More tendon degeneration in patients with shoulder osteoarthritis.

PURPOSE: Tendon disorders are a major problem in the general population. It is known that rotator cuff tendinopathy contributes to osteoarthritis (OA) of the shoulder. The aim of the study was to analyse the presence of tendinopathy in patients with shoulder OA and an intact rotator cuff, using a multimodal approach. METHODS: Thirteen consecutive patients median age 67 (52-84) years, with OA of the shoulder, and 13 consecutive control patients, with a fracture of the proximal humerus, median age 70 (51-84) years, underwent an open biopsy procedure from the biceps and subscapularis tendon in conjunction with shoulder arthroplasty. In addition to a macroscopic evaluation, the samples underwent histologic, morphologic and ultrastructural analyses in light and transmission electron microscopy. RESULTS: Macroscopic degeneration was found in 15 of 26 specimen in the OA group but in seven of 25 in the control group (p = 0.048). The histologic analysis revealed a non-significant difference for the total degeneration score (TDS) between the study groups. The morphologic evaluation of the samples revealed that the OA group had significantly more samples with non-homogeneous extracellular matrix (ECM), (p = 0.048). Ultrastructurally, the OA group revealed a significantly larger fibril diameter in the biceps tendon (p < 0.0001) but not in the subscapularis tendon compared with the control group. CONCLUSION: A significantly worse macroscopic appearance and significantly more morphologically inhomogeneous ECM, indicating more tendon degeneration, were found in the OA group compared with the control group. This indicates that it could be beneficial to treat the tendinosis in an early stage to decrease symptoms from the OA. STUDY DESIGN: Level of evidence, III.

Arthroscopic Rotator Cuff Repair With Graft Augmentation of 3-Dimensional Biological Collagen for Moderate to Large Tears: A Randomized Controlled Study.

BACKGROUND: Due to the highly organized tissue and avascular nature of the rotator cuff, rotator cuff tears have limited ability to heal after the tendon is reinserted directly on the greater tubercle of the humerus. Consequently, retears are among the most common complications after rotator cuff repair. Augmentation of rotator cuff repairs with patches has been an active area of research in recent years to reduce retear rate. HYPOTHESIS: Graft augmentation with 3D collagen could prevent retears of the repaired tendon and improve tendon-bone healing in moderate to large rotator cuff tears. STUDY DESIGN: Randomized controlled study; Level of evidence, 2. METHODS: A prospective, randomized controlled study was performed in a consecutive series of 112 patients age 50 to 85 years who underwent rotator cuff repair with the suture-bridge technique (58 patients, control group) or the suture-bridge technique augmented with 3-dimensional (3D) collagen (54 patients, study group). All patients were followed for 28.2 months (range, 24-36 months). Visual analog scale score for pain, University of California Los Angeles (UCLA) shoulder score, and Constant score were determined. Magnetic resonance imaging was performed pre- and postoperatively (at a minimum of 24 months) to evaluate the integrity of the rotator cuff and the retear rate of the repaired tendon. Three patients in each group had biopsies at nearly 24 months after surgery with histological assessment and transmission electron microscopy. RESULTS: A total of 104 patients completed the final follow-up. At the 12-month follow-up, the UCLA shoulder score was 28.1 ± 1.9 in the study group, which was significantly better than that in the control group (26.9 ± 2.1, P = .002). The Constant score was also significantly better in the study group (87.1 ± 3.2) than in the control group (84.9 ± 4.2, P = .003). However, at the final follow-up, no significant differences were found in the UCLA shoulder scores (29.4 ± 1.9 in the control group and 30.0 ± 1.6 in the study group, P = .052) or Constant scores (89.9 ± 3.2 in the control group and 90.8 ± 3.5 in the study group, P = .18). In terms of structural integrity, more patients in the study group had a favorable type I retear grade (18/51) than in the control group (10/53) ( P = .06). The postoperative retear rate was 34.0% in the control group and 13.7% in the study group, thus indicating a significantly lower retear rate in the study group ( P = .02). Biopsy specimens of the tendon-bone interface in 6 patients revealed more bone formation and more aligned fibers with larger diameters in the study group than in the control group. No intraoperative or postoperative complications were noted in either group. CONCLUSION: 3D collagen augmentation could provide effective treatment of moderate to large rotator cuff tears, providing substantial functional improvement, and could reduce the retear rate. This technique could also promote new tendon-bone formation, thus exerting a prominent effect on tendon-bone healing.

