A multi-layered model of human skin elucidates mechanisms of wrinkling in the forehead
Graphical abstract
(a) A schematic of our six-layered, 3-D skin model; (b) Predicted wrinkling under age-related volumetric tissue loss visualized as through-thickness Green-Lagrange strains with water content (WC) = 36%; (c) Maximum wrinkle depth as a function of age-related volumetric tissue loss shown for three values of WC.
Introduction
Skin wrinkling, especially in the facial area, is a prominent sign of aging and is a growing area of research aimed at developing cosmetics and dermatological treatments. The rising demand for skin care and rejuvenation drives a thriving anti-aging industry with a compound annual growth rate of 5.7% (2018) and expected to reach $66.2B by 2023, in which anti-wrinkle products account for the largest segment (The Express Wire, 2019). To better understand and treat undesirable skin wrinkles, it is vitally important to elucidate the underlying mechanisms of skin wrinkling, a largely mechanical process.
Human skin, a multi-layer composite, has six mechanically distinct layers: from the outermost inward they are the stratum corneum (SC), viable epidermis (VE), dermal-epidermal-junction (DEJ), papillary dermis (PD), reticular dermis (RD), and hypodermis (HD) (Montagna, 2012). The thin SC layer actively interacts with environment, and together with the VE, they constitute the epidermis. The PD and RD layers constitute the dermis and contain collagen, the main load-bearing constituent of skin, which presents as densely packed fibers in the relatively thick RD and a loose-meshed network in the thin PD. The DEJ is an extremely thin, cutaneous membrane with prominent undulations that firmly join the epidermis and dermis. Finally, the HD contains subcutaneous tissues and its thickness largely determines the shape of the human face.
Two main types of wrinkles form in human skin: dynamic and static. Although the morphological patterns vary in facial sites, wrinkles tend to develop perpendicular to the direction of the underlying muscle contraction (Lemperle, 2001), e.g. horizontal wrinkles on the forehead and radiating “crow's feet” near the eyes. Dynamic wrinkles appear at all ages during facial expression, i.e. the underlying skeletal muscles contract, causing large compressive strains and mechanical buckling of the skin (Mazza et al., 2007; Genzer and Groenewold, 2006). Both the shape and depth of these “expressional lines” correlate with the level of muscle contraction (Hara et al., 2017), and they go away when the underlying facial musculature relaxes.
Static or permanent skin wrinkles persist regardless of muscle relaxation and usually emerge in the early 30s and grow in severity with aging (Imokawa, 2008; Tsukahara et al., 2012; Kuwazuru et al., 2012; Hara et al., 2017). The transition from dynamic to static wrinkles may be due to damage from frequent muscle contractions, and the progression of persistent wrinkles follows the aging process.
Aging of human skin is both a morphological and mechanical process.
In particular, aging brings prominent modifications to soft tissues in the focal regions of facial skin. Histological findings highlight architectural changes in fibrous tissues, e.g. the subcutaneous musculo aponeurotic system (SMAS) in the dermis (Sandulescu et al., 2019a, b), and loss of subcutaneous fullness (Coleman and Grover, 2006) underlying wrinkling areas in the cheek and near the mouth and eyes. Wrinkling in aged skin in the forehead correlates less with changes in the SMAS, but with the significant atrophy present in epidermal and dermal layers where the dermis reduces to approximately half of its original thickness (El-Domyati et al., 2014; Tsukahara et al., 2012). Histological evidence from aged, wrinkled skin also shows loss of elastic fibers and a degeneration of collagen bundles in the dermis (Contet-Audonneau et al., 1999; Oba and Edwards, 2006; Lee et al., 2008; Zöllner et al., 2013; Kruglikov and Scherer, 2018; Pan et al., 2019), resulting in a progressive loss of stiffness and elasticity. Agache et al. (1980) measured the elastic modulus under torsion as 0.42 MPa for young skin ( 30 years old) and 0.85 MPa for aged skin ( 30) Additionally, the SC is sensitive to humidity and thus the dryness of skin can drastically change the elastic modulus of young skin (Wu et al., 2006), from MPa (Diridollou et al., 2000; Pailler-Mattei et al., 2008) to GPa (Wu et al., 2006).
