Effect of platelet-rich plasma in Achilles tendon allograft in rabbits.

BACKGROUND: Achilles tendon is composed of dense connective tissue and is one of the largest tendons in the body. In veterinary medicine, acute ruptures are associated with impact injury or sharp trauma. Healing of the ruptured tendon is challenging because of poor blood and nerve supply as well as the residual cell population. Platelet-rich plasma (PRP) contains numerous bioactive agents and growth factors and has been utilized to promote healing in bone, soft tissue, and tendons. OBJECTIVE: The purpose of this study was to evaluate the healing effect of PRP injected into the surrounding fascia of the Achilles tendon after allograft in rabbits. METHODS: Donor rabbits (n = 8) were anesthetized and 16 lateral gastrocnemius tendons were fully transected bilaterally. Transected tendons were decellularized and stored at -80°C prior to allograft. The allograft was placed on the partially transected medial gastrocnemius tendon in the left hindlimb of 16 rabbits. The allograft PRP group (n = 8) had 0.3 mL of PRP administered in the tendon and the allograft control group (n = 8) did not receive any treatment. After 8 weeks, rabbits were euthanatized and allograft tendons were transected for macroscopic, biomechanical, and histological assessment. RESULTS: The allograft PRP group exhibited superior macroscopic assessment scores, greater tensile strength, and a histologically enhanced healing process compared to those in the allograft control group. CONCLUSIONS: Our results suggest administration of PRP on an allograft tendon has a positive effect on the healing process in a ruptured Achilles tendon.

Delayed Diagnosis of Complete Achilles Tendon Rupture in a Teenage Athlete: A Case Report of Nonoperative Treatment.

CASE: A 19-year-old female athlete experienced calf pain during sport. A complete Achilles tendon rupture was diagnosed 4 weeks after injury. Ultrasound revealed discontinuity of the Achilles tendon with 2.0 cm of diastasis, persisting in plantarflexion. Plantarflexion immobilization was initiated, and progressive dorsiflexion was used until 10 weeks from injury. At 1 year from injury, ankle magnetic resonance imaging revealed a contiguous tendon, the patient was pain-free, and had returned to high-level athletics with equivalent sport performance relative to her preoperative status. CONCLUSION: Certain Achilles tendon ruptures in young people may be treated nonoperatively with good clinical outcomes, even if diagnosis and immobilization are delayed and tendon diastasis persists in maximum plantarflexion.

Spontaneous tendon or ligament ruptures in patients undergoing dialysis: First pediatric case report and literature review.

Spontaneous tendon or ligament ruptures are quite rare and mostly associated with chronic systemic diseases such as diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis, and chronic kidney disease (CKD). In this study, we present the first documented case of a spontaneous rupture of the medial patellofemoral ligament (MPFL) in a pediatric patient. The patient was undergoing long-term peritoneal dialysis (PD) and had a history of severe secondary hyperparathyroidism. Additionally, we discussed spontaneous tendon and ligament ruptures associated with CKD or dialysis through a comprehensive literature review. This case report highlights the importance of recognizing that spontaneous tendon or ligament injuries are not exclusive to adults; children with CKD can also be affected. Several factors including poor parathyroid hormone (PTH) and metabolic acidosis control, prolonged CKD duration and presence of malnutrition play role in the pathogenesis. Early diagnosis is crucial as it allows for timely surgical intervention and leads to a favorable functional recovery.

TRIM54 alleviates inflammation and apoptosis by stabilizing YOD1 in rat tendon-derived stem cells.

Tendinopathy is a disorder of musculoskeletal system that primarily affects athletes and the elderly. Current treatment options are generally comprised of various exercise and loading programs, therapeutic modalities, and surgical interventions and are limited to pain management. This study is to understand the role of TRIM54 (tripartite motif containing 54) in tendonitis through in vitro modeling with tendon-derived stem cells (TDSCs) and in vivo using rat tendon injury model. Initially, we observed that TRIM54 overexpression in TDSCs model increased stemness and decreased apoptosis. Additionally, it rescued cells from tumor necrosis factor α-induced inflammation, migration, and tenogenic differentiation. Further, through immunoprecipitation studies, we identified that TRIM54 regulates inflammation in TDSCs by binding to and ubiquitinating YOD1. Further, overexpression of TRIM54 improved the histopathological score of tendon injury as well as the failure load, stiffness, and young modulus in vivo. These results indicated that TRIM54 played a critical role in reducing the effects of tendon injury. Consequently, these results shed light on potential therapeutic alternatives for treating tendinopathy.

iTRAQ-based proteomics reveals potential markers and treatment pathways for acute Achilles tendon rupture.

