Skip to main content
Log in

A morphoelastic model for dermal wound closure

  • Original Paper
  • Published:
Biomechanics and Modeling in Mechanobiology Aims and scope Submit manuscript

Abstract

We develop a model of wound healing in the framework of finite elasticity, focussing our attention on the processes of growth and contraction in the dermal layer of the skin. The dermal tissue is treated as a hyperelastic cylinder that surrounds the wound and is subject to symmetric deformations. By considering the initial recoil that is observed upon the application of a circular wound, we estimate the degree of residual tension in the skin and build an evolution law for mechanosensitive growth of the dermal tissue. Contraction of the wound is governed by a phenomenological law in which radial pressure is prescribed at the wound edge. The model reproduces three main phases of the healing process. Initially, the wound recoils due to residual stress in the surrounding tissue; the wound then heals as a result of contraction and growth; and finally, healing slows as contraction and growth decrease. Over a longer time period, the surrounding tissue remodels, returning to the residually stressed state. We identify the steady state growth profile associated with this remodelled state. The model is then used to predict the outcome of rewounding experiments designed to quantify the amount of stress in the tissue, and also to simulate the application of pressure treatments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16

Similar content being viewed by others

Notes

  1. We note that there is a one-to-one map between all states. Our convention is generally to view all spatially dependent variables as functions of the independent variable \(R_0\). So, for example, we write \(T_{rr}(R)\) as \(T_{rr}(R_0)=T_{rr}(R(R_0))\).

  2. Numerically, we define steady state to be such that each \(\frac{\partial \gamma _i}{\partial t}\) is below a positive threshold value close to zero. For the simulations in Fig. 14, the threshold was taken to be \(10^{-5}\).

  3. To test this, we ran simulations where the axial deformation was not fixed according to \(\lambda (t)=\lambda (T)\), but instead satisfied the spring condition in Eq. (29j). In this case, the sensitivity of the remodelling time to the axial growth parameter was significantly lower than that presented in Fig. 14.

References

  • Alford P, Humphrey J, Taber L (2008) Growth and remodeling in a thick-walled artery model: effects of spatial variations in wall constituents. Biomech Model Mechanobiol 7(4):245–62

    Article  Google Scholar 

  • Ambrosi D, Mollica F (2004) The role of stress in the growth of a multicell spheroid. J Math Biol 48(5):477–99

    Article  MathSciNet  MATH  Google Scholar 

  • Annaidh A, Bruyère K, Destrade M, Gilchrist M, Maurini C, Otténio M, Saccomandi G (2012) Automated estimation of collagen fibre dispersion in the dermis and its contribution to the anisotropic behaviour of skin. Ann Biomed Eng 40(8):1666–78

    Article  Google Scholar 

  • Anzarut A, Olson J, Singh P, Rowe B, Tredget E (2009) The effectiveness of pressure garment therapy for the prevention of abnormal scarring after burn injury: a meta-analysis. J Plast Reconstr Aes 62(1):77–84

    Article  Google Scholar 

  • Bermudez D, Herdrich B, Xu J, Lind R, Beason D, Mitchell M, Soslowsky L, Liechty K (2011) Impaired biomechanical properties of diabetic skin implications in pathogenesis of diabetic wound complications. Am J Pathol 178(5):2215–23

    Article  Google Scholar 

  • Bowden L, Maini P, Moulton D, Tang J, Wang X, Liu P, Byrne H (2014) An ordinary differential equation model for full thickness wounds and the effects of diabetes. J Theor Biol 361:87–100

    Article  MATH  Google Scholar 

  • Chipev C, Simon M (2002) Phenotypic differences between dermal fibroblasts from different body sites determine their responses to tension and tgf\(\beta \)1. BMC Dermatol 2(1):13

    Article  Google Scholar 

  • Chung CY, Funamoto S, Firtel R (2001) Signaling pathways controlling cell polarity and chemotaxis. Trends Biochem Sci 26(9):557–566

    Article  Google Scholar 

  • Ciarletta P, Ben Amar M (2012) Papillary networks in the dermal-epidermal junction of skin: a biomechanical model. Mech Res Commun 42:68–76

