Stem cell-based therapies offer tremendous potential for skin regeneration following injury and disease. Functional stem cell units have been described throughout all layers of human skin and the collective physical and chemical microenvironmental cues that enable this regenerative potential are known as the stem cell niche. Stem cells in the hair follicle bulge, interfollicular epidermis, dermal papillae, and perivascular space have been closely investigated as model systems for niche-driven regeneration. These studies suggest that stem cell strategies for skin engineering must consider the intricate molecular and biologic features of these niches. Innovative biomaterial systems that successfully recapitulate these microenvironments will facilitate progenitor cell-mediated skin repair and regeneration. 1. Introduction Skin serves as the interface with the external world and maintains key homeostatic functions throughout life. This regenerative process is often overlooked until a significant exogenous and/or physiologic insult disrupts our ability to maintain skin homeostasis [1]. Complications of normal repair often result in chronic wounds, excessive scarring, or even malignant transformation, cutaneous diseases that contribute substantially to the global health burden [2, 3]. As human populations prone to inadequate healing (such as the aged, obese, and diabetics) continue to expand, novel therapies to treat dysfunctional skin repair and regeneration will become more critical. Tissue regeneration has been demonstrated in multiple invertebrate and vertebrate species [4]. In humans, even complex tissues can regenerate without any permanent sequelae, such as liver, nerves, and skin. Although the typical result after significant organ injury is the formation of scar, regeneration after extensive skin and soft tissue trauma has been reported, most notably after digit tip amputation [5]. It is well accepted that human skin maintains the ability to regenerate; the question for researchers and clinicians is how to harness this potential to treat cutaneous injury and disease. The integumentary system is a highly complex and dynamic system composed of myriad cell types and matrix components. Numerous stem cell populations have been identified in skin and current research indicates that these cells play a vital role in skin development, repair, and homeostasis [1, 6, 7]. In general, stem cells are defined by their ability to self-renew and their capacity to differentiate into function-specific daughter cells. These progenitor cells have been isolated from all
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