Towards the development of sensation-enabled skin substitutes.

Recent advances in cell and biofabrication technologies have contributed to the development of complex human organs. In particular, several skin substitutes are being generated using tissue engineering and regenerative medicine (TERM) technologies. However, recent studies mainly focus on the restoration of the dermis and epidermis layers rather than the regeneration of a fully functional innervated skin organ. Innervation is a critical step in functional tissue repair which has been overlooked in the current TERM studies. In the current study, we highlight the importance of sensation in the skin as the largest sensory organ in the human body. In large non-healing skin wounds, the skin sensation is severely diminished or completely lost and ultimately lead to chronic pain and wound healing process interruption. Current therapeutics for restoring skin sensation after trauma are limited. Recent regenerative medicine-based studies could successfully induce neural networks in skin substitutes, but the effectiveness of these technologies in enhancing sensory capability needs further investigation.