Skin wrinkling is a complicated, largely mechanical process. Extensive theoretical and computational studies have elucidated the wrinkling and post-buckling behavior of multi-layered composite systems, and such understanding informs simulations targeted at understanding skin wrinkling (Genzer and Groenewold, 2006; Lejeune et al., 2016; Holland et al., 2017; Wang and Zhao, 2015; Zhao et al., 2015; Cao and Hutchinson, 2012; Jia et al., 2012). Researchers specifically studied wrinkling of human skin using the finite element method in combination with experimental data. Existing simulations focused largely on dynamic wrinkles, and offer valuable insights on factors affecting skin folding, e.g. surface defects (Shiihara et al., 2015; Limbert and Kuhl, 2018), mechanics of the stratum corneum (Lévêque and Audoly, 2013; Leyva-Mendivil et al., 2015; Limbert and Kuhl, 2018), and the arrangement of collagen fibers in the dermis (Flynn and McCormack, 2009; Pond et al., 2018). There are many models of human skin including only two or three mechanical layers in 3-D, e.g. probing the anisotropic behavior of the dermis (Flynn and McCormack, 2009) and even incorporating realistic surface microstructures (Limbert and Kuhl, 2018). Four- and five-layered models pioneered transitions in wrinkling modes between skin interfaces to help explain the formation of deep wrinkles (Kuwazuru et al., 2008; Shiihara et al., 2015).
These simulations (above) all excluded the DEJ largely due to lack of experimental data and challenges in modeling methods. Additionally, the current literature has not addressed how age-related tissue loss affects wrinkling formation, cf. Cao et al. (2012).
Contraction of skeletal muscle, as well as age-related changes in both the volume and the mechanical properties of skin layers are plausible mechanisms for the formation of wrinkles in the skin of the forehead. Here we established a six-layered model of human skin (including the DEJ), realized in FEBio (Maas et al., 2012), by leveraging morphological and biomechanical data on human skin of the forehead specifically. Exercising our new model we aimed to quantify the effects of three potential mechanisms of wrinkle formation: (1) skin compression due to muscle contraction (dynamic wrinkles); (2) age-related volumetric tissue loss (static wrinkles); and (3) the combined effects of both mechanisms. Since hydration of the SC significantly affects its stiffness we also aimed to quantify the influence SC hydration with these three potential mechanisms of wrinkle formation. Finally, since we are the first to consider the DEJ in a six-layered model of human skin, we conducted a parametric study on its stiffness to determine the influence on our results. We evaluated our simulation results by comparison with histological examinations of human skin from the forehead (Contet-Audonneau et al., 1999; Tsukahara et al., 2011).
Section snippets
Layered morphology and mesh
Fig. 1 illustrates our 3-D model of the skin of the human forehead: (a) schematic detailing six layers, and (b) the corresponding finite element mesh presented with the same color scheme. Therein, x and y are in-plane coordinates, and z is through the thickness, perpendicular to the x-y plane of the skin surface. The in-plane dimensions of the model are Lx = 5 mm and Ly = 0.5 mm, and the total thickness is Lz = 1.981 mm. We generated the thickness of each layer based on measurements of healthy
Muscle contraction - dynamic wrinkles
In Fig. 3 we illustrate the through-thickness Green-Lagrange strains at different muscle contractions for both young and aged skin, and in Fig. 4 we illustrate the same for young skin at both WC equals 36% and 18%.
The zoomed-in insets highlight the wrinkle morphologies, which concentrate strong tensile strains near the peaks and strong compressive strains in the valleys of wrinkles.
