Advanced Biofabrication Strategies for Skin Regeneration and Repair

Rúben F Pereira; Cristina C Barrias; Pedro L Granja; Paulo J Bartolo


Nanomedicine. 2013;8(4):603-621. 

In This Article

Skin Damage & Wound Healing

Skin is the largest organ of the body, serving primarily as a protective barrier against the environment.[1–3] It also helps to prevent body dehydration and constitutes a physical barrier, limiting the penetration of potentially harmful agents to internal organs. The skin has a three-layer structure composed of epidermis, dermis and hypodermis (Figure 1).[4–6] The epidermis, the superficial layer, is mainly composed of keratinocytes but also contains other cell types, such as Langerhans cells and melanocytes,[5,7] providing a barrier against infection and moisture loss. The dermal layer, situated below the epidermis, is responsible for the elasticity and mechanical integrity of the skin. It contains vascularized extracellular matrix (ECM) rich in collagen, elastin and glycosaminoglycans.[3,5,6] The cellular components of the dermal layer include fibroblasts, endothelial cells, smooth muscle cells and mast cells.[3,5] The hypodermis, located below the dermis, is mainly composed of adipose tissue and collagen, and mainly acts as an energy source.[4,5,7]

Figure 1.

Skin structure showing the three layers, the skin appendages and the main cellular constituents.

Skin damage is mainly caused by burn injuries, chronic wounds (venous, pressure and leg ulcers), excision of skin, tumors and other dermatological conditions.[2,8] According to WHO, 300,000 deaths are annually attributed to burn injuries, while 6 million patients worldwide suffer from burns every year.[4] Additionally, more than 6 million individuals suffer from chronic skin ulcers.[4] In the USA alone more than 3 million patients suffer from chronic wounds.[9]

Skin has a natural healing ability that generates, at the moment of injury, a complex cascade of highly integrated and overlapping events of hemostasis, inflammation, migration, proliferation and maturation, as illustrated in Figure 2.[10–12] This complex, dynamic and continuous process relies on the interaction between cellular components, growth factors and cytokines, acting in concert to repair the damaged tissue.[13,14]

Figure 2.

Phases of the wound healing process.
Hemostasis involves the formation of a fibrin clot occurring simultaneously with the inflammatory phase, in which inflammatory cells are responsible for wound cleaning. During the migration and proliferation phases, epithelial cells and fibroblasts migrate to the wound site in order to synthesize the constituents of the extracellular matrix, leading to the formation of a granulation tissue. In the maturation phase, the composition and properties of the granulation tissue are continuously remodeled in order to achieve values proximal to the healthy skin.
Adapted with permission from [4].