• BMB Reports
• /
• v.56 no.1
• /
• pp.32-42
• /
• 2023

Heart disease is one of the major life-threatening diseases with high mortality and incidence worldwide. Several model systems, such as primary cells and animals, have been used to understand heart diseases and establish appropriate treatments. However, they have limitations in accuracy and reproducibility in recapitulating disease pathophysiology and evaluating drug responses. In recent years, three-dimensional (3D) cardiac tissue models produced using tissue engineering technology and human cells have outperformed conventional models. In particular, the integration of cell reprogramming techniques with bioengineering platforms (e.g., microfluidics, scaffolds, bioprinting, and biophysical stimuli) has facilitated the development of heart-on-a-chip, cardiac spheroid/organoid, and engineered heart tissue (EHT) to recapitulate the structural and functional features of the native human heart. These cardiac models have improved heart disease modeling and toxicological evaluation. In this review, we summarize the cell types for the fabrication of cardiac tissue models, introduce diverse 3D human cardiac tissue models, and discuss the strategies to enhance their complexity and maturity. Finally, recent studies in the modeling of various heart diseases are reviewed.

• Proceedings of the Korean Society of Precision Engineering Conference
• /
• 2005.06a
• /
• pp.915-918
• /
• 2005

Advances in Information Technology and in Biomedicine have created new uses for CAD technology with many novel and important biomedical applications. Such applications can be found, for example, in the design and modeling of orthopedics, medical implants, and tissue modeling in which CAD can be used to describe the morphology, heterogeneity, and organizational structure of tissue and anatomy. CAD has also played an important role in computer-aided tissue engineering for biomimetic design, analysis, simulation and freeform fabrication of tissue scaffolds and substitutes. And all the applications require precision geometry of the organs or bones of each patient. But the geometry information currently used is polygon model with none solid geometry and is so rough that it cannot be utilized for accurate analysis, simulation and fabrication. Therefore a case study is performed to deduce a transformation method to build free form surface from a rough polygon data or medical images currently used in the application. This paper describes the transformation procedure in detail and the considerations for accurate organ modeling are discussed.

• Journal of the Optical Society of Korea
• /
• v.15 no.4
• /
• pp.321-328
• /
• 2011

Various methods have been investigated to increase photon density in soft tissue, an important factor in low-level laser therapy. Previously we developed a compression-controlled low-level laser probe (CCLLP) utilizing mechanical negative compression, and experimentally verified its efficacy. In this study, we used Bezier curves to numerically simulate the skin deformation and photon density variation generated by the CCLLP. In addition, we numerically modeled changes in optical coefficients due to skin deformation using a linearization technique with appropriate parameterization. The simulated results were consistent with both human in vivo and porcine ex vivo experimental results, confirming the efficacy of the CCLLP.

• Tuberculosis and Respiratory Diseases
• /
• v.87 no.1
• /
• pp.52-64
• /
• 2024

Chronic respiratory diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and respiratory infections injure the alveoli; the damage evoked is mostly irreversible and occasionally leads to death. Achieving a detailed understanding of the pathogenesis of these fatal respiratory diseases has been hampered by limited access to human alveolar tissue and the differences between mice and humans. Thus, the development of human alveolar organoid (AO) models that mimic in vivo physiology and pathophysiology has gained tremendous attention over the last decade. In recent years, human pluripotent stem cells (hPSCs) have been successfully employed to generate several types of organoids representing different respiratory compartments, including alveolar regions. However, despite continued advances in three-dimensional culture techniques and single-cell genomics, there is still a profound need to improve the cellular heterogeneity and maturity of AOs to recapitulate the key histological and functional features of in vivo alveolar tissue. In particular, the incorporation of immune cells such as macrophages into hPSC-AO systems is crucial for disease modeling and subsequent drug screening. In this review, we summarize current methods for differentiating alveolar epithelial cells from hPSCs followed by AO generation and their applications in disease modeling, drug testing, and toxicity evaluation. In addition, we review how current hPSC-AOs closely resemble in vivo alveoli in terms of phenotype, cellular heterogeneity, and maturity.

