Pulsatile low shear stress increases susceptibility to endothelial inflammation via upregulation of IFT and activation of YAP.

This study describes the development of a microfluidic chip model of the coronary artery endothelium and its use to examine the mechanism through which pulsatile shear stress regulates inflammation. The chip successfully recapitulates increased susceptibility to cytokine mediated arterial inflammation as observed in areas of low shear stress (LSS). Previous data show that low shear stress in the porcine aorta modulates 36 cilia-associated genes of which five are also Yes-associated protein (YAP) target genes.

Engineering growth factor gradients to drive spatiotemporal tissue patterning in organ-on-a-chip systems.

Spatial heterogeneity plays a key role in the development and function of human tissues and therefore needs to be incorporated within in vitro models to maximise physiological relevance and predictive power. Here, we developed and optimised methods to generate spatial heterogeneity of hydrogel-embedded bioactive signalling molecules within organ-on-a-chip (OOAC) systems, to drive spatiotemporal tissue patterning through controlled stem cell differentiation. As an exemplar application, we spatially patterned bone morphogenetic protein-2 (BMP-2) in both closed-channel and open-chamber OOAC formats.

Human vascularised synovium-on-a-chip: a mechanically stimulated, microfluidic model to investigate synovial inflammation and monocyte recruitment.

Healthy synovium is critical for joint homeostasis. Synovial inflammation (synovitis) is implicated in the onset, progression and symptomatic presentation of arthritic joint diseases such as rheumatoid arthritis and osteoarthritis. Thus, the synovium is a promising target for the development of novel, disease-modifying therapeutics.

Guidelines for ex vivo mechanical testing of tendon.

Tendons are critical for the biomechanical function of joints. Tendons connect muscles to bones and allow for the transmission of muscle forces to facilitate joint motion. Therefore, characterizing the tensile mechanical properties of tendons is important for the assessment of functional tendon health and efficacy of treatments for acute and chronic injuries.

The Interfascicular Matrix of Energy Storing Tendons Houses Heterogenous Cell Populations Disproportionately Affected by Aging.

Energy storing tendons such as the human Achilles and equine superficial digital flexor tendon (SDFT) are prone to injury, with incidence increasing with aging, peaking in the 5 decade of life in the human Achilles tendon. The interfascicular matrix (IFM), which binds tendon fascicles, plays a key role in energy storing tendon mechanics, and aging alterations to the IFM negatively impact tendon function. While the mechanical role of the IFM in tendon function is well-established, the biological role of IFM-resident cell populations remains to be elucidated.

Mild hypercholesterolemia impacts achilles sub-tendon mechanical properties in young rats.

Background: Hypercholesterolemia is associated with tendon pathology, but the reasons underpinning this relationship are not well understood. Cholesterol can accumulate in the tendon non-collagenous matrix which may affect both global and local tissue mechanics. Changes to the local strain environment within tendon may have significant implications for mechanosensitive tenocytes.

Development and application of a novel in vivo overload model of the Achilles tendon in rat.

Repetitive overload is a primary factor in tendon injury, causing progressive accumulation of matrix damage concurrent with a cellular response. However, it remains unclear how these events occur at the initial stages of the disease, making it difficult to identify appropriate treatment approaches. Here, we describe the development of a new model to cyclically load the Achilles tendon (AT) of rats in vivo and investigate the initial structural and cellular responses.

The impact of mild hypercholesterolemia on injury repair in the rat patellar tendon.

Hypercholesterolemia is associated with tendon pathology and injury prevalence. Lipids can accumulate in the tendon's extracellular spaces, which may disrupt its hierarchical structure and the tenocytes physicochemical environment. We hypothesized that the tendon's ability to repair after injury would be attenuated with elevated cholesterol levels, leading to inferior mechanical properties.

Organ-on-a-Chip and Microfluidic Platforms for Oncology in the UK.

