Biomechanics Laboratory

Research on the Biomechanics of Blood Vessels

Blood vessels are not merely tubes; they are intelligent pipes that adaptively change their diameter and wall thickness in response to internal pressure and flow. For instance, prolonged high blood pressure causes the vessel walls to thicken, and sustained increased blood flow results in vessel dilation. Interestingly, the thickening of the vessel walls occurs to maintain circumferential tensile stress, and the dilation happens to maintain wall shear stress (mechanical homeostasis). If this response fails, it can lead to aneurysms or hypertension. Additionally, atherosclerosis tends to develop in areas where stress is concentrated within the vessel walls. Thus, it can be said that atherosclerosis, hypertension, and aneurysms arise from the failure of the vessels' mechanical adaptation. Blood vessels are also suitable for studying responses to mechanical forces due to their relatively simple cylindrical shape. We investigate how the mechanical properties and structure of blood vessels change under various conditions.

Specifically, we measure the mechanical properties of the aorta in rabbits and pigs using various devices developed in our laboratory. We also aim to measure the mechanical properties of cells and fiber bundles within the vessel wall on a microscopic scale to clarify the micron-order stress and strain distribution within the vessel walls.

1. Analysis of the circumferential heterogeneity in the mechanical properties and smooth muscle contraction characteristics of the aorta

2. Analysis of microscopic residual stress and strain distribution within vessel walls

3. Influence of buckling of elastic lamina on the pressure-diameter relationship of the arteries

4. Measurement of mechanical properties of aortic aneurysm tissue using a biaxial tensile tester

5. Development of diagnosis devices for early stages of atherosclerosis

6. Development of a method to introduce FRET-type tension sensors into the aorta

7. Three-dimensional microscopic deformation observation of rat thoracic aortic walls using a tissue clarification method

   
   

Research on the Cell Biomechanics

Cells, the fundamental units composing tissues and organs, are increasingly recognized for their active responses to mechanical stimuli, altering their functions and morphology. To comprehensively analyze these responses, we are advancing the development of devices to meticulously measure the mechanical properties of cells themselves, the magnitude of forces exerted by cells in vivo during development, and even the fine internal structures within cells. Using these devices, we are investigating in detail the mechanical responses of cultured cells to various applied forces. Our ultimate goal is to utilize the nature of these mechanical responses of cells to make cells design and fabricate microscopic structures in the future.

1. Research on the mechanical properties and tension development of cells

2. Research on three-dimensional observation of intra-cellular microstructures

3. Impact of microscopic topography of substrate on cell behavior

4. Evaluation of the effects of compressive stimuli on the nucleus of cells

5. Measurement of intracellular tension using FRET-type tension sensors

6. Quantitative assessment and functional analysis of intercellular substance transport via gap junctions (Assoc. Prof. Maeda)

7. Multi-scale analysis of intracellular strains using FRET-type tension sensors

8. Cell orientation induced by cyclic stretch in stratified MC3T3-E1 cells

9. Fundamental research on mechanical stimulation to the cell nucleus and its responses using microfluidic channels

10. Relationship between changes in nuclear DNA condensation state induced by dynamic compressive stimuli and the cell cycle

    
    

Research on the biomechanics of bone and diatoms

Within bones, a structure resembling slender columns can be observed. These are referred to as trabeculae, and their orientation often aligns with the principal stress directions inside beams subjected to evenly distributed loads at their ends. This observation has long suggested that bones are designed to achieve maximum strength with minimal material (Figure 1). Additionally, bones are believed to dynamically alter their internal structures and external shapes to constantly adapt to mechanical environments. Therefore, from a mechanical engineering perspective, bones can be considered dynamically optimal structures that sense mechanical stimuli and maintain their structure optimally. This study aims to induce an optimal structure that adapts to its environment artificially by cultivating immature bones under various mechanical conditions.

1. Study on the mechanical properties and internal structural changes of cultured bone tissues under cyclic compressive loading

2. Real-time observation of calcification of immature bone tissues under mechanical stimulation

3. Research on the promotion of calcification in osteoblast-like cells MC3T3-E1

   
   
   
   

Research on the formation of frustules under mechanical loading in diatoms

The diatom, a plant cell, possesses a siliceous frustule with intricate and delicate patterns composed of pores (areolae) on the cell wall, each measuring several micrometers. Diatoms create this complex structure solely from natural elements such as sunlight, air, water, and silicon found in the environment. Understanding the formation mechanism of these frustules with such characteristics could potentially lead to the establishment of environmentally friendly new microfabrication techniques by allowing desired forms to be artificially created. Therefore, this study investigates the detailed changes in morphology and the formation process when mechanical stress is applied to elongated diatoms like Aulacoseira, using them as examples.

1. Effects of three-point bending on morphology of diatom Aulacoseira

2. Fundamental study on frustule elongation under mechanical loading in Aulacoseira

3. Study on the robustness of frustule shape during growth in Aulacoseira

   
   

Currently, synthetic polymers are employed as artificial replacements for ruptured tendons and ligaments. However, these synthetic alternatives fail to accurately replicate the intricate mechanical behavior and properties of native tendons and ligaments. They exhibit excessive rigidity or inadequate mechanical strength compared to their natural counterparts. Moreover, as these synthetic grafts degrade over time, they generate wear debris particles, which can trigger undesirable inflammatory responses within the body.

This invention introduces an innovative composite tissue construct designed to mimic the structural and functional properties of natural tendons and ligaments. The composite tissue comprises elastin fibers produced through an electrospinning process, where a solutionized form of elastin is deposited onto a rotating collector, forming continuous fibers. These elastin fibers are then infiltrated with collagen, a key structural protein found in native tendons and ligaments. Crucially, both the elastin and collagen fibers within the composite are subjected to mechanical loading, which aligns and orients their molecular structures in the direction of the applied load. This controlled orientation process is critical in replicating the anisotropic mechanical behavior of natural tendons and ligaments, which exhibit directional dependence in their material properties. Following the fiber orientation step, the elastin-oriented and collagen-oriented fibers are cross-linked, creating a stable, interwoven composite tissue that combines the unique properties of both elastin and collagen. The resulting composite tissue closely resembles the composition and architecture of natural tendons and ligaments, comprising aligned elastin and collagen fibers in a cross-linked network.

• This invention pertains to the development of artificial bio-soft tissue constructs designed to serve as substitutes for grafts during transplantation procedures aimed at treating damaged tendons and ligaments, which often result from sports-related or other physical activities.

• Artificial tendons and ligaments that have the inherent strength and flexibility of natural tendons and ligaments, are highly biocompatible, and do not require removal after regeneration

A significant advantage of this composite tissue is its potential application as a tendon replacement in the treatment of thumb carpometacarpal (CMC) arthropathy, a condition characterized by the degeneration of the joint at the base of the thumb. The composite tissue exhibits dynamic mechanical properties and hysteresis behavior that closely mimic those of natural tendons and ligaments, making it a promising alternative for restoring joint function and mobility in patients suffering from CMC arthropathy.

The university are actively seeking collaborative partnerships with companies that share our vision and are interested in co-developing advanced biocompatible artificial tendons and ligaments leveraging our proprietary and innovative technology platform.