Amadio, Peter C.

The intrinsic healing following tendon injury is ideal, in which tendon progenitor cells proliferate and migrate to the injury site to directly bridge or regenerate tendon tissue. However, the mechanism determining why and how those cells are attracted to the injury site for tendon healing is not understood. Since the tenocytes near the injury site go through apoptosis or necrosis following injury, we hypothesized that secretions from injured tenocytes might have biological effects on cell proliferation and migration to enhance tendon healing. Tenocyte apoptosis was induced by 24 h cell starvation. Apoptotic body-rich media (T-ABRM) and apoptotic body-depleted media (T-ABDM) were collected from culture media after centrifuging. Tenocytes and bone marrow-derived stem cells (BMDSCs) were isolated and cultured with the following four media: (1) T-ABRM, (2) T-ABDM, (3) GDF-5, or (4) basal medium with 2% fetal calf serum (FCS). The cell activities and functions were evaluated. Both T-ABRM and T-ABDM treatments significantly stimulated the cell proliferation, migration, and extracellular matrix synthesis for both tenocytes and BMDSCs compared to the control groups (GDF-5 and basal medium). However, cell proliferation, migration, and extracellular matrix production of T-ABRM-treated cells were significantly higher than the T-ABDM, which indicates the apoptotic bodies are critical for cell activities. Our study revealed the possible mechanism of the intrinsic healing of the tendon in which apoptotic bodies, in the process of apoptosis, following tendon injury promote tenocyte and stromal cell proliferation, migration, and production. Future studies should analyze the components of the apoptotic bodies that play this role, and, thus, the targeting of therapeutics can be developed.

Abstract Rotator cuff injuries increase with age. The enthesis is the most frequent site of rotator cuff injury and degeneration. Understanding age‐related changes of the enthesis are essential to determine the mechanism of rotator cuff injuries, degeneration, and to guide mechanistically driven therapies. In this study, we explored age‐related cellular changes of the rotator cuff enthesis in young, mature, and aged rats. Here we found that the aged enthesis is typified by an increased mineralized zone and decreased nonmineralized zone. Proliferation, migration, and colony‐forming potential of rotator cuff derived cells (RCECs) was attenuated with aging. The tenogenic and chondrogenic potential were significantly reduced, while the osteogenic potential increased in aged RCECs. The adipogenic potential increased in RCECs with age. This study explores the cellular differences found between young, mature, and aged rotator cuff enthesis cells and highlights the importance of using age‐appropriate models, as well as provides a basis for further delineation of mechanisms and potential therapeutics for rotator cuff injuries.

Abstract Objective: The incidence of carpal tunnel syndrome (CTS) is higher in women, and peaks around the age of menopause. Therefore, we investigated whether bilateral oophorectomy is associated with an increased risk of severe CTS. Methods: We included all of the 1,653 premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication between 1988 and 2007, and a random sample of 1,653 age-matched referent women who did not undergo bilateral oophorectomy in Olmsted County, MN. Diagnoses of CTS assigned to women over their entire lifetime were identified in these two cohorts. The risk of de novo severe CTS after bilateral oophorectomy (or index date) was evaluated using Cox proportional hazards models adjusted for potential confounders. Results: Bilateral oophorectomy was associated with an increased risk of severe CTS (adjusted hazard ratio 1.65, 95% confidence interval 1.20-2.25). The risk was suggestively greater in women with lower body mass index, nulliparity, and with a benign ovarian indication for oophorectomy (nonsignificant interactions). We did not observe a protective effect of estrogen therapy after the oophorectomy. The findings were similar in secondary analyses considering the incidence of CTS of any severity or idiopathic CTS. Conclusions: The risk of severe CTS, common in perimenopausal women, is increased after bilateral oophorectomy. The association may be causal or due to confounding. Therefore, the precise biological mechanisms explaining the association and the absence of a mitigating effect of estrogen therapy should be further investigated.

