Tissue engineered skin substitutes: A comprehensive review of basic design, fabrication using 3D printing, recent advances and challenges.

The multi-layered skin structure includes the epidermis, dermis and hypodermis, which forms a sophisticated tissue composed of extracellular matrix (ECM). The wound repair is a well-orchestrated process when the skin is injured. However, this natural wound repair will be ineffective for large surface area wounds. Autografts-based treatment is efficient but, additional pain and secondary healing of the patient limits its successful application. Therefore, there is a substantial need for fabricating tissue-engineered skin constructs. The development of a successful skin graft requires a fundamental understanding of the natural skin and its healing process, as well as design criteria for selecting a biopolymer and an appropriate fabrication technique. Further, the fabrication of an appropriate skin graft needs to meet physicochemical, mechanical, and biological properties equivalent to the natural skin. Advanced 3D bioprinting provides spatial control of the placement of functional components, such as biopolymers with living cells, which can satisfy the prerequisites for the preparation of an ideal skin graft. In this view, here we elaborate on the basic design requirements, constraints involved in the fabrication of skin graft and choice of ink, the probable solution by 3D bioprinting technique, as well as their latest advancements, challenges, and prospects.