Muscular and Tendon Degeneration after Achilles Rupture: New Insights into Future Repair Strategies

Achilles tendon rupture is a frequent injury with an increasing incidence. After clinical surgical repair, aimed at suturing the tendon stumps back into their original position, the repaired Achilles tendon is often plastically deformed and mechanically less strong than the pre-injured tissue, with muscle fatty degeneration contributing to function loss. Despite clinical outcomes, pre-clinical research has mainly focused on tendon structural repair, with a lack of knowledge regarding injury progression from tendon to muscle and its consequences on muscle degenerative/regenerative processes and function. Here, we characterize the morphological changes in the tendon, the myotendinous junction and muscle belly in a mouse model of Achilles tendon complete rupture, finding cellular and fatty infiltration, fibrotic tissue accumulation, muscle stem cell decline and collagen fiber disorganization. We use novel imaging technologies to accurately relate structural alterations in tendon fibers to pathological changes, which further explain the loss of muscle mechanical function after tendon rupture. The treatment of tendon injuries remains a challenge for orthopedics. Thus, the main goal of this study is to bridge the gap between clinicians’ knowledge and research to address the underlying pathophysiology of ruptured Achilles tendon and its consequences in the gastrocnemius. Such studies are necessary if current practices in regenerative medicine for Achilles tendon ruptures are to be improved.

Lysosomal Function Impacts the Skeletal Muscle Extracellular Matrix

Muscle development and homeostasis are critical for normal muscle function. A key aspect of muscle physiology during development, growth, and homeostasis is modulation of protein turnover, the balance between synthesis and degradation of muscle proteins. Protein degradation depends upon lysosomal pH, generated and maintained by proton pumps. Sphingolipid transporter 1 (spns1), a highly conserved gene encoding a putative late endosome/lysosome carbohydrate/H+ symporter, plays a pivotal role in maintaining optimal lysosomal pH and spns1−/− mutants undergo premature senescence. However, the impact of dysregulated lysosomal pH on muscle development and homeostasis is not well understood. We found that muscle development proceeds normally in spns1−/− mutants prior to the onset of muscle degeneration. Dysregulation of the extracellular matrix (ECM) at the myotendinous junction (MTJ) coincided with the onset of muscle degeneration in spns1−/− mutants. Expression of the ECM proteins laminin 111 and MMP-9 was upregulated. Upregulation of laminin 111 mitigated the severity of muscle degeneration, as inhibition of adhesion to laminin 111 exacerbated muscle degeneration in spns1−/− mutants. MMP-9 upregulation was induced by tnfsf12 signaling, but abrogation of MMP-9 did not impact muscle degeneration in spns1−/− mutants. Taken together, these data indicate that dysregulated lysosomal pH impacts expression of ECM proteins at the myotendinous junction.

A Simplified Method for Considering Achilles Tendon Curvature in the Assessment of Tendon Elongation

The consideration of the Achilles tendon (AT) curvature is crucial for the precise determination of AT length and strain. We previously established an ultrasound-kinematic-based method to quantify the curvature, using a line of reflective foil skin markers covering the AT from origin to insertion. The current study aimed to simplify the method by reducing the number of markers while maintaining high accuracy. Eleven participants walked (1.4 m/s) and ran (2.5, 3.5 m/s) on a treadmill, and the AT curvature was quantified using reflective foil markers aligned with the AT between the origin on the gastrocnemius myotendinous-junction (tracked by ultrasound) and a marker on the calcaneal insertion. Foil markers were then systematically removed, and the introduced error on the assessment of AT length and strain was calculated. We found a significant main effect of marker number on the measurement error of AT length and strain (p<0.001). Using more than 30% of the full marker-set for walking and 50% for running, the R2 of the AT length error saturated, corresponding to average errors of <0.1 mm and <0.15% strain. Therefore, a substantially reduced marker-set, associated with a marginal error, can be recommended for considering the AT curvature in the determination of AT length and strain.

