Patellar Tendon Structural Adaptations Occur during Pre-Season and First Competitive Cycle in Male Professional Handball Players

Background: While there is evidence that tendon adapts to training load, structural alterations in the patellar tendon in response to training loads are still unclear. The aim of this study is to identify changes in patellar tendon structure throughout pre-season and after finalizing the first competitive cycle. Methods: Nineteen professional handball players participated in the aforesaid cross-sectional study, in which patellar tendon scan and counter movement jump (CMJ) performance were conducted. Measurements were taken on the first and last day of pre-season training, and at the end of the first competitive cycle. Results: The results revealed that variation on the tendon structure occurred, mainly at the end of pre-season training; for injured tendons this occurred at the proximal (Right p = 0.02), distal (Right p = 0.01), and (Left p = 0.02) tendon, while changes in healthy tendons occurred at the mid (Left p = 0.01) and distal tendon (Right p = 0.01). At the end of the first competitive cycle, changes were observed in the distal injured tendon (p = 0.02). Conclusion: Patellar tendon shows greater structural change after completing pre-season training than at the end of the first competitive cycle, from which it may be inferred that gradual loading during pre-season training allows the tendon to adapt and potentially decrease the onset of patellar tendinopathy.

Treatment of Achilles Tendinopathy in Recreational Runners with Peritendinous Hyaluronic Acid Injections: A Viscoelastometric, Functional, and Biochemical Pilot Study

Background: Achilles tendinopathy (AT) affects ca. 10 million recreational runners in Europe; the practice of hyaluronic acid (HA) infiltration is being increasingly adopted. The aim of this pilot study was to monitor the effects of a three-local time-spaced injections regimen of HA in the treatment of AT in middle-aged runners combining for the first time viscoelastometric, biochemical, and functional methodologies with routine clinical examinations. Methods: Eight male runners (Age 49.3 ± 3.9), diagnosed for unilateral AT, were given three ultrasound (US) guided peritendinous HA injections at the baseline (T0) and every fifteenth day with a follow-up on the forty-fifth day (T1, T2, and T3). At all-time points patients were assessed for viscoelastic tone and stiffness, maximal voluntary isometric contraction (MVIC), and pain level (Likert scale 0–5). The peritendinous effusions of the injured tendon were collected at T0 and T2 to quantify the volume variations and the IL-1β and MMP-3 levels. Results: At T0 MVIC and pain score were significantly lower and higher, respectively, in injured tendons. The volume, IL-1β and MMP-3 levels decreased in the course of treatment and the clinical endpoints ameliorated over time. Tone, stiffness, and functional performance also varied significantly at T2 and T3, as compared to T0. Conclusions: The sequential peritendinous injections of HA were effective in the amelioration of the clinical symptoms, as well as of the functional and viscoelastic state associated with AT. The determination of the viscoelastometric state may help to precisely evaluate the healing process in AT patients.

Synergistic Therapy of Celecoxib-Loaded Magnetism-Responsive Hydrogel for Tendon Tissue Injuries

Tendon tissue injury is very common and always associated with pain, tissue swelling and even malformation if not treated on time. Traditional therapeutic strategies, such as cryotherapy, electrical therapy, ultrasound therapy and anti-inflammatory drug, are still unsatisfying. In this work, a synergistic therapy, based on the combination of celecoxib drug and pulsed electromagnetic field (PEMF) regimens, was developed for the treatment of tendon injury. This celecoxib-loaded magnetism-responsive hydrogel dressing (gelatin/Fe3O4/celecoxib) showed good biocompatibility and coordinated drug release behavior under the PEMF, which could effectively reduce the inflammatory reaction of macrophage cells with the incremental proportion of M2 macrophages at the injury site. CatWalk gait analysis further verified this synergistic effect of combination therapy for achieving the outstanding recovery of the injured tendon tissue. Thus, this magnetism-responsive hydrogel may represent a promising alternative strategy in clinics for promoting tendon healing.

MOFs-Based Nitric Oxide Therapy for Tendon Regeneration

Tendon regeneration is still a great challenge due to its avascular structure and low self-renewal capability. The nitric oxide (NO) therapy emerges as a promising treatment for inducing the regeneration of injured tendon by angiogenesis. Here, in this study, a system that NO-loaded metal–organic frameworks (MOFs) encapsulated in polycaprolactone (PCL)/gelatin (Gel) aligned coaxial scaffolds (NMPGA) is designed and prepared for tendon repair. In this system, NO is able to be released in vitro at a slow and stable average speed of 1.67 nM h−1 as long as 15 d without a burst release stage in the initial 48 h. Furthermore, NMPGA can not only improve the tubular formation capability of endothelial cells in vitro but also obviously increase the blood perfusion near the injured tendon in vivo, leading to accelerating the maturity of collagen and recovery of biomechanical strength of the regenerated tendon tissue. As a NO-loaded MOFs therapeutic system, NMPGA can promote tendon regeneration in a shorter healing period with better biomechanical properties in comparison with control group by angiogenesis. Therefore, this study not only provides a promising scaffold for tendon regeneration, but also paves a new way to develop a NO-based therapy for biomedical application in the future.

