Abstract: Burns care and chronic wound healing are two of the most disabling conditions and one major global health burdens. Tissue engineering skin substitutes and skin surgery are the main treatments. Despite the extensive research and development of skin tissue engineering over the last century, challenges remain unsolved, such as delayed vascularization, absence of essential sweat gland units and impaired skin pigmentation. The emerging 3D bioprinting technology is a promise enabling technology to build complex skin constructs. but before this technology can be fully utilized, issues such as seed cells, bio-ink formulations need to be optimized, bioprinting process and 3D printers must satisfy the regulatory requirements, though the national and international standards have yet to be established. Future studies should focus on the development of scalable printable technology, the exploration of novel cell sources and the exploitation of innovative bio-inks. The aim of this review is to provide an update of skin substitute development and application, summarize the available novel cell sources and bio-ink biomaterial with emphasis on their application with 3D printing technology. Especially, the induced pluripotent stem cells and skin progenitor cells in restoring of functions of hair follicles, receptors, sebaceous and sweat glands of skin, supporting rapid vascularization and nerve regeneration, Harness the power of the new emerging 3D printing techniques in skin tissue engineering and move traditional tissue engineering manufacturing process directly into the era of smart manufacturing. Utilizing 3D printing technology to print biologically, structurally and functionally native like artificial skin witch includes all essential cellular components in the near future.

Key words: skin tissue engineering, 3D bioprinting, keratinocytes, fibroblasts, stem cells