Over the years, conventional skin grafts, such as full-thickness, split-thickness, and pre-sterilized grafts from human or animal sources, have been at the forefront of skin wound care. However, these conventional grafts are associated with major challenges, including supply shortage, rejection by the immune system, and disease transmission following transplantation. Due to recent progress in nanotechnology and material sciences, advanced artificial skin grafts-based on the fundamental concepts of tissue engineering-are quickly evolving for wound healing and regeneration applications, mainly because they can be uniquely tailored to meet the requirements of specific injuries. Despite tremendous progress in tissue engineering, many challenges and uncertainties still face skin grafts in vivo, such as how to effectively coordinate the interaction between engineered biomaterials and the immune system to prevent graft rejection. Furthermore, in-depth studies on skin regeneration at the molecular level are lacking; as a consequence, the development of novel biomaterial-based systems that interact with the skin at the core level has also been slow. This review will discuss 1) the biological aspects of wound healing and skin regeneration, 2) important characteristics and functions of biomaterials for skin regeneration applications, and 3) synthesis and applications of common biomaterials for skin regeneration. Finally, the current challenges and future directions of biomaterial-based skin regeneration will be addressed.

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