More histologic and ultrastructural degenerative signs in the subscapularis tendon and the joint capsule in male patients with shoulder impingement.

PURPOSE: The purpose of the present study was to analyze biopsy samples from the subscapularis tendon and from the joint capsule from male patients with shoulder impingement syndrome (SAIS) and compare them with samples from male patients with post-traumatic recurrent shoulder instability. The hypothesis of the study was that patients with SAIS would have more histologic and ultrastructural degenerative changes in their subscapularis tendon and joint capsule than patients with post-traumatic recurrent shoulder instability. METHODS: Male patients scheduled for surgery, with either subacromial decompression or Bankart reconstruction, were included. Four biopsies from each patient were obtained from the capsule and four from the subscapularis tendon during arthroscopic surgery. The histologic characteristics and the presence of glycosaminoglycans were assessed using the light microscope, and the ultrastructure was assessed using a transmission electron microscope. RESULTS: Eight patients, median age 53 (45-74) years (p < 0.0001), were included in the impingement group, and 12 patients, median age 27 (22-48) years, were included in the instability group. The histologic assessment revealed significantly higher cellularity and total degeneration score in the capsule (p = 0.016 and p = 0.014 respectively) in patients with subacromial impingement compared with the instability patients. The corresponding finding was not made for the subscapularis tendon. The ultrastructural evaluation revealed that the instability patients had more fibrils with a large diameter (indicating less degeneration) in both the subscapularis tendon and the capsule compared with the impingement patients (p < 0.0001). CONCLUSION: Male patients with subacromial impingement have more histologic and ultrastructural degenerative changes in their shoulder compared with patients with post-traumatic recurrent shoulder instability. CLINICAL RELEVANCE: It appears that in patients with subacromial impingement, the whole shoulder joint is affected and not only the subacromial space. It is the opinion of the authors that intra-articular therapeutic injections could be tried more often in these patients. LEVEL OF EVIDENCE: III.

Alignment of collagen fiber in knitted silk scaffold for functional massive rotator cuff repair.

Rotator cuff tear is one of the most common types of shoulder injuries, often resulting in pain and physical debilitation. Allogeneic tendon-derived decellularized matrices do not have appropriate pore size and porosity to facilitate cell infiltration, while commercially-available synthetic scaffolds are often inadequate at inducing tenogenic differentiation. The aim of this study is to develop an advanced 3D aligned collagen/silk scaffold (ACS) and investigate its efficacy in a rabbit massive rotator cuff tear model. ACS has similar 3D alignment of collagen fibers as natural tendon with superior mechanical characteristics. Based on ectopic transplantation studies, the optimal collagen concentration (10mg/ml), pore diameter (108.43±7.25µm) and porosity (97.94±0.08%) required for sustaining a stable macro-structure conducive for cellular infiltration was determined. Within in vitro culture, tendon stem/progenitor cells (TSPCs) displayed spindle-shaped morphology, and were well-aligned on ACS as early as 24h. TSPCs formed intercellular contacts and deposited extracellular matrix after 7days. With the in vivo rotator cuff repair model, the regenerative tendon of the ACS group displayed more conspicuous native microstructures with larger diameter collagen fibrils (48.72±3.75 vs. 44.26±5.03nm) that had better alignment and mechanical properties (139.85±49.36vs. 99.09±33.98N) at 12weeks post-implantation. In conclusion, these findings demonstrate the positive efficacy of the macroporous 3D aligned scaffold in facilitating rotator cuff tendon regeneration, and its practical applications for rotator cuff tendon tissue engineering. STATEMENT OF SIGNIFICANCE: Massive rotator cuff tear is one of the most common shoulder injuries, and poses a formidable clinical challenge to the orthopedic surgeon. Tissue engineering of tendon can potentially overcome the problem. However, more efficacious scaffolds with good biocompatibility, appropriate pore size, favorable inductivity and sufficient mechanical strength for repairing massive rotator cuff tendon injuries need to be developed. In this study, we developed a novel macroporous 3D aligned collagen/silk scaffold, and demonstrated that this novel scaffold enhanced the efficacy of rotator cuff tendon regeneration by inducing aligned supracellular structures similar to natural tendon, which in turn enhanced cellular infiltration and tenogenic differentiation of stem/progenitor cells from both the tendon itself and surrounding tissues. Hence, it can potentially be a clinically useful application for tendon tissue engineering.

