scholarly journals Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip

Micromachines ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 663 ◽  
Author(s):  
Yong Cheol Shin ◽  
Woojung Shin ◽  
Domin Koh ◽  
Alexander Wu ◽  
Yoko M. Ambrosini ◽  
...  
Keyword(s):  
Disease Modeling ◽  
Computational Simulation ◽  
Three Dimensional ◽  
Gastrointestinal Diseases ◽  
Patient Specific ◽  
Epithelial Barrier Function ◽  
Fecal Microbiome ◽  
Particle Mixing ◽  
Dynamic Cell ◽  
Epithelial Layers

The regeneration of the mucosal interface of the human intestine is critical in the host–gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn’s disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic–oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host–microbiome crosstalk to target a patient-specific disease modeling.

MRI-Based Three Dimensional Modeling of Stenting Procedure

2011 ◽  
Author(s):  
Shijia Zhao ◽  
Linxia Gu ◽  
Shailesh Ganpule
Keyword(s):  
Computational Simulation ◽  
Three Dimensional ◽  
Patient Specific ◽  
Open Cell ◽  
Mechanical Responses ◽  
Three Dimensional Modeling ◽  
Dimensional Modeling ◽  
Closed Cell ◽  
Stenosed Artery ◽  
3D Geometry

In this work, the stents-induced mechanical responses of a patient-specific common carotid artery (CCA) were evaluated through computational simulation. The realistic 3D geometry of the artery was constructed from the MRI data. Two types of self-expanding stent design (open-cell and closed-cell) were used to restore the blood flow inside the 60% stenosed artery. The resulting lumen gain, dog-boning effect and arterial stress were estimated. Results suggested that the artery was straightened after stent implantation, and the open-cell design led to bigger lumen gain, better conformability, and less dog-boning effect. This work may facilitate the development of new stent designs.

scholarly journals Applications of 3D Bioprinted-Induced Pluripotent Stem Cells in Healthcare

2020 ◽  
Vol 6 (4) ◽  
Author(s):  
Soja Saghar Soman ◽  
Sanjairaj Vijayavenkataraman
Keyword(s):  
Disease Modeling ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Drug Efficacy ◽  
Patient Specific ◽  
Precision Oncology ◽  
Human Tissues ◽  
3D Bioprinting ◽  
3D Print ◽  
Induced Pluripotent

Induced pluripotent stem cell (iPSC) technology and advancements in three-dimensional (3D) bioprinting technology enable scientists to reprogram somatic cells to iPSCs and 3D print iPSC-derived organ constructs with native tissue architecture and function. iPSCs and iPSC-derived cells suspended in hydrogels (bioinks) allow to print tissues and organs for downstream medical applications. The bioprinted human tissues and organs are extremely valuable in regenerative medicine as bioprinting of autologous iPSC-derived organs eliminates the risk of immune rejection with organ transplants. Disease modeling and drug screening in bioprinted human tissues will give more precise information on disease mechanisms, drug efficacy, and drug toxicity than experimenting on animal models. Bioprinted iPSC-derived cancer tissues will aid in the study of early cancer development and precision oncology to discover patient-specific drugs. In this review, we present a brief summary of the combined use of two powerful technologies, iPSC technology, and 3D bioprinting in health-care applications.

scholarly journals Neuromuscular disease modeling on a chip

2020 ◽  
Vol 13 (7) ◽  
pp. dmm044867
Author(s):  
Jeffrey W. Santoso ◽  
Megan L. McCain
Keyword(s):  
Animal Models ◽  
Drug Development ◽  
Neuromuscular Disease ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Neuromuscular Diseases ◽  
Patient Specific ◽  
New Paradigm ◽  
Cell Sources ◽  
On Chip

ABSTRACTOrgans-on-chips are broadly defined as microfabricated surfaces or devices designed to engineer cells into microscale tissues with native-like features and then extract physiologically relevant readouts at scale. Because they are generally compatible with patient-derived cells, these technologies can address many of the human relevance limitations of animal models. As a result, organs-on-chips have emerged as a promising new paradigm for patient-specific disease modeling and drug development. Because neuromuscular diseases span a broad range of rare conditions with diverse etiology and complex pathophysiology, they have been especially challenging to model in animals and thus are well suited for organ-on-chip approaches. In this Review, we first briefly summarize the challenges in neuromuscular disease modeling with animal models. Next, we describe a variety of existing organ-on-chip approaches for neuromuscular tissues, including a survey of cell sources for both muscle and nerve, and two- and three-dimensional neuromuscular tissue-engineering techniques. Although researchers have made tremendous advances in modeling neuromuscular diseases on a chip, the remaining challenges in cell sourcing, cell maturity, tissue assembly and readout capabilities limit their integration into the drug development pipeline today. However, as the field advances, models of healthy and diseased neuromuscular tissues on a chip, coupled with animal models, have vast potential as complementary tools for modeling multiple aspects of neuromuscular diseases and identifying new therapeutic strategies.

scholarly journals Numerical computation of blood flow for a patient-specific hemodialysis shunt model

2021 ◽  
Author(s):  
Surabhi Rathore ◽  
Tomoki Uda ◽  
Viet Q. H. Huynh ◽  
Hiroshi Suito ◽  
Toshitaka Watanabe ◽  
...  
Keyword(s):  
Stokes Equations ◽  
Three Dimensional ◽  
Arteriovenous Shunt ◽  
Navier Stokes ◽  
Patient Specific ◽  
Stabilized Finite Element ◽  
Computed Tomography Scanning ◽  
Outflow Boundary ◽  
Stage Renal Disease ◽  
End Stage

