Introduction

This chapter discusses cellular growth factors and other secreted components such as exosomes, which are responsible for stimulating cellular growth, proliferation, differentiation, and overall skin health. Growth factors and exosomes, studied in wound healing models, have been adapted as cosmeceuticals for their ability to improve the appearance of aging skin. Exosomes are another key secretory component of cells responsible for many processes involved in wound healing.

Skin aging and repair

Extensive research on skin aging has improved our understanding of the pathophysiology of intrinsic (age‐related) and extrinsic (solar radiation, lifestyle, and pollution) aging. Biochemical processes result in skin damage following exposure to ultraviolet light and other external factors [1, 2]. Figure 39.1 shows the stages of skin damage and repair and role of key growth factors in each stage. Each stage of wound healing is also affected by exosomes secreted from various cells present in the wound bed and surrounding areas, these are most likely the same cells that produce growth factors [4, 5]. A variety of growth factors and exosomes flood the site of skin damage and interact synergistically to initiate and coordinate each phase of wound healing. They help recruit and activate fibroblasts to rapidly produce extracellular matrix (ECM) to repair the damaged dermal structure followed by stimulation and multiplication of keratinocytes to form new epidermis. The overall process is complex and not completely understood [3, 4]. The source of damage can be extrinsic such as solar radiation and pollution, or part of metabolic oxidation from intrinsic ageing.

A variety of inflammatory pathways are activated after skin damage which leads to increased degradation and reduced biosynthesis of ECM components, including collagen and elastin, resulting in loss of dermal structural integrity and formation of photodamaged phenotype as described in Figure 39.2. Presence of reactive oxygen species (ROS or free radicals) generated from inflammatory pathways combined with loss of stored anti‐oxidants from extrinsic factors further potentiates inflammation‐mediated skin damage [6–10]. Successful resolution of skin damage requires a balance between development of inflammation and its rapid resolution which includes involvement of cell‐derived secreted components such as growth factors, cytokines and contents of exosomes (identified in Figure 39.1) during every stage of wound healing [4, 11].

Transition from the inflammatory phase of skin repair to the granulation phase is again mediated by a variety of growth factors, cytokines and exosomes derived from macrophages, epidermal keratinocytes, and fibroblasts. Multiple metabolic pathways lead to formation of new ECM components during this phase. The final phase of skin repair is the beginning of dermal tissue remodeling. During this phase, low strength, unorganized, type 3 collagen and irregular elastin structures produced earlier are replaced by stronger type 1 collagen and structured elastin fibers to provide strength and resiliency to the dermis. This remodeling phase persists for several months and is the key to reversing the visible effects of skin aging [12].