1. Osteoporosis
1.1 Development of Optimizing Treatment in Osteoporotic Bone
The specific aim of this study is to establish a series of animal models with different bone properties and to establish correlations between the structural (from CT scans), mechanical (from biomechanical testing) and biological markers (tissue and serum analysis).

The purpose of investigating these relationships between the properties is to find an improved tool for predicting the risk of fractures in diseased and degenerative bone. By administering the OVX rat model with either PTH, bisphosphonates or a combination of PTH and bisphosphonates, we hope to establish a series of different bone properties, and be able to establish a correlation between the structural, mechanical and biological properties of the bones. The relationships determined from the correlation studies will allow us to establish an improved index for predicting failure loads using CT-based structural analysis.

The study will also allow us to test the hypothesis that the concurrent administration of the two agents (with different dosage combinations) would alter the biomechanical properties and morphological indices more than the use of either one alone. This will provide new data towards optimizing the treatment used, as one application of this proposed clinical tool.

Research Question: As parathyroid hormone (PTH) increases both bone formation and bone resorption and bisphosphonates are known to inhibit osteoclast-mediated bone resorption and reduce bone turn over, we ask if treatment with a combination of PTH with an anti-resorptive bisphosphonate agent (Ibandronate, IBAN) would result in better bone mass and strength in ovariectomized rats.

1.2 New predicting criteria of elderly bone fracture: Instability
The objective of this project is to use a deformable, realistic 3-D model of the proximal femur to show that the normal aging process can cause it to become structurally unstable so that fractures are more likely to occur around femoral neck.

In this study, Finite Strip Method is employed to access the critical local buckling load of the narrowest site of femoral neck while Mimics and ImageJ are used to process the original CT images of human cadaver femurs. In order to make the results more realistic, the variation of bone mineral density (BMD) is incorporated in the instability analysis by modifying the bone elastic modulus and yield strength for different age simulated samples.

According to our preliminary study, when the bone ages, the maximum single-legged stance strength is almost unchanged while it can lose stability in non-physiological loading scenarios, for instance, fall on the greater trochanter. Voronoi tessellation will be used to incorporate trabecular bone into the femoral neck models in future, as the current models take only the cortical part into account. Employing the Voronoi tessellation (Fig. 1) for the spatial geometry of the trabecular bone affords significant advantages when considering the uncertain nature of the actual trabecular geometry, due to insufficient image resolution. In order to realistically model the impact of trabecular bone on the overall bone instability, we perform the Voronoi tessellation using nucleation points at uniform spacing such that the trabecular bone volume fraction is same for the FSM model as that of the CT scan image representing a femoral neck cross section. 

1.3 New Standard of defining Bone Quality: Viscoelasticity
The current screening modalities that are commonly used to diagnose and evaluate osteoporosis (OP) in the human (e.g., DXA, QCT, QUA) measure the mineral density and/or porosity of the structure. These tests are currently neither sensitive nor specific for fracture risk assessment on an individual basis before quite large changes are evident [ref]. Changes in viscoelastic properties that are unaccompanied by changes in mineral density or microarchitecture could potentially lead to either an increase or a decrease in the risk of fracture that would be unrelated to the findings of these clinical tests. Accounting for time-dependent bone material properties in screening protocols could improve these protocols’ predictive value.

2. Biomedical Mechanics
2.1 The effect of cancer induced bone remodelling in Osteolysis
The objective of this project is to evaluate the effect of cancer-induced osteolysis on bone structural and mechanical properties and the relative efficacy of bisphosphonate and chemotherapeutic drug treatments on osteolysis.

By using an immunocompetent animal model of breast cancer-induced osteolysis and administering different treatments, we establish a series of animal models with differing bone properties which would be evaluated using techniques of MicroCT (Fig. 2) and mechanical testing.

As tumor growth progresses (represented by tumor volume and biochemical assays of tumor-induced osteolysis), it is expected that both measured and predicted structural properties as well as mechanical properties of the affected bone will be reduced. Structural properties (axial, bending, and torsional rigidities) will be measured non-invasively on sequential transaxial micro-computed tomography (µCT). Stiffness and hardness of the affected bone tissue will be assessed using mechanical testing.

Research Question:  (1) Whether there will be a synergistic effect and thus, greater efficacy using bisphosphonates and chemotherapeutic drugs together as opposed to using either drug alone.

Figure 2: MicroCT Scanner

2.2 Prediction of pathologic bone fracture in human femur using QCT structural rigidity analysis
The objective of this project is to provide a better guideline for predicting pathological fracture in human femur than current clinical and radiographic criteria by using the structural rigidity of bone which altered by skeletal metastases.