BACKGROUND: Due to its limited blood supply and irregular mechanical loading, the Achilles tendon is the most frequently ruptured tendon. Despite the rising incidence of acute Achilles tendon rupture (AATR), the optimal treatment remains controversial. Missed diagnoses and delayed treatments lead to poor outcomes and limited treatment options. This study aimed to identify potential biomarkers for diagnosing and developing therapies for AATR. METHODS: We employed the coupled isobaric tag for relative and absolute quantitation-liquid chromatography-electrospray ionization-tandem mass spectrometry approach to investigate protein expression in tissues from AATR patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify differentially expressed proteins (DEPs) between AATR patients and healthy individuals. A protein-protein interaction (PPI) network of DEPs was constructed using the Search Tool for the Retrieval of Interacting Genes. The screened hub genes were selectively verified by immunohistochemical staining. RESULTS: We identified 410 DEPs between AATR patients and controls. The DEPs were significantly enriched in GO terms such as the extracellular region, extracellular region part, and defense response, as well as KEGG pathways, including complement and coagulation cascades, focal adhesion, and regulation of actin cytoskeleton. The main hub nodes in the PPI network comprised fibronectin 1 (FN1), major histocompatibility complex, class I, B (HLA-B), filamin A (FLNA), heat shock 27-kDa protein 1 (HSPB1), heat shock protein family A member 5 (HSPA5), apolipoprotein A4 (APOA4), and myosin IC (MYO1C). Although APOA4 and collagens I, II, and III were detectable in healthy tendons, immunohistochemical staining confirmed higher expression of these proteins in the acutely ruptured Achilles tendon. CONCLUSIONS: Our findings lay a foundation for further molecular studies of AATR. Inflammation and age-related degeneration may contribute to the pathogenesis of AATR. Moreover, the identified DEPs could be potential biomarkers for AATR diagnosis and treatment.

Rehabilitation of Annular Pulley Injuries of the Fingers in Climbers: A Clinical Commentary.

ABSTRACT: The annular pulley ligaments of the fingers are one of the most injured anatomical structures in those who participate in climbing. Despite this, there is a paucity of guidance clearly describing the rehabilitation and physical preparation parameters to return to sport following such injuries. The foundation of effective rehabilitation is the judicious application of progressive loading to increase the morphological and material properties of the damaged tissues. We maintain the optimal management of the climbing athlete after a traumatic annular flexor pulley system rupture should be grounded in the principles of strength and conditioning.

Endotenon-Derived Type II Tendon Stem Cells Have Enhanced Proliferative and Tenogenic Potential.

Tendon injuries caused by overuse or age-related deterioration are frequent. Incomplete knowledge of somatic tendon cell biology and their progenitors has hindered interventions for the effective repair of injured tendons. Here, we sought to compare and contrast distinct tendon-derived cell populations: type I and II tendon stem cells (TSCs) and tenocytes (TNCs). Porcine type I and II TSCs were isolated via the enzymatic digestion of distinct membranes (paratenon and endotenon, respectively), while tenocytes were isolated through an explant method. Resultant cell populations were characterized by morphology, differentiation, molecular, flow cytometry, and immunofluorescence analysis. Cells were isolated, cultured, and evaluated in two alternate oxygen concentrations (physiological (2%) and air (21%)) to determine the role of oxygen in cell biology determination within this relatively avascular tissue. The different cell populations demonstrated distinct proliferative potential, morphology, and transcript levels (both for tenogenic and stem cell markers). In contrast, all tendon-derived cell populations displayed multipotent differentiation potential and immunophenotypes (positive for CD90 and CD44). Type II TSCs emerged as the most promising tendon-derived cell population for expansion, given their enhanced proliferative potential, multipotency, and maintenance of a tenogenic profile at early and late passage. Moreover, in all cases, physoxia promoted the enhanced proliferation and maintenance of a tenogenic profile. These observations help shed light on the biological mechanisms of tendon cells, with the potential to aid in the development of novel therapeutic approaches for tendon disorders.

Cerium oxide nanoparticles-carrying human umbilical cord mesenchymal stem cells counteract oxidative damage and facilitate tendon regeneration.

