.

Translational therapy from preclinical animal models for muscle degeneration after rotator cuff injury.

Chronic rotator cuff tears are debilitating diseases which significantly affect patients’ quality of life and pose substantial financial burden to the society. The intraoperative reparability of injured tendon and postoperative probability of tendon retear are highly associated with the quality of torn muscles, specifically, the severity of muscle atrophy and fatty infiltration. Animal models that reproduce the characteristic muscle pathology after rotator cuff injury have been developed and used to provide insight into the underlying biology and pathophysiology. In this review, we briefly summarize the current information obtained from preclinical animal studies regarding the degenerative change of cuff muscle subsequent to tendon release and/or suprascapular nerve denervation. Importantly, we focus on the potential translational therapeutic targets or agents for the prevention or reversal of muscle atrophy and fatty infiltration. While further studies are warranted to assess the safety and efficacy of novel therapies derived from these preclinical animal research, we believe that their clinical translation for the treatment of rotator cuff disorders is on the horizon.The Translational potential of this articleNovel therapeutic strategies described in this review from preclinical animal studies hold a great translational potential for preventing or reversing rotator cuff muscle pathology, while further assessments on their safety and efficacy are warranted.

MSC in Tendon and Joint Disease: The Context-Sensitive Link Between Targets and Therapeutic Mechanisms.

Mesenchymal stromal cells (MSC) represent a promising treatment option for tendon disorders and joint diseases, primarily osteoarthritis. Since MSC are highly context-sensitive to their microenvironment, their therapeutic efficacy is influenced by their tissue-specific pathologically altered targets. These include not only cellular components, such as resident cells and invading immunocompetent cells, but also components of the tissue-characteristic extracellular matrix. Although numerous in vitro models have already shown potential MSC-related mechanisms of action in tendon and joint diseases, only a limited number reflect the disease-specific microenvironment and allow conclusions about well-directed MSC-based therapies for injured tendon and joint-associated tissues. In both injured tissue types, inflammatory processes play a pivotal pathophysiological role. In this context, MSC-mediated macrophage modulation seems to be an important mode of action across these tissues. Additional target cells of MSC applied in tendon and joint disorders include tenocytes, synoviocytes as well as other invading and resident immune cells. It remains of critical importance whether the context-sensitive interplay between MSC and tissue- and disease-specific targets results in an overall promotion or inhibition of the desired therapeutic effects. This review presents the authors’ viewpoint on disease-related targets of MSC therapeutically applied in tendon and joint diseases, focusing on the equine patient as valid animal model.

Autophagy guards tendon homeostasis

Tendons are vital collagen-dense specialized connective tissues transducing the force from skeletal muscle to the bone, thus enabling movement of the human body. Tendon cells adjust matrix turnover in response to physiological tissue loading and pathological overloading (tendinopathy). Nevertheless, the regulation of tendon matrix quality control is still poorly understood and the pathogenesis of tendinopathy is presently unsolved. Autophagy, the major mechanism of degradation and recycling of cellular components, plays a fundamental role in the homeostasis of several tissues. Here, we investigate the contribution of autophagy to human tendons’ physiology, and we provide in vivo evidence that it is an active process in human tendon tissue. We show that selective autophagy of the endoplasmic reticulum (ER-phagy), regulates the secretion of type I procollagen (PC1), the major component of tendon extracellular matrix. Pharmacological activation of autophagy by inhibition of mTOR pathway alters the ultrastructural morphology of three-dimensional tissue-engineered tendons, shifting collagen fibrils size distribution. Moreover, autophagy induction negatively affects the biomechanical properties of the tissue-engineered tendons, causing a reduction in mechanical strength under tensile force. Overall, our results provide the first evidence that autophagy regulates tendon homeostasis by controlling PC1 quality control, thus potentially playing a role in the development of injured tendons.