• Korean Journal of Applied Biomechanics
• /
• v.19 no.2
• /
• pp.197-204
• /
• 2009

It bas been hypothesized that foot ulceration might be internally initiated. Current instruments which merely allow superficial estimate of plantar loading acting on the foot, severely limit the scope of many biomechanical/clinical studies on this issue. Recent studies have suggested that peak plantar pressure may be only 65% specific for the development of ulceration. These limitations are at least partially due to surface pressures not being representative of the complex mechanical stress developed inside the subcutaneous plantar soft-tissue, which are potentially more relevant for tissue breakdown. This study established a three-dimensional and nonlinear finite element model of a human foot complex with comprehensive skeletal and soft-tissue components capable of predicting both the external and internal stresses and deformations of the foot. The model was validated by experimental data of subject-specific plantar foot pressure measures. The stress analysis indicated the internal stresses doses were site-dependent and the observation found a change between 1.5 to 4.5 times the external stresses on the foot plantar surface. The results yielded insights into the internal loading conditions of the plantar soft-tissue, which is important in enhancing our knowledge on the causes of foot ulceration and related stress-induced tissue breakdown in diabetic foot.

• Molecules and Cells
• /
• v.45 no.2
• /
• pp.53-64
• /
• 2022

Three-dimensional cultures of human neural tissue/organlike structures in vitro can be achieved by mimicking the developmental processes occurring in vivo. Rapid progress in the field of neural organoids has fueled the hope (and hype) for improved understanding of brain development and functions, modeling of neural diseases, discovery of new drugs, and supply of surrogate sources of transplantation. In this short review, we summarize the state-of-the-art applications of this fascinating tool in various research fields and discuss the reality of the technique hoping that the current limitations will soon be overcome by the efforts of ingenious researchers.

• BMB Reports
• /
• v.57 no.7
• /
• pp.311-317
• /
• 2024

Brain organoid is a three-dimensional (3D) tissue derived from stem cells such as induced pluripotent stem cells (iPSCs) embryonic stem cells (ESCs) that reflect real human brain structure. It replicates the complexity and development of the human brain, enabling studies of the human brain in vitro. With emerging technologies, its application is various, including disease modeling and drug screening. A variety of experimental methods have been used to study structural and molecular characteristics of brain organoids. However, electrophysiological analysis is necessary to understand their functional characteristics and complexity. Although electrophysiological approaches have rapidly advanced for monolayered cells, there are some limitations in studying electrophysiological and neural network characteristics due to the lack of 3D characteristics. Herein, electrophysiological measurement and analytical methods related to neural complexity and 3D characteristics of brain organoids are reviewed. Overall, electrophysiological understanding of brain organoids allows us to overcome limitations of monolayer in vitro cell culture models, providing deep insights into the neural network complex of the real human brain and new ways of disease modeling.

• Journal of Biomedical Engineering Research
• /
• v.19 no.5
• /
• pp.495-502
• /
• 1998

A mathematical model of viscoelasticity on the material property of human pharyngeal tissue utilizing Y.C. Fung's Quasi-linear viscoelastic theory is proposed based on cyclic load, stress relaxation, incremental load, and uniaxial tensile load tests. The material properties are characterized and compared with other biological materials' results. The mathematical model is proposed by combining two characteristic functions determined from the stress relaxation and uniaxial tensile load tests. The reduced stress relaxation function G(t) and elastic response function S(t) are obtained from stress relaxation test and uniaxial tensile load test results respectively. Then the model describing stress-time history of the tissue is implemented utilizing two functions. The proposed model is evaluated and validated by comparing the model's cyclic behaviour with experimental results. The model data could be utilized as an important information for constructing 3-dimensional biomechanical model of human pharynx using FEM(Finite Element Method).

• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.2
• /
• pp.99-104
• /
• 2015

The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra- abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, $C_{max}$ was $11.151{\mu}g/mL$ at 5 min after the intravenous injection and $t_{1/2}$ was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.

• International Journal of Stem Cells
• /
• v.17 no.2
• /
• pp.158-181
• /
• 2024

This study offers a comprehensive overview of brain organoids for researchers. It combines expert opinions with technical summaries on organoid definitions, characteristics, culture methods, and quality control. This approach aims to enhance the utilization of brain organoids in research. Brain organoids, as three-dimensional human cell models mimicking the nervous system, hold immense promise for studying the human brain. They offer advantages over traditional methods, replicating anatomical structures, physiological features, and complex neuronal networks. Additionally, brain organoids can model nervous system development and interactions between cell types and the microenvironment. By providing a foundation for utilizing the most human-relevant tissue models, this work empowers researchers to overcome limitations of two-dimensional cultures and conduct advanced disease modeling research.