A two-compartment mechanochemical model of the roles of transforming growth factor <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si0127.gif" overflow="scroll"><mml:mi>β</mml:mi></mml:math> and tissue tension in dermal wound healing

Murphy, Kelly E.; Hall, Cameron L.; McCue, Scott W.; McElwain, D. L. S.

doi:10.1016/j.jtbi.2010.12.011

Cited by 26 publications

(28 citation statements)

References 74 publications

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“…These results would suggest that TGF-ß3 is required for fibroblast/myofibroblast transdifferentiation and proper granulation tissue maturation in the wound area and are consistent with the effect of the injection of a viral construct containing a mutant TGF-ß3 into cutaneous wounds [26]. Both studies would be consistent with a mathematical model that predicts an increase in wound size after early elimination of TGF-ß [47].…”

Section: Discussionsupporting

confidence: 77%

Transforming Growth Factor Beta 3 Is Required for Excisional Wound Repair In Vivo

Naridze

Morrison

et al. 2012

PLoS ONE

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Wound healing is a complex process that relies on proper levels of cytokines and growth factors to successfully repair the tissue. Of particular interest are the members of the transforming growth factor family. There are three TGF-ß isoforms–TGF- ß 1, 2, and 3, each isoform showing a unique expression pattern, suggesting that they each play a distinct function during development and repair. Previous studies reported an exclusive role for TGF-ß 3 in orofacial development and a potent anti-scarring effect. However, the role of TGF- ß 3 in excisional wound healing and keratinocyte migration remains poorly understood. We tested the effect of TGF-ß 3 levels on excisional cutaneous wounds in the adult mouse by directly injecting recombinant TGF-ß 3 or neutralizing antibody against TGF-ß 3 (NAB) in the wounds. Our results demonstrate that TGF-ß 3 does not promote epithelialization. However, TGF-ß 3 is necessary for wound closure as wounds injected with neutralizing antibody against TGF-ß 3 showed increased epidermal volume and proliferation in conjunction with a delay in keratinocyte migration. Wild type keratinocytes treated with NAB and Tgfb3-deficient keratinocytes closed an in vitro scratch wound with no delay, suggesting that our in vivo observations likely result from a paracrine effect.

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Section: Discussionsupporting

confidence: 77%

Transforming Growth Factor Beta 3 Is Required for Excisional Wound Repair In Vivo

Naridze

Morrison

et al. 2012

PLoS ONE

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“…Both works suggest that differentiation is guided by stress. Whereas Javierre et al [23] claim that the stress that guides the process is the force exerted by the cells, Murphy et al [24] propose that this stress comes from the elastic component of the ECM. Additionally, Javierre et al [23] investigated the effect of wound shape on the contraction kinetics, whereas Murphy et al [24], [25] focused on a more detailed representation of the biochemical signaling of wound contraction.…”

Section: Introductionmentioning

confidence: 99%

“…Whereas Javierre et al [23] claim that the stress that guides the process is the force exerted by the cells, Murphy et al [24] propose that this stress comes from the elastic component of the ECM. Additionally, Javierre et al [23] investigated the effect of wound shape on the contraction kinetics, whereas Murphy et al [24], [25] focused on a more detailed representation of the biochemical signaling of wound contraction. Furthermore, Javierre et al [23] considered a unique growth factor that regulates differentiation and collagen production, whereas Murphy et al [25] included the chemical kinetics of two different growth factors (PDGF and TGF-) separately.…”

Section: Introductionmentioning

confidence: 99%

A Cell-Regulatory Mechanism Involving Feedback between Contraction and Tissue Formation Guides Wound Healing Progression

et al. 2014

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Wound healing is a process driven by cells. The ability of cells to sense mechanical stimuli from the extracellular matrix that surrounds them is used to regulate the forces that cells exert on the tissue. Stresses exerted by cells play a central role in wound contraction and have been broadly modelled. Traditionally, these stresses are assumed to be dependent on variables such as the extracellular matrix and cell or collagen densities. However, we postulate that cells are able to regulate the healing process through a mechanosensing mechanism regulated by the contraction that they exert. We propose that cells adjust the contraction level to determine the tissue functions regulating all main activities, such as proliferation, differentiation and matrix production. Hence, a closed-regulatory feedback loop is proposed between contraction and tissue formation. The model consists of a system of partial differential equations that simulates the evolution of fibroblasts, myofibroblasts, collagen and a generic growth factor, as well as the deformation of the extracellular matrix. This model is able to predict the wound healing outcome without requiring the addition of phenomenological laws to describe the time-dependent contraction evolution. We have reproduced two in vivo experiments to evaluate the predictive capacity of the model, and we conclude that there is feedback between the level of cell contraction and the tissue regenerated in the wound.

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“…2012). Therefore, we adopted like Murphy et al (2011) and Bowden et al (2016), a morphoelastic framework in this study. With the application of such a framework, it becomes relatively simple to simulate both the long term deformation of a skin graft and the development of residual stresses within the modeled portion of dermal layer.…”

Section: Discussionmentioning

confidence: 99%

Biomedical implications from a morphoelastic continuum model for the simulation of contracture formation in skin grafts that cover excised burns

Koppenol

Vermolen

2017

Biomech Model Mechanobiol

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A continuum hypothesis-based model is developed for the simulation of the (long term) contraction of skin grafts that cover excised burns in order to obtain suggestions regarding the ideal length of splinting therapy and when to start with this therapy such that the therapy is effective optimally. Tissue is modeled as an isotropic, heterogeneous, morphoelastic solid. With respect to the constituents of the tissue, we selected the following constituents as primary model components: fibroblasts, myofibroblasts, collagen molecules, and a generic signaling molecule. Good agreement is demonstrated with respect to the evolution over time of the surface area of unmeshed skin grafts that cover excised burns between outcomes of computer simulations obtained in this study and scar assessment data gathered previously in a clinical study. Based on the simulation results, we suggest that the optimal point in time to start with splinting therapy is directly after placement of the skin graft on its recipient bed. Furthermore, we suggest that it is desirable to continue with splinting therapy until the concentration of the signaling molecules in the grafted area has become negligible such that the formation of contractures can be prevented. We conclude this study with a presentation of some alternative ideas on how to diminish the degree of contracture formation that are not based on a mechanical intervention, and a discussion about how the presented model can be adjusted.

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A two-compartment mechanochemical model of the roles of transforming growth factor β and tissue tension in dermal wound healing

Cited by 26 publications

References 74 publications

Transforming Growth Factor Beta 3 Is Required for Excisional Wound Repair In Vivo

Transforming Growth Factor Beta 3 Is Required for Excisional Wound Repair In Vivo

A Cell-Regulatory Mechanism Involving Feedback between Contraction and Tissue Formation Guides Wound Healing Progression

Biomedical implications from a morphoelastic continuum model for the simulation of contracture formation in skin grafts that cover excised burns

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