    Article  Google Scholar 

  • Ciarletta P, Foret L, Ben Amar M (2011) The radial growth phase of malignant melanoma: multi-phase modelling, numerical simulations and linear stability analysis. J R Soc Interface 8(56):345–368

    Article  Google Scholar 

  • Clark R (1988) The molecular and cellular biology of wound repair. Plenum, New York

    Book  Google Scholar 

  • Cumming B, McElwain D, Upton Z (2010) A mathematical model of wound healing and subsequent scarring. J R Soc Interface 7(42):19–34

    Article  Google Scholar 

  • Dallon J (2000) Biological implications of a discrete mathematical model for collagen deposition and alignment in dermal wound repair. Math Med Biol 17(4):379–393

    Article  MATH  Google Scholar 

  • Dallon J, Sherratt J, Maini P (1999) Mathematical modelling of extracellular matrix dynamics using discrete cells: fiber orientation and tissue regeneration. J Theor Biol 199(4):449–71

    Article  Google Scholar 

  • Davidson L, Ezin A, Keller R (2002) Embryonic wound healing by apical contraction and ingression in xenopus laevis. Cell Motil Cytoskelet 53(3):163–176

    Article  Google Scholar 

  • Diridollou S, Patat F, Gens F, Vaillant L, Black D, Lagarde J, Gall Y, Berson M (2000) In vivo model of the mechanical properties of the human skin under suction. Skin Res Technol 6(4):214–221

    Article  Google Scholar 

  • Ehrlich H (1988) Wound closure: evidence of cooperation between fibroblasts and collagen matrix. Eye 2(2):149–157

    Article  Google Scholar 

  • Ehrlich H, Rajaratnam J (1990) Cell locomotion forces versus cell contraction forces for collagen lattice contraction: an in vitro model of wound contraction. Tissue Cell 22(4):407–417

    Article  Google Scholar 

  • Eringen A (1962) Nonlinear theory of continuous media. McGraw-Hill, New York

    Google Scholar 

  • Flynn C, Taberner A, Nielsen P (2011) Modeling the mechanical response of in vivo human skin under a rich set of deformations. Ann Biomed Eng 39(7):1935–46

    Article  Google Scholar 

  • Ghosh K, Pan Z, Guan E, Ge S, Liu Y, Nakamura T, Ren X, Rafailovich M, Clark RAF (2007) Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic properties. Biomaterials 28(4):671–679

    Article  Google Scholar 

  • Giele H, Liddiard K, Currie K, Wood F (1997) Direct measurement of cutaneous pressures generated by pressure garments. Burns 23(2):137–141

    Article  Google Scholar 

  • Goriely A, Vandiver R (2010) On the mechanical stability of growing arteries. IMA J Appl Math 75(4):549–570

    Article  MathSciNet  MATH  Google Scholar 

  • Goriely A, Moulton D, Vandiver R (2010) Elastic cavitation, tube hollowing, and differential growth in plants and biological tissues. Europhys Lett 91(1):18,001

    Article  Google Scholar 

  • Grinnell F, Zhu M, Carlson MA, Abrams JM (1999) Release of mechanical tension triggers apoptosis of human fibroblasts in a model of regressing granulation tissue. Exp Cell Res 248(2):608–619

    Article  Google Scholar 

  • Gross J, Farinelli W, Sadow P, Anderson R, Bruns R (1995) On the mechanism of skin wound “contraction”: a granulation tissue “knockout” with a normal phenotype. P Natl A Sci USA 92(13):5982–5986

    Article  Google Scholar 

  • Hex N, Bartlett C, Wright D, Taylor M, Varley D (2012) Estimating the current and future costs of type 1 and type 2 diabetes in the UK, including direct health costs and indirect societal and productivity costs. Diabetic Med 29(7):855–62

    Article  Google Scholar 

  • Huang C, Leavitt T, Bayer L, Orgill D (2014) Effect of negative pressure wound therapy on wound healing. Curr Prob Surg 51(7):301–31