AbstractHemodialysis procedure is usually advisable for end-stage renal disease patients. This study is aimed at computational investigation of hemodynamical characteristics in three-dimensional arteriovenous shunt for hemodialysis, for which computed tomography scanning and phase-contrast magnetic resonance imaging are used. Several hemodynamical characteristics are presented and discussed depending on the patient-specific morphology and flow conditions including regurgitating flow from the distal artery caused by the construction of the arteriovenous shunt. A simple backflow prevention technique at an outflow boundary is presented, with stabilized finite element approaches for incompressible Navier–Stokes equations.

scholarly journals Application of subject-specific adaptive mechanical loading for bone healing in a mouse tail vertebral defect

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Angad Malhotra ◽  
Matthias Walle ◽  
Graeme R. Paul ◽  
Gisela A. Kuhn ◽  
Ralph Müller
Keyword(s):  
Mechanical Loading ◽  
Bone Defect ◽  
Bone Healing ◽  
Three Dimensional ◽  
Patient Specific ◽  
Dependent Manner ◽  
Micro Computed Tomography ◽  
Computed Tomography Images ◽  
Bone Defect Healing ◽  
Subject Specific

AbstractMethods to repair bone defects arising from trauma, resection, or disease, continue to be sought after. Cyclic mechanical loading is well established to influence bone (re)modelling activity, in which bone formation and resorption are correlated to micro-scale strain. Based on this, the application of mechanical stimulation across a bone defect could improve healing. However, if ignoring the mechanical integrity of defected bone, loading regimes have a high potential to either cause damage or be ineffective. This study explores real-time finite element (rtFE) methods that use three-dimensional structural analyses from micro-computed tomography images to estimate effective peak cyclic loads in a subject-specific and time-dependent manner. It demonstrates the concept in a cyclically loaded mouse caudal vertebral bone defect model. Using rtFE analysis combined with adaptive mechanical loading, mouse bone healing was significantly improved over non-loaded controls, with no incidence of vertebral fractures. Such rtFE-driven adaptive loading regimes demonstrated here could be relevant to clinical bone defect healing scenarios, where mechanical loading can become patient-specific and more efficacious. This is achieved by accounting for initial bone defect conditions and spatio-temporal healing, both being factors that are always unique to the patient.

scholarly journals Effects of intracorneal ring segments implementation technique and design on corneal biomechanics and keratometry in a personalized computational analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Niksa Mohammadi Bagheri ◽  
Mahmoud Kadkhodaei ◽  
Shiva Pirhadi ◽  
Peiman Mosaddegh
Keyword(s):  
Clinical Data ◽  
Three Dimensional ◽  
Element Model ◽  
Von Mises Stress ◽  
Patient Specific ◽  
Average Error ◽  
Constant Thickness ◽  
Arc Length ◽  
Implementation Techniques ◽  
Von Mises

AbstractThe implementation of intracorneal ring segments (ICRS) is one of the successfully applied refractive operations for the treatment of keratoconus (kc) progression. The different selection of ICRS types along with the surgical implementation techniques can significantly affect surgical outcomes. Thus, this study aimed to investigate the influence of ICRS implementation techniques and design on the postoperative biomechanical state and keratometry results. The clinical data of three patients with different stages and patterns of keratoconus were assessed to develop a three-dimensional (3D) patient-specific finite-element model (FEM) of the keratoconic cornea. For each patient, the exact surgery procedure definitions were interpreted in the step-by-step FEM. Then, seven surgical scenarios, including different ICRS designs (complete and incomplete segment), with two surgical implementation methods (tunnel incision and lamellar pocket cut), were simulated. The pre- and postoperative predicted results of FEM were validated with the corresponding clinical data. For the pre- and postoperative results, the average error of 0.4% and 3.7% for the mean keratometry value ($$\text {K}_{\text{mean}}$$ K mean ) were predicted. Furthermore, the difference in induced flattening effects was negligible for three ICRS types (KeraRing segment with arc-length of 355, 320, and two separate 160) of equal thickness. In contrast, the single and double progressive thickness of KeraRing 160 caused a significantly lower flattening effect compared to the same type with constant thickness. The observations indicated that the greater the segment thickness and arc-length, the lower the induced mean keratometry values. While the application of the tunnel incision method resulted in a lower $$\text {K}_{\text{mean}}$$ K mean value for moderate and advanced KC, the induced maximum Von Mises stress on the postoperative cornea exceeded the induced maximum stress on the cornea more than two to five times compared to the pocket incision and the preoperative state of the cornea. In particular, an asymmetric regional Von Mises stress on the corneal surface was generated with a progressive ICRS thickness. These findings could be an early biomechanical sign for a later corneal instability and ICRS migration. The developed methodology provided a platform to personalize ICRS refractive surgery with regard to the patient’s keratoconus stage in order to facilitate the efficiency and biomechanical stability of the surgery.

scholarly journals Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery

2021 ◽  
Vol 22 (3) ◽  
pp. 1203
Author(s):  
Lu Qian ◽  
Julia TCW
Keyword(s):  
Drug Discovery ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Structural Complexity ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Central Nerve System ◽  
Human Ipscs ◽  
Nerve System

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients’ CNS and serve as a platform for therapeutic development and personalized precision medicine.

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