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CHA PTE R

Skin Mechanobiology and Biomechanics: From

Homeostasis to Wound Healing

,†
,†
Maria G. Fernandes* , Lucı ´lia P. da Silva* , and Alexandra P. Marques* ,†,‡
*I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters
of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho,
‡
†
Guimara ˜es, Portugal ICVS/3B’s—PT Government Associate Laboratory, Guimara ˜es, Portugal The Discoveries Centre
for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimara ˜es, Portugal

17.1 INTRODUCTION

The skin is the outmost and largest organ of the body constituting 6%–10% of the lean body mass. It is a layered
tissue containing in total more than 20 different cell types that in a very coordinated way act to keep skin homeostasis
and function. It is the first line of defense against the external environment, that is, external forces (tension, compres-
sion, and shear), external pathogens, temperature, and radiation. The outermost layer, epidermis, varies in thickness
depending on its location and function. This layer consists of a stratified squamous epithelium of keratinocytes delim-
ited by the basal membrane and contains melanocytes, Langerhans cells, and Merkel cells [1, 2]. The internal layer,
dermis, is a connective tissue that represents most of the skin substance and structure. The dermis is composed of
fibroblasts and extracellular matrix (ECM) enriched in collagen and elastin fibers and can be divided into two layers:
the upper papillary and the thicker lower reticular dermis. The skin mechanical properties, strength, and elasticity are
mostly owed to the composition and organization/orientation of the ECM in the dermis [3–5]. Lastly, beneath the
dermis is the hypodermis, composed primarily of adipose cells used for fat storage, and is usually not regarded as
part of the skin tissue.
Being a tissue constantly exposed to many external and endogenous factors, which disintegrate its structure and
functions, skin requires intrinsic suitable mechanical properties that protect the body from suffering damage. While
it is known that skin has high flexibility and is able to support large deformations, its mechanical properties are com-
plex and difficult to describe or predict due to skin complexity. Moreover, the mechanical properties of skin not only
differentiate between the different layers but also vary with skin anatomical region (heterogeneity), age, sex, pathol-
ogy, body weight, and orientation (anisotropy) (Fig. 17.1). In addition to skin inherent biomechanics variability, the
mechanical testing used to analyze skin biomechanics plays a pivotal role in the measurement [6–10]. Hence, it is not
surprising that the evaluation of skin biomechanics has revealed inconsistent results.
The skin is a tensegrity tissue, and it is in passive tension at homeostasis. Once the mechanical properties of the skin
are unable to support the external conditions or the tissue is removed, the skin tensegrity is compromised. After a
breach, the skin responds with an orchestrated process to heal the wound and restore the integrity of the tissue.
The wound healing process encompasses four interconnected and consecutive phases, namely, hemostasis, inflamma-
tion, proliferation, and remodeling. All of these phases are influenced by mechanical forces, and there is increasing
evidence that mechanical influences regulate postinjury inflammation contributing to the closure of the wound [11]
and the formation of fibrotic tissue [12, 13]. Human skin, as well as skin cells, reacts to mechanical forces and converts
mechanical cues to biochemical signals that are crucial to the way the wound healing progresses [12, 14]. While the
homeostatic and wound cellular and biochemical milieus have been largely studied to create better cues for regener-
ation, skin mechanical environment has not been as explored. Moreover, most of this knowledge has been provided by
in vitro studies assessing the effect of tension over skin cells [15–24]. Mechanical stimuli have also been evaluated

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