Tendon injury and repair - A perspective on the basic mechanisms of tendon disease and future clinical therapy

Tendon is an intricately organized connective tissue that efficiently transfers muscle force to the bony skeleton. Its structure, function, and physiology reflect the extreme, repetitive mechanical stresses that tendon tissues bear. These mechanical demands also lie beneath high clinical rates of tendon disorders, and present daunting challenges for clinical treatment of these ailments. This article aims to provide perspective on the most urgent frontiers of tendon research and therapeutic development. We start by broadly introducing essential elements of current understanding about tendon structure, function, physiology, damage, and repair. We then introduce and describe a novel paradigm explaining tendon disease progression from initial accumulation of damage in the tendon core to eventual vascular recruitment from the surrounding synovial tissues. We conclude with a perspective on the important role that biomaterials will play in translating research discoveries to the patient.STATEMENT OF SIGNIFICANE: Tendon and ligament problems represent the most frequent musculoskeletal complaints for which patients seek medical attention. Current therapeutic options for addressing tendon disorders are often ineffective, and the need for improved understanding of tendon physiology is urgent. This perspective article summarizes essential elements of our current knowledge on tendon structure, function, physiology, damage, and repair. It also describes a novel framework to understand tendon physiology and pathophysiology that may be useful in pushing the field forward.</p

Evidence against proteoglycan mediated collagen fibril load transmission and dynamic viscoelasticity in tendon

The glycosaminoglycan (GAG) dermatan sulfate and chondroitin sulfate side-chains of small leucine-rich proteoglycans have been increasingly posited to act as molecular cross links between adjacent collagen fibrils and to directly contribute to tendon elasticity. GAGs have also been implicated in tendon viscoelasticity, supposedly affecting frictional loss during elongation or fluid flow through the extra cellular matrix. The current study sought to systematically test these theories of tendon structure-function by investigating the mechanical repercussions of enzymatic depletion of GAG complexes by chondroitinase ABC in a reproducible tendon structure-function model (rat tail tendon fascicles). The extent of GAG removal (at least 93%) was verified by relevant spectrophotometric assays and transmission electron microscopy. Dynamic viscoelastic tensile tests on GAG depleted rat tail tendon fascicle were not mechanically different from controls in storage modulus (elastic behavior) over a wide range of strain-rates (0.05, 0.5, and 5% change in length per second) in either the linear or nonlinear regions of the material curve. Loss modulus (viscoelastic behavior) was only affected in the nonlinear region at the highest strain-rate, and even this effect was marginal (19% increased loss modulus, p=0.035). Thus glycosaminoglycan chains of small leucine-rich proteoglycans do not appear to mediate dynamic elastic behavior nor do they appear to regulate the dynamic viscoelastic properties in rat tail tendon fascicles

Linking Meaning to Language: Linguistic Universals and Variation

To use natural language, speakers must map the participants in events or states in the world onto grammatical roles. There remains considerable disagreement about the nature of these so-called linking rules (Levin & Rappaport Hovav, 2005). In order to probe the nature of linking rules, we investigate verbs of psychological state, which demonstrate complex linking patterns both within and between languages. We find that the typical duration of the psychological state guides the application of linking rules to novel verbs in both English and Japanese, consistent with a universal constraint. Nonetheless, there are marked differences in the baseline preferences for the individual linking rules across the two languages. We discuss these findings both in terms of theories of exceptionless linking rules and accounts on which linking rules are governed by probabilistic biases as well as cross-linguistic variation.Psycholog

Psych verbs, the linking problem, and the acquisition of language

In acquiring language, children must learn to appropriately place the different participants of an event (e.g., causal agent, affected entity) into the correct syntactic positions (e.g., subject, object) so that listeners will know who did what to whom. While many of these mappings can be characterized by broad generalizations, both within and across languages (e.g., semantic agents tend to be mapped onto syntactic subjects), not all verbs fit neatly into these generalizations. One particularly striking example is verbs of psychological state: The experiencer of the state can appear as either the subject (Agnes fears/hates/loves Bartholomew) or the direct object (Agnes frightens/angers/delights Bartholomew). The present studies explore whether this apparent variability in subject/object mapping may actually result from differences in these verbs’ underlying meanings. Specifically, we suggest that verbs like fear describe a habitual attitude towards some entity whereas verbs like frighten describe an externally caused emotional episode. We find that this distinction systematically characterizes verbs in English, Mandarin, and Korean. This pattern is generalized to novel verbs by adults in English, Japanese, and Russian, and even by English-speaking children who are just beginning to acquire psych verbs. This results support a broad role for systematic mappings between semantics and syntax in language acquisition

Viscous effects in aircraft trailing vortices

The mechanism of merging of like-signed aircraft vortices leading to a rapid redistribution of trailed vorticity in a wake through both convective and turbulent processes was investigated. Research was done experimentally in a small wind tunnel and analytically through the use of a code which computes turbulent transport using a second-order closure turbulent model. Computations are reported which demonstrate the merging phenomenon, and comparisons are made with experimental results. The usefulness of point vortex computations in predicting merging was explored. Limited computations showed that jet exhaust does not appreciably alter the merging phenomenon. The effect of ambient atmospheric turbulence on the aging of an aircraft wake was investigated at a constant turbulent dissipation rate. It was shown that under stable atmospheric conditions, when atmospheric macroscales are less than or equal to the vortex spacing, misleading results may be obtained

Do Interactions Between Gut Ecology and Environmental Chemicals Contribute to Obesity and Diabetes?

Background: Gut microbiota are important factors in obesity and diabetes, yet little is known about their role in the toxicodynamics of environmental chemicals, including those recently found to be obesogenic and diabetogenic

Optimization of loading protocols for tissue engineering experiments

Tissue engineering (TE) combines cells and biomaterials to treat orthopedic pathologies. Maturation of de novo tissue is highly dependent on local mechanical environments. Mechanical stimulation influences stem cell differentiation, however, the role of various mechanical loads remains unclear. While bioreactors simplify the complexity of the human body, the potential combination of mechanical loads that can be applied make it difficult to assess how different factors interact. Human bone marrow-derived mesenchymal stromal cells were seeded within a fibrin-polyurethane scaffold and exposed to joint-mimicking motion. We applied a full factorial design of experiment to investigate the effect that the interaction between different mechanical loading parameters has on biological markers. Additionally, we employed planned contrasts to analyze differences between loading protocols and a linear mixed model with donor as random effect. Our approach enables screening of multiple mechanical loading combinations and identification of significant interactions that could not have been studied using classical mechanobiology studies. This is useful to screen the effect of various loading protocols and could also be used for TE experiments with small sample sizes and further combinatorial medication studies

Pedicle screw augmentation with bone cement enforced Vicryl mesh

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte, 201