Organ-on-chip systems are capable of replicating complex tissue structures and physiological phenomena. The fine control of biochemical and biomechanical cues within these microphysiological systems provides opportunities for cancer researchers to build complex models of the tumour microenvironment. Interest in applying organ chips to investigate mechanisms such as metastatsis and to test therapeutics has grown rapidly, and this review draws together the published research using these microfluidic platforms to study cancer.

Structure-function specialisation of the interfascicular matrix in the human achilles tendon.

Tendon consists of highly aligned collagen-rich fascicles surrounded by interfascicular matrix (IFM). Some tendons act as energy stores to improve locomotion efficiency, but such tendons commonly obtain debilitating injuries. In equine tendons, energy storing is achieved primarily through specialisation of the IFM.

A Recruitment Model of Tendon Viscoelasticity That Incorporates Fibril Creep and Explains Strain-Dependent Relaxation.

Soft tissues exhibit complex viscoelastic behavior, including strain-rate dependence, hysteresis, and strain-dependent relaxation. In this paper, a model for soft tissue viscoelasticity is developed that captures all of these features and is based upon collagen recruitment, whereby fibrils contribute to tissue stiffness only when taut. We build upon existing recruitment models by additionally accounting for fibril creep and by explicitly modeling the contribution of the matrix to the overall tissue viscoelasticity.

Elastase treatment of tendon specifically impacts the mechanical properties of the interfascicular matrix.

The tendon interfascicular matrix (IFM) binds tendon fascicles together. As a result of its low stiffness behaviour under small loads, it enables non-uniform loading and increased overall extensibility of tendon by facilitating fascicle sliding. This function is particularly important in energy storing tendons, with previous studies demonstrating enhanced extensibility, recovery and fatigue resistance in the IFM of energy storing compared to positional tendons.

Force Transmission Between the Gastrocnemius and Soleus Sub-Tendons of the Achilles Tendon in Rat.

The Achilles tendon (AT) is comprised of three distinct sub-tendons bound together by the inter-subtendon matrix (ISTM). The interactions between sub-tendons will have important implications for AT function. The aim of this study was to investigate the extent to which the ISTM facilitates relative sliding between sub-tendons, and serves as a pathway for force transmission between the gastrocnemius (GAS) and soleus (SOL) sub-tendons of the rat AT.

An in vitro investigation into the effects of 10 Hz cyclic loading on tenocyte metabolism.

Tendinopathy is a prevalent, highly debilitating condition, with poorly defined etiology. A wide range of clinical treatments has been proposed, with systematic reviews largely supporting shock wave therapy or eccentric exercise. Characterizing these treatments have demonstrated both generate perturbations within tendon at a frequency of approximately 8-12 Hz.

Insights into the micromechanics of stress-relaxation and creep behaviours in the aortic valve.

Viscoelastic attributes of the aortic valve (AV) tissue are, in part, reflected in stress-relaxation and creep behaviours observed in vitro. While the extent of AV time-dependent behaviour under physiological conditions is not yet fully understood, in vitro the tissue exhibits clear stress-relaxation but minimal creep under equi-biaxial loading, in contrast to uniaxial loading where creep is evidently exhibited. Tissue-level stress-relaxation behaviour follows the form of (single and double) Maxwell-type exponential decay relaxation modes, and creep occurs in the form of exponential primary followed by linear secondary creep modes.

Guided Cell Attachment via Aligned Electrospinning of Glycopolymers.

The creation of biomaterials with aligned fibers offers broad applications in tissue regeneration, guiding cell organization and physiological cues, and providing appropriate mechanical properties for many biomedical applications. Herein, for the first time, highly aligned electrospun membranes are designed and developed using glycopolymers. The membranes retain the strong mechanical properties of polycaprolactone, and fiber alignment facilitates the creation of anisotropic mechanical properties, enabling failure stress to be manipulated by an order of magnitude relative to randomly ordered fibers.