BACKGROUND: Tendon injuries have a high incidence and limited treatment options. Stem cell transplantation is essential for several medical conditions like tendon injuries. However, high local concentrations of reactive oxygen species (ROS) inhibit the activity of transplanted stem cells and hinder tendon repair. Cerium oxide nanoparticles (CeONPs) have emerged as antioxidant agents with reproducible reducibility. RESULTS: In this study, we synthesized polyethylene glycol-packed CeONPs (PEG-CeONPs), which were loaded into the human umbilical cord mesenchymal stem cells (hUCMSCs) to counteract oxidative damage. H2O2 treatment was performed to evaluate the ROS scavenging ability of PEG-CeONPs in hUCMSCs. A rat model of patellar tendon defect was established to assess the effect of PEG-CeONPs-carrying hUCMSCs in vivo. The results showed that PEG-CeONPs exhibited excellent antioxidant activity both inside and outside the hUCMSCs. PEG-CeONPs protect hUCMSCs from senescence and apoptosis under excessive oxidative stress. Transplantation of hUCMSCs loaded with PEG-CeONPs reduced ROS levels in the tendon injury area and facilitated tendon healing. Mechanistically, NFκB activator tumor necrosis factor α and MAPK activator dehydrocrenatine, reversed the therapeutic effect of PEG-CeONPs in hUCMSCs, indicating that PEG-CeONPs act by inhibiting the NFκB and MAPK signaling pathways. CONCLUSIONS: The carriage of the metal antioxidant oxidase PEG-CeONPs maintained the ability of hUCMSCs in the injured area, reduced the ROS levels in the microenvironment, and facilitated tendon regeneration. The data presented herein provide a novel therapeutic strategy for tendon healing and new insights into the use of stem cells for disease treatment.

Mesenchymal stem cell licensing: enhancing MSC function as a translational approach for the treatment of tendon injury.

Tendon injuries are common in both veterinary and human clinical patients and result in morbidity, pain, and lost athletic performance. Consequently, utilizing naturally occurring injuries in veterinary patients as a comparative model could inform the development of novel therapies and increase translation for the treatment of human tendon injuries. Mesenchymal stem cells (MSCs) have shown considerable efficacy for the treatment of experimental and clinical superficial digital flexor tendon injury in the horse; however, the reinjury rate following treatment can remain high and MSC efficacy in treating other tendons is less well known. Additionally, the translation of MSC therapy to human tendon injury has remained poor. Recent evidence indicates that naïve MSC function can be enhanced through exogenous stimulation or manipulation of their environment. This stimulation or activation, herein termed MSC licensing, markedly alters MSC functions associated with immunomodulation, extracellular matrix remodeling, vascular development, bioactive factor production, and endogenous stromal/progenitor cell support. Additionally, a variety of licensing strategies has proven to influence MSC-secreted factors that have positively influenced outcome parameters in both in vitro and in vivo disease models separate from musculoskeletal tissues. Therefore, identifying the optimal licensing strategy for MSCs could ultimately provide an avenue for reliable and repeatable treatment of a broad range of tendon injuries of both veterinary and human clinical patients. This article details current evidence on the effects of licensed MSCs in both in vitro and in vivo disease models of different species and provides commentary on how those effector functions identified may be translated to the treatment of tendon injuries.

A Review of the Role of Tendon Stem Cells in Tendon-Bone Regeneration.

Tendon-bone injuries are a prevalent health concern associated with sports and other physically demanding activities. These injuries have a limited innate healing ability, often leading to the formation of scar tissue rather than the regeneration of healthy tendon tissue. This scar tissue results from excessive fibrosis during the early healing process and often leads to reduced tendon function and an increased risk of reinjury. Traditionally, surgical reconstruction has been the primary treatment for tendon-bone injuries. However, restoring the natural structure and mechanical properties of tendons after surgical reconstruction presents a considerable challenge. Recently, the potential of stem cell therapy has been explored as an alternative treatment approach. In particular, a new type of pluripotent stem cell known as tendon stem cells (TDSCs) has been identified within tendon tissue. These cells exhibit the potential for self-renewal and multidirectional differentiation, meaning they can differentiate into fibroblasts and chondrocytes. These differentiated cells can aid in the repair and regeneration of new tissues by producing collagen and other matrix molecules that provide structural support. TDSCs have become a focal point in research for treating tendon-bone injuries and related conditions. The potential use of these cells provides a basis for both basic research and clinical applications, particularly in understanding the tendon-bone healing process and identifying factors that affect the ability of TDSCs to promote this healing. This review article aims to analyze the role of TDSCs in tendon-bone healing, understanding their therapeutic potential and contributing to the development of effective treatment strategies for tendon-bone injuries.