In Fig. 3 at low contraction (7.5%), young skin retains a smooth appearance but aged skin shows PD wrinkling
Discussion
We performed wrinkling simulations exercising our new six-layered model to elucidate wrinkling in the forehead with both dynamic and static wrinkles, and as a function of humidity in the SC. The periodicity and amplitude of the wrinkles appearing at the skin surface tracks a buckling process from superficial to the inner layers under mechanisms of increased skin compression and tissue loss, during which wrinkle formation starts with fine lines and turns into visible grooves. For the specific
CRediT authorship contribution statement
Y. Zhao: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Visualization, Writing - original draft, Writing - review & editing. B. Feng: Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Visualization, Writing - original draft, Writing - review & editing. J. Lee: Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Writing - review & editing. N. Lu:
Declaration of competing interest
None.
Acknowledgement
We are thankful for funding from Unilever Research and Development, Trumbull, CT, USA.
References (55)
- et al.
Mechanics of cell growth
Mech. Res. Commun.
(2012) - et al.
Biomechanical modeling of surface wrinkling of soft tissues with growth-dependent mechanical properties
Acta Mech. Solida Sin.
(2012) - et al.
The anatomy of the aging face: volume loss and changes in 3-dimensional topography
Aesthetic Surg. J.
(2006) - et al.
The relative contributions of different skin layers to the mechanical behavior of human skin in vivo using suction experiments
Med. Eng. Phys.
(2006) - et al.
Instabilities of soft films on compliant substrates
J. Mech. Phys. Solid.
(2017) - et al.
Mechanical approach to aging and wrinkling of human facial skin based on the multistage buckling theory
Med. Eng. Phys.
(2008) - et al.
Loss of elastic fibers causes skin wrinkles in sun-damaged human skin
J. Dermatol. Sci.
(2008) - et al.
An algorithmic approach to multi-layer wrinkling
Extreme Mech. Lett.
(2016) - et al.
A mechanistic insight into the mechanical role of the stratum corneum during stretching and compression of the skin
J. Mech. Behav. Biomed. Mater.
(2015) - et al.
Interactions between fibroblasts and keratinocytes in morphogenesis of dermal epidermal junction in a model of reconstructed skin
J. Invest. Dermatol.
(2006)
In vivo measurements of the elastic mechanical properties of human skin by indentation tests
Med. Eng. Phys.
Nonlinear viscoelastic properties of native male human skin and in vitro 3d reconstructed skin models under Laos stress
J. Mech. Behav. Biomed. Mater.
Microstructurally-based constitutive modelling of the skin–linking intrinsic ageing to microstructural parameters
J. Theor. Biol.
Histological, sem and three-dimensional analysis of the midfacial smas–new morphological insights
Ann. Anat.
Variables influencing the frictional behaviour of in vivo human skin
J. Mech. Behav. Biomed. Mater.
Mechanical properties of human stratum corneum: effects of temperature, hydration, and chemical treatment
Biomaterials
3d finite element modeling for instabilities in thin films on soft substrates
Int. J. Solid Struct.
Growth on demand: reviewing the mechanobiology of stretched skin
J. Mech. Behav. Biomed. Mater.
Mechanical properties and young's modulus of human skin in vivo
Arch. Dermatol. Res.
Wrinkling phenomena in neo-hookean film/substrate bilayers
J. Appl. Mech.
A comprehensive examination of topographic thickness of skin in the human face
Aesthetic Surg. J.
A histological study of human wrinkle structures: comparison between sun-exposed areas of the face, with or without wrinkles, and sun-protected areas
Br. J. Dermatol.
In vivo model of the mechanical properties of the human skin under suction
Skin Res. Technol.
Forehead wrinkles: a histological and immunohistochemical evaluation
J. Cosmet. Dermatol.
A three-layer model of skin and its application in simulating wrinkling
Comput. Methods Biomech. Biomed. Eng.
Skin anti-aging strategies
Dermatoendocrinol
Skin Layer Mechanics
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