Overuse of training increases mechanoreceptors in supraspinatus tendon of rats SHR

The presence of mechanoreceptors in tendon after overuse activities can be a further step to learn about tendinopathy and overuse. Studies of tendons mechanoreceptors in rats are rare. We studied 12 isogenic spontaneous hypertensive rats (SHR), which underwent an overuse protocol consisting of an hour per daily session of treadmill running at a speed of 17 m/min, 5 times/week for 4 months. Supraspinatus tendons were evaluated with immunohistochemistry using S100 protein antibodies and histological protocol. Supraspinatus tendons at the end of 4 months of overuse protocol had a high number of media mechanoreceptors (4.3) than controls (0.6). The overexpression of S100 protein antibody in overuse activities maybe could represent a adaptative effort to tendon before the tear. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1771–1774, 2011     

Development of a mouse model of supraspinatus tendon insertion site healing

Supraspinatus (SS) tendon tears are common musculoskeletal injuries whose surgical repair exhibits the highest incidence of re‐tear of any tendon. Development of therapeutics for improving SS tendon healing is impaired by the lack of a model that allows biological perturbations to identify mechanisms that underlie ineffective healing. The objective of this study was to develop a mouse model of supraspinatus insertion site healing by creating a reproducible SS tendon detachment and surgical repair which can be applied to a wide array of inbred mouse strains and genetic mutants. Anatomical and structural analyses confirmed that the rotator cuff of the mouse is similar to that of human, including the presence of a coracoacromial (CA) arch and an insertion site that exhibits a fibrocartilagenous transition zone. The surgical repair was successfully conducted on seven strains of mice that are commonly used in Orthopaedic Research suggesting that the procedure can be applied to most inbred strains and genetic mutants. The quality of the repair was confirmed with histology through 14 days after surgery in two mouse strains that represent the variation in mouse strains evaluated. The developed mouse model will allow us to investigate mechanisms involved in insertion site healing. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:25–32, 2015.     

Effect of overuse‐induced tendinopathy on tendon healing in a rat supraspinatus repair model

Supraspinatus tears often result in the setting of chronic tendinopathy. However, the typical repair model utilizes an acute injury. In recognition of that distinction, our laboratory developed an overuse animal model; however it is unclear whether induced overuse is necessary in the repair model. We studied the repair properties of overuse‐induced tendons compared to normal tendons. We hypothesized that histological and mechanical properties would not be altered between the overuse‐induced and normal tendons 1 and 4 weeks after repair. Thirty‐one adult male Sprague‐Dawley rats were subjected to either overuse or cage activity for 4 weeks prior to bilateral supraspinatus tendon repair surgery. Rats were sacrificed at 1 and 4 weeks post‐surgery and evaluated for histology and mechanics. Results at 1 week showed no clear histologic changes, but increased inflammatory protein expression in overuse tendons. At 4 weeks, percent relaxation was slightly increased in the overuse group. No other alterations in mechanics or histology were observed. Our results suggest that the effects of the surgical injury overshadow the changes evoked by overuse. Because clinically relevant mechanical parameters were not altered in the overuse group, we conclude that when examining tendons 4 weeks after repair in the classic rat supraspinatus model, inducing overuse prior to surgery is likely to be unnecessary. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:161–166, 2016.     

Effect of fiber distribution and realignment on the nonlinear and inhomogeneous mechanical properties of human supraspinatus tendon under longitudinal tensile loading

Tendon exhibits nonlinear stress–strain behavior that may be partly due to movement of collagen fibers through the extracellular matrix. While a few techniques have been developed to evaluate the fiber architecture of other soft tissues, the organizational behavior of tendon under load has not been determined. The supraspinatus tendon (SST) of the rotator cuff is of particular interest for investigation due to its complex mechanical environment and corresponding inhomogeneity. In addition, SST injury occurs frequently with limited success in treatment strategies, illustrating the need for a better understanding of SST properties. Therefore, the objective of this study was to quantitatively evaluate the inhomogeneous tensile mechanical properties, fiber organization, and fiber realignment under load of human SST utilizing a novel polarized light technique. Fiber distributions were found to become more aligned under load, particularly during the low stiffness toe‐region, suggesting that fiber realignment may be partly responsible for observed nonlinear behavior. Fiber alignment was found to correlate significantly with mechanical parameters, providing evidence for strong structure–function relationships in tendon. Human SST exhibits complex, inhomogeneous mechanical properties and fiber distributions, perhaps due to its complex loading environment. Surprisingly, histological grade of degeneration did not correlate with mechanical properties. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1596–1602, 2009     

