Creation of replacement tissue to repair articular surface defects remains a challenge. Normal zonal characteristics of articular cartilage throughout its thickness, particularly the superficial tangential zone (STZ), and normal material properties have not been reproduced in vitro in scaffolds nor in vivo in repairing defects. Without sufficient quality, such transplanted scaffolds in vivo may be doomed mechanically from the outset. Removal of the STZ from normal cartilage negatively affects the remaining cartilage’s ability to support axial loads and retain fluids [1–3]. Previous studies have modeled excessive axial deformation of repair cartilage [4–5]. Studies have shown that modeling the STZ of normal cartilage as transversely isotropic provides better agreement with indentation experimental results than isotropic models [6–9]. Others have modeled experimental conditions by incorporating tension and compression nonlinearity [10]. Previous analyses have indicated that strain-dependent permeability within the STZ can positively affect the ability of free-draining normal and repair models to withstand imposed surface loads [11,12]. This finite element study further examined the role of an STZ with strain-dependent permeability on the behavior of normal and repaired articular surfaces under contact loading from rigid permeable and impermeable spheres. Nonlinear geometry permitted finite deformations to occur while the differential stiffness in tension and compression was also represented.

The Eustachian Tube (ET) is a collapsible tube that connects the Middle Ear (ME) to the nasopharynx (NP). The ET is responsible for three primary functions: 1) regulation of ME pressure 2) protection of the ME from foreign pathogens and 3) drainage of fluid from the ME. [1] In healthy patients, the ET opens during swallowing because the surrounding tissue is deformed by muscle activity. If the ET fails to open, the ME develops painful sub-ambient pressure and fluid accumulates in the ME. ET dysfunction results in Otitis Media (OM), the most common ME disorder in children. The overall goal of our lab is to identify the mechanisms responsible for ET dysfunction and to develop novel treatments for OM that target the ET.

Surface tension on an air-liquid interface induces liquid flows, which may cause the lung’s airways to close due to the formation of a liquid plug as a result of drainage of the liquid lining coating the airways. Formation of the plug occurs more frequently when lung-surfactant availability is reduced. [1] Mechanical stresses due to fluid motion cause pulmonary epithelial cells to be damaged. [2, 3] Our previous studies for plug propagation in a rigid wall channel show that mechanical stresses are significantly large in the front transition region of the plug compared to the rear transition region. [7, 8] Pulmonary airways are flexible tubes which are surrounded by elastic parenchyma. In this study, the steady propagation of a liquid plug in a flexible tube is investigated numerically and mechanical stresses acting on the epithelial cells are estimated.

End-stage renal disease (ESRD) occurs as a result of any renal injury that chronically decreases renal excretory and regulatory function. ESRD patients are most commonly treated with hemodialysis (HD) to manage their renal failure while awaiting kidney transplant. Current practices for maintenance of HD vascular access consist of arteriovenous fistulas (AVFs) or grafts (AVGs), which are both fraught with problems that compromise the patency and use of these surgically created shunts. The major cause of shunt failure is thrombosis caused by occlusion of the outflow venous anastomosis and draining vein. Intimal hyperplasia (IH), which consists of the thickening of the innermost layer of the vessel wall, is the initial pathological event leading to shunt stenosis/thrombosis and has been associated with the presence of flow disturbances and abnormal wall shear stress (WSS) at the graft-vein anastomosis. Therefore, the improvement of HD via the enhancement of vascular access patency requires the development of a novel vascular access technology preserving the normal hemodynamics of the native vein.

Immunotherapy-based approaches for cancer treatment are of increasing clinical interest. Principles of drug delivery and the emerging field of material design for immunomodulation might hold significant promise for novel approaches in cancer immunotherapy since biomaterials engineering strategies enable enhanced delivery of immune modulatory agents to tissues and cells of the immune system 1 . One tissue of significant clinical interest in a cancer setting is the tumor-draining lymph node (TDLN), which participates in cancer progression by enabling both metastatic dissemination as well as tumor-induced immune escape. Hence, the TDLN represents a novel target for drug delivery schemes for cancer immunotherapy. We hypothesize that targeted delivery of adjuvants (Adjs) to the TDLN using a biomaterials-based approach might promote antitumor immunity and hinder tumor growth.