Using the KI-67 proliferation marker to evaluate tendon regeneration in rabbits in an experiment

The goal is to assess the influence of platelet autoplasm on healing damaged tendons in rabbits.Materials and methods. The study on the effect of platelet autoplasma on the regeneration of damaged tendon fabric was carried out on rabbits.In the experiment, rabbits were applied in the field of Achille tendons, since this tendon in animals is injured quite often [1]. Then in the area of ​​damage to the tendon, the experimental group of rabbits was administered tap, while the injured tendons of rabbits of the control group were left without treatment. An intradermal seam was imposed on wounds in the field of leather. A month later, animals of experimental and control groups took samples of tendon fabric in places of damage to immunohistochemical research using the Ki-67 marker, which made it possible to visually demonstrate the action of platelet autoplasm for the regeneration of damaged tendons.Results. The Ki-67 proliferation marker made it possible to clearly reveal the effect of tap on regeneration during damage to the tendon fabric in rabbits. In damaged tendon tissues in rabbits, proliferative processes go more active than in a healthy tendon. Thanks to the studies carried out, it was established that TAP stimulates proliferative processes in tendon tissues. The proliferation index is higher in the tendon tissues of the experimental group of rabbits, which was administered by TAP than in the control group and in a healthy tendon fabric.

Current State of Platelet-Rich Plasma and Cell-Based Therapies for the Treatment of Osteoarthritis and Tendon and Ligament Injuries.

Orthobiologics encompass numerous substances that are naturally found in the human body including platelet-rich plasma (PRP), isolated growth factors, and cell therapy approaches to theoretically optimize and improve the healing of cartilage, fractures, and injured muscles, tendons, and ligaments. PRP is an autologous derivative of whole blood generated by centrifugation and is perhaps the most widely used orthobiologic treatment modality. Despite a vast amount of literature on its use in osteoarthritis as well as in tendon and ligament pathology, clinical efficacy results remain mixed, partly as a result of insufficient reporting of experimental details or exact compositions of PRP formulations used. Mesenchymal stromal cells (MSCs) can be isolated from a variety of tissues, with the most common being bone marrow aspirate concentrate. Similar to PRP, clinical results in orthopaedics with MSCs have been highly variable, with the quality and concentration of MSCs being highly contingent on the site of procurement and the techniques of harvesting and preparation. Advances in novel orthobiologics, therapeutic targets, and customized orthobiologic therapy will undoubtedly continue to burgeon, with some early promising results from studies targeting fibrosis and senescence.

Disulfiram Suppressed Peritendinous Fibrosis Through Inhibiting Macrophage Accumulation and Its Pro-inflammatory Properties in Tendon Bone Healing

The communication between macrophages and tendon cells plays a critical role in regulating the tendon-healing process. However, the potential mechanisms through which macrophages can control peritendinous fibrosis are unknown. Our data showed a strong pro-inflammatory phenotype of macrophages after a mouse tendon–bone injury. Moreover, by using a small-molecule compound library, we identified an aldehyde dehydrogenase inhibitor, disulfiram (DSF), which can significantly promote the transition of macrophage from M1 to M2 phenotype and decrease macrophage pro-inflammatory phenotype. Mechanistically, DSF targets gasdermin D (GSDMD) to attenuate macrophage cell pyroptosis, interleukin-1β, and high mobility group box 1 protein release. These pro-inflammatory cytokines and damage-associated molecular patterns are essential for regulating tenocyte and fibroblast proliferation, migration, and fibrotic activity. Deficiency or inhibition of GSDMD significantly suppressed peritendinous fibrosis formation around the injured tendon and was accompanied by increased regenerated bone and fibrocartilage compared with the wild-type littermates. Collectively, these findings reveal a novel pathway of GSDMD-dependent macrophage cell pyroptosis in remodeling fibrogenesis in tendon–bone injury. Thus, GSDMD may represent a potential therapeutic target in tendon–bone healing.

Promethazine Downregulates Wnt/β-Catenin Signaling and Increases the Biomechanical Forces of the Injured Achilles Tendon in the Early Stage of Healing

