Ingenium 2021
Fluid flow simulation of microphysiological knee joint-on-a-chip Eileen N. Lia,b, Zhong Lib, Ryan M. Ronczkab, Hang Lina,b Department of Bioengineering, bDepartment of Orthopaedic Surgery, University of Pittsburgh School of Medicine
a
Eileen Li is a senior bioengineering student from northern Virginia. She has a passion in tissue engineering geared towards bone regeneration. After graduation she wishes to pursue a PhD and a career in academia. Eileen N. Li
Dr. Lin is an Assistant Professor in the Department of Orthopaedic Surgery and Department of Bioengineering. His research is focused on investigating the association between aging and OA, establishing an in vitro microphysiological OA model for OA pathogenesis study and drug development, and Hang Lin, Ph.D. testing stem cell-based therapy for the repair of cartilage injury.
Significance Statement
The progression of disease-modifying drugs to combat osteoarthritis (OA) has been limited due to the absence of an appropriate OA model that can effectively simulate the pathologies in humans. Our lab has constructed a 3-dimensional, human cell-derived, multi-tissue microphysiological system (microJoint) and high-throughput microJoint (HTP-microJoint) to mimic the native joint and model OA pathogenesis. Through the utilization of finite element analysis, both microJoints were investigated for characteristics that promote joint tissue development and maintenance.
Category: Computational Research
Keywords: microphysiological system, finite element analysis, shear stress, joint disease, osteoarthritis, model Abbreviations: osteoarthritis (OA), high-throughput microJoint (HTP-microJoint), finite element analysis (FEA)
Abstract
Osteoarthritis (OA) is a degenerative disorder that effects 240 million people globally, leading to inflammation, chronic pain and restricted movement of joints [1]. Current osteoarthritis (OA) drugs are merely palliative. The development of drugs for OA treatment has been limited by the unavailability of a suitable OA model. To address this issue, we have developed a 3-dimensional (3D), human cell-derived, multi-tissue microphysiological system (microJoint); and further, an additional high-throughput microJoint (HTP-microJoint) chip was designed for high-throughput drug testing and convenient real-time imaging analysis. The 3-dimensionality and multi-tissue nature of the microJoint chips establish many similarities to the native joint and can therefore enhance our investigation of OA in comparison to models that are 2-dimensional or do not have multiple joint tissues. However, the fluid flow characteristics of the chips and their effects on the tissue maturation and maintenance are not fully understood, therefore finite element analysis (FEA) was conducted for both chips to quantify the fluid flow-induced shear stress and flow trajectory parameters within the tissue chambers. Volumetric flow rates utilized in the lab for tissue culture within the microJoint chips were applied to the geometry for the analysis. Laminar flow and the continuum hypothesis assumptions were validated through calculations. Fluid velocity analysis indicated no stagnant media areas within the microJoint chips. Quantified fluid-induced shear stress on the tissues within the microJoint chips have been previously reported to enhance osteogenic and chondrogenic tissue differentiation. The analysis suggests that both microJoint chips provide environments that enhance joint tissue development. Therefore, the microJoint chips can closely mimic native joint tissues and will establish a physiologically relevant model of OA progression.
1. Introduction
Osteoarthritis (OA) is a painful and debilitating disease that affects multiple joint components, including articular cartilage, subchondral bone, synovium, and infrapatellar fat pad. The limited progress in the development of disease-modifying OA drugs is mainly due to the absence of an effective OA model that mimics complex and active tissue crosstalk within the joint.
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