Arthroscopic repair of partial articular supraspinatus tendon avulsion lesions by conversion to full-thickness tears through a small incision

Purpose: To assess the clinical efficacy of converting partial articular supraspinatus tendon avulsion (PASTA) lesions to full-thickness tears through a small local incision of the bursal-side supraspinatus tendon followed by repair. Methods: We retrospectively analyzed 41 patients with Ellman grade 3 PASTA lesions and an average age of (54.7 ± 11.4) years from March 2013 to July 2017. Patients without regular conservative treatment and concomitant with other shoulder pathologies or previous shoulder surgery were excluded from the study. The tears were confirmed via arthroscopy, and a polydioxanone suture was placed to indicate the position of each tear. A small incision of approximately 6 mm was made using a plasma scalpel on the bursal-side supraspinatus tendon around the positioned suture to convert the partial tear into a fullthickness tear. The torn rotator cuff was sutured through the full thickness using a suture passer after inserting a 4.5-mm double-loaded suture anchor. Data were analyzed using a paired Student’s t-test with statistical significance defined as p <0.05. Results: At the final follow-up of 2 years, the pain-free shoulder joint range of motion and visual analog scale score were significantly improved compared to those before surgery (p < 0.001). The postoperative American Shoulder and Elbow Surgeons shoulder score was (90.6 ± 6.2), which was significantly higher than the preoperative score of (47.9 ± 8.3) (p < 0.001). The University of California at Los Angeles shoulder rating scale score increased from (14.7 ± 4.1) prior to surgery to (32.6 ± 3.4) points after surgery (p < 0.001). No patient had joint stiffness. Conclusion: This modified tear completion repair, by conversion to full-thickness tears through a small incision, has less damage to the supraspinatus tendon on the side of the bursa compared to traditional tear completion repair in the treatment of PASTA lesions. This surgical method is a simple and effective treatment that can effectively alleviate pain and improve shoulder joint function.     

Improving bone density at the rotator cuff footprint increases supraspinatus tendon failure stress in a rat model

The purpose of this study was to investigate whether supraspinatus tendon failure stress at the footprint can increase by improving the bone density at the rotator cuff footprint in a rat model. Bilateral ovariectomies were performed in twenty‐four 4‐month‐old Sprague‐Dawley rats. Half received bisphosphonate (zoledronic acid) and the other half received no treatment (OVX + ZOM and OVX, respectively). Twelve additional rats did not undergo ovariectomy or receive bisphosphonate treatment (CON). All rats were sacrificed at 7 months of age. Quantitative micro‐computed tomography was used to assess bone density in the proximal humerus. A series of stress–relaxation tests were performed to assess stiffness and failure stress of the supraspinatus tendon. Bone density in OVX + ZOM was significantly higher at the rotator cuff footprint when compared to CON and OVX rats (p < 0.0001). The supraspinatus tendons in the OVX group were significantly stiffer when compared to the CON and OVX + ZOM groups (p < 0.05). The failure stress of the OVX + ZOM group was significantly greater than the CON and OVX groups (22.89 ± 4.43 MPa vs. 18.36 ± 3.16 and 17.70 ± 4.92, respectively). In conclusion, improving the bone density at the rotator cuff footprint enhances failure stress of the suprapinatus tendon. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:308–314, 2010     

Decreased muscle loading delays maturation of the tendon enthesis during postnatal development.

