Mechano-biological and bio-mechanical pathways in cutaneous wound healing.
Injuries to the skin heal through coordinated action of fibroblast-mediated extracellular matrix (ECM) deposition, ECM remodeling, and wound contraction. Defects involving the dermis result in fibrotic scars featuring increased stiffness and altered collagen content and organization. Although comput...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1010902 |
| _version_ | 1797850278866714624 |
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| author | Marco Pensalfini Adrian Buganza Tepole |
| author_facet | Marco Pensalfini Adrian Buganza Tepole |
| author_sort | Marco Pensalfini |
| collection | DOAJ |
| description | Injuries to the skin heal through coordinated action of fibroblast-mediated extracellular matrix (ECM) deposition, ECM remodeling, and wound contraction. Defects involving the dermis result in fibrotic scars featuring increased stiffness and altered collagen content and organization. Although computational models are crucial to unravel the underlying biochemical and biophysical mechanisms, simulations of the evolving wound biomechanics are seldom benchmarked against measurements. Here, we leverage recent quantifications of local tissue stiffness in murine wounds to refine a previously-proposed systems-mechanobiological finite-element model. Fibroblasts are considered as the main cell type involved in ECM remodeling and wound contraction. Tissue rebuilding is coordinated by the release and diffusion of a cytokine wave, e.g. TGF-β, itself developed in response to an earlier inflammatory signal triggered by platelet aggregation. We calibrate a model of the evolving wound biomechanics through a custom-developed hierarchical Bayesian inverse analysis procedure. Further calibration is based on published biochemical and morphological murine wound healing data over a 21-day healing period. The calibrated model recapitulates the temporal evolution of: inflammatory signal, fibroblast infiltration, collagen buildup, and wound contraction. Moreover, it enables in silico hypothesis testing, which we explore by: (i) quantifying the alteration of wound contraction profiles corresponding to the measured variability in local wound stiffness; (ii) proposing alternative constitutive links connecting the dynamics of the biochemical fields to the evolving mechanical properties; (iii) discussing the plausibility of a stretch- vs. stiffness-mediated mechanobiological coupling. Ultimately, our model challenges the current understanding of wound biomechanics and mechanobiology, beside offering a versatile tool to explore and eventually control scar fibrosis after injury. |
| first_indexed | 2024-04-09T18:58:57Z |
| format | Article |
| id | doaj.art-129f11753b81447b8e80e032e77ca468 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-04-09T18:58:57Z |
| publishDate | 2023-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-129f11753b81447b8e80e032e77ca4682023-04-09T05:31:37ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582023-03-01193e101090210.1371/journal.pcbi.1010902Mechano-biological and bio-mechanical pathways in cutaneous wound healing.Marco PensalfiniAdrian Buganza TepoleInjuries to the skin heal through coordinated action of fibroblast-mediated extracellular matrix (ECM) deposition, ECM remodeling, and wound contraction. Defects involving the dermis result in fibrotic scars featuring increased stiffness and altered collagen content and organization. Although computational models are crucial to unravel the underlying biochemical and biophysical mechanisms, simulations of the evolving wound biomechanics are seldom benchmarked against measurements. Here, we leverage recent quantifications of local tissue stiffness in murine wounds to refine a previously-proposed systems-mechanobiological finite-element model. Fibroblasts are considered as the main cell type involved in ECM remodeling and wound contraction. Tissue rebuilding is coordinated by the release and diffusion of a cytokine wave, e.g. TGF-β, itself developed in response to an earlier inflammatory signal triggered by platelet aggregation. We calibrate a model of the evolving wound biomechanics through a custom-developed hierarchical Bayesian inverse analysis procedure. Further calibration is based on published biochemical and morphological murine wound healing data over a 21-day healing period. The calibrated model recapitulates the temporal evolution of: inflammatory signal, fibroblast infiltration, collagen buildup, and wound contraction. Moreover, it enables in silico hypothesis testing, which we explore by: (i) quantifying the alteration of wound contraction profiles corresponding to the measured variability in local wound stiffness; (ii) proposing alternative constitutive links connecting the dynamics of the biochemical fields to the evolving mechanical properties; (iii) discussing the plausibility of a stretch- vs. stiffness-mediated mechanobiological coupling. Ultimately, our model challenges the current understanding of wound biomechanics and mechanobiology, beside offering a versatile tool to explore and eventually control scar fibrosis after injury.https://doi.org/10.1371/journal.pcbi.1010902 |
| spellingShingle | Marco Pensalfini Adrian Buganza Tepole Mechano-biological and bio-mechanical pathways in cutaneous wound healing. PLoS Computational Biology |
| title | Mechano-biological and bio-mechanical pathways in cutaneous wound healing. |
| title_full | Mechano-biological and bio-mechanical pathways in cutaneous wound healing. |
| title_fullStr | Mechano-biological and bio-mechanical pathways in cutaneous wound healing. |
| title_full_unstemmed | Mechano-biological and bio-mechanical pathways in cutaneous wound healing. |
| title_short | Mechano-biological and bio-mechanical pathways in cutaneous wound healing. |
| title_sort | mechano biological and bio mechanical pathways in cutaneous wound healing |
| url | https://doi.org/10.1371/journal.pcbi.1010902 |
| work_keys_str_mv | AT marcopensalfini mechanobiologicalandbiomechanicalpathwaysincutaneouswoundhealing AT adrianbuganzatepole mechanobiologicalandbiomechanicalpathwaysincutaneouswoundhealing |