Standardized Tendon Fenestration with Injection of Autologous Blood for Treatment of Lateral Epicondylitis

Lateral epicondylitis (LE) of the elbow is often treated with conservative methods. Several techniques including injections with different substances are widely performed. No standardization exists. This prospective study describes the results of the short-term follow-up of 56 patients with mean age 48 years (range: 30–68 years) treated with the Instant Tennis Elbow Cure Medical device, which fenestrates the injured tendon in a standardized way through a holder of 12 small needles. Depth and position of the needles are determined beforehand by ultrasonography. Unprepared autologous blood was injected through the holder in the tendon. Visual analog pain scale (VAS) decreased significantly in rest by 61% and during activity by 47% after 6 weeks. VAS decreased significantly in rest by 79% and during activity by 66% after 3 months. VAS did not remain significantly different after 6 months. Satisfaction rates were 71% after 6 weeks and 82% after 6 months. This suggests that the therapeutical effect sustains and in some cases increases over time. Patient Related Tennis Elbow Evaluation score ameliorated after 3 months by 71%. Comparative studies are needed to confirm this effect versus other techniques as physiotherapy, shockwave therapy, and injections with other substances.

Tendon stem cell-derived exosomes regulate inflammation and promote the high-quality healing of injured tendon

Background Tendon stem cells (TSCs) have been reported to hold promises for tendon repair and regeneration. However, less is known about the effects of exosomes derived from TSCs. Therefore, we aimed to clarify the healing effects of TSC-derived exosomes (TSC-Exos) on tendon injury. Methods The Achilles tendons of Sprague-Dawley male rats were used for primary culture of TSCs and tenocytes, and exosomes were isolated from TSCs. The proliferation of tenocytes induced by TSC-Exos was analyzed using an EdU assay; cell migration was measured by cell scratch and transwell assays. We used western blot to analyze the role of the PI3K/AKT and MAPK/ERK1/2 signaling pathways. In vivo, Achilles tendon injury models were created in Sprague-Dawley rats. Rats (n = 54) were then randomly assigned to three groups: the TSC-Exos group, the GelMA group, and the control group. We used immunofluorescence to detect changes in the expression of inflammatory and apoptotic markers at 1 week after surgery. Histology and changes in expression of extracellular matrix (ECM)-related indices were assessed by hematoxylin-eosin (H&E) staining and immunohistochemistry at 2 and 8 weeks. The collagen fiber diameter of the healing tendon was analyzed at 8 weeks by transmission electron microscopy (TEM). Results TSC-Exos were taken up by tenocytes, which promoted the proliferation and migration of cells in a dose-dependent manner; this process may depend on the activation of the PI3K/AKT and MAPK/ERK1/2 signaling pathways. At 1 week after surgery, we found that inflammation and apoptosis were significantly suppressed by TSC-Exos. At 2 and 8 weeks, tendons treated with TSC-Exos showed more continuous and regular arrangement in contrast to disorganized tendons in the GelMA and control groups, and TSC-Exos may help regulate ECM balance and inhibited scar formation. Further, at 8 weeks, the TSC-Exos group had a larger diameter of collagen compared to the control group. Conclusions Our data suggest that TSC-Exos could promote high-quality healing of injured tendon, which may be a promising therapeutic approach for tendon injury.

Mesenchymal Stem Cells Seeded Decellularized Tendon Scaffold for Tissue Engineering

: Tendon is a collagenous tissue to connect bone and muscle. Healing of damaged/injured tendon is the primary clinical challenge in musculoskeletal regeneration because they often react poorly to treatment. Tissue engineering (a triad strategy of scaffolds, cells and growth factors) may have the potential to improve the quality of tendon tissue healing under such impaired situations. Tendon tissue engineering aims to synthesize graft alternatives to repair the injured tendon. Biological scaffolds derived from decellularized tissue may be a better option as their biomechanical properties are similar to the native tissue. This review is designed to provide background information on the current challenges in curing torn/worn out the tendon and the clinical relevance of decellularized scaffolds for such applications.