Physical environment influences the development and maintenance of musculoskeletal tissues. The current study uses an animal model to explore the role of the physical environment on the postnatal development of the supraspinatus tendon enthesis. A supraspinatus intramuscular injection of botulinum toxin A was used to paralyze the left shoulders of mice at birth. The supraspinatus muscles of right shoulders were injected with saline to serve as contralateral controls. The supraspinatus enthesis was examined after 14, 21, 28, and 56 days of postnatal development. Histologic assays were used to examine fibrocartilage morphology and percentage osteoclast surface. Micro-computed tomography was used to examine muscle geometry and bone architecture. At 14 days there were no differences between groups in fibrocartilage formation, muscle geometry, bone architecture, or osteoclast surface. When comparing groups at 21, 28, and 56 days, muscle volume was decreased, fibrocartilage development was delayed, mineralized bone was decreased, and osteoclast surface was higher at each timepoint in the botulinum group compared to the contralateral saline control group. Our results indicate that the development of the tendon enthesis is sensitive to its mechanical environment. A reduction in muscle loading delayed the development of the tendon-to-bone insertion site by impeding the accumulation of mineralized bone. Physical factors did not play a significant role in enthesis maturation in the first 14 days postnatally, implying that biologic factors may drive early postnatal development.     

Characteristics of the rat supraspinatus tendon during tendon-to-bone healing after acute injury.

Rotator cuff repair is known to have a high failure rate. Little is known about the natural healing process of the rotator cuff repair site, hence little can be done to improve the tendon's ability to heal. The purpose of this study was to investigate the collagen formation at the early repair site and to localize TGFbeta-1 and 3 during early healing and compare their levels to cell proliferation and histological changes. Bilateral supraspinatus tendons were transected and repaired in 60 rats. Specimens were harvested and evaluated at 0, 1, 3, 7, 10, 28, and 56 days. Histological sections were evaluated for cell morphology. Immunohistochemistry and in situ hybridization was performed to localize protein and mRNA for collagen types I and III and TGFbeta-1 and 3. Proliferating cell nuclear antigen (PCNA) assay was performed to measure cell proliferation, and cells were counted to determine cell density. Biomechanical properties were evaluated. Repair tissue demonstrated an initial inflammatory response with multinucleated cells present at 1 and 3 days, and lymphocytes and plasma cells presents at 7 and 10 days. Capillary proliferation began at 3 days and peaked at 10 days. Ultimate force increased significantly over the time period studied. Collagen I protein and mRNA significantly increased at 10 days, and reached a plateau by 28 and 56 days. Collagen III showed a similar trend, with an early increase, and remained high until 56 days. TGFbeta-1 was localized to the forming scar tissue and showed a distinct peak at 10 days. TGFbeta-3 was not seen at the healing insertion site. Cell proliferation and density followed the same trend as TGFbeta-1. A wound healing response does occur at the healing rotator cuff insertion site, however, the characteristics of the tendon after healing differ significantly from the uninjured tendon insertion site at the longest time-point studied. A distinctive collagen remodeling process occurred with an initial increase in the formation of collagen types I and III followed by a decrease toward baseline levels seen at time 0. Growth factor TGFbeta-1 was localized to repair tissue and coincided with a peak in cell proliferation and cellularity. Repair sites remained unorganized histologically and biomechanically inferior in comparison to previously described uninjured insertion sites.     

Development of the supraspinatus tendon‐to‐bone insertion: Localized expression of extracellular matrix and growth factor genes

The adult healing response of the rotator cuff tendon‐to‐bone insertion site differs from the ordered process of insertion site development. Healing is characterized by disorganized scar and a lack of fibrocartilage formation, in contrast to the well organized fibrocartilaginous transition which forms during the normal development of the tendon‐to‐bone insertion. The purpose of this study was to localize the expression of a number of extracellular matrix and growth factor genes during insertion site development in order to guide future strategies for augmenting adult rotator cuff healing. The rotator cuff was morphologically distinct at 13.5 dpc (days postconception). Neo‐tendon was evident as a condensation of cells adjacent to bone. The interface between tendon and bone did not form into a mature fibrocartilaginous insertion until 21‐days postnatally, based upon the appearance of four distinct zones with a mineralized humeral head. Fibroblasts of the supraspinatus tendon expressed type I collagen at all timepoints. Type II collagen was first expressed by chondrocytes in the fibrocartilage and mineralized fibrocartilage at 7 days and persisted in the mineralized fibrocartilage at 56 days. Type X collagen was first expressed by the chondrocytes in the mineralized fibrocartilage at 14 days and persisted in the mineralized fibrocartilage at 56 days. A shift from TGF‐β3 to TGF‐β1 expression occurred at 15.5 dpc. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1621–1628, 2007     

