The rotator cuff consists of several tendons and muscles that provide stability and force transmission in the shoulder joint. Whereas most rotator cuff tears are amenable to suture repair, the overall success rate of repair is low, and massive tears are prone to re-tear. Extracellular matrix (ECM) patches are used to augment suture repair, but they have limitations. Tissue-engineered approaches provide a promising solution for massive rotator cuff tears. Previous studies have shown that, compared to nonaligned scaffolds, aligned electrospun polymer scaffolds exhibit greater anisotropy and exert a greater tenogenic effect. Nevertheless, achieving rapid cell infiltration through the full thickness of the scaffold is challenging, and scaling to a translationally relevant size may be difficult. Our goal was to evaluate whether a novel method of alignment, combining a multilayered electrospinning technique with a hybrid of several electrospinning alignment techniques, would permit cell infiltration and collagen deposition through the thickness of poly(ε-caprolactone) scaffolds following seeding with human adipose-derived stem cells. Furthermore, we evaluated whether multilayered aligned scaffolds enhanced collagen alignment, tendon-related gene expression, and mechanical properties compared to multilayered nonaligned scaffolds. Both aligned and nonaligned multilayered scaffolds demonstrated cell infiltration and ECM deposition through the full thickness of the scaffold after only 28 days of culture. Aligned scaffolds displayed significantly increased expression of tenomodulin compared to nonaligned scaffolds and exhibited aligned collagen fibrils throughout the full thickness, the presence of which may account for the increased yield stress and Young’s modulus of cell-seeded aligned scaffolds along the axis of fiber alignment.
Full-thickness rotator cuff tears are one of the most common causes of shoulder pain in people over the age of 65. High retear rates and poor functional outcomes are common after surgical repair, and currently available extracellular matrix scaffold patches have limited abilities to enhance new tendon formation. In this regard, tissue-engineered scaffolds may provide a means to improve repair of rotator cuff tears. Electrospinning provides a versatile method for creating nanofibrous scaffolds with controlled architectures, but several challenges remain in its application to tissue engineering, such as cell infiltration through the full thickness of the scaffold as well as control of cell growth and differentiation. Previous studies have shown that ligament-derived extracellular matrix may enhance differentiation toward a tendon or ligament phenotype by human adipose stem cells (hASCs). In this study, we investigated the use of tendon-derived extracellular matrix (TDM)-coated electrospun multilayered scaffolds compared to fibronectin (FN) or phosphate-buffered saline (PBS) coating for use in rotator cuff tendon tissue engineering. Multilayered poly(ɛ-caprolactone) scaffolds were prepared by sequentially collecting electrospun layers onto the surface of a grounded saline solution into a single scaffold. Scaffolds were then coated with TDM, FN, or PBS and seeded with hASCs. Scaffolds were maintained without exogenous growth factors for 28 days in culture and evaluated for protein content (by immunofluorescence and biochemical assay), markers of tendon differentiation, and tensile mechanical properties. The collagen content was greatest by day 28 in TDM-scaffolds. Gene expression of type I collagen, decorin, and tenascin C increased over time, with no effect of scaffold coating. Sulfated glycosaminoglycan and dsDNA contents increased over time in culture, but there was no effect of scaffold coating. The Young's modulus did not change over time, but yield strain increased with time in culture. Histology demonstrated cell infiltration through the full thickness of all scaffolds and immunofluorescence demonstrated greater expression of type I, but not type III collagen through the full thickness of the scaffold in TDM-scaffolds compared to other treatment groups. Together, these data suggest that nonaligned multilayered electrospun scaffolds permit tenogenic differentiation by hASCs and that TDM may promote some aspects of this differentiation.
Background and Aims:There is a paucity of data on the safety of joint replacement surgery in patients with inflammatory bowel disease [IBD], including those on tumour necrosis factor-alpha inhibitors [anti-TNF]. We explored the risk of serious infections in this population. Methods: A retrospective case-control study [2006][2007][2008][2009][2010][2011][2012][2013][2014] was performed using the MarketScan Database. All patients aged 18-64 years with an International Classification of Diseases code for IBD and an IBD-specific medication, with ≥ 6 months of enrollment prior to hip, knee or shoulder replacement surgery, were included. Ten non-IBD controls were frequency-matched to each case on length of enrollment, year and the joint replaced. Primary outcome was serious infection [composite of joint infection, surgical site infection, pneumonia, sepsis] within 90 days of the operation. Cox proportional hazards models were used to assess the association of IBD and IBD medications with serious infection. Results: More patients with IBD [N = 1455] had serious infections than controls [3.2% vs 2.3%, p = 0.04], but not after controlling for comorbidities (hazard ratio [HR], 1.3; 95% confidence interval [CI], 0.95-1.76). Among IBD patients, corticosteroids were associated with increased risk of serious infection [HR, 4.6; 95% CI,; p < 0.01] while anti-TNFs were not. Opioids were also associated with increased risk of infection [HR, 1.5; 95% CI, 1.2-1.8; p < 0.01]. Conclusions: After controlling for comorbidities, IBD patients were not at increased risk of serious infection following joint replacement. Corticosteroids, but not anti-TNFs or immunomodulators, were associated with increased risk of serious infections in IBD patients.
A thorough physical examination of the shoulder and cervical spine is critical in establishing a focused differential diagnosis of the pathology in and around the shoulder joint. Numerous tests have been described in the literature to help improve the diagnostic accuracy of specific shoulder or cervical spine pathology. A comprehensive approach for the physical examination of the cervical spine, scapula, and rotator cuff is presented and descriptions on how the tests are performed and the evidence behind why specific tests are used in enabling improved diagnosis of shoulder pathology are discussed.
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