A multi-layered model of human skin elucidates mechanisms of wrinkling in the forehead

https://doi.org/10.1016/j.jmbbm.2020.103694Get rights and content

Highlights

  • Propose the first six-layered, 3-D skin model to simulate dynamic and static wrinkles.

  • Apply compression up to 25% to model muscle contraction (dynamic wrinkles).

  • Apply age-related volumetric loss within the reticular dermis to model static wrinkles.

  • Simulation results agree well with histological images from forehead wrinkles.

  • Wrinkling mode tracks the development of wrinkles from surface to inner layers.

Abstract

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. 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, viable epidermis, dermal-epidermal-junction, papillary dermis, reticular dermis, and hypodermis. To better address the through-thickness hierarchy, and the development of wrinkling within this complicated hierarchy, we established a six-layered model of human skin realized with finite element modeling, by leveraging available morphological and biomechanical data on human skin of the forehead. 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 stratum corneum significantly affects its stiffness we also aimed to quantify the influence its hydration with these three potential mechanisms of wrinkle formation. Our six-layered skin model, combined with the proposed wrinkling mechanisms, successfully predicts the formation of dynamic and static wrinkles in the forehead consistent with the experimental literature. We observed three wrinkling modes in the forehead where the deepest wrinkles could reach to the reticular dermis. With further refinement our new six-layered model of human skin can be applied to study other region-specific wrinkle types such as the “crow's feet” and the nasolabial folds.

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.

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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 Ezz 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.

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