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A numerical framework for mechano-regulated tendon healing-Simulation of early regeneration of the Achilles tendon

Notermans, Thomas LU ; Tanska, Petri ; Korhonen, Rami K. ; Khayyeri, Hanifeh LU and Isaksson, Hanna LU orcid (2021) In PLoS Computational Biology 17(2). p.1008636-1008636
Abstract

Mechano-regulation during tendon healing, i.e. the relationship between mechanical stimuli and cellular response, has received more attention recently. However, the basic mechanobiological mechanisms governing tendon healing after a rupture are still not well-understood. Literature has reported spatial and temporal variations in the healing of ruptured tendon tissue. In this study, we explored a computational modeling approach to describe tendon healing. In particular, a novel 3D mechano-regulatory framework was developed to investigate spatio-temporal evolution of collagen content and orientation, and temporal evolution of tendon stiffness during early tendon healing. Based on an extensive literature search, two possible relationships... (More)

Mechano-regulation during tendon healing, i.e. the relationship between mechanical stimuli and cellular response, has received more attention recently. However, the basic mechanobiological mechanisms governing tendon healing after a rupture are still not well-understood. Literature has reported spatial and temporal variations in the healing of ruptured tendon tissue. In this study, we explored a computational modeling approach to describe tendon healing. In particular, a novel 3D mechano-regulatory framework was developed to investigate spatio-temporal evolution of collagen content and orientation, and temporal evolution of tendon stiffness during early tendon healing. Based on an extensive literature search, two possible relationships were proposed to connect levels of mechanical stimuli to collagen production. Since literature remains unclear on strain-dependent collagen production at high levels of strain, the two investigated production laws explored the presence or absence of collagen production upon non-physiologically high levels of strain (>15%). Implementation in a finite element framework, pointed to large spatial variations in strain magnitudes within the callus tissue, which resulted in predictions of distinct spatial distributions of collagen over time. The simulations showed that the magnitude of strain was highest in the tendon core along the central axis, and decreased towards the outer periphery. Consequently, decreased levels of collagen production for high levels of tensile strain were shown to accurately predict the experimentally observed delayed collagen production in the tendon core. In addition, our healing framework predicted evolution of collagen orientation towards alignment with the tendon axis and the overall predicted tendon stiffness agreed well with experimental data. In this study, we explored the capability of a numerical model to describe spatial and temporal variations in tendon healing and we identified that understanding mechano-regulated collagen production can play a key role in explaining heterogeneities observed during tendon healing.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Computational Biology
volume
17
issue
2
pages
1008636 - 1008636
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:33556080
  • scopus:85102221001
ISSN
1553-7358
DOI
10.1371/journal.pcbi.1008636
language
English
LU publication?
yes
additional info
Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
id
bdb75358-0e05-45e7-9365-d8127a05b3b7
date added to LUP
2021-03-19 09:38:37
date last changed
2024-04-18 04:47:02
@article{bdb75358-0e05-45e7-9365-d8127a05b3b7,
  abstract     = {{<p>Mechano-regulation during tendon healing, i.e. the relationship between mechanical stimuli and cellular response, has received more attention recently. However, the basic mechanobiological mechanisms governing tendon healing after a rupture are still not well-understood. Literature has reported spatial and temporal variations in the healing of ruptured tendon tissue. In this study, we explored a computational modeling approach to describe tendon healing. In particular, a novel 3D mechano-regulatory framework was developed to investigate spatio-temporal evolution of collagen content and orientation, and temporal evolution of tendon stiffness during early tendon healing. Based on an extensive literature search, two possible relationships were proposed to connect levels of mechanical stimuli to collagen production. Since literature remains unclear on strain-dependent collagen production at high levels of strain, the two investigated production laws explored the presence or absence of collagen production upon non-physiologically high levels of strain (&gt;15%). Implementation in a finite element framework, pointed to large spatial variations in strain magnitudes within the callus tissue, which resulted in predictions of distinct spatial distributions of collagen over time. The simulations showed that the magnitude of strain was highest in the tendon core along the central axis, and decreased towards the outer periphery. Consequently, decreased levels of collagen production for high levels of tensile strain were shown to accurately predict the experimentally observed delayed collagen production in the tendon core. In addition, our healing framework predicted evolution of collagen orientation towards alignment with the tendon axis and the overall predicted tendon stiffness agreed well with experimental data. In this study, we explored the capability of a numerical model to describe spatial and temporal variations in tendon healing and we identified that understanding mechano-regulated collagen production can play a key role in explaining heterogeneities observed during tendon healing.</p>}},
  author       = {{Notermans, Thomas and Tanska, Petri and Korhonen, Rami K. and Khayyeri, Hanifeh and Isaksson, Hanna}},
  issn         = {{1553-7358}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{2}},
  pages        = {{1008636--1008636}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS Computational Biology}},
  title        = {{A numerical framework for mechano-regulated tendon healing-Simulation of early regeneration of the Achilles tendon}},
  url          = {{http://dx.doi.org/10.1371/journal.pcbi.1008636}},
  doi          = {{10.1371/journal.pcbi.1008636}},
  volume       = {{17}},
  year         = {{2021}},
}