Histomorphometric and ultrastructural analysis of the tendon-bone interface after rotator cuff repair in a rat model.

Successful rotator cuff repair requires biological anchoring of the repaired tendon to the bone. However, the histological structure of the repaired tendon-bone interface differs from that of a normal tendon insertion. We analysed differences between the normal tendon insertion and the repaired tendon-bone interface after surgery in the mechanical properties, histomorphometric analysis, and 3-dimensional ultrastructure of the cells using a rat rotator cuff repair model. Twenty-four adult Sprague-Dawley (SD) rats underwent complete cuff tear and subsequent repair of the supraspinatus tendon. The repaired tendon-bone interface was evaluated at 4, 8, and 12 weeks after surgery. At each time point, shoulders underwent micro-computed tomography scanning and biomechanical testing (N = 6), conventional histology and histomorphometric analysis (N = 6), and ultrastructural analysis with focused ion beam/scanning electron microscope (FIB/SEM) tomography (N = 4). We demonstrated that the cellular distribution between the repaired tendon and bone at 12 weeks after surgery bore similarities to the normal tendon insertion. However, the ultrastructure of the cells at any time point had a different morphology than those of the normal tendon insertion. These morphological differences affect the healing process, partly contributing to re-tearing at the repair site. These results may facilitate future studies of the regeneration of a normal tendon insertion.

Effect of mechanical stimulation on bone marrow stromal cell-seeded tendon slice constructs: a potential engineered tendon patch for rotator cuff repair.

Cell-based tissue engineered tendons have potential to improve clinical outcomes following rotator cuff repair, especially in large or massive rotator cuff tears, which pose a great clinical challenge. The aim of this study was to develop a method of constructing a functional engineered tendon patch for rotator cuff repair with cyclic mechanical stimulation. Decellularized tendon slices (DTSs) were seeded with BMSCs and subjected to cyclic stretching for 1, 3, or 7 days. The mechanical properties, morphologic characteristics and tendon-related gene expression of the constructs were investigated. Viable BMSCs were observed on the DTS after 7 days. BMSCs penetrated into the DTSs and formed dense cell sheets after 7 days of mechanical stretching. Gene expression of type I collagen, decorin, and tenomodulin significantly increased in cyclically stretched BMSC-DTS constructs compared with the unstrained control group (P < 0.05). The ultimate tensile strength and stiffness of the cyclically stretched tendon constructs were similar to the unstrained control group (P > 0.05). In conclusion, mechanical stimulation of BMSC-DTS constructs upregulated expression of tendon-related proteins, promoted cell tenogenic differentiation, facilitated cell infiltration and formation of cell sheets, and retained mechanical properties. The patch could be used as a graft to enhance the surgical repair of rotator cuff tears.

Characterization of deposits in patients with calcific tendinopathy of the supraspinatus. Role of phytate and osteopontin.

Calcific tendinopathy of the tendons of the rotator cuff is common in adults. These calcifications tend to be reabsorbed after a period of acute pain. This study evaluated the morphologic characteristics of calcific deposits and the participation of phytate and osteopontin (OPN) in their development. Calcific deposits were removed from 21 patients with calcific tendinopathy by ultrasound-guided needle puncture under local anesthesia. The removed deposits were evaluated by scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. The amounts of calcium and phosphorus in the deposits were semi-quantitatively determined by energy dispersive X-ray analysis. Phytate was determined in 2 h urine samples, and OPN was extracted from a pool of deposits. The calcific deposits consisted of amorphous and poorly crystalline carbonated hydroxyapatite containing molecular water and organic matter. OPN was associated with the hydroxyapatite deposits. Phytate concentrations were significantly lower in the urine of patients with calcific tendinopathy than in healthy controls. The deficit in crystallization inhibitors such as phytate, and the presence of regulators such as OPN, may play important roles in the development of calcific tendinopathy.

