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Rahman, M.M., Watton, P.N. orcid.org/0000-0002-5531-5953, Neu, C.P. et al. (1 more author) (2023) A chemo-mechano-biological modeling framework for cartilage evolving in health, disease, injury, and treatment. Computer Methods and Programs in Biomedicine, 231. 107419. ISSN 0169-2607
Abstract
Background and Objective:Osteoarthritis (OA) is a pervasive and debilitating disease, wherein degeneration of cartilage features prominently. Despite extensive research, we do not yet understand the cause or progression of OA. Studies show biochemical, mechanical, and biological factors affect cartilage health. Mechanical loads influence synthesis of biochemical constituents which build and/or break down cartilage, and which in turn affect mechanical loads. OA-associated biochemical profiles activate cellular activity that disrupts homeostasis. To understand the complex interplay among mechanical stimuli, biochemical signaling, and cartilage function requires integrating vast research on experimental mechanics and mechanobiology—a task approachable only with computational models. At present, mechanical models of cartilage generally lack chemo-biological effects, and biochemical models lack coupled mechanics, let alone interactions over time.
Methods:We establish a first-of-its kind virtual cartilage: a modeling framework that considers time-dependent, chemo-mechano-biologically induced turnover of key constituents resulting from biochemical, mechanical, and/or biological activity. We include the “minimally essential” yet complex chemical and mechanobiological mechanisms. Our 3-D framework integrates a constitutive model for the mechanics of cartilage with a novel model of homeostatic adaptation by chondrocytes to pathological mechanical stimuli, and a new application of anisotropic growth (loss) to simulate degradation clinically observed as cartilage thinning.
Results:Using a single set of representative parameters, our simulations of immobilizing and overloading successfully captured loss of cartilage quantified experimentally. Simulations of immobilizing, overloading, and injuring cartilage predicted dose-dependent recovery of cartilage when treated with suramin, a proposed therapeutic for OA. The modeling framework prompted us to add growth factors to the suramin treatment, which predicted even better recovery.
Conclusions:Our flexible framework is a first step toward computational investigations of how cartilage and chondrocytes mechanically and biochemically evolve in degeneration of OA and respond to pharmacological therapies. Our framework will enable future studies to link physical activity and resulting mechanical stimuli to progression of OA and loss of cartilage function, facilitating new fundamental understanding of the complex progression of OA and elucidating new perspectives on causes, treatments, and possible preventions.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: | cartilage; mechanobiology; mathematical modeling; growth and remodeling; osteoarthritis; homeostatic adaptation |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Computer Science (Sheffield) |
Funding Information: | Funder Grant number ENGINEERING AND PHYSICAL SCIENCE RESEARCH COUNCIL EP/N014642/1 ENGINEERING AND PHYSICAL SCIENCE RESEARCH COUNCIL EP/T017899/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 15 Feb 2023 17:05 |
Last Modified: | 06 Mar 2023 16:55 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.cmpb.2023.107419 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:192970 |
Available Versions of this Item
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A coupled chemo-mechano-biological model of evolving osteoarthritis in cartilage. (deposited 15 Feb 2023 16:46)
- A chemo-mechano-biological modeling framework for cartilage evolving in health, disease, injury, and treatment. (deposited 15 Feb 2023 17:05) [Currently Displayed]