CD44 Signaling in Skin Wound Healing and Regeneration

August 2025 in “ Journal of Translational Medicine ”

Annie Y Guan, Yanlin Chen, Scheffer C.G. Tseng, Qing Lin

CD44 hyaluronic acid keratinocytes epithelial cells vascular endothelial cells fibroblasts HC-HA/PTX3 complex HA

Studysummary This comprehensive review suggests that CD44 signaling plays a significant role in post-natal skin wound healing and scar formation, with potential for therapeutic approaches targeting CD44 to shift from fibrotic scarring towards regenerative healing, including wound regeneration and hair neogenesis. Our plain-language summary of this paper — not a Tressless recommendation.

The document reviews the role of CD44 signaling in skin wound healing and regeneration, emphasizing its involvement in immune and cellular processes across the four phases of wound healing. CD44, activated by hyaluronic acid (HA), influences immune cell behavior, keratinocyte and epithelial cell function, angiogenesis, and fibroblast activity, which are crucial for wound healing and scar formation. The review introduces the HC-HA/PTX3 complex from human amniotic membrane as a novel approach to enhance CD44's regenerative properties. CD44 signaling is vital for modulating immune responses, influencing inflammation, and facilitating transitions between wound healing phases. It also plays a role in hair follicle regeneration and stem cell biology, promoting pro-regenerative activities. Targeting CD44 pathways could enhance wound healing, reduce scarring, and offer therapeutic applications for conditions like diabetic wounds, psoriatic lesions, and aged skin. Understanding these interactions is crucial for developing targeted therapies to improve wound healing outcomes.

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