Mitsugu Todo

Kyushu University, Hukuoka, Fukuoka, Japan

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Publications (116)103.67 Total impact

  • Takaaki Arahira, Mitsugu Todo
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    ABSTRACT: The primary aim of this study is to characterize the effects of cell culture on the compressive mechanical behavior of the collagen/β-tricalcium phosphate (TCP) composite scaffold. The composite and pure collagen scaffolds were fabricated by the solid-liquid phase separation technique and the subsequent freeze-drying method. Rat bone marrow mesenchymal stem cells (rMSCs) were then cultured in these scaffolds up to 28 days. Compression test of the scaffolds with rMSCs were conducted periodically. Biological properties such as cell number, alkaline phosphatase (ALP) activity, and gene expressions of osteogenetic bone markers were evaluated during cell culture. The microstructural changes in the scaffolds during cell culture were also examined using a scanning electron microscope. The compressive elastic modulus was then correlated with those of the biological properties and microstructures to understand the mechanism of variational behavior of the macroscopic elastic property. The composite scaffold exhibited higher ALP activity and more active generation of osteoblastic markers than the collagen scaffold, indicating that β-TCP can activate the differentiation of rMSCs into osteoblasts and extracellular matrix (ECM) formation such as type I collagen and the following mineralization. The variational behavior of the compressive modulus of the composite scaffold was affected by both the material degradation and the proliferation of cells and the ECM formation. In the first stage, the modulus of the composite scaffold tended to increase due to cell proliferation and the following formation of network structure. In the second stage, the modulus tended to decrease because the material degradation such as ductile deformation of collagen and decomposition of β-TCP were more effective on the property than the ECM formation. In the third stage, active calcification by formation and growth of mineralized nodules resulted in the recovery of modulus. It is concluded that the introduction of β-TCP powder into the porous collagen matrix is very effective to improve the mechanical and biological properties of collagen scaffold prepared for bone tissue engineering. Furthermore, the compressive modulus of the composite scaffold is strongly affected by the material degradation and the ECM formation by stem cells under in vitro culture condition.
    Journal of the Mechanical Behavior of Biomedical Materials 07/2014; 39C:218-230. · 3.05 Impact Factor
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    TheScientificWorldJournal. 01/2014; 2014:459408.
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    ABSTRACT: One of the most common errors of total knee arthroplasty procedure is a malrotation of tibial component. The stress on tibial insert is closely related to polyethylene failure. The objective of this study is to analyze the effect of malrotation of tibial component for the stress on tibial insert during high flexion using a finite element analysis. We used Stryker NRG PS for analysis. Three different initial conditions of tibial component including normal, 15° internal malrotation, and 15° external malrotation were analyzed. The tibial insert made from ultra-high-molecular-weight polyethylene was assumed to be elastic-plastic while femoral and tibial metal components were assumed to be rigid. Four nonlinear springs attached to tibial component represented soft tissues around the knee. Vertical load was applied to femoral component which rotated from 0° to 135° while horizontal load along the anterior posterior axis was applied to tibial component during flexion. Maximum equivalent stresses on the surface were analyzed. Internal malrotation caused the highest stress which arose up to 160% of normal position. External malrotation also caused higher stress. Implanting prosthesis in correct position is important for reducing the risk of abnormal wear and failure.
    TheScientificWorldJournal. 01/2014; 2014:695028.
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    ABSTRACT: The primary objective of this study is to distinguish between mobile bearing and fixed bearing posterior stabilized knee prostheses in the mechanics performance using the finite element simulation. Quantifying the relative mechanics attributes and survivorship between the mobile bearing and the fixed bearing prosthesis remains in investigation among researchers. In the present study, 3-dimensional computational model of a clinically used mobile bearing PS type knee prosthesis was utilized to develop a finite element and dynamic simulation model. Combination of displacement and force driven knee motion was adapted to simulate a flexion motion from 0° to 135° with neutral, 10°, and 20° internal tibial rotation to represent deep knee bending. Introduction of the secondary moving articulation in the mobile bearing knee prosthesis has been found to maintain relatively low shear stress during deep knee motion with tibial rotation.
    TheScientificWorldJournal. 01/2014; 2014:586921.
