Mechanobiochemical finite element model to analyze impact-loading-induced cell damage, subsequent proteoglycan loss, and anti-oxidative treatment effects in articular cartilage

Joonas P Kosonen; Atte S A Eskelinen; Gustavo A Orozco; Mitchell C Coleman; Jessica E Goetz; Donald D Anderson; Alan J Grodzinsky; Petri Tanska; Rami K Korhonen

doi:10.1007/s10237-025-01961-8

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Mechanobiochemical finite element model to analyze impact-loading-induced cell damage, subsequent proteoglycan loss, and anti-oxidative treatment effects in articular cartilage

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Mechanobiochemical finite element model to analyze impact-loading-induced cell damage, subsequent proteoglycan loss, and anti-oxidative treatment effects in articular cartilage

Joonas P Kosonen, Atte S A Eskelinen, Gustavo A Orozco, Mitchell C Coleman, Jessica E Goetz, Donald D Anderson, Alan J Grodzinsky, Petri Tanska and Rami K Korhonen

Biomechanics and modeling in mechanobiology, Vol.24(4), pp.1191-1206

08/2025

DOI: 10.1007/s10237-025-01961-8

PMCID: PMC12246027

PMID: 40348944

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Abstract

Joint trauma often leads to articular cartilage degeneration and post-traumatic osteoarthritis (PTOA). Pivotal determinants include trauma-induced excessive tissue strains that damage cartilage cells. As a downstream effect, these damaged cells can trigger cartilage degeneration via oxidative stress, cell death, and proteolytic tissue degeneration. N-acetylcysteine (NAC) has emerged as an antioxidant capable of inhibiting oxidative stress, cell death, and cartilage degeneration post-impact. However, the temporal effects of NAC are not fully understood and remain difficult to assess solely by physical experiments. Thus, we developed a computational finite element analysis framework to simulate a drop-tower impact of cartilage in Abaqus, and subsequent oxidative stress-related cell damage, and NAC treatment upon cartilage proteoglycan content in Comsol Multiphysics, based on prior ex vivo experiments. Model results provide evidence that immediate NAC treatment can reduce proteoglycan loss by mitigating oxidative stress, cell death (improved proteoglycan biosynthesis), and enzymatic proteoglycan depletion. Our simulations also indicate that delayed NAC treatment may not inhibit cartilage proteoglycan loss despite reduced cell death after impact. These results enhance understanding of the temporal effects of impact-related cell damage and treatment that are critical for the development of effective treatments for PTOA. In the future, our modeling framework could increase understanding of time-dependent mechanisms of oxidative stress and downstream effects in injured cartilage and aid in developing better treatments to mitigate PTOA progression.

Oxidative Stress

Proteoglycan

Post-traumatic osteoarthritis

Finite element model

Anti-oxidative treatment

Cell death

Details

Title: Subtitle: Mechanobiochemical finite element model to analyze impact-loading-induced cell damage, subsequent proteoglycan loss, and anti-oxidative treatment effects in articular cartilage
Creators: Joonas P Kosonen - University of Eastern Finland
Atte S A Eskelinen - University of Eastern Finland
Gustavo A Orozco - University of Eastern Finland
Mitchell C Coleman - Departments of Orthopedics and Rehabilitation and Biomedical Engineering, University of Iowa, Iowa, USA
Jessica E Goetz - Departments of Orthopedics and Rehabilitation and Biomedical Engineering, University of Iowa, Iowa, USA
Donald D Anderson - Departments of Orthopedics and Rehabilitation and Biomedical Engineering, University of Iowa, Iowa, USA
Alan J Grodzinsky - Massachusetts Institute of Technology
Petri Tanska - University of Eastern Finland
Rami K Korhonen - University of Eastern Finland
Resource Type: Journal article
Publication Details: Biomechanics and modeling in mechanobiology, Vol.24(4), pp.1191-1206
DOI: 10.1007/s10237-025-01961-8
PMID: 40348944
PMCID: PMC12246027
NLM abbreviation: Biomech Model Mechanobiol
ISSN: 1617-7959
eISSN: 1617-7940
Publisher: SPRINGER HEIDELBERG
Grant note: 354916 / Strategic funding of the University of Eastern Finland, Academy of Finland 240098 / Sigrid Juselius Foundation 363459 / Strategic funding of the University of Eastern Finland, Academy of Finland NNF21OC0065373 / Novo Nordisk Foundation (the Center for Mathematical Modeling of Knee Osteoarthritis (MathKOA)) 240074 / Päivikki and Sakari Sohlberg Foundation
Language: English
Electronic publication date: 05/10/2025
Date published: 08/2025
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Orthopedics and Rehabilitation; Industrial and Systems Engineering; Radiation Oncology
Record Identifier: 9984822965002771

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