    Article  Google Scholar 

  • Jacquet E, Josse G, Khatyr F, Garcin C (2008) A new experimental method for measuring skin’s natural tension. Skin Res Technol 14(1):1–7

    Google Scholar 

  • Jeffcoate W, Price P, Harding K (2004) Wound healing and treatments for people with diabetic foot ulcers. Diabetes Metab Res 20(Suppl 1):S78–89

    Article  Google Scholar 

  • Kessler D, Dethlefsen S, Haase I, Plomann M, Hirche F, Krieg T, Eckes B (2001) Fibroblasts in mechanically stressed collagen lattices assume a synthetic phenotype. J Biol Chem 276(39):36,575–36,585

    Article  Google Scholar 

  • Kischer C (1975) Alteration of hypertrophic scars induced by mechanical pressure. Arch Dermatol 111(1):60

    Article  Google Scholar 

  • Lin I, Taber L (1995) A model for stress-induced growth in the developing heart. J Biomech Eng 117(3):343

    Article  Google Scholar 

  • Maggelakis S (2004) Modelling the role of angiogenesis in epidermal wound healing. Discrete Contin Syst 4:267–273

    Article  MathSciNet  MATH  Google Scholar 

  • Martin P (1997) Wound healing: aiming for perfect skin regeneration. Science 276(5309):75–81

    Article  Google Scholar 

  • Martin P, Lewis J (1992) Actin cables and epidermal movement in embryonic wound healing. Nature 360(6400):179–83

    Article  Google Scholar 

  • McDougall S, Dallon J, Sherratt J, Maini P (2006) Fibroblast migration and collagen deposition during dermal wound healing: mathematical modelling and clinical implications. Philos T Roy Soc A 364(1843):1385–405

    Article  MathSciNet  Google Scholar 

  • McGrath M, Simon R (1983) Wound geometry and the kinetics of wound contraction. Plast Reconstr Surg 72(1):66–72

    Article  Google Scholar 

  • Mendez-Eastman S (2001) Guidelines for using negative pressure wound therapy. Adv Skin Wound Care 14(6):314–323

    Article  Google Scholar 

  • Monaco J, Lawrence W (2003) Acute wound healing an overview. Clin Plast Surg 30(1):1–12

    Article  Google Scholar 

  • Moulton D, Goriely A (2011) Possible role of differential growth in airway wall remodeling in asthma. J Appl Physiol 110(4):1003–12

    Article  Google Scholar 

  • North J, Gibson F (1978) Volume compressibility of human abdominal skin. J Biomech 11(4):203–207

    Article  Google Scholar 

  • Olsen L, Maini P, Sherratt J, Dallon J (1999) Mathematical modelling of anisotropy in fibrous connective tissue. Math Biosci 158(2):145–170

    Article  MATH  Google Scholar 

  • Pierce G, Mustoe T, Lingelbach J, Masakowski V, Griffin G, Senior R, Deuel T (1989) Platelet-derived growth factor and transforming growth factor-beta enhance tissue repair activities by unique mechanisms. J Cell Biol 109(1):429–440

    Article  Google Scholar 

  • Press W, Vetterling W, Teukolsky S, Flannery B, Greenwell Yanik E (1994) Numerical recipes in fortran-the art of scientific computing. SIAM Rev 36(1):149–149

    Google Scholar 

  • Rachev A, Stergiopulos N, Meister J (1998) A model for geometric and mechanical adaptation of arteries to sustained hypertension. J Biomech Eng 120(1):9

    Article  Google Scholar 

  • Rivlin R (1948a) Large elastic deformations of isotropic materials I. Philos T Roy Soc A 240(822):459–490

    Article  MathSciNet  MATH  Google Scholar 

  • Rivlin R (1948b) Large elastic deformations of isotropic materials III. Philos T Roy Soc A 240(823):509–525

    Article  MathSciNet  MATH  Google Scholar 

  • Rodriguez E, Hoger A, McCulloch A (1994) Stress-dependent finite growth in soft elastic tissues. J Biomech 27(4):455–467