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    ABSTRACT: Simple epitheliums in normal glandular systems are regulated not to stratify even though the constituent cells proliferate and will rise from the epithelium. Since epithelial cells have the potential to establish cell-cell adhesions, the avoidance of stratification must be related to the intracellular signal cascades and the extracellular conditions. The contributions of the former are becoming clarified, but the influence of the latter is poorly understood. In the present study, we examined whether the frequency of cell-on-cell adhesion, which mimics the early stage of multilayering, is dependent on the type of the extracellular scaffold protein. Wild-type epithelial cells were cultured on E-cadherin-Fc (a cell-cell adhesion protein) or collagen (an extracellular matrix protein), and then, green fluorescent protein (GFP)-positive cells were seeded onto these wild-type cells. We observed that the cell-on-cell adhesion (adhesion of the GFP-positive cell to the wild-type cells) was more frequent in the E-cadherin-Fc treatment than the collagen treatment. The cell-on-cell adhesions that were observed in the E-cadherin treatment were transient and decreased in frequency to that of the collagen treatment after the 12 h of cell culture. We observed the disappearance of E-cadherin-Fc but not collagen during cell culture. These results suggest that transient multilayering in simple epithelium is possible, depending on the types of extracellular scaffold protein, and they imply that cells can modify the extracellular conditions to meet normal cellular conditions.
    Histochemie 12/2013; · 2.93 Impact Factor
  • Mitsugu Todo, Takaaki Arahira
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    ABSTRACT: Recent years, various kinds of natural polymers and bioceramics has been used to develop porous scaffolds for bone tissue engineering. Among of them, collagen guarantees good biological conditions, and β-tricalcium phosphate (β-TCP) possesses good oseteoconductivity, cellular adhesion, accelerated differentiation and mechanical property. In this study, rat bone marrow mesenchymal stem cells (rMSC) were cultured in β-TCP/collagen composite scaffolds up to 28 days in order to assess the time-dependent behavior of the extracellular matrix formation and the mechanical performance of the scaffold-cell sysytem. The cell number and ALP activity were evaluated using a spectrophotometric plate reader. Gene expression of osteogenesis was analyzed using the real-time PCR reactions. Compression tests were also conducted periodically by using a conventional testing machine to evaluate the elastic modulus. The increasing behaviors of cell number and ALP activity in the composite scaffold were much better than in the collagen scaffold. The gene expression of osteocalcin and collagen type-I in collagen/β-TCP scaffold was higher than that of the collagen scaffold. The compressive modulus also increased up to 28 days. These results clearly showed that the distribution of micro β-TCP particles is very effective to increase the elastic modulus and promote cell growth.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 07/2013; 2013:409-412.
  • Vilay Vannaladsaysy, Mitsugu Todo
    Journal of Solid Mechanics and Materials Engineering 01/2013; 7(3):463-472.
  • Sunghyen Hwang, Mitsugu Todo
    Journal of Solid Mechanics and Materials Engineering 01/2013; 7(2):293-302.
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    ABSTRACT: Effects of particle size distribution on physical properties such as viscosity, heat and mechanical properties of injection-molded hydroxyapatite (HA)/poly lactic acid (PLA) were investigated. The melting temperature of PLA was shifted to a lower temperature because of the dispersion of HA particles. However, the cold crystallization temperature shifted to a lower temperature at high HA composition, suggesting that HA particles acted as a nuclear agent. x c,PLA of the composites with bimodal particle size distribution showed the lowest of all three composites, suggesting that mobility of PLA polymer chain was reduced by bimodal particle size distribution, which means the increase of restriction at interface between polymer matrix and particle. Melt flow rate (MFR) increased because of dispersed HA particle. The reason was thought that hydrolysis degradation of PLA occurred during melt-mixing process is accelerated by HAp particle dispersion. The MFR of composites increased concomitantly with increased particle size. Mechanical properties such as flexural strength and the modulus of bimodal-HA/PLA composite with both 5 and 1 μm of representative size were higher than those of monomodal-HA/PLA composites with 5 or 1 μm of representative size within the range of the results of this paper. Fracture surfaces were affected by the particle size distribution. It was suggested for the reasons to relate the interparticle distance and restriction of the interface between the matrix and particles.
    Advanced Composite Materials 01/2013; 22(5). · 0.48 Impact Factor
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    ABSTRACT: Calcium phosphate-based bioceramics have been widely used as artificial bone substitute materials because of their superior biocompatibility and osteoconductivity. In the present study, mechanical properties changes of two hydroxyapatite (HA) ceramics induced by bone ingrowth were tested and evaluated in a rabbit model. Both materials (NEOBONE®, Apaceram-AX®) have highly interconnected pores with a porosity of 75–85%. The major structural difference between them lies in that Apaceram-AX® has micropores smaller than 10 micrometers in diameter, whereas NEOBONE® does not contain such micropores. Both materials were implanted into the femoral condyles of rabbits for the specified observation period (1, 5, 12, 24, and 48 weeks) and then evaluated by experimental approach in combination with finite element method (FEM). Results indicate that two porous bioceramics exhibit different degradability in vivo, and remarkably different variation of total stiffness, elastic modulus distribution, as well as strain energy density distribution calculated by FE simulation. These results demonstrate how the internal microstructures affect the progress of bone regeneration and mechanical properties with the duration of implantation, emphasizing the importance of biomaterial design tailored to various clinic applications. Additionally, this study showed a potential for applying the computational method to monitor the time-dependent biomechanical changes of implanted porous bioceramics.