Repeated subrupture overload causes progression of nanoscaled discrete plasticity damage in tendon collagen fibrils

A critical feature of tendons and ligaments is their ability to resist rupture when overloaded, resulting in strains or sprains instead of ruptures. To treat these injuries more effectively, it is necessary to understand how overload affects the primary load‐bearing elements of these tissues: collagen fibrils. We have investigated how repeated subrupture overload alters the collagen of tendons at the nanoscale. Using scanning electron microscopy to examine fibril morphology and hydrothermal isometric tension testing to look at molecular stability, we demonstrated that tendon collagen undergoes a progressive cascade of discrete plasticity damage when repeatedly overloaded. With successive overload cycles, fibrils develop an increasing number of kinks along their length. These kinks—discrete zones of plastic deformation known to contain denatured collagen molecules—are accompanied by a progressive and eventual total loss of D‐banding along the surface of fibrils, indicating a loss of native molecular packing and further molecular denaturation. Thermal analysis of molecular stability showed that the destabilization of collagen molecules within fibrils is strongly related to the amount of strain energy dissipated by the tendon after yielding during tensile overload. These novel findings raise new questions about load transmission within tendons and their fibrils and about the interplay between crosslinking, strain‐energy dissipation ability, and molecular denaturation within these structures. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 731–737, 2013     

手术治疗钙化性冈上肌腱炎

<正>钙化性冈上肌腱炎,又被称为冈上肌腱钙化或石灰盐性冈上肌腱炎,是肩关节常见疾病。对于成形期的患者,可以有慢性疼痛,渐进性加重。2011年2月~2012年11月,笔者手术切除钙化灶5例,效果良好,报道如下。1材料与方法1.1病例资料本组5例,男1例,女4例。年龄42~56岁。均有反复发作的肩关节疼痛史,病程3~5年。患者均曾行按摩推拿热敷等治疗,其中3例封闭     

Strain distribution due to propagation of tears in the anterior supraspinatus tendon

Rotator cuff tears are a significant clinical problem. Tears in the anterior supraspinatus might behave differently compared to central tears due to differences in regional structural properties. The objective of this study was to determine strain distributions for anterior supraspinatus tendon tears and the relationship to tear propagation during cyclic loading. It was hypothesized that highest maximum principal strain would be posterior to the tear, and tears would propagate in the direction of the maximum principal strain. Eight human cadaveric supraspinatus tendons with surgically created small tears in the anterior third were tested with increasing levels of cyclic loads. The position of strain markers was recorded on the bursal surface of the tendon to calculate strain. Tendons reached a 2 cm critical tendon retraction at 580 ± 181 N. Largest strains were found medial and posterior to the tear (26.1 ± 9.4%). In five tendons, the strain direction for the initial (114 ± 28°) and final loading sets (86 ± 20°) indicated the strain direction shifted from an anterior to posterior orientation (p < 0.01), corresponding to the direction of tear propagation. Based on the results, anterior supraspinatus tears would remain isolated to the supraspinatus tendon during activities of daily living. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1283–1289, 2014.     

肩关节镜下清理治疗钙化性冈上肌腱炎的疗效分析

[目的]探讨肩关节镜下清理冈上肌腱内钙化灶治疗钙化性冈上肌腱炎的手术疗效。[方法]自2010年1月～2011年7月对在本院就诊的9例确诊为钙化性冈上肌腱炎的患者行肩关节镜下清理冈上肌腱内钙化灶治疗,术前患者肩关节疼痛剧烈伴活动受限,经正规保守治疗3个月以上无效。术中清理肩峰下间隙,切除炎性滑囊,常规行肩峰成形术,彻底清理冈上肌腱内的钙化灶。术前及术后随访均采用VAS疼痛评分、Constant-Murley评分和X线检查对患者进行评估并做手术前后的对比分析。[结果]术后平均随访6个月,所有患者肩关节疼痛及活动受限均得到明显改善或完全缓解,VAS疼痛评分术前(8.33±1.0)分,术后最后一次复查为(1.44±0.88)分,术前、术后VAS评分差异有统计学意义(P<0.01)。Constant-Murley评分术前为(50.44±10.06)分,术后最后一次复查为(93±4.21)分,术前、术后Constant-Murley评分差异有统计学意义(P<0.01)。术后复查X线片显示冈上肌腱内钙化灶均已完整清除。[结论]关节镜下行冈上肌腱内钙化灶清理,具有手术创伤小、病灶清除彻底、对肩袖及盂肱关节损伤小、术后康复快等优点,临床疗效确切。     