Background: Wnt/β-catenin signaling suppresses the differentiation of cultured tenocytes, but its roles in tendon repair remain mostly elusive. No chemical compounds are currently available to treat tendon injury. Hypothesis: We hypothesized that the inhibition of Wnt/β-catenin signaling would accelerate tendon healing. Study Design: Controlled laboratory study. Methods: Tendon-derived cells (TDCs) were isolated from rat Achilles tendons. The right Achilles tendon was injured via a dermal punch, while the left tendon was sham operated. A Wnt/β-catenin inhibitor, IWR-1, and an antihistamine agent, promethazine (PH), were locally and intramuscularly injected, respectively, for 2 weeks after surgery. The healing tendons were histologically and biomechanically evaluated. Results: The amount of β-catenin protein was increased in the injured tendons from postoperative weeks 0.5 to 2. Inhibition of Wnt/β-catenin signaling by IWR-1 in healing tendons improved the histological abnormalities and decreased β-catenin, but it compromised the biomechanical properties. As we previously reported that antihistamine agents suppressed Wnt/β-catenin signaling in human chondrosarcoma cells, we examined the effects of antihistamines on TDCs. We found that a first-generation antihistamine agent, PH, increased the expression of the tendon marker genes Mkx and Tnmd in TDCs. Intramuscular injection of PH did not improve histological abnormalities, but it decreased β-catenin in healing tendons and increased the peak force and stiffness of the healing tendons on postoperative week 2. On postoperative week 8, however, the biomechanical properties of vehicle-treated tendons became similar to those of PH-treated tendons. Conclusion: IWR-1 and PH suppressed Wnt/β-catenin signaling and improved the histological abnormalities of healing tendons. IWR-1, however, compromised the biomechanical properties of healing tendons, whereas PH improved them. Clinical Relevance: PH is a candidate repositioned drug that potentially accelerates tendon repair.

Dexamethasone Enhances Achilles Tendon Healing in an Animal Injury Model, and the Effects Are Dependent on Dose, Administration Time, and Mechanical Loading Stimulation

Background: Corticosteroid treatments such as dexamethasone are commonly used to treat tendinopathy but with mixed outcomes. Although this treatment can cause tendon rupture, it can also stimulate the tendon to heal. However, the mechanisms behind corticosteroid treatment during tendon healing are yet to be understood. Purpose: To comprehend when and how dexamethasone treatment can ameliorate injured tendons by using a rat model of Achilles tendon healing. Study Design: Controlled laboratory study. Methods: An overall 320 rats were used for a sequence of 6 experiments. We investigated whether the drug effect was time-, dose-, and load-dependent. Additionally, morphological data and drug administration routes were examined. Healing tendons were tested mechanically or used for histological examination 12 days after transection. Blood was collected for flow cytometry analysis in 1 experiment. Results: We found that the circadian rhythm and drug injection timing influenced the treatment outcome. Dexamethasone treatment at the right time point (days 7-11) and dose (0.1 mg/kg) significantly improved the material properties of the healing tendon, while the adverse effects were reduced. Local dexamethasone treatment did not lead to increased peak stress, but it triggered systemic granulocytosis and lymphopenia. Mechanical loading (full or moderate) is essential for the positive effects of dexamethasone, as complete unloading leads to the absence of improvements. Conclusion: We conclude that dexamethasone treatment to improve Achilles tendon healing is dose- and time-dependent, and positive effects are perceived even in a partly unloaded condition. Clinical Relevance: These findings are promising from a clinical perspective, as the positive effect of this drug was seen even when given at lower doses and in a moderate loading condition, which better mimics the load level in patients with tendon ruptures.

Exosomes from tendon derived stem cells promote tendon repair through miR-144-3p-regulated tenocyte proliferation and migration

