We hypothesised that diet-induced obesity (DIO) would result in inferior enthesis healing in a rat model of rotator cuff (RC) repair and that dietary intervention in the peri-operative period would improve enthesis healing. A total of 78 male Sprague-Dawley rats were divided into three weight-matched groups from weaning and fed either: control diet (CD), high-fat diet (HFD), or HFD until surgery, then CD thereafter (HF-CD). After 12 weeks, the left supraspinatus tendon was detached, followed by immediate surgical repair. At 2 and 12 weeks post-surgery, animals were culled, and RCs harvested for biomechanical and histological evaluation. Body composition and metabolic markers were assessed via DEXA and plasma analyses, respectively. DIO was established in the HFD and HF-CD groups before surgery and subsequently reversed in the HF-CD group after surgery. Histologically, the appearance of the repaired entheses was poorer in both the HFD and HF-CD groups compared with the CD group at 12 weeks after surgery, with semiquantitative scores of 6.2 (P<0.01), 4.98 (P<0.01), and 8.7 of 15, respectively. The repaired entheses in the HF-CD group had a significantly lower load to failure (P=0.03) at 12 weeks after surgery compared with the CD group, while the load to failure in the HFD group was low but not significantly different (P=0.10). Plasma leptin were negatively correlated with histology scores and load to failure at 12 weeks after surgery. DIO impaired enthesis healing in this rat RC repair model, with inferior biomechanical and histological outcomes. Restoring normal weight with dietary change after surgery did not improve healing outcomes. Circulating levels of leptin significantly correlated with poor healing outcomes. This pre-clinical rodent model demonstrates that obesity is a potentially modifiable factor that impairs RC healing and increases the risk of failure after RC surgery

This study looks at the dynamic tendon-to-bone contact properties of rotator cuff (RC) repairs—comparing single row repairs (SRR) with double row transosseous- equivalent (TOE) repairs. It was postulated that relaxation during, and movement following, the repair would significantly compromise contact properties and therefore, the ability of the tendon healing. Simulated tears were created in the supraspinatus tendon of six cadaveric human shoulders. A SRR was then performed using the OPUS System, creating two horizontal mattress sutures. An I-Scan electronic pressure-sensor (Tekscan, Boston, MA) was placed between the supraspinatus tendon and bone. The arm was then rested for 300secs (relaxation) before being passively moved twice through a range-of-motion (0-90 degrees abduction, 0-45 external and 0-45 internal rotation) and finally returned to neutral. The contact properties were recorded throughout each movement. The procedure was then repeated using two TOE techniques: parallel sutures (TOE-P) and a cross over suture pattern (TOE-C). While peak pressures during the repair were higher in the two TOE repairs, all three methods demonstrated relaxation over 300s such that there was no significant diference in contact pressures at the end of this time. TOE parallel and cross-over repairs demonstrated no significant change in mean TTB contact pressure, force and area during abduction, external rotation and return to neutral, when compared to the 300sec relaxation state. TOE-C demonstrated a higher contact force on internal rotation (+53%). The SRR demonstrated a significant drop in contact force on abduction (−63%), and return to neutral (−43%) and a trend on external rotation (−34%). SRR exhibited no change on internal rotation. There have been very few biomechanical studies with which observe RC repair contact properties dynamically. Relaxation of the repair can be partially reversed. Significant decrease in contact area with SRR during movement occurred, compared to the TOE repairs, which remains unaltered. This is an important consideration when determining postoperative rehabilitation

The cellular mechanisms of tendinopathy remain unclear, particularly with respect to the role of inflammation in early disease. We have previously identified increased levels of inflammatory cytokines in an early human model of tendinopathy and sought to extend these studies to the cellular analysis of tissue. Purpose. To characterise inflammatory cell subtypes in early human tendinopathy we explored the phenotype and quantification of inflammatory cells in torn and control tendon samples. Design. Controlled laboratory study. Methods. Torn supraspinatus tendon and matched intact subscapularis tendon samples were collected from twenty patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from ten patients undergoing arthroscopic stabilisation surgery. Tendon biopsies were evaluated immunohistochemically by quantifying the presence of macrophages (CD68 and CD206), T cells (CD3), mast cells (Mast cell tryptase) and vascular endothelium (CD34). Results. Subscapularis tendon biopsies obtained from patients with torn supraspinatus tendon exhibited significantly greater macrophage, mast cell and T cell expression compared to either torn supraspinatus samples or control subscapularis derived tissue (p< 0.01). Inflammatory cell infiltrate correlated inversely (r=0.5, p< 0.01) with rotator cuff tear size, with larger tears correlating with a marked reduction in all cell lineages. There was a modest but significant correlation between mast cells and CD 34 expression (r= 0.4, p< 0.01) in pre-rupture subscapularis tendon. Conclusion. We provide evidence for an inflammatory cell infiltrate in early mild/moderate human supraspinatus tendinopathy. In particular, we demonstrate significant infiltration of mast cells and macrophages suggesting a role for innate immune pathways in the events that mediate early tendinopathy. Further mechanistic studies to evaluate the net contribution and hence therapeutic utlity of these cellular lineages and their downstream processes may reveal novel therapeutic approaches to the management of early tendinopathy

