The tremendous ability of the skin epidermis to regenerate is due to the presence of epidermal stem cells that continuously produce keratinocytes which undergo terminal differentiation to a keratinized layer that provides the skin’s barrier properties. The ability to control this process in vitro has made it possible to develop various types of tissue engineered skin grafts, some of which being among the first tissue engineered products to ever reach the marketplace. In the past 30 years these products have been applied with some success to the treatment of chronic skin wounds, such as diabetic and venous ulcers, as well as deep acute wounds, such as burns. Current technologies remain partially effective in their ability to restore other skin structures, for example the dermis, which is critical to the overall long-term appearance and function of the skin. Furthermore, to this day none of these approaches regenerate skin appendages (e.g. hair follicles, sweat glands). The use of earlier progenitor and stem cells, including embryonic stem cells is gaining interest to overcome such limitations. Furthermore, recent evidence suggests that “adult” stem cells, which are present in the circulation of the patient, home into areas of injury and likely participate in the wound healing process. In this paper, we start with an overview of the wound healing process and current methods used for wound treatment, both conventional and tissue engineered-based. We then review current research on the various types of stem cells used for skin tissue engineering and wound healing, and provide future directions.
Over the past two decades, there has been a surge in the development of nanoparticle technologies for therapeutic applications. In the area of skin wound healing, silver nanoparticles have been long used as topical antibacterials, but new types of multifunctional nanosystems that can provide more comprehensive therapeutic effects on wounds are being rolled out. The ability to provide a reservoir of bioactive molecules that can be released over time is a feature of many of these systems, which is critically important for nonhealing wounds, where there often is a persistent bacterial load and a chronic lack of growth factors necessary for healing. A great advantage of nanosystems is that by virtue of their extremely small size, they can be easily incorporated into a wide variety of topical treatments that are currently available for use in the clinic. For example, nanoparticles can be easily introduced into decellularized skin products as well as other bioengineered skin substitutes. The design options available for the nanocarriers are very diverse, including encapsulating the drug in the particle's core or presenting it on the outside of the particle, which can also be decorated with a targeting agent, and the ability to change conformation in response to environmental cues (e.g., pH). These various design elements have been optimized differently to treat different types of wounds.
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