Bioprinted Nanoparticles for Tissue Engineering Applications

Tissue engineering may require precise patterning of cells and bioactive components to recreate the complex, 3D architecture of native tissue. However, it is difficult to image and track cells and bioactive factors once they are incorporated into the tissue engineered construct. These bioactive factors and cells may also need to be moved during tissue growth in vitro or after implantation in vivo to achieve the desired tissue properties, or they may need to be removed entirely prior to implantation for biosafety concerns.

Electromechanical Control of Atrium Function

The heart is a very efficient mechanical pump whose function is to controls the blood flow in the body. Two physical systems, namely mechanical for the pumping action and electrical for the control interact within the heart. Cardiac function can only be studied if both mechanical and electrical systems are considered. In particular, we are interested in the electromechanical control of the atrium pump function which is less studied then the electromechanical control of the ventricle pump function and none the less is a crucial factor in the development of atrial fibrillation.

Inter-Subject Variability in Ground Reaction Force - Walking Speed Relationship Is Related to Different Motion of the Center of Mass

Walking programs provide an attractive intervention to address the preservation of bone mass in the aging population. Research suggests one in three women and one in five men over 50 will experience fractures due to osteoporosis [1,2]. Bone is a mechanically modulated tissue and thus, training programs that prescribe physical activities that dynamically load the skeleton through either muscle contractions (strength training) or locomotion (walking/running) would be expected to have a positive influence on bone mineral density (BMD) preservation. However, attempts to implement activity programs in populations at risk for developing osteoporosis to accrue or simply preserve bone mass have had limited success [3] due to a variable response between subjects. It has been suggested that the failure of these programs to significantly influence bone mass or density may be due to individual differences in the loads generated by the prescribed exercise regimes and/or the knowledge of specific types, intensities and volumes needed for effective osteogenic exercise. Walking, a simple, common activity, presents an interesting opportunity to examine the potential for individual differences in the style of walking to explain the variability in individual results to training programs designed to preserve bone density.

Mechanical Anisotropy of Individual Osteons in Bone Tissue at High Spatial Resolutions

Secondary osteons, the fundamental units of cortical bone, consist of cylindrical lamellar composites composed of mineralized collagen fibrils. Due to its lamellar structure, a multiscale knowledge of the mechanical properties of cortical bone is required to understand the biomechanical function of the tissue. In this light, nanoindentation tests were performed along the axial and transverse directions following a radial path from the Haversian canal to the osteonal edges. Different length scales are explored by means of indentations at different maximum penetration depths. Indentation moduli and hardness data were then interpreted in the context of the known microstructure. Results suggest that secondary osteons hierarchical structure is responsible for an observed length scale effect, homogenization phenomena and anisotropy of mechanical properties.

Effect of Blood Viscosity on Thrombosis Potential Near a Step Wall Transition

Thrombosis and hemolysis are two problems encountered when processing blood in artificial organs. Physical factors of blood flow alone can influence the interaction of proteins and cells with the vessel wall, induce platelet aggregation and influence coagulation factors responsible for the formation of thrombus, even in the absence of chemical factors in the blood. These physical factors are related to the magnitude of the shear rate/stress, the duration of the applied force and the local geometry. Specifically, high blood shear rates (or stress) lead to damage (hemolysis, platelet activation), while low shear rates lead to stagnation and thrombosis [1].

A Dynamic Stochastic Model of Frequency-Dependent Stress Fiber Alignment Induced by Cyclic Stretch

Actin stress fibers (SFs) are bundles of actin filaments anchored at each end via focal adhesions. Myosin-generated contraction leads to the development of tension, which extends SFs beyond their unloaded lengths. In human aortic ECs, the level of SF extension is maintained at a set-point level of ∼1.10 (1). SFs are also dynamic structures and their continuous assembly and disassembly is critical to cellular functions involving changes in cell shape. Further, deformation of the extracellular matrix perturbs SF extension, leading to compensatory responses such as the gradual alignment of SFs perpendicular to the principal direction of cyclic stretch. The extent of cell alignment has been shown to depend on the pattern of matrix stretch; however, it is unclear how cells distinguish between different patterns of stretch to determine their unique responses.

Effects of CSF Properties on Brain Response Under Impact Loading

In the central nervous system, the subarachnoid space is the interval between the arachnoid membrane and the pia mater. It is filled with a clear, watery liquid called cerebrospinal fluid (CSF). The CSF buffers the brain against mechanical shocks and creates buoyancy to protect it from the forces of gravity. The relative motion of the brain due to a simultaneous loading is caused because the skull and brain have different densities and the CSF surrounds the brain. The impact experiments are usually carried out on cadavers with no CSF included because of the autolysis. Even in the cadaveric head impact experiments by Hardy et al. [1], where the specimens are repressurized using artificial CSF, this is not known how far this can replicate the real functionality of CSF. With such motivation, a special interest lies on how to model this feature in a finite element (FE) modeling of the human head because it is questionable if one uses in vivo CSF properties (i.e. bulk modulus of 2.19 GPa) to validate a FE human head against cadaveric experimental data.

Secondary Structures and Mechanical Properties of Biomimetic Protein Polymers

Silk may possess superior mechanical strength while its resilience is very poor. In contrast, elastin in human arteries is very soft but extremely durable with an estimated half-life of 70 years. By combing polypeptide sequences derived from native silk and elastin, we have produced a series of silk-elastin-like proteins (SELPs), which have displayed a set of outstanding properties such as good biocompatibility and controllable biodegradation rates [1]. In this study, we will examine the crystallization of the silk-like blocks and the crosslinking of the elastin-like blocks, as well as their influences on the mechanical behavior of SELPs. The ultimate goal of this study is to explore the potential of SELPs for applications in the engineering of load-bearing tissues such as arteries.

Development and Biocompatibility Characterization of a BioMEMS Sensor for Monitoring the Progression of Fracture Healing

Orthopaedic extremity injuries present a large medical and financial burden to the United States and world-wide communities [1]. Approximately six million long bone fractures are reported annually in the United States and approximately 10% of these fractures do not heal properly. Though the exact mechanism of impaired healing is poorly understood, many of these non-unions result when there is a communited condition that does not proceed through a stabilized healing pathway [2]. Currently, clinicians may monitor healing visually by radiographs, or via manual manipulation of the bone at the fracture [3]. Unfortunately, the course of aberrant fracture healing is not easily diagnosed in the early period when standard radiographic information of the fracture is not capable of discriminating the healing pathway. Manual assessment of fracture healing is also an inadequate diagnostic tool in the early stages of healing [4].

Osteogenesis Imperfecta: Molecular and Mesoscale Disease Mechanisms

Osteogenesis Imperfecta (OI) is a genetic disorder in collagen characterized by mechanically weakened tendon and fragile bones that affects more than 1 in 10,000 individuals. Even though many studies have attempted to associate specific mutation types with phenotypic severity, the mechanisms by which a single point mutation influences the mechanical behavior of tissues at multiple length-scales remain unknown. Here we show by a hierarchy of full atomistic and mesoscale simulation that OI mutations severely compromise the mechanical properties of collagenous tissues at multiple scales, from single molecules to collagen fibrils.