Bone marrow concentrates are being used to augment soft tissue healing. However, only 0.01% of these cells meet the criteria of a mesenchymal stem cell (MSC), which likely accounts for the variability in reported results. Previous studies using an established rat rotator cuff repair model have demonstrated that bone marrow-derived MSCs had no effect on healing. In this study we evaluated the effect of purified human MSCs on rotator cuff healing in an athymic rat model. Hypothesis: Purified human MSCs added to the repair site will improve biomechanical strength and fibrocartilage formation of the healing tendon. Fifty-two athymic rats underwent unilateral detachment and repair of the supraspinatus tendon with either fibrin glue (control) or fibrin glue with 106 hMSCs (experimental) applied at the repair site. Flow cytometry verified the stem cell phenotype of the cells as CD73+, CD90+, CD105+, CD14-, CD34- and CD45-. Rats were sacrificed at 2 and 4 weeks, with 10 used for biomechanical testing and 3 for histologic analysis from each group. Biomechanical testing revealed a significant increase in failure load (11.5±2.4N vs. 8.5±2.4N, p=0.002) and stiffness (7.1±1.2 N/mm vs. 5.7±2.1 N/mm, p0.17). These data demonstrate the potential for stem cells to augment tendon healing. This is the first study to use purified stem cells, rather than simple bone marrow concentrate. In the future, cell sorting techniques and culture expansion could be used to select and expand the small population of true stem cells in bone marrow. Furthermore, healing could potentially be improved with repeat cell injection at an additional post-operative time point

INTRODUCTION. Rotator cuff tears are common injuries which often require surgical repair. Unfortunately, repairs often fail [1] and improved repair strength is essential. P2 Porous titanium (DJO Surgical, Austin TX) has been shown to promote osseointegration [2,3] and subdermal integration [4]. However, the ability of P2Porous titanium to aid in supraspinatus tendon-to-bone repair has not been evaluated. Therefore, the purpose of this study was to investigate P2 implants used to augment supraspinatus tendon-to-bone repair in a rat model [5]. We hypothesized that supraspinatus tendon-to-bone repairs with P2 implants would allow for ingrowth and increased repair strength when compared to standard repair alone. METHODS. Thirty-four adult male Sprague-Dawley rats were used (IACUC approved). Rats received bilateral supraspinatus detachment and repair with one limb receiving P2 implant. Animals were sacrificed at time 0 (n=3), 2 weeks (n=8), 4 weeks (n=9) and 12 weeks (n=14). Limbs were either dissected for histological and SEM analysis or mechanical testing as described previously [5]. Specimens for histology and SEM were embedded in PMMA for tissue-implant interface analysis. Specimens were first viewed in SEM under BSE to detect bony ingrowth, then stained with Sanderson's Rapid Bone Stain and viewed under transmitted and polarized light for tissue ingrowth. Comparisons were made using Student's t-tests with significance at p≤0.05. RESULTS. No differences in cross-sectional area were detected at any time point (Fig 1A). Percent relaxation was significantly increased in the P2 group at 2 weeks, but not at 4 and 12 weeks (Fig 1B). Maximum load was significantly increased in the P2 group at 2 weeks, but not at 4 weeks (Fig 1C – maximum load not reported due to failure at grip at 12 weeks). Modulus was significantly increased in the P2 group at 4 weeks, but not at 2 or 12 weeks (Fig 1D). No differences were detected in stiffness at any time point (data not shown). BSE analysis demonstrated bone ingrowth (Fig 2) and histological analysis showed soft tissue integration (Fig 3). DISCUSSION. Results indicate superior mechanical properties in the P2 group at 2 and 4 weeks, and tissue ingrowth at all time points. Importantly, at 2 weeks, the P2group had 76% increased maximum load compared to standard repair. As supraspinatus tendon re-tears are extremely common early [1] and occur at the tendon-to-bone interface, this finding supports the reduction of re-tear risk with the P2 implant. Although no differences were detected in maximum load at 4 weeks, the increase at 2 weeks denotes that P2 implants improved early tendon-to-bone healing. Additionally, at 4 weeks, the P2 implant group had significantly increased elastic modulus, further supporting increased mechanical properties due to the P2 implant. Clinically, improved early healing might allow faster rehabilitation and associated recovery. This study demonstrates that the P2 implant improves tendon-to-bone healing up to 4 weeks (with no detrimental effects at longer time points), suggesting that P2 porous titanium may be of benefit for use in clinical rotator cuff repairs