Stable Gastric Pentadecapeptide BPC 157 as a Therapy for the Disable Myotendinous Junctions in Rats

(1) Aim: The stable gastric pentadecapeptide BPC 157 is known to heal transected muscle, tendon, and ligament. Thereby, in this study, we investigated the effect of BPC 157 on the dissection of the quadriceps tendon from the quadriceps muscle in rats. (2) Materials and Methods: Myotendinous junction defect, which cannot heal spontaneously in rats, as evidenced with consistent macro/microscopic, biomechanical, functional assessments, eNOS, and COX-2 mRNA levels and oxidative stress and NO-levels in the myotendinous junctions. BPC 157 (10 µg/kg, 10 ng/kg) regimen was given (i) intraperitoneally, first application immediately after surgery, last 24 h before sacrifice; (ii) per-orally, in drinking water (0.16 µg/mL, 0.16 ng/mL, 12 mL/rat/day), till the sacrifice at 7, 14, 28 and 42 postoperative days. (3) Results: These BPC 157 regimens document prominent therapy effects (macro/microscopic, biomechanical, functional much like eNOS and COX-2 mRNA levels and counteracted oxidative stress and NO-levels in the myotendinous junctions), while controls have a poor presentation. Especially, in rats with the disabled myotendinous junction, along with full functional recovery, BPC 157 counteracts muscle atrophy that is regularly progressive and brings muscle presentation close to normal. Accordingly, unlike the perilous course in controls, those rats, when receiving BPC 157 therapy, exhibit a smaller defect, and finally defects completely disappear. Microscopically, there are no more inflammatory infiltrate, well-oriented recovered tissue of musculotendon junction appears in BPC 157 treated rats at the 28 days and 42 days. (4) Conclusions: BPC 157 restores myotendinous junction in accordance with the healing of the transected muscle, tendon, and ligament.

Indirect markers for length adjustment in distal biceps tendon allograft reconstruction

Chronic musculotendinous retraction, shortening and fibrosis after distal biceps tendon tears makes a primary reconstruction often difficult or even impossible. Interposition reconstruction with allograft provides a solution, however there is no consensus about appropriate intraoperative graft length adjustment. Therefore, the purpose of this study was to find a practical reference value for distal biceps tendon length adjustment. Three-dimensional surface models of healthy distal biceps tendons were created based on 85 MRI scans. The tendon length was measured from the myotendinous junction to the insertion on the bicipital tuberosity. Inter-epicondylar distance (IED) and radial head diameter (RHD) were measured on antero-posterior radiographs as a surrogate for patient size. Correlations between the tendon length and IED, RHD and patient’s height (PH) were calculated. Mean length of the external part of the distal biceps tendon was 69mm (female 64mm, male 71mm). The tendon length in mm was on average 1.1 times of the IED (mm), 3 times of the RHD (mm) and 0.4 times of PH (cm). Herewith, the tendon length could be predicted within a narrow range of +/-1cm in 84% by using IED, 82% by using RHD and 80% by using PH. Intra- and inter-reader reliabililty of IED and RHD was excellent (R2 = 0.938–0.981). The distal biceps tendon length can be best predicted within 1cm with an accuracy of 82–84% using the IED and RHD with an excellent intra- and inter-reader reliability.

Latissimus Dorsi Tendon Reconstruction at the Myotendinous Junction With Acellular Dermal Allograft

Background: Limited available data have shown latissimus dorsi tendon reconstruction to be an effective treatment for tendon tears in specific subpopulations of elite overhead throwing athletes. Indications: Primary indication for latissimus dorsi tendon reconstruction is a symptomatic, full-thickness humeral avulsion with or without a concomitant teres major tendon tear. Surgical candidates are typically young, high-demand, elite or professional overhead throwing athletes. In this case, the patient is a 29-year-old male former minor league pitcher and current pitching coach with a full-thickness avulsion of the latissimus dorsi tendon. Technique Description: The patient was positioned left lateral decubitus with a dynamic limb positioner maintaining the arm in 90° abduction and maximal internal rotation. This technique used a single posterior axillary incision, which was performed and dissected down to the ruptured latissimus dorsi tendon. We circumferentially applied an acellular dermal allograft to augment the reconstruction at the myotendinous junction. Subsequently, the construct was prepared for transfer with a Krackow suture technique. Suture buttons were used to secure the reconstructed latissimus dorsi tendon to the anatomic footprint on the proximal humerus with a tension slide technique. Results: One case series showed return to the previous level of competition for all baseball pitchers who underwent a latissimus dorsi reconstruction with excellent improvement in visual analog scale pain, American Shoulder and Elbow Surgeons, and Kerlan-Jobe Orthopaedic Clinic scores. Another larger study demonstrated equal return to play rates for professional baseball pitchers with a latissimus dorsi tear treated either nonoperatively or operatively. However, those treated operatively had no decline in performance, whereas the nonoperative cohort saw decline in some statistics. Conclusion: Latissimus dorsi tendon reconstruction using an acellular dermal allograft at the myotendinous junction is a viable treatment option for elite overhead throwing athletes with full-thickness tendon avulsions. It allows for full return to play, particularly if the patient has failed nonoperative management.