Effect of proximal humeral fractures on the age-specific prevalence of rotator cuff tears.

BACKGROUND: This study examined the effect of proximal humeral fractures on the age- and shoulder-specific prevalence of rotator cuff tears (RCTs) as well as the association with fracture severity, patient age, and clinical outcome. METHODS: Sixty-three fractures were treated conservatively; in 114 cases, minimally invasive osteosynthesis, and in 125 cases, open reduction and plate fixation were performed without rotator cuff reconstruction. After 4.4 years, all 302 patients were clinically and sonographically examined. RESULTS: We examined 139 two-part, 95 three-part, and 68 four-part fractures according to Neer and 134 A, 86 B, and 82 C fractures according to the AO classification. There were 52 patients (17%) with a complete rotator tear (RCT) only at the injured shoulder and 11 patients (4%) with a complete RCT only at the contralateral shoulder (p < 0.0001). Independent of the patient's age at follow-up, the prevalence of an RCT in the fractured shoulder was 13% higher than the prevalence in the opposite shoulder. Four-part fractures showed a significant association with a complete RCT (p = 0.047).Of 74 patients with a satisfactory or poor Constant Score, 33 (44.6%) had RCTs. In the remaining 228 patients with a good to excellent result, only 26 (11.4%) had RCTs. We showed that 66% of the RCTs observed at the fractured shoulder were caused by trauma. There was no association between treatment modality and a complete RCT. CONCLUSION: RCTs may need special attention in initial diagnostics, management, and follow-up especially in severe proximal humeral fractures.

Biocompatibility of a polymer patch for rotator cuff repair.

Both mechanical and biological factors influence the high re-tear rate after rotator cuff repair. Mechanical factors have largely been addressed by the introduction of better implants and modification of suture configuration, but further improvements are needed to address the often poor tissue quality of the degenerated rotator cuff tendons. Current biological solutions provide only short-term reinforcement and have been associated with pseudo-infectious reactions. This pre-clinical animal study investigates the biological response to a novel polycarbonate polyurethane patch used for tissue augmentation in a rat rotator cuff repair model. Bilateral defects were created in the supraspinatus tendons of 12 Sprague Dawley rats. One side was repaired with a patch as a tissue augmentation device. The contralateral side acted as internal control without patch augmentation. After 6 weeks the tissues were harvested and underwent histologic and histomorphometric analyses. Histological evaluation demonstrated no inflammatory reaction; histomorphometry revealed tissue ingrowth of 79.9%. In conclusion, the polycarbonate polyurethane patch for tissue extension or augmentation in rotator cuff repair has demonstrated no inflammatory response and excellent tissue integration in a rat rotator cuff repair model.

The insertional footprint of the rotator cuff: an anatomic study.