Purpose. Full-thickness tendon tears of the supraspinatus (SP) are common and can have a significant impact on shoulder function. To optimally treat supraspinatus tendon tears an accurate understanding of its musculotendinous architecture is needed. We have previously shown that the architecture of supraspinatus is complex. It has architecturally distinct regions: anterior and posterior, each of which is further subdivided into superficial, middle and deep parts (Kim et al., 2007). Data of FBL and PA of the torn supraspinatus could enhance clinical decision making and guide rehabilitative treatments (Ward et al., 2006). Currently, however, in vivo US quantification of the fiber bundle architecture of the distinct regions of supraspinatus in subjects with full-thickness tendon tears has not been investigated. PURPOSE: To quantify architectural parameters within the distinct regions of supraspinatus in subjects with a full-thickness tendon tear using the US protocol that we previously developed (Kim et al., 2010), and to compare findings with age and gender matched normal controls. Method. Twelve SP from eight subjects, mean age 576.0 years, were scanned using an US scanner (12 MHz). The SP was scanned in relaxed and contracted states. For the contracted state, SP was scanned with the shoulder in neutral rotation and 60 of active abduction. Fiber bundles of the anterior region (middle and deep) and posterior region (deep) could be visualized and measured. Muscle thickness, FBL, and PA were computed from US scans. Data was analyzed using Mann-Whitney and Wilcoxon Signed Rank Tests (P<0.05). Results. Intra-and inter-rater measurements of FBL were strongly correlated with no significant difference between measurements (P<0.001). In the anterior region, mean FBL did not significantly differ between the pathologic subjects and normal controls. In the pathologic subjects, mean PA was smaller compared to normal controls. The difference was significant between the subjects with a tear and retraction and normal controls (P<0.05). For the posterior region, mean FBL was shorter in the pathologic subjects compared to normal controls. The difference was significant between the subjects with a tear and retraction and normal controls (P<0.05). Conclusion. Findings suggest that significant FBL and PA changes are found with full-thickness tendon tears of SP and different regions of the muscle are impacted differently. Pennation angles are largely impacted in the anterior region and FBL in the posterior. The presence of tendon retraction was found to be related to the amount of change in architectural parameters. Data from this study may be useful to model muscle-joint behavior of the pathologic shoulder. This US protocol may be beneficial to carry out a larger study to determine which comes first, architectural changes in the muscle, or tendon tearing. If we identify changes in muscle architecture predate tendon pathology, we could develop techniques to prevent tendon tearing

Purpose. Chronic massive rotator cuff tears are challenging to repair completely because of the development of tendon retraction with inelasticity, muscle atrophy and fatty infiltration. The objective of this study was to investigate the clinical outcome and MRI findings after arthroscopic superior capsule reconstruction (ASCR) for symptomatic irreparable rotator cuff tears. Methods. From 2011 to 2013, 12 shoulders in 12 consecutive patients (mean, 70.8 years) with irreparable massive rotator cuff tears underwent ASCR using fascia lata. We used suture anchors to attach the graft medially to the glenoid superior tubercle and laterally to the greater tuberosity as same technique by Mihata et al. We added side-to-side sutures between the graft and infraspinatus tendon and between the graft and residual anterior supraspinatus/subscapularis tendon to improve force coupling. Physical examination, clinical rating system, and magnetic resonance imaging (MRI) were performed before surgery; at 6 and 12 months after surgery; and 6 months thereafter. Average follow-up was 19.1 months (12 to 28 months) after surgery. We assessed patients preoperatively by using the scoring systems of the shoulder index of the American Shoulder and Elbow Surgeons (ASES), the Japanese Orthopaedic Association, and the University of California, Los Angeles. Results. Mean active elevation increased from 59° to 111° significantly and external rotation increased from 28 to 33. The average preoperative scores were 16.0 points by ASES, 48.0 points by JOA, and 10.8 points by UCLA. Average clinical outcome scores all improved significantly after ASCR at the final follow-up (ASES, 73.3 points; JOA, 73.7 points; UCLA, 22.7 points). There was surgical complication as infection. Although infection was controlled by arthroscopic irrigation, the transplanted tendon was absorbed, and preoperative conditions did not functionally improve. Five patients had graft tear during follow-up. Postoperative active range of motion in the healed patients was significantly greater than in the unhealed patients who had graft tears. Conclusions. ASCR restored superior glenohumeral stability and function of the shoulder joint with irreparable rotator cuff tears compared to preoperative function in the cases without postoperative complications. However ratio of graft tears were 50% and clinical results of these cases were not improved sufficiently

Tendinopathy is a debilitating musculoskeletal condition which can cause significant pain and lead to complete rupture of the tendon, which often requires surgical repair. Due in part to the large spectrum of tendon pathologies, these disorders continue to be a clinical challenge. Animal models are often used in this field of research as they offer an attractive framework to examine the cascade of processes that occur throughout both tendon pathology and repair. This review discusses the structural, mechanical, and biological changes that occur throughout tendon pathology in animal models, as well as strategies for the improvement of tendon healing.

Cite this article: Bone Joint Res 2014;3:193–202.