ABSTRACT Introduction Flexor tendon injuries are common hand injuries among the military population often resulting in functional impairment. Flexor tendon gliding friction has been linked to adhesion formation, especially with the use of extrasynovial grafts. Carbodiimide-derivatized hyaluronic acid with gelatin (cd-HA-gelatin) can reduce gliding friction of the tendon graft; however, the effects of gelatin molecular weight (MW) have not been studied. The turkey model has been shown to better match humans, but extrasynovial tendons are unavailable. The purpose of this study was to (1) manually roughen turkey flexor digitorum profundus (FDP) tendons to simulate extrasynovial tendons and (2) investigate the effects of gelatin MW on tendon friction. Materials and Methods The third digit of (n = 48) turkeys were dissected with the proximal pulley, and FDP tendon and the flexor superficialis tendon were preserved. Digits were randomly assigned into four groups: one saline control and three cd-HA-gelatin-treated groups of varying gelatin MW. Flexor digitorum profundus tendon friction was measured at its original condition, serving as a baseline. Tendons were roughened using a custom rig, and tendon friction was measured again. All four groups received treatment and gliding friction was measured every 100 cycles to a total of 1,000 cycles. Results Tendon friction significantly increased (P < 0.05) after roughening. Friction in the saline control group increased steadily over repeated cycles, whereas friction of all gelatin-treated tendons decreased significantly compared with the saline control group (P < 0.05), maintaining low friction to 1,000 cycles representing human tendons. There was no significant difference found between gelatin-treated groups. Conclusions We have developed a method to roughen synovial FDP tendons to create extrasynovial-like tendons for lubrication material evaluations. Cd-HA-gelatin effectively reduces tendon friction in this model. Our data suggest medium or low MW gelatin may provide a better reduction in friction compared with high MW gelatin.

ObjectivesThe mobility (transverse movement) of the median nerve (MN) is decreased in patients with carpal tunnel syndrome and can be measured noninvasively by ultrasound. To date, there are few prognostic features to help predict the outcome of 2 commonly performed treatments: surgical carpal tunnel release and corticosteroid injection. This study aimed to assess the changes in nerve mobility after the intervention and to correlate this with treatment and the disease severity.MethodsA total of 181 patients with carpal tunnel syndrome with different electrophysiologic severities were recruited and assessed by dynamic ultrasound scanning of the MN before and after treatment. The dynamic ultrasound images were collected while the patients performed finger and wrist flexion.ResultsFor both injection and carpal tunnel release, the nerve displacement increased with wrist flexion, from a mean ± SD of 7.0 ± 2.4 to 7.9 ± 2.7 mm (P < .005). Patients who underwent surgery showed greater improvement (P < .005) in nerve mobility compared to those who underwent injection. We also observed that the increase in nerve mobility was predominantly in patients with more nerve damage at baseline.ConclusionsThis study shows that the dynamic behavior of the MN changes in response to treatment and lays a foundation for future studies to assess the prognostic potential of nerve mobility measurement.

AbstractReducing tendon failure after repair remains a challenge due to its poor intrinsic healing ability. The purpose of this study is to investigate the effect of a novel tissue‐engineered purified exosome product (PEP) patch on tendon healing in a canine ex vivo model. Lacerated flexor digitorum profundus (FDP) tendons from three canines' paws underwent simulated repair with Tisseel patch alone or biopotentiated with PEP. For the ex vivo model, FDP tendons were randomly divided into three groups: FDP tendon repair alone group (Control), Tisseel patch alone group, and the Tisseel plus PEP (TEPEP) patch group. Following 4 weeks of tissue culture, the failure load, stiffness, histology, and gene expression of the healing tendon were evaluated. Transmission electron microscopy revealed that in exosomes of PEP the diameters ranged from 93.70 to 124.65 nm, and the patch release test showed this TEPEP patch could stably release the extracellular vesicle over 2 weeks. The failure strength of the tendon in the TEPEP patch group was significantly higher than that of the Control group and Tisseel alone group. The results of histology showed that the TEPEP patch group had the smallest healing gap and the largest number of fibroblasts on the surface of the injured tendon. Quantitative reverse transcription polymerase chain reaction showed that TEPEP patch increased the expression of collagen type III, matrix metallopeptidase 2 (MMP2), MMP3, MMP14, and reduced the expression of transforming growth factor β1, interleukin 6. This study shows that the TEPEP patch could promote tendon repair by reducing gap formation and inflammatory response, increasing the activity of endogenous cells, and formation of type III collagen.