    Applied Surface Science 12/2012; 262:81–88. · 2.54 Impact Factor
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    ABSTRACT: Coefficients of Cowper-Symonds constitutive equation for PLLA/PCL = 80/20 were determined using the results of compressive tests at high and low strain rates. The simulation of split Hopkinson pressure bar using the coefficients was carried out under the same condition as the experiments. The diameter and thickness of specimens were measured by a high-speed video camera. The stress and strain histories of specimens, the thickness and the diameter in the simulations at high strain rate were compared with those in the experiments.
    The European Physical Journal Conferences 08/2012; 26:03001-.
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    ABSTRACT: Knee joint implants developed by western companies have been imported to Korea and used for Korean patients. However, many clinical problems occur in knee joints of Korean patients after total knee joint replacement owing to the geometric mismatch between the western implants and Korean knee joint structures. To solve these problems, a method to determine the representative dimension parameter values of Korean knee joints is introduced to aid in the design of knee joint implants appropriate for Korean patients. Measurements of the dimension parameters of 88 male Korean knee joint subjects were carried out. The distribution of the subjects versus each measured parameter value was investigated. The measured dimension parameter values of each parameter were grouped by suitable intervals called the "size group," and average values of the size groups were calculated. The knee joint subjects were grouped as the "patient group" based on "size group numbers" of each parameter. From the iterative calculations to decrease the errors between the average dimension parameter values of each "patient group" and the dimension parameter values of the subjects, the average dimension parameter values that give less than the error criterion were determined to be the representative dimension parameter values for designing knee joint implants for Korean patients.
    Proceedings of the Institution of Mechanical Engineers Part H Journal of Engineering in Medicine 05/2012; 226(5):368-76. · 1.14 Impact Factor
  • Vilay Vannaladsaysy, Mitsugu Todo
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    ABSTRACT: Poly(L-lactic acid) (PLLA) was toughened by blending with three different ductile biopolymers such as poly (ε-caprolactone) (PCL), poly(butylene succinate-co-e-caprolactone) (PBSC), poly (butylene succinate-co-L-lactate) (PBSL). The blend ratio was fixed to 50:50. Lysine triisocyanate (LTI) was added to the blends as a compatibilizer. Characterizations such as Fourier transform infra-red (FT-IR) spectroscopy, field-emission electron microscope (FE-SEM), and mode I fracture test were used to characterize the effectiveness of LTI on the mechanical and morphological properties of various PLLA blends. It was found that PLLA/PCL blend shows the highest toughness energy among the binary blends. On the other hand, addition of LTI in PLLA/PBSC blend exhibits the best toughness property. Based on the FE-SEM observation, fractured surfaces of PLLA blends with LTI indicate ductile fracture with dense elongated fibrils. The largest damage zone is generated in the vicinity of crack-trip, suggesting that high energy dissipation occurred in the crack-trip region. FT-IR analysis also suggested that the NCO groups of LTI were acted as a compatibilizer, as the results of interaction between the two phases of the polymer blends.
    Journal of Solid Mechanics and Materials Engineering 01/2012; 6(4):314-322.
  • Joo-Eon Park, Mitsugu Todo
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    ABSTRACT: Porous biodegradable polymeric scaffolds are developed by physically blending two different kinds of biodegradable polymers, PCL, and PLLA, for application in tissue engineering. The main objective of the development of this material is to control the mechanical properties, such as, elastic modulus and strength. The results from mechanical testing showed that the compressive mechanical properties of PCL/PLLA scaffold can be varied by changing the blend ratio. It also showed that these properties can be well predicted by the rule of mixture. The primary deformation mechanism of the scaffolds was found to be localized buckling of struts surrounding the pores. Localized ductile failure caused by PCL phase tends to be suppressed with increasing PLLA content. The immiscibility of PCL and PLLA caused the phase-separation morphology that strongly affected the macroscopic mechanical properties and the microscopic deformation behavior.
    Journal of Materials Science 12/2011; 46(24):7850-7857. · 2.31 Impact Factor
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    ABSTRACT: Hydroxyapatite ceramics have been widely investigated for bone regeneration due to their high biocompatibility. However, few studies focus on their mechanical characteristics after implantation. In this study, the finite element (FE) method was used to evaluate the mechanical properties of a fully interconnected porous hydroxyapatite (IPHA) over time of implantation. Based on the micro-CT images obtained from the experiments dealing with IPHA implanted into rabbit femoral condyles, three-dimensional FE models of IPHA (1, 5, 12, 24, and 48 weeks after implantation) were developed. FE analysis indicated that the elastic modulus gradually increased from 1 week and reached the peak value at 24 weeks, and then it kept at high level until 48 weeks postoperatively. In addition, as a local biomechanical response, strain energy density became to distribute evenly over time after the implantation. Results confirmed that the mechanical properties of IPHA are strongly correlated to bone ingrowth. The efficiency of the proposed numerical approach was validated in combination with experimental studies, and the feasibility of applying this approach to study such implanted porous bioceramics was proved.