Clinical Practice Update: Achilles Tendon Rupture.

Achilles tendon rupture is a common injury. It most often occurs in middle aged men who participate in recreational sports. The injury classically presents with a loud popping noise and immediate pain and weakness of the lower extremity during actions such as jumping or running. The diagnosis is made clinically, but an MRI is often obtained for confirmation of rupture and to aid in surgical planning. Treatment is either operative, with open or minimally invasive approaches, or non-operative, with functional bracing or plaster casting. Surgical treatment was preferred for much of the 20th century, but non-operative treatment has gained significant favor in the past 15 years as new evidence has demonstrated similar long-term outcomes to surgery. Neither treatment option is currently considered superior to the other in all cases. Surgery is associated with a risk for surgical complications and is, therefore, often a poor option for the elderly and those with significant comorbidities. Non-operative management is associated with an increased risk for re-injury which is often undesirable for young and highly active patients. Ultimately, the goals and priorities of each individual patient should guide the decision of which treatment option to pursue.

Acute Distal Biceps Tendon Injury: Diagnosis and Treatment / Lesões agudas do tendão distal do bíceps: Diagnóstico e tratamento

Abstract Acute distal biceps injuries clinically present with sudden pain and acute loss of flexion and supination strength. The main injury mechanism occurs during the eccentric load of the biceps. The hook test is the most significant examination test, presenting the highest sensibility and specificity for this lesion. Magnetic resonance imaging, the gold standard imaging test, can provide information regarding integrity and identify partial and/or complete tears. The surgical treatment uses an anterior or double approach and several reattachment techniques. Although there is no clinical evidence to recommend one fixation method over the other, biomechanical studies show that the cortical button resists better to failure. Although surgical treatment led to an 89% rate of return to work in 14 weeks, the recovery of high sports performance occurred in 1 year, with unsustainable outcomes.

Resumo As lesões agudas do tendão distal do bíceps se apresentam, clinicamente, com uma dor súbita associada a perda aguda de força de flexão e supinação. Seu principal mecanismo de lesão ocorre durante contração excêntrica do bíceps. O "Hook Test" é o principal teste semiológico, sendo o mais sensível e específico. A ressonância magnética, exame padrão ouro para o diagnóstico, pode fornecer informações sobre a integridade, identificando as lesões parciais e/ou completas. O tratamento cirúrgico pode ser realizado por duas vias principais: anterior e por dupla via porém as técnicas de reinserção tendínea são diversas não havendo evidência clínica que recomende um método de fixação em detrimento ao outro; embora o botão cortical apresente maior resistência a falha nos estudos biomecânicos. Com o tratamento cirúrgico o retorno as atividades laborais foi de 89% em 14 semanas (média) porém ao esporte de alto rendimento o prazo foi longo, média de 1 ano, e não duradouro.

Matrix stiffness-mediated tenogenesis of tendon stem/progenitor cells via integrin-αm for tendon regeneration.

Tendon injuries, commonly associated with sports activities, pose significant challenges in terms of treatment and recovery due to limited tendon regeneration and the formation of proliferative scars. Stem cell-based therapy has shown promising application, but there are still challenges. Physical and biological cues are instrumental in guiding stem cell differentiation and maturation. This study focuses on exploring the effects of matrix biomechanics on tendon stem/progenitor cells (TSPCs) differentiation. We fabricated polydimethylsiloxane (PDMS) substrates with different elastic modulus to mimic the mechanical characteristics of healthy tendons. A tissue-engineered culture system was developed for tenogenesis, and pre-differentiated tissue-engineered tendons were transplanted in vivo to assess their efficacy in regenerating patella tendon injuries. Furthermore, we demonstrated that the biomechanical stimuli activated the integrin-αm to enhance the tenogenesis capacity of TSPCs. Our findings highlight the importance of biomechanics in tendon tissue engineering and provide a novel perspective for enhancing tendon regeneration.

Application of Nondegradable Synthetic Materials for Tendon and Ligament Injury.

Tendon and ligament injuries, prevalent requiring surgical intervention, significantly impact joint stability and function. Owing to excellent mechanical properties and biochemical stability, Nondegradable synthetic materials, including polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE), have demonstrated significant potential in the treatment of tendon and ligament injuries. These above materials offer substantial mechanical support, joint mobility, and tissue healing promotion of the shoulder, knee, and ankle joint. This review conclude the latest development and application of nondegradable materials such as artificial patches and ligaments in tendon and ligament injuries including rotator cuff tears (RCTs), anterior cruciate ligament (ACL) injuries, and Achilles tendon ruptures.