Mechanical loading induces primary cilia disassembly in tendon cells via TGFβ and HDAC6.

This study used isolated human tenocytes to test the hypothesis that cyclic mechanical strain directly stimulates primary cilia disassembly, and to elucidate the mechanisms involved. Cells were seeded onto flexible membranes and strained at 0-3%; 1 Hz, for up to 24 hours. Cilia length and prevalence progressively reduced with increasing strain duration but showed full recovery within 2 hours of strain removal.

Effects of cell adhesion motif, fiber stiffness, and cyclic strain on tenocyte gene expression in a tendon mimetic fiber composite hydrogel.

We recently developed a fiber composite consisting of tenocytes seeded onto discontinuous fibers embedded within a hydrogel, designed to mimic physiological tendon micromechanics of tension and shear. This study examined if cell adhesion peptide (DGEA or YRGDS), fiber modulus (50 or 1300 kPa) and/or cyclic strain (5% strain, 1 Hz) influenced bovine tenocyte gene expression. Ten genes were analyzed and none were sensitive to peptide or fiber modulus in the absence of cyclic tensile strain.

Structure and collagen crimp patterns of functionally distinct equine tendons, revealed by quantitative polarised light microscopy (qPLM).

Unlabelled: Structure-function relationships in tendons are directly influenced by the arrangement of collagen fibres. However, the details of such arrangements in functionally distinct tendons remain obscure. This study demonstrates the use of quantitative polarised light microscopy (qPLM) to identify structural differences in two major tendon compartments at the mesoscale: fascicles and interfascicular matrix (IFM).

Elastin is Localised to the Interfascicular Matrix of Energy Storing Tendons and Becomes Increasingly Disorganised With Ageing.

Tendon is composed of fascicles bound together by the interfascicular matrix (IFM). Energy storing tendons are more elastic and extensible than positional tendons; behaviour provided by specialisation of the IFM to enable repeated interfascicular sliding and recoil. With ageing, the IFM becomes stiffer and less fatigue resistant, potentially explaining why older tendons become more injury-prone.

The relative compliance of energy-storing tendons may be due to the helical fibril arrangement of their fascicles.

A nonlinear elastic microstructural model is used to investigate the relationship between structure and function in energy-storing and positional tendons. The model is used to fit mechanical tension test data from the equine common digital extensor tendon (CDET) and superficial digital flexor tendon (SDFT), which are used as archetypes of positional and energy-storing tendons, respectively. The fibril crimp and fascicle helix angles of the two tendon types are used as fitting parameters in the mathematical model to predict their values.

AB-Miktoarm Glycopolymer Fibers and Their Interactions with Tenocytes.

Electrospun biodegradable membranes have attracted great attention for a range of tissue engineering applications. Among them, poly(ε-caprolactone) (PCL) is one of the most widely used polymers, owing to its well-controlled biocompatibility and biodegradability. However, PCL also has a number of limitations, such as its hydrophobic nature and the lack of functional groups on its side chain, limiting its ability to interact with cells.

Fascicles and the interfascicular matrix show decreased fatigue life with ageing in energy storing tendons.

Unlabelled: Tendon is composed of rope-like fascicles bound together by interfascicular matrix (IFM). The IFM is critical for the function of energy storing tendons, facilitating sliding between fascicles to allow these tendons to cyclically stretch and recoil. This capacity is required to a lesser degree in positional tendons.

A transverse isotropic viscoelastic constitutive model for aortic valve tissue.

A new anisotropic viscoelastic model is developed for application to the aortic valve (AV). The directional dependency in the mechanical properties of the valve, arising from the predominantly circumferential alignment of collagen fibres, is accounted for in the form of transverse isotropy. The rate dependency of the valve's mechanical behaviour is considered to stem from the viscous () dissipative effects of the AV matrix, and is incorporated as an explicit function of the deformation rate ([Formula: see text]).