From Basic Biology to Engineered Therapies: The Keratinocyte Stem Cell Playbook

February 2026 in “ Frontiers in Medical Technology ”

Adnan Uddin, Mohamad Rahmani, Abdulrahim A. Sajini

keratinocyte stem cells epidermal renewal self-renewal differentiation identity switch cell-cycle lock mechanotransduction lock external signals intrinsic mechanisms human keratinocytes 3D models hydrogel delivery systems keratinocyte-derived products wound healing immunomodulation pigment restoration ocular tissue regeneration mucosal tissue regeneration

TLDR Keratinocyte stem cells are crucial for skin renewal and have potential in wound healing and tissue regeneration.

This review explores the role of keratinocyte stem cells (KSCs) in epidermal renewal, focusing on their ability to balance self-renewal and differentiation through three "fate locks": identity switch, cell-cycle lock, and mechanotransduction lock. It discusses how external signals and intrinsic mechanisms guide KSC fate, and highlights advancements in isolating and expanding human keratinocytes. The review also covers 3D models, hydrogel delivery systems, and keratinocyte-derived products for wound healing, while noting emerging applications in immunomodulation, pigment restoration, and regeneration of ocular and mucosal tissues.

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