BackgroundTendon derived stem cells (TDSCs) have proven to be effective in tendon repair by secreting paracrine factors, which modulate the function of resident cells and inflammatory process. Exosomes, which are secreted from cells to mediate intercellular communication, may be used to treat tendon injuries. Here, we aimed to determine the effects of exosomes from TDSCs (TDSC-Exos) on tendon repair and to explore the underlying mechanism by investigating the role of microRNAs (miRNAs).MethodsTDSC-Exos were isolated from TDSC conditioned medium. In vitro studies were performed to investigate the effects of TDSC-Exos on the proliferation, migration, cytoprotection, collagen production and tendon-specific markers expression in tenocytes. In order to determine the therapeutic effects of TDSC-Exos in vivo, we used a scaffold of photopolymerizable hyaluronic acid (p-HA) loaded with TDSC-Exos (pHA-TDSC-Exos) to treat tendon defects in the rat model. Subsequently, RNA sequencing and bioinformatic analyses were used to screen for enriched miRNAs in TDSC-Exos and predict target genes. The miRNA-target transcript interaction was confirmed by a dual-luciferase reporter assay system. In order to determine the role of candidate miRNA and its target gene in TDSC-Exos-regulated tendon repair, miRNA mimic and inhibitor were transfected into tenocytes to evaluate cell proliferation and migration.ResultsTreatment with TDSC-Exos promoted proliferation, migration, type I collagen production and tendon-specific markers expression in tenocytes, and also protected tenocytes from oxidative stress and serum deprivation. The scaffold of pHA-TDSC-Exos could sever as a sustained release system to treat the rat model of tendon defects. In vivo study showed that TDSC-Exos promoted early healing of injured tendons. Rats treated with TDSC-Exos had better fiber arrangement and histological scores at the injury site. Besides, the injured tendons treated with TDSC-Exos had better performance in the biomechanical testing. Therefore, the pHA-TDSC-Exos scaffold proved to facilitate tendon repair in the rat model. miR-144-3p was enriched in TDSC-Exos and promoted tenocyte proliferation and migration via targeting AT-rich interactive domain 1A (ARID1A).ConclusionsTDSC-Exos enhanced tenon repair through miR-144-3p-regulated tenocyte proliferation and migration. These results suggest that TDSC-Exos can serve as a promising strategy to treat tendon injuries.

Altered TGFB1 regulated pathways promote accelerated tendon healing in the superhealer MRL/MpJ mouse

To better understand the molecular mechanisms of tendon healing, we investigated the Murphy Roth’s Large (MRL) mouse, which is considered a model of mammalian tissue regeneration. We show that compared to C57Bl/6J (C57) mice, injured MRL tendons have reduced fibrotic adhesions and cellular proliferation, with accelerated improvements in biomechanical properties. RNA-seq analysis revealed that differentially expressed genes in the C57 healing tendon at 7 days post injury were functionally linked to fibrosis, immune system signaling and extracellular matrix (ECM) organization, while the differentially expressed genes in the MRL injured tendon were dominated by cell cycle pathways. These gene expression changes were associated with increased α-SMA+ myofibroblast and F4/80+ macrophage activation and abundant BCL-2 expression in the C57 injured tendons. Transcriptional analysis of upstream regulators using Ingenuity Pathway Analysis showed positive enrichment of TGFB1 in both C57 and MRL healing tendons, but with different downstream transcriptional effects. MRL tendons exhibited of cell cycle regulatory genes, with negative enrichment of the cell senescence-related regulators, compared to the positively-enriched inflammatory and fibrotic (ECM organization) pathways in the C57 tendons. Serum cytokine analysis revealed decreased levels of circulating senescence-associated circulatory proteins in response to injury in the MRL mice compared to the C57 mice. These data collectively demonstrate altered TGFB1 regulated inflammatory, fibrosis, and cell cycle pathways in flexor tendon repair in MRL mice, and could give cues to improved tendon healing.

The Role of Diffusion Weighted MR Imaging in the Diagnosis of Tendon Injuries of the Ankle and Foot.

Background and objectives: Our aim is to determine the diagnostic performance and utility of Diffusion Weighted MR Imaging (DWI) against the routine Magnetic Resonance Imaging (MRI) for the evaluation of patients with tendon injuries of the ankle and foot. Materials and Method: After institutional review board approval and informed consent taken from all the patients, ankle and foot MR imaging and DWI-Apparent Diffusion Coefficient (ADC) mapping were performed on the 81 injured tendons of 50 patients. All tendon injuries were named as Rupture (R), Partial tear (PT), and Tenosynovitis (T). Diagnostic interpretation was based on the MRI-DWI and ADC mapping, verified by either open surgery, diagnostic arthroscopy, or conservative procedures-splint application. Statistical analysis of this research was assessed by Fischer’s exact test, variance analysis test between dependent groups, Receiver Operating Characteristics (ROC) curve, and Pearson chi square statistics. Results: MRI depicted all tendon injuries with 70% sensitivity and 100% specificity, and showed a significant statistical relationship to surgical and arthroscopic references with high agreement (p < 0.05, k: 0.609). DWI had 100% sensitivity and 83–90% specificity for the visualization of tendon injuries with certain agreement and a significant statistical relationship to the gold standard (p < 0.05, k: 0.890–0.899). For all those injured tendons, DWI had 100% sensitivity for the diagnosis of R, and 92–97% sensitivity corresponding to PT and T over routine ankle MR imaging. The specificity of DWI to MRI ranged from 75 to 44% for all the injured tendons. DWI had significant statistical superiority over MRI for the visualization of R, PT, and T of all tendons included in this research (p < 0.05). Conclusions: DWI is a good imaging modality for the visualization of ankles with tendon injuries, possibly further improving the sensitivity of the classical ankle and foot MRI, and supplying more beneficial and diagnostic information than routine MR imaging on the basis of R, PT, and T of tendons at the ankle and foot.