PURPOSE: The purpose of this study was to define the entire rotator cuff footprint and relate it to known, easily identifiable landmarks as a guide for both open and arthroscopic rotator cuff repair. Anatomic: Gross and microscopic. METHODS: The myotendinous units of the rotator cuff and their insertions onto the humerus were dissected in 20 fresh-frozen cadavers. The separate tendon insertions were identified, and their length and width measured. The character and exact anatomy of the tendons were also noted. The entire insertion was measured and referenced to the articular surface, biceps groove, and bare area of the humerus. In a separate part of the study, 6 cadavers were decalcified and thin-sliced through the supraspinatus tendon insertion. This insertion was evaluated via scanning electron microscopy (SEM). RESULTS: Our findings demonstrated a consistent pattern at the insertion of the rotator cuff. The horseshoe-shaped insertion tapers away from the articular surface in a superior-to-inferior direction. Interdigitation of the muscle units may be noted, particularly between the supraspinatus and the infraspinatus. Average maximum insertional lengths and widths were as follows: subscapularis (SC): 40 x 20 mm; infraspinatus (IS): 29 x 19 mm; supraspinatus (SS): 23 x 16 mm; and teres minor (TM): 29 x 21 mm. The SC inserted on the lesser tuberosity adjacent to the biceps groove at the edge of the articular surface. It tapered away 18 mm at its inferior border. The SS inserted at the articular surface along its entire insertion from the bicipital groove to the top of the bare area. The IS wrapped the posterior border of the SS superiorly at the articular surface and tapered away inferiorly, framing the bare area. SEM microscopy showed the SS to be adherent to the edge of the articular surface medially. As it filled the sulcus, its lateral edge extended over the edge of the greater tuberosity. CONCLUSIONS: A consistent pattern was noted at the insertional anatomy of the rotator cuff. This anatomy was related to known, easily identifiable landmarks and may serve as a guide for evaluation of size, location, and propagation patterns of rotator cuff tears, as well as for their repair. CLINICAL RELEVANCE: Knowledge of the insertional anatomy of the rotator cuff can facilitate grading and repair of rotator cuff tears.

[Histological and electron microscopic study of rotator cuff tear].

OBJECTIVE: To understand the changes of rotator cuff during tear and observe the pathologic and ultramicroscopic structure of rotator cuff. METHOD: Histological and ultra thin slides of samples of 36 cases of rotator cuff were made. RESULT: The degeneration of rotator cuff happened in synovium side, and then extended to the middle and deep sides of tendon. The deep side of cuff tendon could degenerate without synovium. The repair of tendon could be achieved with two types of healing. CONCLUSION: It would be difficult to achieve full repair when complete tear and deep side tear occurred to the rotator cuff.

Cell and matrix changes associated with pathological calcification of the human rotator cuff tendons.

The causative mechanism of tendon calcification ('calcifying tendinitis') is unknown. In this report, pathological human tendon samples were examined to give morphological and ultrastructural detail of the calcified regions and these findings were compared with those from normal tendon. Selected specimens were cryosectioned to enable histochemical and immunohistochemical comparison of the occurrence and distribution of specific matrix molecules in diseased and normal tendon tissues. The lack of collagen type II and alkaline phosphatase in the pathological regions suggests that the calcification process is not mediated through an endochondral transition. In contrast, the pathological areas were characterised by widespread labelling for chondroitin-4-sulphate/dermatan sulphate and intense pericellular localisation of chondroitin-6-sulphate.

Degenerative change and rotator cuff tears. An anatomical study in 160 shoulders of 80 cadavers.

In order to determine the effects of friction and rubbing in the development of rotator cuff tear, we studied 160 shoulders of 80 cadavers (age at death 43-93 years, mean 69.3 years). Seventy-two cadavers were fixed with formalin and eight were fresh cadavers. The surface of the cuff and the undersurface of the acromion were observed macroscopically. Eight shoulders of fresh cadavers were examined by scanning electron microscopy. Ninety-eight specimens (61%) showed degenerative changes of the supraspinatus tendon. The number of tendons with degeneration and tear increased from the fifth to sixth decade of life, and the size of the tear increased with age. However, there was no sustained increase in the incidence with aging from the age of 60 to 90 years, and the percentage with degenerative changes of the cuff remained at approximately 60% in each decade. Ninety-six specimens (60%) showed degeneration of the subacromial surface. The percentage with degeneration of the undersurface of the acromion remained at approximately 60% from the sixth to ninth decade. There was a significant correlation between the severity of the changes in the rotator cuff and the subacromial surface. Scanning electron microscopy showed changes suggesting effects of friction and rubbing on the rotator cuff, such as regularly arranged wool-like spherical structures on the surface of the tendon and rounded ruptured ends of the tendon fibers. These results indicate that degenerative change of the rotator cuff is aggravated by a friction and rubbing mechanism with the undersurface of the acromion and leads to development of a complete tear.