    Article  Google Scholar 

  • Segal R, Diegelmann R, Ward K, Reynolds A (2012) A differential equation model of collagen accumulation in a healing wound. B Math Biol 74(9):2165–82

    Article  MathSciNet  MATH  Google Scholar 

  • Sherratt J, Murray J (1990) Models of epidermal wound healing. P Biol Sci 241(1300):29–36

    Article  Google Scholar 

  • Sherratt J, Murray J (1991) Mathematical analysis of a basic model for epidermal wound healing. J Math Biol 29:389–404

    Article  MATH  Google Scholar 

  • Sherratt J, Murray J (1992) Epidermal wound healing: the clinical implications of a simple mathematical model. Cell Transpl 1(5):365–371

    Google Scholar 

  • Singer A, Clark R (1999) Cutaneous wound healing. N Eng J Med 341:738–746

    Article  Google Scholar 

  • Taber L (1998) A model for aortic growth based on fluid shear and fiber stresses. J Biomech Eng 120(3):348

    Article  Google Scholar 

  • Taber L (2001) Biomechanics of cardiovascular development. Annu Rev Biomed Eng 3:1–25

    Article  Google Scholar 

  • Taber L (2009) Towards a unified theory for morphomechanics. Philos T R Soc A 367(1902):3555–83

    Article  MathSciNet  MATH  Google Scholar 

  • Taber L, Eggers D (1996) Theoretical study of stress-modulated growth in the aorta. J Theor Biol 180(4):343–57

    Article  Google Scholar 

  • Tracqui P, Woodward D, Cruywagen G, Cook J, Murray J (1995) A mechanical model for fibroblast-driven wound healing. J Biol Syst 3(4):1075–1084

    Article  Google Scholar 

  • Tranquillo R, Murray J (1992) Continuum model of fibroblast-driven wound contraction: Inflammation-mediation. J Theor Biol 158(2):135–172

    Article  Google Scholar 

  • Uhal B, Ramos C, Joshi I, Bifero A, Pardo A, Selman M (1998) Cell size, cell cycle, and alpha -smooth muscle actin expression by primary human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol 275(5):998–1005

    Google Scholar 

  • Vermolen F, Javierre E (2012) A finite-element model for healing of cutaneous wounds combining contraction, angiogenesis and closure. J Math Biol 65(5):967–96

    Article  MathSciNet  MATH  Google Scholar 

  • Wahl S, Wong H, McCartney-Francis N (1989) Role of growth factors in inflammation and repair. J Cell Bioch 40(2):193–9

    Article  Google Scholar 

  • Wrobel L, Fray T, Molloy J, Adams J, Armitage M, Sparrow J (2002) Contractility of single human dermal myofibroblasts and fibroblasts. Cell Motil Cytoskelet 52(2):82–90

    Article  Google Scholar 

  • Wu M, Ben Amar M (2015) Growth and remodelling for profound circular wounds in skin. Biomech Model Mechanobiol 14(2):357–370

    Article  Google Scholar 

  • Wyczalkowski M, Varner V, Taber L (2013) Computational and experimental study of the mechanics of embryonic wound healing. J Mech Behav Biomed 28:125–146

    Article  Google Scholar 

  • Yang L, Witten T, Pidaparti R (2013) A biomechanical model of wound contraction and scar formation. J Theor Biol 332(null):228–248

    Article  MathSciNet  MATH  Google Scholar 

Download references

Acknowledgments

LGB gratefully acknowledges the UK’s Engineering and Physical Sciences Research Council for funding through a studentship at the Systems Biology programme of the University of Oxford’s Doctoral Training Centre. The authors thank Dr. P.Y. Liu and Dr. X.T. Wang (Department of Plastic Surgery, Alpert Medical School of Brown University) for valuable discussions.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. G. Bowden.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bowden, L.G., Byrne, H.M., Maini, P.K. et al. A morphoelastic model for dermal wound closure. Biomech Model Mechanobiol 15, 663–681 (2016). https://doi.org/10.1007/s10237-015-0716-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10237-015-0716-7

Keywords

Navigation