A randomized controlled trial of stem cell injection for tendon tear

Tendons have limited reparative ability and perform a relatively simple mechanical function via the extracellular matrix. Thus, the injured tendon might be treated successfully by stem cell transplantation. We performed a randomized, controlled study to investigate the effects of mesenchymal stem cell injection for treating partial tears in the supraspinatus tendon. We enrolled 24 patients with shoulder pain lasting more than 3 months and partial tears in the supraspinatus tendon. Participants were assigned to three groups: stem cells in fibrin glue, normal saline/fibrin glue mixture, and normal saline only, with which intra-lesional injection was performed. Pain at activity and rest, shoulder function and tear size were evaluated. For safety measures, laboratory tests were taken and adverse events were recorded at every visit. Participants were followed up at 6, 12 weeks, 6, 12 months and 2 years after injection. The primary outcome measure was the improvement in pain at activity at 3 months after injection. Twenty-three patients were included in the final analysis. Primary outcome did not differ among groups (p = 0.35). A mixed effect model revealed no statistically significant interactions. Only time significantly predicted the outcome measure. All participants reported transient pain at the injection site. There were no differences in post-injection pain duration or severity. Safety measures did not differ between groups, and there were no persistent adverse events. Stem cell injection into supraspinatus partial tears in patients with shoulder pain lasting more than 3 months was not more effective than control injections.ClinicalTrials.gov Identifier: NCT02298023

Muscle-tendon morphomechanical properties of non-surgically treated Achilles tendon 1-year post-rupture

BackgroundAchilles tendon rupture appears to alter stiffness and length of the tendon. These alterations may affect the function of tendon in force transmission and in energy storage and recovery. We studied the mechanical properties of the Achilles' tendon post-rupture and their association with function. MethodsTwenty-four (20 males, 4 females) participants (mean age: 43 y, 176 cm, 81 kg) were recruited. Ultrasonography and dynamometry were used to assess the muscle-tendon unit morphological and mechanical properties of non-surgically treated patients 1-year post rupture. FindingsInjured tendons were longer with difference of 1.8 cm (95%CI: 0.5–1.9 cm; P < 0.001), and thicker by 0.2 mm (0.2–0.3 mm; P < 0.01). Medial gastrocnemius cross-sectional area was 1.0 cm2 smaller (0.8–1.1 cm2; P < 0.001), fascicles were 0.6 cm shorter (0.5–0.7 cm; P < 0.001) and pennation angle was 2.5° higher (1.3–3.6°; P < 0.001) when compared to the uninjured limb. We found no differences between injured and uninjured tendon stiffness 1-year post-rupture (mean difference: 29.8 N/mm, −7.7–67.3 N/mm; P = 0.170). The injured tendon showed 1.8 mm (1.2–2.4 mm; P < 0.01) lower elongation during maximal voluntary isometric contractions. Patient-reported functional outcome was related to the tendon resting length (β = 0.68, r(10) = 4.079, P = 0.002). Inter-limb differences in the medial gastrocnemius fascicle length were related to inter-limb differences in maximum contractions (β = 1.17, r(14) = 2.808, P = 0.014). InterpretationLonger Achilles tendon resting length was associated with poorer self-evaluated functional outcome. Although the stiffness of non-surgically treated and uninjured tendons was similar 1-year post rupture, plantar flexion strength deficit was still present, possibly due to shorter medial gastrocnemius fascicle length.