    Journal of Materials Science Materials in Medicine 11/2011; 23(2):463-72. · 2.14 Impact Factor
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    Mitsugu Todo, Tetsuo Takayama
    Biomaterials - Physics and Chemistry, 11/2011; , ISBN: 978-953-307-418-4
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    ABSTRACT: Biodegradable polymer blends of poly(l-lactic acid) (PLLA) and poly(butylene succinate-co-l-lactate) (PBSL) at various blending ratios are prepared. The blending of PLLA with PBSL results in an increase in the ductility and thermal stability of the blend. However, flexural strength and modulus, as well as loss modulus, decrease with an increase in PBSL content. Annealing is employed to increase blend crystallinity and subsequently improve the mechanical properties of the PLLA/PBSL blend. The influences of annealing time on the crystal modification, thermal properties, and mechanical properties of the PLLA/PBSL blend are investigated by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and three-point bending test, respectively. Crystalline peaks are found in the XRD patterns of all annealed samples. DSC analysis reveals that the degree of crystallinity is enhanced with an increase in annealing time. The flexural modulus also increases with annealing time due to the change in crystalline phases. However, longer periods of annealing, especially over 20h, result in thermal degradation and subsequently reduce the modulus value of the PLLA/PBSL blend. KeywordsPoly(l-lactic acid) (PLLA)–Poly(butylene succinate-co-l-lactate) (PBSL)–Annealing–Crystallization behavior
    Polymer Bulletin 09/2011; 67(5):815-830. · 1.49 Impact Factor
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    ABSTRACT: To assess the effect of each step of medial soft-tissue releases on the joint gap angle during posterior-stabilised total knee arthroplasty (TKA). 82 women and 9 men (mean age, 72 years) with medial osteoarthritic knees underwent 100 posterior-stabilised TKAs, in which release of superficial fibres of the medial collateral ligament (MCL) were required using the gap control technique. The order of releases was the superficial MCL, the pes anserinus, and then the semi-membranosus. The superficial MCL was released selectively. The effect of each step of medial soft-tissue releases in full extension and in 90º flexion was compared. After all medial soft-tissue releases, the mean joint gap angles decreased from 8.7º to 3.8º varus in flexion and from 4.4º to 1.4º varus in extension. The total effect of medial soft-tissue releases was significantly larger in flexion than in extension (4.9º±3.2º vs. 3.0º±2.0º, p<0.0001), except for the release of posterior fibres of the superficial MCL. The effect of release of the semi-membranosus in flexion was largest. The release effect was significantly greater in flexion than in extension during posterior-stabilised TKA; the joint gap technique may be more reliable in medial osteoarthritic knees with moderate and severe varus instability.
    Journal of orthopaedic surgery (Hong Kong) 08/2011; 19(2):230-3.
  • Applied Mechanics and Materials. 07/2011;
  • Tetsuo Takayama, Mitsugu Todo, Hideto Tsuji
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    ABSTRACT: The effects of annealing on the mechanical properties of polymer blends of poly(lactic acid) (PLA) and poly(ε-caprolactone) (PCL) were investigated. The bending strength and modulus of PLA/PCL tend to increase due to crystallization of the PLA phase by annealing. The mode I fracture energy, J(in), of PLA/PCL decreases dramatically due to the suppression of the ductile deformation of the spherical PCL phase by annealing. The immiscibility of PLA and PCL can be improved by adding lysine triisocyanate (LTI) as a result of additional polymerization. The phase transformation due to LTI addition reduces the size of the spherical PCL phase, resulting in higher fracture energy. An annealing process applied to PLA/PCL/LTI further strengthens the microstructure, resulting in effective improvement of the fracture energy.
    Journal of the mechanical behavior of biomedical materials. 04/2011; 4(3):255-60.

Publication Stats

456 Citations
103.67 Total Impact Points


  • 1997–2014
    • Kyushu University
      • Research Institute for Applied Mechanics
      Hukuoka, Fukuoka, Japan
  • 2011
    • Kokura Memorial Hospital
      Kitakyūshū, Fukuoka, Japan
  • 2008
    • University of Science Malaysia
      • School of Material and Mineral Resources Engineering
      Nibong Tebal, Pulau Pinang, Malaysia
  • 1998
    • Australian National University
      Canberra, Australian Capital Territory, Australia