Collagen I membranes for tendon repair: Effect of collagen fiber orientation on cell behavior

Tendons have poor spontaneous regenerative capabilities, and complete regeneration is never achieved despite intensive remodeling. In this in vitro study, we characterized two multilamellar collagen I membranes differing in the arrangement of collagen fiber deposition (oriented vs. nonoriented) and compared their mechanical properties. Human dermal fibroblasts and tenocytes were seeded on the two membranes to evaluate the effect of fiber orientation on cell viability and cytoskeletal organization. Results demonstrate that the multilamellar collagen I membrane with oriented fibers has the better mechanical properties and affords optimum cell proliferation and adhesion. Its fiber arrangement provides an instructive pattern for cell growth and may serve to guide the alignment of cells migrating from the ends of a crushed or frayed tendon to obtain a strong, correctly structured tendon, thus providing a viable clinical option for tendon repair. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 826–832, 2009     

Effect of timing of surgical SSP tendon repair on muscle alterations

To investigate the impacts of delayed repairs of a supraspinatus tendon tear on the supraspinatus muscle, we used an animal model data from two previously published studies in which one supraspinatus (SSP) tendon was detached. In one cohort, the rabbits were killed in groups of 10 at 4, 8, and 12 weeks. In the other cohort, a repair was done at these time points, 12 rabbits each, and the animals killed were 12 weeks later. SSP fossa volume (Muscle belly plus extramuscular fat [e‐fat] volume), percentage of intramuscular fat (i‐fat), and muscle tissue volume (muscle belly volume minus i‐fat), as well as CT determination of e‐fat and i‐fat of both cohorts, were compared. Fossa volume increased (p < 0.05). Muscle belly and muscle tissue volumes did not increase after repair (p > 0.05), but early repair prevented further volume losses, a fact not seen after 8 and 12 weeks delay of repair. No reversal of e‐fat or of i‐fat occurred, in fact i‐fat almost doubled after 4 weeks delay of repair (p < 0.05). CT studies confirmed the fat results. We conclude that early repair prevented loss of muscle belly and muscle tissue volumes, but that it has no positive influence on fat accumulation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1430–1435, 2014.     

Collagen V haploinsufficiency in a murine model of classic Ehlers–Danlos syndrome is associated with deficient structural and mechanical healing in tendons

Classic Ehlers–Danlos syndrome (EDS) patients suffer from connective tissue hyperelasticity, joint instability, skin hyperextensibility, tissue fragility, and poor wound healing due to heterozygous mutations in COL5a1 or COL5a2 genes. This study investigated the roles of collagen V in establishing structure and function in uninjured patellar tendons as well as in the injury response using a Col5a1^+/− mouse, a model for classic EDS. These analyses were done comparing tendons from a classic EDS model (Col5a1^+/− ) with wild‐type controls. Tendons were subjected to mechanical testing, histological, and fibril analysis before injury as well as 3 and 6 weeks after injury. We found that Col5a1^+/− tendons demonstrated diminished recovery of mechanical competency after injury as compared to normal wild‐type tendons, which recovered their pre‐injury values by 6 weeks post injury. Additionally, the Col5a1^+/− tendons demonstrated altered fibril morphology and diameter distributions compared to the wild‐type tendons. This study indicates that collagen V plays an important role in regulating collagen fibrillogenesis and the associated recovery of mechanical integrity in tendons after injury. In addition, the dysregulation with decreased collagen V expression in EDS is associated with a diminished injury response. The results presented herein have the potential to direct future targeted therapeutics for classic EDS patients. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2707–2715, 2017.