Hyaluronic Acid: A Key Regulator of Scarless versus Scarred Wound Healing

Regeneration varies widely across organisms, from whole-body regrowth in planarians to limited, scarred wound healing in humans. A unified model of regeneration requires understanding the interplay of cellular, biochemical, biomechanical, and spatial factors. The extracellular matrix (ECM), particularly hyaluronic acid (HA), is pivotal in determining regenerative outcomes. HA’s presence has been shown to distinguish complete regeneration from impaired, scarred healing in multiple contexts. We propose a multiscale model to explore the effects of HA density on ECM interactions with evolutionarily conserved biochemical (gene regulation and signalling networks) and biomechanical pathways during regeneration. Our model evaluates how HA metabolism influences tissue repair, focusing on the viscoelastic properties of HA-rich ECM and CD44-mediated signaling. These interactions drive critical regenerative phenotypes, including stemness, cell migration, and proliferation, enabling enhanced tissue regeneration. Our findings mechanistically explain how HA acts as a key determinant between complete regeneration and scarred healing. This model, among the few integrating biomechanical and biochemical pathways, highlights HA’s role in regeneration across organisms. Our results pave the way for a unified theory of regeneration, with potential applications in tissue engineering and regenerative medicine.

Hyaluronic Acid: A Key Regulator of Scarless versus Scarred Wound Healing

Monday, July 14 at 6:00pm in

SMB2025 Follow

Kishore Hari

"Hyaluronic Acid: A Key Regulator of Scarless versus Scarred Wound Healing"

#SMB2025 Follow