Surrogate modeling of articular cartilage degradation to understand the synergistic role of MMP-1 and MMP-9: a case study

Tanvir R. Faisal, Malek Adouni, Yasin Y. Dhaher

Research output: Contribution to journalArticlepeer-review

Abstract

A characteristic feature of arthritic diseases is cartilage extracellular matrix (ECM) degradation, often orchestrated by the overexpression of matrix metalloproteinases (MMPs) and other proteases. The interplay between fibril level degradation and the tissue-level aggregate response to biomechanical loading was explored in this work by a computational multiscale cartilaginous model. We considered the relative abundance of collagenases (MMP-1) and gelatinases (MMP-9) in surrogate models, where the diffusion (spatial distribution) of these enzymes and the subsequent, co-localized fibrillar damage were spatially randomized with Latin Hypercube Sampling. The computational model was constructed by incorporating the results from prior molecular dynamics simulations (tensile test) of microfibril degradation into a hyper-elastoplastic fibril-reinforced cartilage model. Including MMPs-mediated collagen fibril-level degradation in computational models may help understand the ECM pathomechanics at the tissue level. The mechanics of cartilage tissue and fibril show variations in mechanical integrity depending on the different combinations of MMPs-1 and 9 with a concentration ratio of 1:1, 3:1, and 1:3 in simulated indentation tests. The fibril yield (local failure) was initiated at 20.2 ± 3.0 (%) and at 23.0 ± 2.8 (%) of bulk strain for col 1:gel 3 and col 3: gel 1, respectively. The reduction in failure stress (global response) was 39.8% for col 1:gel 3, 37.5% for col 1:gel 1, and 36.7% for col 3:gel 1 compared with the failure stress of the degradation free tissue. These findings indicate that cartilage's global and local mechanisms of failure largely depend on the relative abundance of the two key enzymes—collagenase (MMP-1) and gelatinase (MMP-9) and the spatial characteristics of diffusion across the layers of the cartilage ECM.

Original languageEnglish (US)
JournalBiomechanics and Modeling in Mechanobiology
DOIs
StateAccepted/In press - 2022

Keywords

  • Cartilage degradation
  • Matrix metalloproteinases
  • MMP-1
  • MMP-9
  • Multiscale modeling

ASJC Scopus subject areas

  • Biotechnology
  • Modeling and Simulation
  • Mechanical Engineering

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