Mussel-Derived Bioadaptive Artificial Tendon Facilitates the Cell Proliferation and Tenogenesis to Promote Tendon Functional Reconstruction.

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.

Equine tendon mechanical behaviour: Prospects for repair and regeneration applications.

Tendons are dense connective tissues that play an important role in the biomechanical function of the musculoskeletal system. The mechanical forces have been implicated in every aspect of tendon biology. Tendon injuries are frequently occurring and their response to treatments is often unsatisfactory. A better understanding of tendon biomechanics and mechanobiology can help develop treatment options to improve clinical outcomes. Recently, tendon tissue engineering has gained more attention as an alternative treatment due to its potential to overcome the limitations of current treatments. This review first provides a summary of tendon mechanical properties, focusing on recent findings of tendon mechanobiological responses. In the next step, we highlight the biomechanical parameters of equine energy-storing and positional tendons. The final section is devoted to how mechanical loading contributes to tenogenic differentiation using bioreactor systems. This study may help develop novel strategies for tendon injury prevention or accelerate and improve tendon healing.

Three-Dimensional Cell Culture System for Tendon Tissue Engineering.

Tendon, connective tissue between bone and muscle has unique component of the musculoskeletal system. It plays important role for transporting mechanical stress from muscle to bone and enabling locomotive motion of the body. There are some restoration capacities in the tendon tissue, but the injured tendons are not completely regenerated after acute and chronic tendon injury. At this point, the treatment options for tendon injuries are limited and not that successful. Therefore, biomedical engineering approaches are emerged to cope with this issue. Among them, three-dimensional cell culture platforms provided similarity to in vivo conditions and suggested opportunities for new therapeutic approaches for treatment of tendon injuries. In this review, we focus on the characteristics of tendon tissue and tendon pathologies which can be targets for tendon tissue engineering strategies. Then proof-of-concept and pre-clinical studies leveraging advanced 3-dimensional cell culture platforms for tendon tissue regeneration have been discussed.

Mesenchymal stem cells: An efficient cell therapy for tendon repair (Review).

Tendon injury is a common disorder of the musculoskeletal system caused by overuse or trauma. With increasing incidence of tendon injuries, it is necessary to find an effective treatment. Mesenchymal stem cells (MSCs) are attracting attention because of their high proliferative and self­renewal capacity. These functions of MSCs show promise in treating a variety of diseases, including immune and musculoskeletal system disorder and cardiovascular disease, and show especially satisfactory effects in the treatment of tendon injury. First, since MSCs have multidirectional differentiation potential, they differentiate into specific cells after induction in vivo and in vitro. Furthermore, MSCs have paracrine functions and can secrete biologically active molecules and exosomes such as cytokines, growth factors and chemokines to promote tissue repair and regeneration. In tendon injury, MSCs promote tendon repair through four mechanisms: Decreasing inflammation and promoting neovascularization and cell proliferation and differentiation. They are also involved in extracellular matrix reorganization by promoting collagen production and transforming type III collagen fibers to type I collagen fibers. The present review summarized preclinical experiments with different sources of MSCs and their mechanisms in tendon repair, as well as the limitations of MSCs in current clinical applications and directions that need to be explored in the future.

Establishing in vivo and ex vivo chick embryo models to investigate fetal tendon healing.

Injured adult tendons heal fibrotically and possess high re-injury rates, whereas fetal tendons appear to heal scarlessly. However, knowledge of fetal tendon wound healing is limited due in part to the need for an accessible animal model. Here, we developed and characterized an in vivo and ex vivo chick embryo tendon model to study fetal tendon healing. In both models, injury sites filled rapidly with cells and extracellular matrix during healing, with wound closure occurring faster in vivo. Tendons injured at an earlier embryonic stage improved mechanical properties to levels similar to non-injured controls, whereas tendons injured at a later embryonic stage did not. Expression levels of tendon phenotype markers, collagens, collagen crosslinking regulators, matrix metalloproteinases, and pro-inflammatory mediators exhibited embryonic stage-dependent trends during healing. Apoptosis occurred during healing, but ex vivo tendons exhibited higher levels of apoptosis than tendons in vivo. Future studies will use these in vivo and ex vivo chick embryo tendon injury models to elucidate mechanisms of stage-specific fetal tendon healing to inform the development of therapeutic approaches to regeneratively heal adult tendons.