A biomechanical mathematical model for the collagen bundle distribution-dependent contraction and subsequent retraction of healing dermal wounds

Koppenol, Daniël C.; Vermolen, F.J.; Niessen, Frank B.; Zuijlen, Paul P. M. van; Vuik, C.

doi:10.1007/s10237-016-0821-2

Cited by 17 publications

(16 citation statements)

References 63 publications

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“…More recently, continuum models have appeared where the dermis is modeled as a hyperelastic solid (Koppenol et al. 2017a ; Valero et al. 2013 , 2015 ).…”

Section: Discussionmentioning

confidence: 99%

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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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“…More recently, continuum models have appeared where the dermis is modeled as a hyperelastic solid (Koppenol et al. 2017a ; Valero et al. 2013 , 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“… 1995 ; Koppenol et al. 2017a , b ): The parameter represents the total generated stress by the myofibroblast population, is the generated stress per unit cell density and the inverse of the unit collagen molecule concentration, and R is a fixed constant.…”

Section: Development Of the Mathematical Modelmentioning

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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“…Hence, an important potential application of this theory is the development of a mechanochemical model of dermal wound healing. Indeed, it would be fruitful to build on recent theoretical models of the wound healing process that have considered aspects of the interplay between fibroblasts, keratinocytes and growth factors (Menon et al, 2012), the complementary rôles of TGF-β and tissue tension (Murphy et al, 2011a(Murphy et al, , 2012, the interplay between these components and ECM deformation (Valero et al, 2014), and their rôle in hypertrophic scar formation (Koppenol et al, 2017b) and wound retraction (Koppenol et al, 2017a).…”

Section: Discussionmentioning

confidence: 99%

A model for one-dimensional morphoelasticity and its application to fibroblast-populated collagen lattices

Menon

Hall

McCue

et al. 2017

Biomech Model Mechanobiol

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The mechanical behaviour of solid biological tissues has long been described using models based on classical continuum mechanics. However, the classical continuum theories of elasticity and viscoelasticity cannot easily capture the continual remodelling and associated structural changes in biological tissues. Furthermore, models drawn from plasticity theory are difficult to apply and interpret in this context, where there is no equivalent of a yield stress or flow rule. In this work, we describe a novel one-dimensional mathematical model of tissue remodelling based on the multiplicative decomposition of the deformation gradient. We express the mechanical effects of remodelling as an evolution equation for the effective strain, a measure of the difference between the current state and a hypothetical mechanically relaxed state of the tissue. This morphoelastic model combines the simplicity and interpretability of classical viscoelastic models with the versatility of plasticity theory. A novel feature of our model is that while most models describe growth as a continuous quantity, here we begin with discrete cells and develop a continuum representation of lattice remodelling based on an appropriate limit of the behaviour of discrete cells. To demonstrate the utility of our approach, we use this framework to capture qualitative aspects of the continual remodelling observed in fibroblast-populated collagen lattices, in particular its contraction and its subsequent sudden re-expansion when remodelling is interrupted.

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“…Collagen (COL) fibers represent 60-80% of skin dry weight and confer skin its resistance to mechanical stress [1][2][3][4]. The skin is a layered tissue, and the collagen composition and morphology of each layer is different [5,6].…”

Section: Introductionmentioning

confidence: 99%

Exogenous supply of Hsp47 triggers fibrillar collagen deposition in skin cell cultures in vitro

Khan

Sankaran

Llontop

et al. 2020

BMC Mol and Cell Biol

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Background: Collagen is a structural protein that provides mechanical stability and defined architectures to skin. In collagen-based skin disorders this stability is lost, either due to mutations in collagens or in the chaperones involved in collagen assembly. This leads to chronic wounds, skin fragility, and blistering. Existing approaches to treat such conditions rely on administration of small molecules to simulate collagen production, like 4phenylbutyrate (4-PBA) or growth factors like TGF-β. However, these molecules are not specific for collagen synthesis, and result in unsolicited side effects. Hsp47 is a collagen-specific chaperone with a major role in collagen biosynthesis. Expression levels of Hsp47 correlate with collagen deposition. This article explores the stimulation of collagen deposition by exogenously supplied Hsp47 (collagen specific chaperone) to skin cells, including specific collagen subtypes quantification. Results: Here we quantify the collagen deposition level and the types of deposited collagens after Hsp47 stimulation in different in vitro cultures of cells from human skin tissue (fibroblasts NHDF, keratinocytes HaCat and endothelial cells HDMEC) and mouse fibroblasts (L929 and MEF). We find upregulated deposition of fibrillar collagen subtypes I, III and V after Hsp47 delivery. Network collagen IV deposition was enhanced in HaCat and HDMECs, while fibril-associated collagen XII was not affected by the increased intracellular Hsp47 levels. The deposition levels of fibrillar collagen were cell-dependent i.e. Hsp47-stimulated fibroblasts deposited significantly higher amount of fibrillar collagen than Hsp47-stimulated HaCat and HDMECs. Conclusions: A 3-fold enhancement of collagen deposition was observed in fibroblasts upon repeated dosage of Hsp47 within the first 6 days of culture. Our results provide fundamental understanding towards the idea of using Hsp47 as therapeutic protein to treat collagen disorders.

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A biomechanical mathematical model for the collagen bundle distribution-dependent contraction and subsequent retraction of healing dermal wounds

Cited by 17 publications

References 63 publications

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

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

A model for one-dimensional morphoelasticity and its application to fibroblast-populated collagen lattices

Exogenous supply of Hsp47 triggers fibrillar collagen deposition in skin cell cultures in vitro

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