Background: The retear rate after rotator cuff repair remains unacceptably high. Various biological engineered scaffolds have been proposed to reduce the retear rate. We have developed a double rip-stop repair with medial row knot (DRSK) technique to enhance suture-tendon strength and a novel engineered tendon-fibrocartilage-bone composite (TFBC) for rotator cuff repair. Hypothesis: DRSK rotator cuff repair augmented with TFBC will have better biomechanical properties than that of DRSK repair with an acellular dermal graft (DG). Study Design: Controlled laboratory study. Methods: Fresh-frozen canine shoulders (n = 30) and knees (n = 10) were used. TFBCs were harvested from the patellar tendon–tibia complex and prepared for rotator cuff repair. The infraspinatus tendon was sharply detached from its bony attachment and randomly assigned to the (1) control group: DRSK repair alone, (2) TFBC group: DRSK repair with TFBC, and (3) DG group: DRSK repair with DG. All specimens were tested to failure, and videos were recorded. The footprint area, tendon thickness, load to create 3-mm gap formation, failure load, failure modes, and stiffness were recorded and compared. Data were recorded as mean ± SD. Results: The mean load to create a 3-mm gap in both the control group (206.8 ± 55.7 N) and TFBC group (208.9 ± 39.1 N) was significantly higher than that in the DG group (157.7 ± 52.3 N) ( P < .05 for all). The failure load of the control group (275.7 ± 75.0 N) and TFBC group (275.2 ± 52.5 N) was significantly higher compared with the DG group (201.5 ± 49.7 N) ( P < .05 for both comparisons). The stiffness of the control group (26.4 ± 4.7 N/mm) was significantly higher than of the TFBC group (20.4 ± 4.4 N/mm) and the DG group (21.1 ± 4.8 N/mm) ( P < .05 for both comparisons). Conclusion: TFBC augmentation showed superior biomechanical performance to DG augmentation in rotator cuff tears repaired using the DRSK technique, while there was no difference between the TFBC and control groups. Clinical Relevance: TFBC may help to reduce retear or gap formation after rotator cuff repair using the DRSK technique.

With the widespread use of high-resolution ultrasonography, ultrasonic examination has been shown to be useful as a diagnostic method for carpal tunnel syndrome. The main advantages of ultrasonography are that it is simple, quick, non-invasive, and economical. Another advantage is that tissue dynamics can be observed with real-time imaging. In recent reports, it has been shown that ultrasonic examination can provide similar diagnostic accuracy as nerve conduction study in the diagnosis of carpal tunnel syndrome. It has been expected that ultrasound demand in daily medical care will continue to increase. Ultrasonography in carpal tunnel syndrome shows an enlarged median nerve in proximal carpal tunnel, thickening of the flexor retinaculum, and edema around flexor tendons in cross-sectional images. In addition, with the introduction of new technologies such as ultrasonic elastography and speckle tracking, it has become possible to quantify dynamics and material property changes of nerves, tendons, and their surrounding structures. In this review, we describe recent advancements of carpal tunnel syndrome diagnosis based on ultrasound dynamic images, and discuss its pathology.

AimsMany biomechanical studies have shown that the weakest biomechanical point of a rotator cuff repair is the suture-tendon interface at the medial row. We developed a novel double rip-stop (DRS) technique to enhance the strength at the medial row for rotator cuff repair. The objective of this study was to evaluate the biomechanical properties of the DRS technique with the conventional suture-bridge (SB) technique and to evaluate the biomechanical performance of the DRS technique with medial row knots.MethodsA total of 24 fresh-frozen porcine shoulders were used. The infraspinatus tendons were sharply dissected and randomly repaired by one of three techniques: SB repair (SB group), DRS repair (DRS group), and DRS with medial row knots repair (DRSK group). Specimens were tested to failure. In addition, 3 mm gap formation was measured and ultimate failure load, stiffness, and failure modes were recorded.ResultsThe mean load to create a 3 mm gap formation in the DRSK and DRS groups was significantly higher than in the SB group. The DRSK group had the highest load to failure with a mean ultimate failure load of 395.0 N (SD 56.8) compared to the SB and DRS groups, which recorded 147.1 N (SD 34.3) and 285.9 N (SD 89.8), respectively (p < 0.001 for both). The DRS group showed a significantly higher mean failure load than the SB group (p = 0.006). Both the DRS and DRSK groups showed significantly higher mean stiffness than the SB group.ConclusionThe biomechanical properties of the DRS technique were significantly improved compared to the SB technique. The DRS technique with medial row knots showed superior biomechanical performance than the DRS technique alone.