ABSTRACT
The skin is the most complex and largest organ of the human body, accounting for about 15% of the total adult body weight and serving mainly as a primary protective physical barrier against external environmental signals. It helps to maintain body homeostasis by preventing dehydration, maintaining thermoregulation, and limiting the direct penetration of potentially harmful agents to internal organs (Kanitakis 2002, Groeber, Holeiter et al. 2012; Pereira, Barrias et al. 2013; Mathes, Ruffner et al. 2014). Furthermore, other immunologic, endocrine, metabolic, neurosensory, and psychosocial functions of skin are essential and these multiple roles are closely related to and harmoniously coordinated by three layer structures of skin (composed of epidermis, dermis, and hypodermis) and other skin components such as hair, sensory nerves, the immune system, and various glands (Chuong, Nickoloff et al. 2002; Kanitakis 2002; Brohem, Cardeal et al. 2011; Eungdamrong, Higgins et al. 2014). The epidermis, the outermost stratified epithelium layer of the skin, is made of various cell types to perform such multiple functions as a whole; namely, keratinocytes (90-95%), specialized dendritic Langerhans cells (3-6%), pigment-producing melanocytes, neuroendocrine and epithelial Merkel cells, lymphocytes (<1.3%), and Toker cells. Keratinocytes in the epidermal layer undergo the continuous process of proliferation, differentiation, and cornification (ultimate cell death and shedding), which leads to compartmentalization into a number of complex layers with different stages of keratinocyte maturation. This complex compartmentalization and continuous alignment of epidermal layers (the basal layer [single], the stratum spinous layer [5-15 layers], the granular layer [1-3 ayers], and the cornified layer [5-10 layers]) (Figure 10.1) (Kanitakis 2002; Stark, Szabowski et al. 2004; Brohem, Cardeal et al. 2011; Mathes,
10.1 Introduction: Background .............................................................................209 10.2 State of the Art for 3D Skin Tissue Models ................................................. 212
10.2.1 Reconstructed Human Epidermis ..................................................... 213 10.2.2 Full Thickness Tissue-Engineered Skin Models
with Multiple Cell Types .................................................................. 214 10.3 Novel Biofabrication Technology-Driven Skin Models ........................... 217
10.3.1 3D Bioprinting .................................................................................. 217 10.3.2 3D Multicellular Spheroids ...............................................................220 10.3.3 Skin-on-a-Chip ................................................................................. 221
10.4 Conclusions ...................................................................................................225 References ..............................................................................................................225