Any method that predicts fracture risk must be able to measure both changes in bone material and changes in bone structural geometry. We will non-invasively measure that bone structural rigidity, i.e. the product of elastic modulus (determined from bone density) and cross-sectional geometry using QCT to predict bone fracture with skeletal metastases.
This project aims to use QCT in conjunction with engineering beam theory to monitor fracture risk associated with skeletal metastases. The hypothesis is that bone structural rigidity measured by QCT is more specific than and is as sensitive as current clinical guidelines for predicting pathologic fracture in cancer patients with metastasis to the skeleton.

2.3 Bone Mechanics using RUS
The objectives of this project are to:

RUS is a recent technique which involves scanning the resonance structure of a compact specimen such as cube, parallelepiped, or short cylinder. With the proper configuration and specimen material, a single measurement yields enough frequencies to determine all of the elastic constants for the material (as many as 21 for a crystal with low symmetry). RUS is also capable of determining viscoelastic properties (mechanical damping, tan ) of materials. The purpose of this study is to evaluate the spatial distribution of bone elastic and viscoelastic properties. It is hypothesized, based on an interpretation of bone remodelling, that the elastic moduli would be greatest in the mid-shaft of the bone where tan d would be smallest.

3. Biomedical Materials
Development of High-Damping, High-Stiffness Composite Materials
Submarine Propeller
For military application, noise reduction on the submarine propeller is an important matter as water is a good sound transmitter. Propeller noise itself can be categorized into cavitation noise, flow noise, and noise due to blade vibration. Due to water pressure on the large depths, cavitation noise in submarines is usually suppressed. While travelling at low speeds help to reduce the flow noise generated, propeller blade vibration will initiate hull vibration and finally it will be broadcasted into the seawater. Thus, high mechanical damping material is required to dissipate the propeller vibration within the material itself.

Besides, high stiffness material is also desired for propeller application. However, materials with high stiffness usually come with low damping properties and vice versa. In the stiffness-loss map (Fig. 3), most materials occupy the region on to the left of the diagonal line. The diagonal line represents the largest product (0.6GPa) of stiffness (E) and linear damping (tan δ) found in common materials. The objective of the study is to develop a high stiffness and high damping material for submarine propeller application that is located on the right of the line on the stiffness loss map.

Figure 3: Stiffness loss map

Shoe shole
The objective of the on-going research is to develop the next generation combat shoe with an optimum, anisotropic shoe sole which can reduce the fatigue of general infantry. Skin trauma in plantar foot surface often occurs due to the repetitive loading, i.e. combination of peak load magnitude and number of loading cycles. However, recent studies have shown that fatigue induced by plantar shear stress results in acute trauma and pain of the foot. This fatigue on foot would be even more severe in military actions which usually require heavy activities of lower limb. Thus the proposed research aims the improvement of fighting strength of infantry by minimizing acute trauma as well as reducing the foot plantar fatigue.

The specific aims of the project are as follows:
1.  Understanding the mechanism of plantar shear fatigue (PSF) induced skin lesions in foot by gait analysis with pressure-shear sensors.
2. Development of an optimum shoe sole which enables to reduce the shear fatigue during foot-ground interaction using finite element analysis (FEA).

4. Fast Evaluation of Elastic Properties of Human Iliac Crest Trabeculae using The Reduced-Basis Methods

Computationally expensive Finite element (FE) methods are generally used for indirect evaluation of tissue mechanical properties of trabecular specimens, which is vital for fracture risk prediction in elderly. Our work proposes reduced basis (RB) methods for rapid evaluation of material properties. We intend to explore the accuracy of reduced basis methods, which enable us to solve parameter-based inverse problem in order to rapidly predict the elastic properties of the trabecular samples.

Three cylindrical trans-iliac crest specimens (diameter: 5mm, length: 10~12mm) were obtained from healthy subjects (20, 22 and 24 year-old females) and scanned for micro-CT images. Cubic samples of dimensions 1.5x1.5 x1.5 mm3 were extracted from the core of the cylindrical specimens for FE analysis. Subsequently, a FE solution library (test space) was constructed for each of the specimens by varying the material property parameters: tissue elastic modulus and Poisson’s ratio, to develop RB algorithms. Speed gains greater than 2000 were obtained for all three specimens for a loss in accuracy of less than 1% in the maxima of von-Mises stress, with respect to the FE-based value. The computational times decreased from more than 1 hour to less than 3 seconds.

This study will allow us to apply reduced basis methods to develop a fast tool to indirectly evaluate the elastic properties of trabecular bones.

Research Question: In future, we plan to ask if the results from reduced basis methods correlate well with respect to the traditional finite element analysis for samples that are more anisotropic.

Figure 4: Visualization of boundary conditions in a typical sample

Figure 5: Contours of von-Mises stresses (MPa) of the samples