Changes in tissue mechanical properties are often the first indication of malignant disease, with the detection of a stiff lump by a patient. These changes include growth-induced solid stresses, increased matrix stiffness, high fluid pressure, and increased interstitial flow, which in turn enhance fluid flux away from the tumor to downstream lymph nodes (LNs). But in addition to changing the way a tumor feels to a patient, altered tumor tissue mechanics promote cancer cell invasion into lymphatic vessels, allowing their metastatic dissemination to draining LNs. LN swelling and stiffening is another common indicator of tumor growth, and the presence of metastatic cells in the sentinel LN, or tumor draining lymph node (TDLN), is used clinically to stage disease. Recent studies indicate the LN microenvironment determines whether metastatic cancers can spread to the sentinel LNs. Yet despite the known correlation of LN swelling and stiffening with tumorigenesis and the role of the LN microenvironment in metastasis, our understanding of how changes in LN mechanical properties relate to tumor progression, anti-tumor immune response and metastatic colonization of the LN is limited. This lack of a quantitative understanding limits functional analyses of the role of LN mechanics in determining cancer cell colonization of the TDLN, their influence on immune suppression taking place within the TDLN, as well as the development of strategies to mitigate these effects.

As solid tumors develop, a variety of physical stresses arise including growth induced compressive force, matrix stiffening due to desmoplasia, and increased interstitial fluid pressure and altered flow patterns due to leaky vasculature and poor lymphatic drainage [1]. These microenvironmental stresses likely contribute to the abnormal cell behavior that drives tumor progression, and have become an increasingly significant area of cancer research. Of particular importance, is the role of flow shear stress on tumor-endothelial signaling, vascular function, and angiogenesis. Compared to normal vasculature, blood vessels in tumors are poorly functional due to dysregulated expression of angiogenic growth factors, such as vascular endothelial growth factor (VEGF) or the angiopoietins. Also, because of the abnormal vessel structure, blood velocities can be an order of magnitude lower than that of normal microvessels. Recently published work utilizing intravital microscopy to measure blood velocities in mouse mammary fat pad tumors, demonstrated for the first time that shear rate gradients in tumors may help guide branching and growth of new vessels [2]. However, much still remains unknown about how shear stress regulates endothelial organization, permeability, or expression of growth factors within the context of the tumor microenvironment.

Prolonged mechanical loading of soft tissues, as present when individuals are bedridden or wheelchair-bound, can lead to degeneration of skeletal muscle tissue. This can result in a condition termed pressure-related deep tissue injury (DTI), a severe kind of pressure ulcer that initiates in deep tissue layers, e.g. skeletal muscle, near bony prominences and progresses towards the skin. Complications associated with DTI include sepsis, renal failure, and myocardial infarction. Damage pathways leading to DTI involve ischemia, ischemia-reperfusion injury, impaired lymphatic drainage, and sustained tissue deformation. Recently, the role of tissue deformation in the onset of skeletal muscle damage was established by combining animal experiments with finite element (FE) modeling [1]. After 2 hours of continuous loading, a clear correlation between maximum shear strain and damage was found.

Sustained mechanical loading of soft tissues covering bony prominences, as experienced by bedridden and wheelchair-bound individuals, may cause skeletal muscle damage. This can result in a condition termed pressure-related deep tissue injury (DTI), a severe kind of pressure ulcer that initiates in deep tissue layers, and progresses towards the skin. Damage pathways leading to DTI can involve ischemia, ischemia/reperfusion injury, impaired lymphatic drainage, and sustained tissue deformation. Recently, we have provided evidence that in a controlled animal model, deformation is the main trigger for damage within a 2h loading period [1,2]. However, ischemia and reperfusion may play a more important role in the damage process during prolonged loading periods.

Contact problems are fundamental to the study of biological tissues, especially in the area of diarthrodial joint biomechanics. Finite element formulations and implementations of the contact mechanics of porous media remain challenging, and only a limited number of studies have proposed solution schemes for these types of problems [1–3]. Unfortunately, finite element codes using these formulations are not generally available to the public. A commonly used commercial finite element implementation of porous media contact is provided by Abaqus FEA (www.simulia.com), which has been used for studying articular contact mechanics [4–6]. This implementation is also able to analyze large sliding and finite deformations. The Abaqus implementation allows the application of a ‘drainage-only-flow’ boundary condition that is inconsistent with conservation of mass across the contact interface. Furthermore, it does not automatically enforce free-draining conditions outside of the contact region while enforcing continuity of the contact traction and fluid flux across the contact interface.